Contraception

TOPLINE: 

Despite the risk of worsening acne with progestin-only long-acting reversible contraception (LARC) in a study of adolescents and young adults, acne alone was not a common reason for discontinuation.

METHODOLOGY:

• Progestin-only LARC may increase the risk for acne, but this has not been well studied in adolescents and young adults.
• In the study, researchers evaluated the incidence of acne, acne as a reason for removal, and strategies used to manage acne after insertion of a progestin-only intrauterine device (IUD) or contraceptive implant in 1319 adolescents and young adults across four Adolescent Medicine LARC Collaborative study sites from January 2017 to June 2021.The mean age at insertion was 18.6 years.
• Overall, 24% of participants had acne at the time of LARC insertion.
• Worsening acne was defined as new patient reports of concern about acne, observations of acne, or addition of an acne medication after insertion; increased severity noted on an exam during follow-up or at the time of LARC removal; or acne reported as a side effect and/or reason for LARC removal.

TAKEAWAY: 

• During the study period, 376 participants (28.5%) experienced worsening acne after LARC insertion, and 17% reported acne as a new concern, with no differences between those who received an IUD or an implant.
• Only 44 of the 376 participants (11.7%) who reported worsening acne were being treated with an oral agent at follow-up.
• Of the 542 individuals (41% of the total) who had the LARC device removed, 40 (7.4%) cited concerns about acne for removing the device, although just 5 (0.92%) said that acne was the only reason for removal. Of the 40 with concerns about acne when the device was removed, 18 (45%) had documented acne at the time of insertion.

IN PRACTICE:

The authors recommend that clinicians prescribing progestin-only LARC should counsel patients that acne may be a side effect, reassuring them that if they develop acne, “it typically is not problematic enough to warrant discontinuation,” and concluded that “concerns about the development or worsening of acne should not be cause to avoid these forms of contraception.”

[embed:render:related:node:267688]

SOURCE:

The study, led by Markus D. Boos, MD, PhD, of the division of dermatology in the Department of Pediatrics, University of Washington in Seattle and Seattle Children’s Hospital, was published in Pediatric Dermatology.

LIMITATIONS:

Individuals without documented acne were assumed to be acne-free, creating potential bias. Acne evaluation and treatment were not standardized and were not performed by dermatologists; acne severity was not recorded for many participants, possibly underestimating severity, and excluding LARC insertions without follow-up or with removal within 8 weeks may have underestimated the percentage of participants who developed new or worsening acne.

DISCLOSURES: 

The study was supported by Investigator-Initiated Studies Program of Organon and by the Health Resources and Services Administration of the US Department of Health and Human Services. Many authors received grants for this work. The authors did not disclose any other competing interests.

A version of this article appeared on Medscape.com.

TOPLINE: 

Despite the risk of worsening acne with progestin-only long-acting reversible contraception (LARC) in a study of adolescents and young adults, acne alone was not a common reason for discontinuation.

METHODOLOGY:

• Progestin-only LARC may increase the risk for acne, but this has not been well studied in adolescents and young adults.
• In the study, researchers evaluated the incidence of acne, acne as a reason for removal, and strategies used to manage acne after insertion of a progestin-only intrauterine device (IUD) or contraceptive implant in 1319 adolescents and young adults across four Adolescent Medicine LARC Collaborative study sites from January 2017 to June 2021.The mean age at insertion was 18.6 years.
• Overall, 24% of participants had acne at the time of LARC insertion.
• Worsening acne was defined as new patient reports of concern about acne, observations of acne, or addition of an acne medication after insertion; increased severity noted on an exam during follow-up or at the time of LARC removal; or acne reported as a side effect and/or reason for LARC removal.

TAKEAWAY: 

• During the study period, 376 participants (28.5%) experienced worsening acne after LARC insertion, and 17% reported acne as a new concern, with no differences between those who received an IUD or an implant.
• Only 44 of the 376 participants (11.7%) who reported worsening acne were being treated with an oral agent at follow-up.
• Of the 542 individuals (41% of the total) who had the LARC device removed, 40 (7.4%) cited concerns about acne for removing the device, although just 5 (0.92%) said that acne was the only reason for removal. Of the 40 with concerns about acne when the device was removed, 18 (45%) had documented acne at the time of insertion.

IN PRACTICE:

The authors recommend that clinicians prescribing progestin-only LARC should counsel patients that acne may be a side effect, reassuring them that if they develop acne, “it typically is not problematic enough to warrant discontinuation,” and concluded that “concerns about the development or worsening of acne should not be cause to avoid these forms of contraception.”

[embed:render:related:node:267688]

SOURCE:

The study, led by Markus D. Boos, MD, PhD, of the division of dermatology in the Department of Pediatrics, University of Washington in Seattle and Seattle Children’s Hospital, was published in Pediatric Dermatology.

LIMITATIONS:

Individuals without documented acne were assumed to be acne-free, creating potential bias. Acne evaluation and treatment were not standardized and were not performed by dermatologists; acne severity was not recorded for many participants, possibly underestimating severity, and excluding LARC insertions without follow-up or with removal within 8 weeks may have underestimated the percentage of participants who developed new or worsening acne.

DISCLOSURES: 

The study was supported by Investigator-Initiated Studies Program of Organon and by the Health Resources and Services Administration of the US Department of Health and Human Services. Many authors received grants for this work. The authors did not disclose any other competing interests.

A version of this article appeared on Medscape.com.

TOPLINE: 

Despite the risk of worsening acne with progestin-only long-acting reversible contraception (LARC) in a study of adolescents and young adults, acne alone was not a common reason for discontinuation.

METHODOLOGY:

• Progestin-only LARC may increase the risk for acne, but this has not been well studied in adolescents and young adults.
• In the study, researchers evaluated the incidence of acne, acne as a reason for removal, and strategies used to manage acne after insertion of a progestin-only intrauterine device (IUD) or contraceptive implant in 1319 adolescents and young adults across four Adolescent Medicine LARC Collaborative study sites from January 2017 to June 2021.The mean age at insertion was 18.6 years.
• Overall, 24% of participants had acne at the time of LARC insertion.
• Worsening acne was defined as new patient reports of concern about acne, observations of acne, or addition of an acne medication after insertion; increased severity noted on an exam during follow-up or at the time of LARC removal; or acne reported as a side effect and/or reason for LARC removal.

TAKEAWAY: 

• During the study period, 376 participants (28.5%) experienced worsening acne after LARC insertion, and 17% reported acne as a new concern, with no differences between those who received an IUD or an implant.
• Only 44 of the 376 participants (11.7%) who reported worsening acne were being treated with an oral agent at follow-up.
• Of the 542 individuals (41% of the total) who had the LARC device removed, 40 (7.4%) cited concerns about acne for removing the device, although just 5 (0.92%) said that acne was the only reason for removal. Of the 40 with concerns about acne when the device was removed, 18 (45%) had documented acne at the time of insertion.

IN PRACTICE:

The authors recommend that clinicians prescribing progestin-only LARC should counsel patients that acne may be a side effect, reassuring them that if they develop acne, “it typically is not problematic enough to warrant discontinuation,” and concluded that “concerns about the development or worsening of acne should not be cause to avoid these forms of contraception.”

[embed:render:related:node:267688]

SOURCE:

The study, led by Markus D. Boos, MD, PhD, of the division of dermatology in the Department of Pediatrics, University of Washington in Seattle and Seattle Children’s Hospital, was published in Pediatric Dermatology.

LIMITATIONS:

Individuals without documented acne were assumed to be acne-free, creating potential bias. Acne evaluation and treatment were not standardized and were not performed by dermatologists; acne severity was not recorded for many participants, possibly underestimating severity, and excluding LARC insertions without follow-up or with removal within 8 weeks may have underestimated the percentage of participants who developed new or worsening acne.

DISCLOSURES: 

The study was supported by Investigator-Initiated Studies Program of Organon and by the Health Resources and Services Administration of the US Department of Health and Human Services. Many authors received grants for this work. The authors did not disclose any other competing interests.

A version of this article appeared on Medscape.com.

Primary care clinicians have largely welcomed the arrival of Opill, the first over-the-counter (OTC) birth control pill from Perrigo, which will reach US pharmacy shelves this month. Although the medicine has a long-track record of safe use, physicians and nurse practitioners may want to ready themselves to answer questions from patients about shifting to the option.

The switch to OTC status for the norgestrel-only contraceptive has the support of many physician groups, including the American Medical Association, the American Academy of Family Physicians, and the American College of Obstetricians and Gynecologists (ACOG).

The end of the prescription-requirement removes a barrier to access for many women, especially those who lack insurance. But it also will take away a chief reason many women in their childbearing years make appointments with doctors, as they will no longer need prescriptions for birth control pills.

Anne-Marie Amies Oelschlager, MD, professor of obstetrics and gynecology at University of Washington School of Medicine, in Seattle, Washington, said she is also worried that the availability of an OTC pill will lead to missed opportunities to help patients avoid sexually transmitted diseases. For example, patients can get counseling about the need for testing for sexually transmitted diseases at the start of new relationships during a visit made to obtain a prescription for the pill.

“My hope is that they still follow our recommendations, which is to get tested with every partner,” said Dr. Oelschlager, who cares for many patients in their teens. “Adolescents are at a particularly high risk of infection compared to older ones.”

When clinicians do see patients, they may want to raise the issue of the OTC option and proper use. Patients will need to closely read materials provided for Opill, a step they might skip due to the ready access, according to Diana Zuckerman, PhD, president of the nonprofit National Center for Health Research, which scrutinizes the safety of medical products.

“When something is sold over the counter, it’s perceived by individuals as being safe,” Dr. Zuckerman told this news organization. “There’s less concern and a little less interest in reading the instructions and reading the warnings.”
 

Considerations for Safety

The US Food and Drug Administration (FDA) in July approved the sales of a daily 0.075 mg norgestrel tablet without prescription. Perrigo told this news organization that it spent the intervening months ensuring retailers and consumers will receive education on the drug.

One of the biggest challenges for people using Opill may be sticking with the dosing schedule, according to Dr. Oelschlager.

“There are going to be people that have a harder time remembering to take a pill every day,” at the same time, said Dr. Oelschlager, who is chair of ACOG’s Clinical Consensus Gynecology Committee. “We need to watch and see what happens as it becomes more widely available, and people start using it.”

Unexpected vaginal bleeding is the most common adverse event linked to this form of birth control, with over one fifth of participants from one study of the OTC drug reporting this side effect, according to an FDA memo.

“It is more likely to be a tolerability issue rather than a safety issue,” the FDA wrote.

Many prescription of birth control options contain estrogen, which is associated with venous thromboembolism (VTE). But Opill contains only norgestrel, a form of progestin, which is not associated with thrombosis. Patients may be more likely to overestimate their potential risks for VTE than to underestimate them, according to Kwuan Paruchabutr, DNP, president of National Association of Nurse Practitioners in Women’s Health and an assistant professor at Georgetown University in Washington, DC.

“This is a progesterone-only pill: The risk is relatively low” of VTE, Dr. Paruchabutr said.

Clinicians should also take special care with patients who are prescribed drugs for seizures, tuberculosis, HIV/AIDS, and pulmonary hypertension or who are taking supplements containing St John’s wort.

Patients in their childbearing years who take isotretinoin are already expected to use some form of birth control.

“All patients on isotretinoin must be registered in the iPLEDGE program, which mandates monthly contraception counseling and monthly pregnancy tests for persons of childbearing potential,” Terrence A. Cronin, Jr, MD, president of the American Academy of Dermatology, told news organization through email.

Dr. Oelschlager noted that many patients who take isotretinoin may benefit from taking a birth control pill containing estrogen, for which they will need a prescription. At least three pills have an FDA-approved indication for treating moderate acne, including Ortho Tri-Cyclen, Estrostep, and Yaz.

The FDA has posted consumer-friendly information about the OTC pill that clinicians can refer their patients to. For clinicians who want more information, ACOG released a practice advisory about the switch in status for this progestin-only pill.
 

The Cost

While federal laws mandate employer-based and Medicaid plans cover prescription birth control pills for free, the OTC version will carry a cost, according to A. Mark Fendrick, MD, director of the University of Michigan Center for Value-Based Insurance Design in Ann Arbor, Michigan. 

Seven states, including New Mexico and New York, already have laws in effect that require health plans to cover certain OTC contraceptives without a prescription, according to a tally kept by the nonprofit research organization KFF.

Dr. Fendrick said it would be helpful for health plans to offer coverage for the OTC pill without copays even if they are not required to do so.

Priced at about $20 a month, Opill “is likely out of reach for many of the individuals who would most benefit from an OTC option,” Dr. Fendrick told this news organization in an email.

The new pill may be utilized most by those who do not have health insurance or have low incomes and cannot afford to see a doctor for a prescription, according to Sally Rafie, PharmD, a pharmacist specialist at University of California San Diego Health and founder of the Birth Control Pharmacist.

The manufacturer’s suggested retail prices will be $19.99 for a 1-month supply and $49.99 for a 3-month supply. Dublin-based Perrigo said it plans to offer a cost-assistance program for the drug in the coming weeks for people who have low incomes and lack insurance.

A version of this article appeared on Medscape.com.

Primary care clinicians have largely welcomed the arrival of Opill, the first over-the-counter (OTC) birth control pill from Perrigo, which will reach US pharmacy shelves this month. Although the medicine has a long-track record of safe use, physicians and nurse practitioners may want to ready themselves to answer questions from patients about shifting to the option.

The switch to OTC status for the norgestrel-only contraceptive has the support of many physician groups, including the American Medical Association, the American Academy of Family Physicians, and the American College of Obstetricians and Gynecologists (ACOG).

The end of the prescription-requirement removes a barrier to access for many women, especially those who lack insurance. But it also will take away a chief reason many women in their childbearing years make appointments with doctors, as they will no longer need prescriptions for birth control pills.

Anne-Marie Amies Oelschlager, MD, professor of obstetrics and gynecology at University of Washington School of Medicine, in Seattle, Washington, said she is also worried that the availability of an OTC pill will lead to missed opportunities to help patients avoid sexually transmitted diseases. For example, patients can get counseling about the need for testing for sexually transmitted diseases at the start of new relationships during a visit made to obtain a prescription for the pill.

“My hope is that they still follow our recommendations, which is to get tested with every partner,” said Dr. Oelschlager, who cares for many patients in their teens. “Adolescents are at a particularly high risk of infection compared to older ones.”

When clinicians do see patients, they may want to raise the issue of the OTC option and proper use. Patients will need to closely read materials provided for Opill, a step they might skip due to the ready access, according to Diana Zuckerman, PhD, president of the nonprofit National Center for Health Research, which scrutinizes the safety of medical products.

“When something is sold over the counter, it’s perceived by individuals as being safe,” Dr. Zuckerman told this news organization. “There’s less concern and a little less interest in reading the instructions and reading the warnings.”
 

Considerations for Safety

The US Food and Drug Administration (FDA) in July approved the sales of a daily 0.075 mg norgestrel tablet without prescription. Perrigo told this news organization that it spent the intervening months ensuring retailers and consumers will receive education on the drug.

One of the biggest challenges for people using Opill may be sticking with the dosing schedule, according to Dr. Oelschlager.

“There are going to be people that have a harder time remembering to take a pill every day,” at the same time, said Dr. Oelschlager, who is chair of ACOG’s Clinical Consensus Gynecology Committee. “We need to watch and see what happens as it becomes more widely available, and people start using it.”

Unexpected vaginal bleeding is the most common adverse event linked to this form of birth control, with over one fifth of participants from one study of the OTC drug reporting this side effect, according to an FDA memo.

“It is more likely to be a tolerability issue rather than a safety issue,” the FDA wrote.

Many prescription of birth control options contain estrogen, which is associated with venous thromboembolism (VTE). But Opill contains only norgestrel, a form of progestin, which is not associated with thrombosis. Patients may be more likely to overestimate their potential risks for VTE than to underestimate them, according to Kwuan Paruchabutr, DNP, president of National Association of Nurse Practitioners in Women’s Health and an assistant professor at Georgetown University in Washington, DC.

“This is a progesterone-only pill: The risk is relatively low” of VTE, Dr. Paruchabutr said.

Clinicians should also take special care with patients who are prescribed drugs for seizures, tuberculosis, HIV/AIDS, and pulmonary hypertension or who are taking supplements containing St John’s wort.

Patients in their childbearing years who take isotretinoin are already expected to use some form of birth control.

“All patients on isotretinoin must be registered in the iPLEDGE program, which mandates monthly contraception counseling and monthly pregnancy tests for persons of childbearing potential,” Terrence A. Cronin, Jr, MD, president of the American Academy of Dermatology, told news organization through email.

Dr. Oelschlager noted that many patients who take isotretinoin may benefit from taking a birth control pill containing estrogen, for which they will need a prescription. At least three pills have an FDA-approved indication for treating moderate acne, including Ortho Tri-Cyclen, Estrostep, and Yaz.

The FDA has posted consumer-friendly information about the OTC pill that clinicians can refer their patients to. For clinicians who want more information, ACOG released a practice advisory about the switch in status for this progestin-only pill.
 

The Cost

While federal laws mandate employer-based and Medicaid plans cover prescription birth control pills for free, the OTC version will carry a cost, according to A. Mark Fendrick, MD, director of the University of Michigan Center for Value-Based Insurance Design in Ann Arbor, Michigan. 

Seven states, including New Mexico and New York, already have laws in effect that require health plans to cover certain OTC contraceptives without a prescription, according to a tally kept by the nonprofit research organization KFF.

Dr. Fendrick said it would be helpful for health plans to offer coverage for the OTC pill without copays even if they are not required to do so.

Priced at about $20 a month, Opill “is likely out of reach for many of the individuals who would most benefit from an OTC option,” Dr. Fendrick told this news organization in an email.

The new pill may be utilized most by those who do not have health insurance or have low incomes and cannot afford to see a doctor for a prescription, according to Sally Rafie, PharmD, a pharmacist specialist at University of California San Diego Health and founder of the Birth Control Pharmacist.

The manufacturer’s suggested retail prices will be $19.99 for a 1-month supply and $49.99 for a 3-month supply. Dublin-based Perrigo said it plans to offer a cost-assistance program for the drug in the coming weeks for people who have low incomes and lack insurance.

A version of this article appeared on Medscape.com.

Primary care clinicians have largely welcomed the arrival of Opill, the first over-the-counter (OTC) birth control pill from Perrigo, which will reach US pharmacy shelves this month. Although the medicine has a long-track record of safe use, physicians and nurse practitioners may want to ready themselves to answer questions from patients about shifting to the option.

The switch to OTC status for the norgestrel-only contraceptive has the support of many physician groups, including the American Medical Association, the American Academy of Family Physicians, and the American College of Obstetricians and Gynecologists (ACOG).

The end of the prescription-requirement removes a barrier to access for many women, especially those who lack insurance. But it also will take away a chief reason many women in their childbearing years make appointments with doctors, as they will no longer need prescriptions for birth control pills.

Anne-Marie Amies Oelschlager, MD, professor of obstetrics and gynecology at University of Washington School of Medicine, in Seattle, Washington, said she is also worried that the availability of an OTC pill will lead to missed opportunities to help patients avoid sexually transmitted diseases. For example, patients can get counseling about the need for testing for sexually transmitted diseases at the start of new relationships during a visit made to obtain a prescription for the pill.

“My hope is that they still follow our recommendations, which is to get tested with every partner,” said Dr. Oelschlager, who cares for many patients in their teens. “Adolescents are at a particularly high risk of infection compared to older ones.”

When clinicians do see patients, they may want to raise the issue of the OTC option and proper use. Patients will need to closely read materials provided for Opill, a step they might skip due to the ready access, according to Diana Zuckerman, PhD, president of the nonprofit National Center for Health Research, which scrutinizes the safety of medical products.

“When something is sold over the counter, it’s perceived by individuals as being safe,” Dr. Zuckerman told this news organization. “There’s less concern and a little less interest in reading the instructions and reading the warnings.”
 

Considerations for Safety

The US Food and Drug Administration (FDA) in July approved the sales of a daily 0.075 mg norgestrel tablet without prescription. Perrigo told this news organization that it spent the intervening months ensuring retailers and consumers will receive education on the drug.

One of the biggest challenges for people using Opill may be sticking with the dosing schedule, according to Dr. Oelschlager.

“There are going to be people that have a harder time remembering to take a pill every day,” at the same time, said Dr. Oelschlager, who is chair of ACOG’s Clinical Consensus Gynecology Committee. “We need to watch and see what happens as it becomes more widely available, and people start using it.”

Unexpected vaginal bleeding is the most common adverse event linked to this form of birth control, with over one fifth of participants from one study of the OTC drug reporting this side effect, according to an FDA memo.

“It is more likely to be a tolerability issue rather than a safety issue,” the FDA wrote.

Many prescription of birth control options contain estrogen, which is associated with venous thromboembolism (VTE). But Opill contains only norgestrel, a form of progestin, which is not associated with thrombosis. Patients may be more likely to overestimate their potential risks for VTE than to underestimate them, according to Kwuan Paruchabutr, DNP, president of National Association of Nurse Practitioners in Women’s Health and an assistant professor at Georgetown University in Washington, DC.

“This is a progesterone-only pill: The risk is relatively low” of VTE, Dr. Paruchabutr said.

Clinicians should also take special care with patients who are prescribed drugs for seizures, tuberculosis, HIV/AIDS, and pulmonary hypertension or who are taking supplements containing St John’s wort.

Patients in their childbearing years who take isotretinoin are already expected to use some form of birth control.

“All patients on isotretinoin must be registered in the iPLEDGE program, which mandates monthly contraception counseling and monthly pregnancy tests for persons of childbearing potential,” Terrence A. Cronin, Jr, MD, president of the American Academy of Dermatology, told news organization through email.

Dr. Oelschlager noted that many patients who take isotretinoin may benefit from taking a birth control pill containing estrogen, for which they will need a prescription. At least three pills have an FDA-approved indication for treating moderate acne, including Ortho Tri-Cyclen, Estrostep, and Yaz.

The FDA has posted consumer-friendly information about the OTC pill that clinicians can refer their patients to. For clinicians who want more information, ACOG released a practice advisory about the switch in status for this progestin-only pill.
 

The Cost

While federal laws mandate employer-based and Medicaid plans cover prescription birth control pills for free, the OTC version will carry a cost, according to A. Mark Fendrick, MD, director of the University of Michigan Center for Value-Based Insurance Design in Ann Arbor, Michigan. 

Seven states, including New Mexico and New York, already have laws in effect that require health plans to cover certain OTC contraceptives without a prescription, according to a tally kept by the nonprofit research organization KFF.

Dr. Fendrick said it would be helpful for health plans to offer coverage for the OTC pill without copays even if they are not required to do so.

Priced at about $20 a month, Opill “is likely out of reach for many of the individuals who would most benefit from an OTC option,” Dr. Fendrick told this news organization in an email.

The new pill may be utilized most by those who do not have health insurance or have low incomes and cannot afford to see a doctor for a prescription, according to Sally Rafie, PharmD, a pharmacist specialist at University of California San Diego Health and founder of the Birth Control Pharmacist.

The manufacturer’s suggested retail prices will be $19.99 for a 1-month supply and $49.99 for a 3-month supply. Dublin-based Perrigo said it plans to offer a cost-assistance program for the drug in the coming weeks for people who have low incomes and lack insurance.

A version of this article appeared on Medscape.com.

A journal and publisher have retracted three papers about abortion, including one that has been used in court cases to support the suspension of FDA approval for mifepristone, aka an “abortion pill.”

Sage, the publisher of Health Services Research and Managerial Epidemiology, announced the retractions yesterday and posted a retraction notice covering the three articles.

For one of those articles, initially flagged by a reader, “an independent reviewer with expertise in statistical analyses evaluated the concerns and opined that the article’s presentation of the data in Figures 2 and 3 leads to an inaccurate conclusion and that the composition of the cohort studied has problems that could affect the article’s conclusions,” according to the notice.

The notice also said Sage “confirmed that all but one of the article’s authors had an affiliation with one or more of Charlotte Lozier Institute, Elliot Institute, and American Association of Pro-Life Obstetricians and Gynecologists, all pro-life advocacy organizations, despite having declared they had no conflicts of interest when they submitted the article for publication or in the article itself.” 

One of the peer reviewers, Sage learned, “was affiliated with Charlotte Lozier Institute at the time of the review,” leading the publisher and journal editor to determine “the peer review for initial publication was unreliable.” That referee also reviewed the other two now-retracted papers, according to Sage.

James Studnicki, the lead author of the three papers, told Retraction Watch the retractions were “a blatant attempt to discredit excellent research which is incongruent with a preferred abortion narrative.” He told The Daily Wire, a conservative news outlet that was first to report on the retractions, the move was “completely unjustified.” The Daily Wire notes that “The Supreme Court is set to hear arguments in March on the legality of restricting the abortion pill based on [Judge Matthew] Kacsmaryk’s ruling, proceedings that will certainly be impacted by the retractions.”

Sage had subjected one of the papers to an expression of concern in August 2023, saying they were investigating “potential issues regarding the representation of data in the article and author conflicts of interest” after being alerted by a reader. As News From The States reported then, the notice came after Chris Adkins, a professor at South University who teaches pharmaceutical sciences, raised concerns with Sage. As News From The States noted in August:

Kacsmaryk leaned hard on a 2021 study that was designed, funded and produced by the research arm of one of the most powerful anti-abortion political groups in the U.S. The judge cited this paper — which looked at Medicaid patients’ visits to the emergency room within 30 days of having an abortion — to justify that a group of anti-abortion doctors and medical groups have legal standing to force the FDA to recall mifepristone.

In a point-by-point response to Sage’s critiques of the paper sent to the publisher in November and now shared with Retraction Watch, Studnicki and colleagues pointed out they had noted their affiliations in the original manuscript and the then-proposed retractions “misrepresent ICMJE disclosure standards,” referring to the International Committee of Medical Journal Editors’ guidelines. They also call some of the post-publication peer reviewers’ critiques “factually incorrect” and “unfounded.” They conclude:

No single specific finding in any of the three papers has been explicitly challenged, let alone invalidated.

There is no evidence of a major error, miscalculation, fabrication, or falsification.

There is no breach of any of the COPE guidelines that could permit Sage to retract any of our published papers.

The retraction of any of these papers, let alone all three, is demonstrably unwarranted.

Adkins told Retraction Watch he is “pleased the journal approached my concerns with legitimate and serious consideration.” He continued:

It is reassuring that my initial concerns with the 2021 Studnicki et al. article were verified and affirmed by other experts. Despite the length of time spanning my initial communications with the journal and today’s retractions, I understand that thorough investigations and re-review processes take time. Given that these now-retracted articles have been excessively cited by parties involved in ongoing federal judicial cases, now positioned before the SCOTUS, Sage’s retractions should help our courts remain informed by the highest standards and quality in scientific and medical evidence.

Update, 2/6/24, 2100 UTC: We note that — contrary to best industry practices described by the Committee on Publication Ethics — Sage has removed the original versions of the articles. They are available at these links:

“A Longitudinal Cohort Study of Emergency Room Utilization Following Mifepristone Chemical and Surgical Abortions, 1999–2015”

“Doctors Who Perform Abortions: Their Characteristics and Patterns of Holding and Using Hospital Privileges”

“A Post Hoc Exploratory Analysis: Induced Abortion Complications Mistaken for Miscarriage in the Emergency Room are a Risk Factor for Hospitalization”

DISCLOSURE: Adam Marcus, a cofounder of Retraction Watch, is an editor at Medscape.

A version of this article appeared on Medscape.com.

A journal and publisher have retracted three papers about abortion, including one that has been used in court cases to support the suspension of FDA approval for mifepristone, aka an “abortion pill.”

Sage, the publisher of Health Services Research and Managerial Epidemiology, announced the retractions yesterday and posted a retraction notice covering the three articles.

For one of those articles, initially flagged by a reader, “an independent reviewer with expertise in statistical analyses evaluated the concerns and opined that the article’s presentation of the data in Figures 2 and 3 leads to an inaccurate conclusion and that the composition of the cohort studied has problems that could affect the article’s conclusions,” according to the notice.

The notice also said Sage “confirmed that all but one of the article’s authors had an affiliation with one or more of Charlotte Lozier Institute, Elliot Institute, and American Association of Pro-Life Obstetricians and Gynecologists, all pro-life advocacy organizations, despite having declared they had no conflicts of interest when they submitted the article for publication or in the article itself.” 

One of the peer reviewers, Sage learned, “was affiliated with Charlotte Lozier Institute at the time of the review,” leading the publisher and journal editor to determine “the peer review for initial publication was unreliable.” That referee also reviewed the other two now-retracted papers, according to Sage.

James Studnicki, the lead author of the three papers, told Retraction Watch the retractions were “a blatant attempt to discredit excellent research which is incongruent with a preferred abortion narrative.” He told The Daily Wire, a conservative news outlet that was first to report on the retractions, the move was “completely unjustified.” The Daily Wire notes that “The Supreme Court is set to hear arguments in March on the legality of restricting the abortion pill based on [Judge Matthew] Kacsmaryk’s ruling, proceedings that will certainly be impacted by the retractions.”

Sage had subjected one of the papers to an expression of concern in August 2023, saying they were investigating “potential issues regarding the representation of data in the article and author conflicts of interest” after being alerted by a reader. As News From The States reported then, the notice came after Chris Adkins, a professor at South University who teaches pharmaceutical sciences, raised concerns with Sage. As News From The States noted in August:

Kacsmaryk leaned hard on a 2021 study that was designed, funded and produced by the research arm of one of the most powerful anti-abortion political groups in the U.S. The judge cited this paper — which looked at Medicaid patients’ visits to the emergency room within 30 days of having an abortion — to justify that a group of anti-abortion doctors and medical groups have legal standing to force the FDA to recall mifepristone.

In a point-by-point response to Sage’s critiques of the paper sent to the publisher in November and now shared with Retraction Watch, Studnicki and colleagues pointed out they had noted their affiliations in the original manuscript and the then-proposed retractions “misrepresent ICMJE disclosure standards,” referring to the International Committee of Medical Journal Editors’ guidelines. They also call some of the post-publication peer reviewers’ critiques “factually incorrect” and “unfounded.” They conclude:

No single specific finding in any of the three papers has been explicitly challenged, let alone invalidated.

There is no evidence of a major error, miscalculation, fabrication, or falsification.

There is no breach of any of the COPE guidelines that could permit Sage to retract any of our published papers.

The retraction of any of these papers, let alone all three, is demonstrably unwarranted.

Adkins told Retraction Watch he is “pleased the journal approached my concerns with legitimate and serious consideration.” He continued:

It is reassuring that my initial concerns with the 2021 Studnicki et al. article were verified and affirmed by other experts. Despite the length of time spanning my initial communications with the journal and today’s retractions, I understand that thorough investigations and re-review processes take time. Given that these now-retracted articles have been excessively cited by parties involved in ongoing federal judicial cases, now positioned before the SCOTUS, Sage’s retractions should help our courts remain informed by the highest standards and quality in scientific and medical evidence.

Update, 2/6/24, 2100 UTC: We note that — contrary to best industry practices described by the Committee on Publication Ethics — Sage has removed the original versions of the articles. They are available at these links:

“A Longitudinal Cohort Study of Emergency Room Utilization Following Mifepristone Chemical and Surgical Abortions, 1999–2015”

“Doctors Who Perform Abortions: Their Characteristics and Patterns of Holding and Using Hospital Privileges”

“A Post Hoc Exploratory Analysis: Induced Abortion Complications Mistaken for Miscarriage in the Emergency Room are a Risk Factor for Hospitalization”

DISCLOSURE: Adam Marcus, a cofounder of Retraction Watch, is an editor at Medscape.

A version of this article appeared on Medscape.com.

A journal and publisher have retracted three papers about abortion, including one that has been used in court cases to support the suspension of FDA approval for mifepristone, aka an “abortion pill.”

Sage, the publisher of Health Services Research and Managerial Epidemiology, announced the retractions yesterday and posted a retraction notice covering the three articles.

For one of those articles, initially flagged by a reader, “an independent reviewer with expertise in statistical analyses evaluated the concerns and opined that the article’s presentation of the data in Figures 2 and 3 leads to an inaccurate conclusion and that the composition of the cohort studied has problems that could affect the article’s conclusions,” according to the notice.

The notice also said Sage “confirmed that all but one of the article’s authors had an affiliation with one or more of Charlotte Lozier Institute, Elliot Institute, and American Association of Pro-Life Obstetricians and Gynecologists, all pro-life advocacy organizations, despite having declared they had no conflicts of interest when they submitted the article for publication or in the article itself.” 

One of the peer reviewers, Sage learned, “was affiliated with Charlotte Lozier Institute at the time of the review,” leading the publisher and journal editor to determine “the peer review for initial publication was unreliable.” That referee also reviewed the other two now-retracted papers, according to Sage.

James Studnicki, the lead author of the three papers, told Retraction Watch the retractions were “a blatant attempt to discredit excellent research which is incongruent with a preferred abortion narrative.” He told The Daily Wire, a conservative news outlet that was first to report on the retractions, the move was “completely unjustified.” The Daily Wire notes that “The Supreme Court is set to hear arguments in March on the legality of restricting the abortion pill based on [Judge Matthew] Kacsmaryk’s ruling, proceedings that will certainly be impacted by the retractions.”

Sage had subjected one of the papers to an expression of concern in August 2023, saying they were investigating “potential issues regarding the representation of data in the article and author conflicts of interest” after being alerted by a reader. As News From The States reported then, the notice came after Chris Adkins, a professor at South University who teaches pharmaceutical sciences, raised concerns with Sage. As News From The States noted in August:

Kacsmaryk leaned hard on a 2021 study that was designed, funded and produced by the research arm of one of the most powerful anti-abortion political groups in the U.S. The judge cited this paper — which looked at Medicaid patients’ visits to the emergency room within 30 days of having an abortion — to justify that a group of anti-abortion doctors and medical groups have legal standing to force the FDA to recall mifepristone.

In a point-by-point response to Sage’s critiques of the paper sent to the publisher in November and now shared with Retraction Watch, Studnicki and colleagues pointed out they had noted their affiliations in the original manuscript and the then-proposed retractions “misrepresent ICMJE disclosure standards,” referring to the International Committee of Medical Journal Editors’ guidelines. They also call some of the post-publication peer reviewers’ critiques “factually incorrect” and “unfounded.” They conclude:

No single specific finding in any of the three papers has been explicitly challenged, let alone invalidated.

There is no evidence of a major error, miscalculation, fabrication, or falsification.

There is no breach of any of the COPE guidelines that could permit Sage to retract any of our published papers.

The retraction of any of these papers, let alone all three, is demonstrably unwarranted.

Adkins told Retraction Watch he is “pleased the journal approached my concerns with legitimate and serious consideration.” He continued:

It is reassuring that my initial concerns with the 2021 Studnicki et al. article were verified and affirmed by other experts. Despite the length of time spanning my initial communications with the journal and today’s retractions, I understand that thorough investigations and re-review processes take time. Given that these now-retracted articles have been excessively cited by parties involved in ongoing federal judicial cases, now positioned before the SCOTUS, Sage’s retractions should help our courts remain informed by the highest standards and quality in scientific and medical evidence.

Update, 2/6/24, 2100 UTC: We note that — contrary to best industry practices described by the Committee on Publication Ethics — Sage has removed the original versions of the articles. They are available at these links:

“A Longitudinal Cohort Study of Emergency Room Utilization Following Mifepristone Chemical and Surgical Abortions, 1999–2015”

“Doctors Who Perform Abortions: Their Characteristics and Patterns of Holding and Using Hospital Privileges”

“A Post Hoc Exploratory Analysis: Induced Abortion Complications Mistaken for Miscarriage in the Emergency Room are a Risk Factor for Hospitalization”

DISCLOSURE: Adam Marcus, a cofounder of Retraction Watch, is an editor at Medscape.

A version of this article appeared on Medscape.com.

Symptoms of anxiety and depression increased in adults living in trigger states that immediately banned abortions after the US Supreme Court Dobbs decision overturned Roe v. Wade, which revoked a woman’s constitutional right to an abortion, new research shows.

This could be due to a variety of factors, investigators led by Benjamin Thornburg, Johns Hopkins Bloomberg School of Public Health, Baltimore, noted. These include fear about the imminent risk of being denied an abortion, uncertainty around future limitations on abortion and other related rights such as contraception, worry over the ability to receive lifesaving medical care during pregnancy, and a general sense of violation and powerlessness related to loss of the right to reproductive autonomy.

The study was published online on January 23, 2024, in JAMA. 
 

Mental Health Harm

In June 2022, the US Supreme Court overturned Roe vs Wade, removing federal protections for abortion rights. Thirteen states had “trigger laws” that immediately banned or severely restricted abortion — raising concerns this could negatively affect mental health.

The researchers used data from the Household Pulse Survey to estimate changes in anxiety and depression symptoms after vs before the Dobbs decision in nearly 160,000 adults living in 13 states with trigger laws compared with roughly 559,000 adults living in 37 states without trigger laws.

The mean age of respondents was 48 years, and 51% were women. Anxiety and depression symptoms were measured via the Patient Health Questionnaire-4 (PHQ-4). 

In trigger states, the mean PHQ-4 score at baseline (before Dobbs) was 3.51 (out of 12) and increased to 3.81 after the Dobbs decision. In nontrigger states, the mean PHQ-4 score at baseline was 3.31 and increased to 3.49 after Dobbs.

Living in a trigger state was associated with a small but statistically significant worsening (0.11-point; P < .001) in anxiety/depression symptoms following the Dobbs decision vs living in a nontrigger state, the investigators report.

Women aged 18-45 years faced greater worsening of anxiety and depression symptoms following Dobbs in trigger vs nontrigger states, whereas men of a similar age experienced minimal or negligible changes. 
 

Implications for Care 

In an accompanying editorial, Julie Steinberg, PhD, with University of Maryland in College Park, notes the study results provide “emerging evidence that at an individual level taking away reproductive autonomy (by not having legal access to an abortion) may increase symptoms of anxiety and depression in all people and particularly females of reproductive age.”

These results add to findings from two other studies that examined abortion restrictions and mental health outcomes. Both found that limiting access to abortion was associated with more mental health symptoms among females of reproductive age than among others,” Dr. Steinberg pointed out.

“Together these findings highlight the need for clinicians who practice in states where abortion is banned to be aware that female patients of reproductive age may be experiencing significantly more distress than before the Dobbs decision,” Dr. Steinberg added. 

The study received no specific funding. The authors had no relevant conflicts of interest. Dr. Steinberg reported serving as a paid expert scientist on abortion and mental health in seven cases challenging abortion policies.

A version of this article appeared on Medscape.com.

Symptoms of anxiety and depression increased in adults living in trigger states that immediately banned abortions after the US Supreme Court Dobbs decision overturned Roe v. Wade, which revoked a woman’s constitutional right to an abortion, new research shows.

This could be due to a variety of factors, investigators led by Benjamin Thornburg, Johns Hopkins Bloomberg School of Public Health, Baltimore, noted. These include fear about the imminent risk of being denied an abortion, uncertainty around future limitations on abortion and other related rights such as contraception, worry over the ability to receive lifesaving medical care during pregnancy, and a general sense of violation and powerlessness related to loss of the right to reproductive autonomy.

The study was published online on January 23, 2024, in JAMA. 
 

Mental Health Harm

In June 2022, the US Supreme Court overturned Roe vs Wade, removing federal protections for abortion rights. Thirteen states had “trigger laws” that immediately banned or severely restricted abortion — raising concerns this could negatively affect mental health.

The researchers used data from the Household Pulse Survey to estimate changes in anxiety and depression symptoms after vs before the Dobbs decision in nearly 160,000 adults living in 13 states with trigger laws compared with roughly 559,000 adults living in 37 states without trigger laws.

The mean age of respondents was 48 years, and 51% were women. Anxiety and depression symptoms were measured via the Patient Health Questionnaire-4 (PHQ-4). 

In trigger states, the mean PHQ-4 score at baseline (before Dobbs) was 3.51 (out of 12) and increased to 3.81 after the Dobbs decision. In nontrigger states, the mean PHQ-4 score at baseline was 3.31 and increased to 3.49 after Dobbs.

Living in a trigger state was associated with a small but statistically significant worsening (0.11-point; P < .001) in anxiety/depression symptoms following the Dobbs decision vs living in a nontrigger state, the investigators report.

Women aged 18-45 years faced greater worsening of anxiety and depression symptoms following Dobbs in trigger vs nontrigger states, whereas men of a similar age experienced minimal or negligible changes. 
 

Implications for Care 

In an accompanying editorial, Julie Steinberg, PhD, with University of Maryland in College Park, notes the study results provide “emerging evidence that at an individual level taking away reproductive autonomy (by not having legal access to an abortion) may increase symptoms of anxiety and depression in all people and particularly females of reproductive age.”

These results add to findings from two other studies that examined abortion restrictions and mental health outcomes. Both found that limiting access to abortion was associated with more mental health symptoms among females of reproductive age than among others,” Dr. Steinberg pointed out.

“Together these findings highlight the need for clinicians who practice in states where abortion is banned to be aware that female patients of reproductive age may be experiencing significantly more distress than before the Dobbs decision,” Dr. Steinberg added. 

The study received no specific funding. The authors had no relevant conflicts of interest. Dr. Steinberg reported serving as a paid expert scientist on abortion and mental health in seven cases challenging abortion policies.

A version of this article appeared on Medscape.com.

Symptoms of anxiety and depression increased in adults living in trigger states that immediately banned abortions after the US Supreme Court Dobbs decision overturned Roe v. Wade, which revoked a woman’s constitutional right to an abortion, new research shows.

This could be due to a variety of factors, investigators led by Benjamin Thornburg, Johns Hopkins Bloomberg School of Public Health, Baltimore, noted. These include fear about the imminent risk of being denied an abortion, uncertainty around future limitations on abortion and other related rights such as contraception, worry over the ability to receive lifesaving medical care during pregnancy, and a general sense of violation and powerlessness related to loss of the right to reproductive autonomy.

The study was published online on January 23, 2024, in JAMA. 
 

Mental Health Harm

In June 2022, the US Supreme Court overturned Roe vs Wade, removing federal protections for abortion rights. Thirteen states had “trigger laws” that immediately banned or severely restricted abortion — raising concerns this could negatively affect mental health.

The researchers used data from the Household Pulse Survey to estimate changes in anxiety and depression symptoms after vs before the Dobbs decision in nearly 160,000 adults living in 13 states with trigger laws compared with roughly 559,000 adults living in 37 states without trigger laws.

The mean age of respondents was 48 years, and 51% were women. Anxiety and depression symptoms were measured via the Patient Health Questionnaire-4 (PHQ-4). 

In trigger states, the mean PHQ-4 score at baseline (before Dobbs) was 3.51 (out of 12) and increased to 3.81 after the Dobbs decision. In nontrigger states, the mean PHQ-4 score at baseline was 3.31 and increased to 3.49 after Dobbs.

Living in a trigger state was associated with a small but statistically significant worsening (0.11-point; P < .001) in anxiety/depression symptoms following the Dobbs decision vs living in a nontrigger state, the investigators report.

Women aged 18-45 years faced greater worsening of anxiety and depression symptoms following Dobbs in trigger vs nontrigger states, whereas men of a similar age experienced minimal or negligible changes. 
 

Implications for Care 

In an accompanying editorial, Julie Steinberg, PhD, with University of Maryland in College Park, notes the study results provide “emerging evidence that at an individual level taking away reproductive autonomy (by not having legal access to an abortion) may increase symptoms of anxiety and depression in all people and particularly females of reproductive age.”

These results add to findings from two other studies that examined abortion restrictions and mental health outcomes. Both found that limiting access to abortion was associated with more mental health symptoms among females of reproductive age than among others,” Dr. Steinberg pointed out.

“Together these findings highlight the need for clinicians who practice in states where abortion is banned to be aware that female patients of reproductive age may be experiencing significantly more distress than before the Dobbs decision,” Dr. Steinberg added. 

The study received no specific funding. The authors had no relevant conflicts of interest. Dr. Steinberg reported serving as a paid expert scientist on abortion and mental health in seven cases challenging abortion policies.

A version of this article appeared on Medscape.com.

SAN DIEGO — Only half of teens and young adults on teratogenic medication report being asked about sexual activity by their rheumatologist, and 38% did not know that their medication would be harmful to a fetus, according to a new survey.

While pediatric rheumatology providers may think that health screenings and contraceptive counseling are happening elsewhere, “this study suggests that a lot of patients are being missed, including those on teratogens,” noted Brittany M. Huynh, MD, MPH, a pediatric rheumatology fellow at the Indiana University School of Medicine in Indianapolis. She led the study and presented the findings at the American College of Rheumatology annual meeting.

Huynh_Brittany_IN_web.jpg

For the study, Dr. Huynh and colleagues recruited patients aged 14-23 years who were assigned female at birth and were followed at pediatric rheumatology clinics affiliated with Indiana University. Participants completed a one-time survey between October 2020 and July 2022 and were asked about their sexual reproductive health experience and knowledge. Notably, all but four surveys were completed prior to the US Supreme Court Dobbs decision overturning Roe v. Wade.

Of responses from 108 participants, the most common diagnoses were juvenile idiopathic arthritis (52%) and systemic lupus erythematosus (16%). About one third (36%) of patients were on teratogenic medication, with the most common being methotrexate. About three fourths (76%) were White, and the average age of respondents was 16.7.

Most participants (82%) said they had been asked about sexual activity by a health care provider, but only 38% said their pediatric rheumatologist discussed this topic with them. Of the 39 patients on teratogenic medication, 54% said they had been asked about sexual activity by their pediatric rheumatologist, and only 51% said they had received teratogenicity counseling.

A larger percentage (85%) of this group reported receiving sexual activity screenings by any provider, but there was little difference in counseling about teratogenic medication.

This suggests that this type of risk counseling “is almost exclusively done by (pediatric rheumatologists), if at all,” Dr. Huynh noted during her presentation.

In total, 56% of all patients said a provider had talked to them about how to prevent pregnancy, and 20% said they had been counseled about how to get and use emergency contraception. Only 6% of patients said their pediatric rheumatologist had discussed emergency contraception during appointments.

Although sexual activity screenings were associated with current teratogen use, pregnancy prevention counseling and emergency contraceptive counseling were not associated with teratogen use or reported sexual activity.

The survey also revealed that there were gaps in knowledge about the health effects of rheumatic medication. Of the patients on teratogens, 38% did not know that their medication could harm a fetus if they became pregnant. Only 9% of patients not on teratogens correctly answered that their medication would not harm a fetus.

Previous studies have also shown that rheumatology patients do not know that their medications can be teratogenic, noted Cuoghi Edens, MD, a rheumatologist at the University of Chicago, who sees both adult and pediatric patients. She was not involved with the study. The larger challenge is how to best educate patients, she said.

While hopefully a patient’s primary care provider is discussing these issues with them, these patients often see their rheumatologist more frequently and more consistently than other providers, Dr. Edens said.

Edens_Cuoghi_IL_web.jpg

“We are sometimes the continuity of care for the patient versus their primary care, even though it should be a group effort of trying to some of these questions,” she said.

Conducting reproductive health screenings in pediatric rheumatology clinics can be difficult though, Dr. Edens noted, not only because of time constraints but also because parents often attend appointments with their child and likely have been for years. These screenings are most accurate when done one-on-one, so pivoting and removing the parents from the room can be awkward for providers, Dr. Edens said.

She advised that starting these conversations early on can be one way to ease into talking about reproductive health. In her own practice, Dr. Huynh sets aside time during appointments to speak with adolescent patients privately.

“We always discuss teratogenic medication. I always talk to them about the fact that I’m going to be doing pregnancy testing with their other screening labs because of the risks associated,” she said. “I also specifically set time aside for patients on teratogens to talk about emergency contraception and offer a prescription, if they’re interested.”

Dr. Huynh emphasized that providing easy access to emergency contraception is key. The ACR reproductive health guidelines — although geared toward adults — recommend discussing emergency contraception with patients, and Dr. Huynh advocates writing prescriptions for interested patients.

“They can fill it and have it easily accessible, so that there are no additional barriers, particularly for people who have these higher risks,” she said.

While emergency contraceptives are also available over the counter, it can be awkward for young people to ask for them, she said, and they can be expensive if not covered under insurance. Providing a prescription is one way to avoid those issues, Dr. Huynh said.

“Certainly, you have to have some parent buy-in, because if there is going to be a script, it’s probably going to be under insurance,” she said. “But in my experience, parents are happy to have it around as long as you’re talking it through with them as well as the young person.”

Dr. Huynh and Dr. Edens had no disclosures.

A version of this article appeared on Medscape.com.

SAN DIEGO — Only half of teens and young adults on teratogenic medication report being asked about sexual activity by their rheumatologist, and 38% did not know that their medication would be harmful to a fetus, according to a new survey.

While pediatric rheumatology providers may think that health screenings and contraceptive counseling are happening elsewhere, “this study suggests that a lot of patients are being missed, including those on teratogens,” noted Brittany M. Huynh, MD, MPH, a pediatric rheumatology fellow at the Indiana University School of Medicine in Indianapolis. She led the study and presented the findings at the American College of Rheumatology annual meeting.

Huynh_Brittany_IN_web.jpg

For the study, Dr. Huynh and colleagues recruited patients aged 14-23 years who were assigned female at birth and were followed at pediatric rheumatology clinics affiliated with Indiana University. Participants completed a one-time survey between October 2020 and July 2022 and were asked about their sexual reproductive health experience and knowledge. Notably, all but four surveys were completed prior to the US Supreme Court Dobbs decision overturning Roe v. Wade.

Of responses from 108 participants, the most common diagnoses were juvenile idiopathic arthritis (52%) and systemic lupus erythematosus (16%). About one third (36%) of patients were on teratogenic medication, with the most common being methotrexate. About three fourths (76%) were White, and the average age of respondents was 16.7.

Most participants (82%) said they had been asked about sexual activity by a health care provider, but only 38% said their pediatric rheumatologist discussed this topic with them. Of the 39 patients on teratogenic medication, 54% said they had been asked about sexual activity by their pediatric rheumatologist, and only 51% said they had received teratogenicity counseling.

A larger percentage (85%) of this group reported receiving sexual activity screenings by any provider, but there was little difference in counseling about teratogenic medication.

This suggests that this type of risk counseling “is almost exclusively done by (pediatric rheumatologists), if at all,” Dr. Huynh noted during her presentation.

In total, 56% of all patients said a provider had talked to them about how to prevent pregnancy, and 20% said they had been counseled about how to get and use emergency contraception. Only 6% of patients said their pediatric rheumatologist had discussed emergency contraception during appointments.

Although sexual activity screenings were associated with current teratogen use, pregnancy prevention counseling and emergency contraceptive counseling were not associated with teratogen use or reported sexual activity.

The survey also revealed that there were gaps in knowledge about the health effects of rheumatic medication. Of the patients on teratogens, 38% did not know that their medication could harm a fetus if they became pregnant. Only 9% of patients not on teratogens correctly answered that their medication would not harm a fetus.

Previous studies have also shown that rheumatology patients do not know that their medications can be teratogenic, noted Cuoghi Edens, MD, a rheumatologist at the University of Chicago, who sees both adult and pediatric patients. She was not involved with the study. The larger challenge is how to best educate patients, she said.

While hopefully a patient’s primary care provider is discussing these issues with them, these patients often see their rheumatologist more frequently and more consistently than other providers, Dr. Edens said.

Edens_Cuoghi_IL_web.jpg

“We are sometimes the continuity of care for the patient versus their primary care, even though it should be a group effort of trying to some of these questions,” she said.

Conducting reproductive health screenings in pediatric rheumatology clinics can be difficult though, Dr. Edens noted, not only because of time constraints but also because parents often attend appointments with their child and likely have been for years. These screenings are most accurate when done one-on-one, so pivoting and removing the parents from the room can be awkward for providers, Dr. Edens said.

She advised that starting these conversations early on can be one way to ease into talking about reproductive health. In her own practice, Dr. Huynh sets aside time during appointments to speak with adolescent patients privately.

“We always discuss teratogenic medication. I always talk to them about the fact that I’m going to be doing pregnancy testing with their other screening labs because of the risks associated,” she said. “I also specifically set time aside for patients on teratogens to talk about emergency contraception and offer a prescription, if they’re interested.”

Dr. Huynh emphasized that providing easy access to emergency contraception is key. The ACR reproductive health guidelines — although geared toward adults — recommend discussing emergency contraception with patients, and Dr. Huynh advocates writing prescriptions for interested patients.

“They can fill it and have it easily accessible, so that there are no additional barriers, particularly for people who have these higher risks,” she said.

While emergency contraceptives are also available over the counter, it can be awkward for young people to ask for them, she said, and they can be expensive if not covered under insurance. Providing a prescription is one way to avoid those issues, Dr. Huynh said.

“Certainly, you have to have some parent buy-in, because if there is going to be a script, it’s probably going to be under insurance,” she said. “But in my experience, parents are happy to have it around as long as you’re talking it through with them as well as the young person.”

Dr. Huynh and Dr. Edens had no disclosures.

A version of this article appeared on Medscape.com.

SAN DIEGO — Only half of teens and young adults on teratogenic medication report being asked about sexual activity by their rheumatologist, and 38% did not know that their medication would be harmful to a fetus, according to a new survey.

While pediatric rheumatology providers may think that health screenings and contraceptive counseling are happening elsewhere, “this study suggests that a lot of patients are being missed, including those on teratogens,” noted Brittany M. Huynh, MD, MPH, a pediatric rheumatology fellow at the Indiana University School of Medicine in Indianapolis. She led the study and presented the findings at the American College of Rheumatology annual meeting.

Huynh_Brittany_IN_web.jpg

For the study, Dr. Huynh and colleagues recruited patients aged 14-23 years who were assigned female at birth and were followed at pediatric rheumatology clinics affiliated with Indiana University. Participants completed a one-time survey between October 2020 and July 2022 and were asked about their sexual reproductive health experience and knowledge. Notably, all but four surveys were completed prior to the US Supreme Court Dobbs decision overturning Roe v. Wade.

Of responses from 108 participants, the most common diagnoses were juvenile idiopathic arthritis (52%) and systemic lupus erythematosus (16%). About one third (36%) of patients were on teratogenic medication, with the most common being methotrexate. About three fourths (76%) were White, and the average age of respondents was 16.7.

Most participants (82%) said they had been asked about sexual activity by a health care provider, but only 38% said their pediatric rheumatologist discussed this topic with them. Of the 39 patients on teratogenic medication, 54% said they had been asked about sexual activity by their pediatric rheumatologist, and only 51% said they had received teratogenicity counseling.

A larger percentage (85%) of this group reported receiving sexual activity screenings by any provider, but there was little difference in counseling about teratogenic medication.

This suggests that this type of risk counseling “is almost exclusively done by (pediatric rheumatologists), if at all,” Dr. Huynh noted during her presentation.

In total, 56% of all patients said a provider had talked to them about how to prevent pregnancy, and 20% said they had been counseled about how to get and use emergency contraception. Only 6% of patients said their pediatric rheumatologist had discussed emergency contraception during appointments.

Although sexual activity screenings were associated with current teratogen use, pregnancy prevention counseling and emergency contraceptive counseling were not associated with teratogen use or reported sexual activity.

The survey also revealed that there were gaps in knowledge about the health effects of rheumatic medication. Of the patients on teratogens, 38% did not know that their medication could harm a fetus if they became pregnant. Only 9% of patients not on teratogens correctly answered that their medication would not harm a fetus.

Previous studies have also shown that rheumatology patients do not know that their medications can be teratogenic, noted Cuoghi Edens, MD, a rheumatologist at the University of Chicago, who sees both adult and pediatric patients. She was not involved with the study. The larger challenge is how to best educate patients, she said.

While hopefully a patient’s primary care provider is discussing these issues with them, these patients often see their rheumatologist more frequently and more consistently than other providers, Dr. Edens said.

Edens_Cuoghi_IL_web.jpg

“We are sometimes the continuity of care for the patient versus their primary care, even though it should be a group effort of trying to some of these questions,” she said.

Conducting reproductive health screenings in pediatric rheumatology clinics can be difficult though, Dr. Edens noted, not only because of time constraints but also because parents often attend appointments with their child and likely have been for years. These screenings are most accurate when done one-on-one, so pivoting and removing the parents from the room can be awkward for providers, Dr. Edens said.

She advised that starting these conversations early on can be one way to ease into talking about reproductive health. In her own practice, Dr. Huynh sets aside time during appointments to speak with adolescent patients privately.

“We always discuss teratogenic medication. I always talk to them about the fact that I’m going to be doing pregnancy testing with their other screening labs because of the risks associated,” she said. “I also specifically set time aside for patients on teratogens to talk about emergency contraception and offer a prescription, if they’re interested.”

Dr. Huynh emphasized that providing easy access to emergency contraception is key. The ACR reproductive health guidelines — although geared toward adults — recommend discussing emergency contraception with patients, and Dr. Huynh advocates writing prescriptions for interested patients.

“They can fill it and have it easily accessible, so that there are no additional barriers, particularly for people who have these higher risks,” she said.

While emergency contraceptives are also available over the counter, it can be awkward for young people to ask for them, she said, and they can be expensive if not covered under insurance. Providing a prescription is one way to avoid those issues, Dr. Huynh said.

“Certainly, you have to have some parent buy-in, because if there is going to be a script, it’s probably going to be under insurance,” she said. “But in my experience, parents are happy to have it around as long as you’re talking it through with them as well as the young person.”

Dr. Huynh and Dr. Edens had no disclosures.

A version of this article appeared on Medscape.com.

On July 13, 2023, the US Food and Drug Administration (FDA) approved norgestrel 0.075 mg (Opill, HRA Pharma, Paris, France) as the first nonprescription oral contraceptive pill (FIGURE). This progestin-only pill was originally FDA approved in 1973, with prescription required, and was available as Ovrette until 2005, when product distribution ceased for marketing reasons and not for safety or effectiveness concerns.¹ In recent years, studies have been conducted to support converted approval from prescription to nonprescription to increase access to safe and effective contraception. Overall, norgestrel is more effective than other currently available nonprescription contraceptive options when used as directed, and widespread accessibility to this method has the potential to decrease the risk of unintended pregnancies. This product is expected to be available in drugstores, convenience stores, grocery stores, and online in 2024.

obgm035120e11_chen_fig.jpg

How it works

The indication for norgestrel 0.075 mg is pregnancy prevention in people with the capacity to become pregnant; this product is not intended for emergency contraception. Norgestrel is a racemic mixture of 2 isomers, of which only levonorgestrel is bioactive. The mechanism of action for contraception is primarily through cervical mucus thickening, which inhibits sperm movement through the cervix. About 50% of users also have an additional contraceptive effect of ovulation suppression.²

Instructions for use. In the package label, users are instructed to take the norgestrel 0.075 mg pill daily, preferably at the same time each day and no more than 3 hours from the time taken on the previous day. This method can be started on any day of the cycle, and backup contraception (a barrier method) should be used for the first 48 hours after starting the method if it has been more than 5 days since menstrual bleeding started.3 Product instructions indicate that, if users miss a dose, they should take the next dose as soon as possible. If a pill is taken 3 hours or more later than the usual time, they should take a pill immediately and then resume the next pill at the usual time. In addition, backup contraception is recommended for 48 hours.²

Based on the Centers for Disease Control and Prevention (CDC) Selected Practice Recommendations for Contraceptive Use, no examinations or tests are required prior to initiation of progestin-only pills for safe and effective use.³

Efficacy

The product label indicates that the pregnancy rate is approximately 2 per 100 women-years based on over 21,000 28-day exposure cycles from 8 US clinical studies.² In a recent review by Glasier and colleagues, the authors identified 13 trials that assessed the efficacy of the norgestrel 0.075 mg pill, all published several decades ago.⁴ Given that breastfeeding can have contraceptive impact through ovulation inhibition, studies that included breastfeeding participants were evaluated separately. Six studies without breastfeeding participants included 3,184 women who provided more than 35,000 months of use. The overall failure rates ranged from 0 to 2.4 per hundred woman-years with typical use; an aggregate Pearl Index was calculated to be 2.2 based on the total numbers of pregnancies and cycles. The remaining 7 studies included individuals who were breastfeeding for at least part of their study participation. These studies included 5,445 women, and the 12-month life table cumulative pregnancy rates in this group ranged from 0.0% to 3.4%. This review noted that the available studies are limited by incomplete descriptions of study participant information and differences in reporting of failure rates; however, the overall data support the effectiveness of the norgestrel 0.075 mg pill for pregnancy prevention.

Continue to: Norgestrel’s mechanism of action on ovarian activity and cervical mucus...

Norgestrel’s mechanism of action on ovarian activity and cervical mucus

More recently, a prospective, multicenter randomized, crossover study was performed to better understand this pill’s impact on cervical mucus and ovulation during preparation for nonprescription approval. In this study, participants were evaluated with frequent transvaginal ultrasonography, cervical mucus, and blood assessments (including levels of follicular-stimulating hormone, luteinizing hormone, progesterone, and estradiol) for three 28-day cycles. Cervical mucus was scored on a modified Insler scale to indicate if the mucus was favorable (Insler score ≥9), intermediate (Insler score 5-8), or unfavorable to fertility (Insler score ≤4).⁵

In the first cycle, participants were instructed to use the pills as prescribed (described as “correct use”). During this cycle, most participants (n = 34/51; 67%) did not ovulate, confirming that norgestrel 0.075 mg does impact ovulation.6 Most participants also had unfavorable cervical mucus (n = 39/51; 76%).⁶ Overall, 94% had full protection against pregnancy, either through lack of ovulation (n = 9), unfavorable mucus (n = 14), or both (n = 25). The remaining 3 participants ovulated and had intermediate mucus scores; ultimately, these participants were considered to have medium protection against pregnancy.^7,8 (See the contraceptive protection algorithm [TABLE]).⁸

obgm035120e11_chen_table.jpg

In the second and third cycles, the investigators evaluated ovulation and cervical mucus changes in the setting of either a delayed (by 6 hours) or missed dose midcycle.⁸ Of the 46 participants with evaluable data during the intervention cycles, 32 (70%) did not ovulate in each of the delayed- and missed-dose cycles. Most participants (n = 27; 59%) also demonstrated unfavorable mucus scores (modified Insler score ≤4) over the entire cycle despite delaying or missing a pill. There was no significant change to the cervical mucus score when comparing the scores on the days before, during, and after the delayed or missed pills (P = .26), nor when comparing between delayed pill use and missed pill use (P = .45). With the delayed pill intervention, 4 (9%) had reduced contraceptive protection (ie, medium protection) based on ovulation with intermediate mucus scores. With the missed pill intervention, 5 (11%) had reduced protection, of whom 3 had medium protection and 2 had minimum protection with ovulation and favorable mucus scores. Overall, this study shows that delaying or missing one pill may not impact contraceptive efficacy as much as previously thought given the strict 3-hour window for progestin-only pills. However, these findings are theoretical as information about pregnancy outcomes with delaying or missing pills are lacking.

Safety

Progestin-only methods are one of the safest options for contraception, with few contraindications to use; those listed include known or suspected pregnancy, known or suspected carcinoma of the breast or other progestinsensitive cancer, undiagnosed abnormal uterine bleeding, hypersensitivity to any component of the product, benign or malignant liver tumors, and acute liver disease.²

The CDC Medical Eligibility Criteria for Contraceptive Use guidelines offer guidance for progestin-only pills, indicating a category 3 (theoretical or proven risks usually outweigh the advantages) or category 4 (unacceptable health risk, method not to be used) for only a select number of additional conditions. These conditions include a history of malabsorptive bariatric surgery (category 3) and concurrent use of medications that induce hepatic enzyme activity (category 3)— such as phenytoin, carbamazepine, barbiturates, primidone, topiramate, oxcarbazepine, rifampin, and rifabutin.⁹ These conditions are included primarily due to concerns of decreased effectivenessof the contraception and not necessarily because of evidence of harm with use.

The prevalence of consumers with contraindications to progestin-only pills appears to be low. In a large database study, only 4.36% seeking preventive care and 2.29% seeking both preventive and contraceptive services had a contraindication to progestin-only pills.10 Therefore, candidates for norgestrel use include individuals who have commonly encountered conditions, including those who⁹:

• have recently given birth
• are breastfeeding
• have a history of venous thromboembolism
• smoke
• have cardiovascular disease, hypertension, migraines with aura, or longstanding diabetes.

Adverse effects

The most common adverse effects (AEs) related to norgestrel use are bleeding changes.² In the initial clinical studies for FDA approval, about half of enrolled participants reported a change in bleeding; about 9% discontinued the contraceptive due to bleeding. Breakthrough bleeding and spotting were reported by 48.6% and 47.3% of participants, respectively. About 6.1% had amenorrhea in their first cycle; 28.7% of participants had amenorrhea overall. Other reported AEs were headache, dizziness, nausea, increased appetite, abdominal pain, cramps or bloating, breast tenderness, and acne.

Continue to:  FDA approval required determining appropriate direct-to-patient classification...

FDA approval required determining appropriate direct-to-patient classification

As part of the process for obtaining nonprescription approval, studies needed to determine that patients can safely and effectively use norgestrel without talking to a health care provider first. As part of that process, label comprehension, self-selection, and actualuse studies were required to demonstrate that consumers can use the package information to determine their eligibility and take the medication appropriately.

The ACCESS study Research Q: Do patients appropriately determine if the contraceptive is right for them?

Study A: Yes, 99% of the time. In the Adherence with Continuous-dose Oral Contraceptive: Evaluation of Self-Selection and Use (ACCESS) pivotal study, which evaluated prescription to nonprescription approval, participants were asked to review the label and determine whether the product was appropriate for them to use based on their health history.¹¹ Approximately 99% of participants (n = 1,234/1,246) were able to correctly self-select whether norgestrel was appropriate for their own use.¹²

Research Q: After beginning the contraceptive, do patients adhere to correct use?

Study A: Yes, more than 90% of the time (and that remained true for subpopulations).

In the next phase of the ACCESS study, eligible participants from the self-selection population who purchased norgestrel and reported using the product at least once in their e-diary over a 6-month study period comprised the “User Population.”¹² The overall adherence to daily pill intake was 92.5% (95% confidence interval [CI], 92.3–92.6%) among the 883 participants who contributed more than 90,000 days of study participation, and adherence was similarly high in subpopulations of individuals with low health literacy (92.6%; 95% CI, 92.1–93.0), adolescents aged 12–14 years (91.8%; 95% CI, 91.0–92.5%), and adolescents aged 15–17 years (91.9%; 95% CI, 91.4%–92.3%).

Research Q: When a pill was missed, did patients use backup contraception?

Study A: Yes, 97% of the time.

When including whether participants followed label instructions for mitigating behaviors when the pill was missed (eg, take a pill as soon as they remember, use backup contraception for 2 days after restarting the pill), adherence was 97.1% (95% CI, 97.0–97.2%). Most participants missed a single day of taking pills, and the most common reported reason for missing pills was issues with resupply as participants needed to get new packs from their enrolled research site, which should be less of a barrier when these pills are available over the counter.

Clinical implications of expanded access

Opportunities to expand access to effective contraception have become more critical in the increasingly restrictive environment for abortion care in the post-Dobbs era, and the availability of norgestrel to patients without prescription can advance contraceptive equity. Patients encounter many barriers to accessing prescription contraception, such as lack of insurance; difficulty with scheduling an appointment or getting to a clinic; not having a regular clinician or clinic; or health care providers requiring a visit, exam, or test prior to prescribing contraception.13,14 For patients who face these challenges, an alternative option is to use a nonprescription contraceptive, such as barrier or fertility awareness–based methods, which are typically associated with higher failure rates. With the introduction of norgestrel as a nonprescription contraceptive product, people can have direct access to a more effective contraceptive option.

A follow-up study of participants who had participated in the ACCESS actual-use study demonstrated that most (83%) would be likely to use the nonprescription method if available in the future for many reasons, including convenience, ease of access, ability to save time and money, not needing to visit a clinic, and flexibility of accessing the pills while traveling or having someone else get their pills for them.¹⁴ Furthermore, a nonprescription method could be beneficial for people who have concerns about privacy, such as adolescents or individuals affected by contraception sabotage (an act that can intentionally limit or prohibit a person's contraception access or use, ie, damaging condoms or hiding a person’s contraception method). This expansion of access can ultimately lead to a decrease in unintended pregnancies. In a model using the ACCESS actual-use data, about 1,500 to 34,000 unintended pregnancies would be prevented per year based on varying model parameters, with all scenarios demonstrating a benefit to nonprescription access to norgestrel.¹⁵

After norgestrel is available, where will patients be able to seek more information?

Patients who have questions or concerns about starting or taking norgestrel should talk to their clinician or a pharmacist for additional information (FIGURE 2). Examples of situations when additional clinical evaluation or counseling are recommended include:

• when a person is taking any medications with possible drug-drug interactions
• if a person is starting norgestrel after taking an emergency contraceptive in the last 5 days
• if there is a concern about pregnancy
• when there are any questions about adverse effects while taking norgestrel.

Bottom line

The nonprescription approval of norgestrel, a progestin-only pill, has the potential to greatly expand patient access to a safe and effective contraceptive method and advance contraceptive equity. The availability of informational materials for consumers about potential issues that may arise (for instance, changes in bleeding) will be important for initiation and continuation of this method. As this product is not yet available for purchase, several unknown factors remain, such as the cost and ease of accessibility in stores or online, that will ultimately determine its public health impact on unintended pregnancies. ●

On July 13, 2023, the US Food and Drug Administration (FDA) approved norgestrel 0.075 mg (Opill, HRA Pharma, Paris, France) as the first nonprescription oral contraceptive pill (FIGURE). This progestin-only pill was originally FDA approved in 1973, with prescription required, and was available as Ovrette until 2005, when product distribution ceased for marketing reasons and not for safety or effectiveness concerns.¹ In recent years, studies have been conducted to support converted approval from prescription to nonprescription to increase access to safe and effective contraception. Overall, norgestrel is more effective than other currently available nonprescription contraceptive options when used as directed, and widespread accessibility to this method has the potential to decrease the risk of unintended pregnancies. This product is expected to be available in drugstores, convenience stores, grocery stores, and online in 2024.

obgm035120e11_chen_fig.jpg

How it works

The indication for norgestrel 0.075 mg is pregnancy prevention in people with the capacity to become pregnant; this product is not intended for emergency contraception. Norgestrel is a racemic mixture of 2 isomers, of which only levonorgestrel is bioactive. The mechanism of action for contraception is primarily through cervical mucus thickening, which inhibits sperm movement through the cervix. About 50% of users also have an additional contraceptive effect of ovulation suppression.²

Instructions for use. In the package label, users are instructed to take the norgestrel 0.075 mg pill daily, preferably at the same time each day and no more than 3 hours from the time taken on the previous day. This method can be started on any day of the cycle, and backup contraception (a barrier method) should be used for the first 48 hours after starting the method if it has been more than 5 days since menstrual bleeding started.3 Product instructions indicate that, if users miss a dose, they should take the next dose as soon as possible. If a pill is taken 3 hours or more later than the usual time, they should take a pill immediately and then resume the next pill at the usual time. In addition, backup contraception is recommended for 48 hours.²

Based on the Centers for Disease Control and Prevention (CDC) Selected Practice Recommendations for Contraceptive Use, no examinations or tests are required prior to initiation of progestin-only pills for safe and effective use.³

Efficacy

The product label indicates that the pregnancy rate is approximately 2 per 100 women-years based on over 21,000 28-day exposure cycles from 8 US clinical studies.² In a recent review by Glasier and colleagues, the authors identified 13 trials that assessed the efficacy of the norgestrel 0.075 mg pill, all published several decades ago.⁴ Given that breastfeeding can have contraceptive impact through ovulation inhibition, studies that included breastfeeding participants were evaluated separately. Six studies without breastfeeding participants included 3,184 women who provided more than 35,000 months of use. The overall failure rates ranged from 0 to 2.4 per hundred woman-years with typical use; an aggregate Pearl Index was calculated to be 2.2 based on the total numbers of pregnancies and cycles. The remaining 7 studies included individuals who were breastfeeding for at least part of their study participation. These studies included 5,445 women, and the 12-month life table cumulative pregnancy rates in this group ranged from 0.0% to 3.4%. This review noted that the available studies are limited by incomplete descriptions of study participant information and differences in reporting of failure rates; however, the overall data support the effectiveness of the norgestrel 0.075 mg pill for pregnancy prevention.

Continue to: Norgestrel’s mechanism of action on ovarian activity and cervical mucus...

Norgestrel’s mechanism of action on ovarian activity and cervical mucus

More recently, a prospective, multicenter randomized, crossover study was performed to better understand this pill’s impact on cervical mucus and ovulation during preparation for nonprescription approval. In this study, participants were evaluated with frequent transvaginal ultrasonography, cervical mucus, and blood assessments (including levels of follicular-stimulating hormone, luteinizing hormone, progesterone, and estradiol) for three 28-day cycles. Cervical mucus was scored on a modified Insler scale to indicate if the mucus was favorable (Insler score ≥9), intermediate (Insler score 5-8), or unfavorable to fertility (Insler score ≤4).⁵

In the first cycle, participants were instructed to use the pills as prescribed (described as “correct use”). During this cycle, most participants (n = 34/51; 67%) did not ovulate, confirming that norgestrel 0.075 mg does impact ovulation.6 Most participants also had unfavorable cervical mucus (n = 39/51; 76%).⁶ Overall, 94% had full protection against pregnancy, either through lack of ovulation (n = 9), unfavorable mucus (n = 14), or both (n = 25). The remaining 3 participants ovulated and had intermediate mucus scores; ultimately, these participants were considered to have medium protection against pregnancy.^7,8 (See the contraceptive protection algorithm [TABLE]).⁸

obgm035120e11_chen_table.jpg

In the second and third cycles, the investigators evaluated ovulation and cervical mucus changes in the setting of either a delayed (by 6 hours) or missed dose midcycle.⁸ Of the 46 participants with evaluable data during the intervention cycles, 32 (70%) did not ovulate in each of the delayed- and missed-dose cycles. Most participants (n = 27; 59%) also demonstrated unfavorable mucus scores (modified Insler score ≤4) over the entire cycle despite delaying or missing a pill. There was no significant change to the cervical mucus score when comparing the scores on the days before, during, and after the delayed or missed pills (P = .26), nor when comparing between delayed pill use and missed pill use (P = .45). With the delayed pill intervention, 4 (9%) had reduced contraceptive protection (ie, medium protection) based on ovulation with intermediate mucus scores. With the missed pill intervention, 5 (11%) had reduced protection, of whom 3 had medium protection and 2 had minimum protection with ovulation and favorable mucus scores. Overall, this study shows that delaying or missing one pill may not impact contraceptive efficacy as much as previously thought given the strict 3-hour window for progestin-only pills. However, these findings are theoretical as information about pregnancy outcomes with delaying or missing pills are lacking.

Safety

Progestin-only methods are one of the safest options for contraception, with few contraindications to use; those listed include known or suspected pregnancy, known or suspected carcinoma of the breast or other progestinsensitive cancer, undiagnosed abnormal uterine bleeding, hypersensitivity to any component of the product, benign or malignant liver tumors, and acute liver disease.²

The CDC Medical Eligibility Criteria for Contraceptive Use guidelines offer guidance for progestin-only pills, indicating a category 3 (theoretical or proven risks usually outweigh the advantages) or category 4 (unacceptable health risk, method not to be used) for only a select number of additional conditions. These conditions include a history of malabsorptive bariatric surgery (category 3) and concurrent use of medications that induce hepatic enzyme activity (category 3)— such as phenytoin, carbamazepine, barbiturates, primidone, topiramate, oxcarbazepine, rifampin, and rifabutin.⁹ These conditions are included primarily due to concerns of decreased effectivenessof the contraception and not necessarily because of evidence of harm with use.

The prevalence of consumers with contraindications to progestin-only pills appears to be low. In a large database study, only 4.36% seeking preventive care and 2.29% seeking both preventive and contraceptive services had a contraindication to progestin-only pills.10 Therefore, candidates for norgestrel use include individuals who have commonly encountered conditions, including those who⁹:

• have recently given birth
• are breastfeeding
• have a history of venous thromboembolism
• smoke
• have cardiovascular disease, hypertension, migraines with aura, or longstanding diabetes.

Adverse effects

The most common adverse effects (AEs) related to norgestrel use are bleeding changes.² In the initial clinical studies for FDA approval, about half of enrolled participants reported a change in bleeding; about 9% discontinued the contraceptive due to bleeding. Breakthrough bleeding and spotting were reported by 48.6% and 47.3% of participants, respectively. About 6.1% had amenorrhea in their first cycle; 28.7% of participants had amenorrhea overall. Other reported AEs were headache, dizziness, nausea, increased appetite, abdominal pain, cramps or bloating, breast tenderness, and acne.

Continue to:  FDA approval required determining appropriate direct-to-patient classification...

FDA approval required determining appropriate direct-to-patient classification

As part of the process for obtaining nonprescription approval, studies needed to determine that patients can safely and effectively use norgestrel without talking to a health care provider first. As part of that process, label comprehension, self-selection, and actualuse studies were required to demonstrate that consumers can use the package information to determine their eligibility and take the medication appropriately.

The ACCESS study Research Q: Do patients appropriately determine if the contraceptive is right for them?

Study A: Yes, 99% of the time. In the Adherence with Continuous-dose Oral Contraceptive: Evaluation of Self-Selection and Use (ACCESS) pivotal study, which evaluated prescription to nonprescription approval, participants were asked to review the label and determine whether the product was appropriate for them to use based on their health history.¹¹ Approximately 99% of participants (n = 1,234/1,246) were able to correctly self-select whether norgestrel was appropriate for their own use.¹²

Research Q: After beginning the contraceptive, do patients adhere to correct use?

Study A: Yes, more than 90% of the time (and that remained true for subpopulations).

In the next phase of the ACCESS study, eligible participants from the self-selection population who purchased norgestrel and reported using the product at least once in their e-diary over a 6-month study period comprised the “User Population.”¹² The overall adherence to daily pill intake was 92.5% (95% confidence interval [CI], 92.3–92.6%) among the 883 participants who contributed more than 90,000 days of study participation, and adherence was similarly high in subpopulations of individuals with low health literacy (92.6%; 95% CI, 92.1–93.0), adolescents aged 12–14 years (91.8%; 95% CI, 91.0–92.5%), and adolescents aged 15–17 years (91.9%; 95% CI, 91.4%–92.3%).

Research Q: When a pill was missed, did patients use backup contraception?

Study A: Yes, 97% of the time.

When including whether participants followed label instructions for mitigating behaviors when the pill was missed (eg, take a pill as soon as they remember, use backup contraception for 2 days after restarting the pill), adherence was 97.1% (95% CI, 97.0–97.2%). Most participants missed a single day of taking pills, and the most common reported reason for missing pills was issues with resupply as participants needed to get new packs from their enrolled research site, which should be less of a barrier when these pills are available over the counter.

Clinical implications of expanded access

Opportunities to expand access to effective contraception have become more critical in the increasingly restrictive environment for abortion care in the post-Dobbs era, and the availability of norgestrel to patients without prescription can advance contraceptive equity. Patients encounter many barriers to accessing prescription contraception, such as lack of insurance; difficulty with scheduling an appointment or getting to a clinic; not having a regular clinician or clinic; or health care providers requiring a visit, exam, or test prior to prescribing contraception.13,14 For patients who face these challenges, an alternative option is to use a nonprescription contraceptive, such as barrier or fertility awareness–based methods, which are typically associated with higher failure rates. With the introduction of norgestrel as a nonprescription contraceptive product, people can have direct access to a more effective contraceptive option.

A follow-up study of participants who had participated in the ACCESS actual-use study demonstrated that most (83%) would be likely to use the nonprescription method if available in the future for many reasons, including convenience, ease of access, ability to save time and money, not needing to visit a clinic, and flexibility of accessing the pills while traveling or having someone else get their pills for them.¹⁴ Furthermore, a nonprescription method could be beneficial for people who have concerns about privacy, such as adolescents or individuals affected by contraception sabotage (an act that can intentionally limit or prohibit a person's contraception access or use, ie, damaging condoms or hiding a person’s contraception method). This expansion of access can ultimately lead to a decrease in unintended pregnancies. In a model using the ACCESS actual-use data, about 1,500 to 34,000 unintended pregnancies would be prevented per year based on varying model parameters, with all scenarios demonstrating a benefit to nonprescription access to norgestrel.¹⁵

After norgestrel is available, where will patients be able to seek more information?

Patients who have questions or concerns about starting or taking norgestrel should talk to their clinician or a pharmacist for additional information (FIGURE 2). Examples of situations when additional clinical evaluation or counseling are recommended include:

• when a person is taking any medications with possible drug-drug interactions
• if a person is starting norgestrel after taking an emergency contraceptive in the last 5 days
• if there is a concern about pregnancy
• when there are any questions about adverse effects while taking norgestrel.

Bottom line

The nonprescription approval of norgestrel, a progestin-only pill, has the potential to greatly expand patient access to a safe and effective contraceptive method and advance contraceptive equity. The availability of informational materials for consumers about potential issues that may arise (for instance, changes in bleeding) will be important for initiation and continuation of this method. As this product is not yet available for purchase, several unknown factors remain, such as the cost and ease of accessibility in stores or online, that will ultimately determine its public health impact on unintended pregnancies. ●

On July 13, 2023, the US Food and Drug Administration (FDA) approved norgestrel 0.075 mg (Opill, HRA Pharma, Paris, France) as the first nonprescription oral contraceptive pill (FIGURE). This progestin-only pill was originally FDA approved in 1973, with prescription required, and was available as Ovrette until 2005, when product distribution ceased for marketing reasons and not for safety or effectiveness concerns.¹ In recent years, studies have been conducted to support converted approval from prescription to nonprescription to increase access to safe and effective contraception. Overall, norgestrel is more effective than other currently available nonprescription contraceptive options when used as directed, and widespread accessibility to this method has the potential to decrease the risk of unintended pregnancies. This product is expected to be available in drugstores, convenience stores, grocery stores, and online in 2024.

obgm035120e11_chen_fig.jpg

How it works

The indication for norgestrel 0.075 mg is pregnancy prevention in people with the capacity to become pregnant; this product is not intended for emergency contraception. Norgestrel is a racemic mixture of 2 isomers, of which only levonorgestrel is bioactive. The mechanism of action for contraception is primarily through cervical mucus thickening, which inhibits sperm movement through the cervix. About 50% of users also have an additional contraceptive effect of ovulation suppression.²

Instructions for use. In the package label, users are instructed to take the norgestrel 0.075 mg pill daily, preferably at the same time each day and no more than 3 hours from the time taken on the previous day. This method can be started on any day of the cycle, and backup contraception (a barrier method) should be used for the first 48 hours after starting the method if it has been more than 5 days since menstrual bleeding started.3 Product instructions indicate that, if users miss a dose, they should take the next dose as soon as possible. If a pill is taken 3 hours or more later than the usual time, they should take a pill immediately and then resume the next pill at the usual time. In addition, backup contraception is recommended for 48 hours.²

Based on the Centers for Disease Control and Prevention (CDC) Selected Practice Recommendations for Contraceptive Use, no examinations or tests are required prior to initiation of progestin-only pills for safe and effective use.³

Efficacy

The product label indicates that the pregnancy rate is approximately 2 per 100 women-years based on over 21,000 28-day exposure cycles from 8 US clinical studies.² In a recent review by Glasier and colleagues, the authors identified 13 trials that assessed the efficacy of the norgestrel 0.075 mg pill, all published several decades ago.⁴ Given that breastfeeding can have contraceptive impact through ovulation inhibition, studies that included breastfeeding participants were evaluated separately. Six studies without breastfeeding participants included 3,184 women who provided more than 35,000 months of use. The overall failure rates ranged from 0 to 2.4 per hundred woman-years with typical use; an aggregate Pearl Index was calculated to be 2.2 based on the total numbers of pregnancies and cycles. The remaining 7 studies included individuals who were breastfeeding for at least part of their study participation. These studies included 5,445 women, and the 12-month life table cumulative pregnancy rates in this group ranged from 0.0% to 3.4%. This review noted that the available studies are limited by incomplete descriptions of study participant information and differences in reporting of failure rates; however, the overall data support the effectiveness of the norgestrel 0.075 mg pill for pregnancy prevention.

Continue to: Norgestrel’s mechanism of action on ovarian activity and cervical mucus...

Norgestrel’s mechanism of action on ovarian activity and cervical mucus

More recently, a prospective, multicenter randomized, crossover study was performed to better understand this pill’s impact on cervical mucus and ovulation during preparation for nonprescription approval. In this study, participants were evaluated with frequent transvaginal ultrasonography, cervical mucus, and blood assessments (including levels of follicular-stimulating hormone, luteinizing hormone, progesterone, and estradiol) for three 28-day cycles. Cervical mucus was scored on a modified Insler scale to indicate if the mucus was favorable (Insler score ≥9), intermediate (Insler score 5-8), or unfavorable to fertility (Insler score ≤4).⁵

In the first cycle, participants were instructed to use the pills as prescribed (described as “correct use”). During this cycle, most participants (n = 34/51; 67%) did not ovulate, confirming that norgestrel 0.075 mg does impact ovulation.6 Most participants also had unfavorable cervical mucus (n = 39/51; 76%).⁶ Overall, 94% had full protection against pregnancy, either through lack of ovulation (n = 9), unfavorable mucus (n = 14), or both (n = 25). The remaining 3 participants ovulated and had intermediate mucus scores; ultimately, these participants were considered to have medium protection against pregnancy.^7,8 (See the contraceptive protection algorithm [TABLE]).⁸

obgm035120e11_chen_table.jpg

In the second and third cycles, the investigators evaluated ovulation and cervical mucus changes in the setting of either a delayed (by 6 hours) or missed dose midcycle.⁸ Of the 46 participants with evaluable data during the intervention cycles, 32 (70%) did not ovulate in each of the delayed- and missed-dose cycles. Most participants (n = 27; 59%) also demonstrated unfavorable mucus scores (modified Insler score ≤4) over the entire cycle despite delaying or missing a pill. There was no significant change to the cervical mucus score when comparing the scores on the days before, during, and after the delayed or missed pills (P = .26), nor when comparing between delayed pill use and missed pill use (P = .45). With the delayed pill intervention, 4 (9%) had reduced contraceptive protection (ie, medium protection) based on ovulation with intermediate mucus scores. With the missed pill intervention, 5 (11%) had reduced protection, of whom 3 had medium protection and 2 had minimum protection with ovulation and favorable mucus scores. Overall, this study shows that delaying or missing one pill may not impact contraceptive efficacy as much as previously thought given the strict 3-hour window for progestin-only pills. However, these findings are theoretical as information about pregnancy outcomes with delaying or missing pills are lacking.

Safety

Progestin-only methods are one of the safest options for contraception, with few contraindications to use; those listed include known or suspected pregnancy, known or suspected carcinoma of the breast or other progestinsensitive cancer, undiagnosed abnormal uterine bleeding, hypersensitivity to any component of the product, benign or malignant liver tumors, and acute liver disease.²

The CDC Medical Eligibility Criteria for Contraceptive Use guidelines offer guidance for progestin-only pills, indicating a category 3 (theoretical or proven risks usually outweigh the advantages) or category 4 (unacceptable health risk, method not to be used) for only a select number of additional conditions. These conditions include a history of malabsorptive bariatric surgery (category 3) and concurrent use of medications that induce hepatic enzyme activity (category 3)— such as phenytoin, carbamazepine, barbiturates, primidone, topiramate, oxcarbazepine, rifampin, and rifabutin.⁹ These conditions are included primarily due to concerns of decreased effectivenessof the contraception and not necessarily because of evidence of harm with use.

The prevalence of consumers with contraindications to progestin-only pills appears to be low. In a large database study, only 4.36% seeking preventive care and 2.29% seeking both preventive and contraceptive services had a contraindication to progestin-only pills.10 Therefore, candidates for norgestrel use include individuals who have commonly encountered conditions, including those who⁹:

• have recently given birth
• are breastfeeding
• have a history of venous thromboembolism
• smoke
• have cardiovascular disease, hypertension, migraines with aura, or longstanding diabetes.

Adverse effects

The most common adverse effects (AEs) related to norgestrel use are bleeding changes.² In the initial clinical studies for FDA approval, about half of enrolled participants reported a change in bleeding; about 9% discontinued the contraceptive due to bleeding. Breakthrough bleeding and spotting were reported by 48.6% and 47.3% of participants, respectively. About 6.1% had amenorrhea in their first cycle; 28.7% of participants had amenorrhea overall. Other reported AEs were headache, dizziness, nausea, increased appetite, abdominal pain, cramps or bloating, breast tenderness, and acne.

Continue to:  FDA approval required determining appropriate direct-to-patient classification...

FDA approval required determining appropriate direct-to-patient classification

As part of the process for obtaining nonprescription approval, studies needed to determine that patients can safely and effectively use norgestrel without talking to a health care provider first. As part of that process, label comprehension, self-selection, and actualuse studies were required to demonstrate that consumers can use the package information to determine their eligibility and take the medication appropriately.

The ACCESS study Research Q: Do patients appropriately determine if the contraceptive is right for them?

Study A: Yes, 99% of the time. In the Adherence with Continuous-dose Oral Contraceptive: Evaluation of Self-Selection and Use (ACCESS) pivotal study, which evaluated prescription to nonprescription approval, participants were asked to review the label and determine whether the product was appropriate for them to use based on their health history.¹¹ Approximately 99% of participants (n = 1,234/1,246) were able to correctly self-select whether norgestrel was appropriate for their own use.¹²

Research Q: After beginning the contraceptive, do patients adhere to correct use?

Study A: Yes, more than 90% of the time (and that remained true for subpopulations).

In the next phase of the ACCESS study, eligible participants from the self-selection population who purchased norgestrel and reported using the product at least once in their e-diary over a 6-month study period comprised the “User Population.”¹² The overall adherence to daily pill intake was 92.5% (95% confidence interval [CI], 92.3–92.6%) among the 883 participants who contributed more than 90,000 days of study participation, and adherence was similarly high in subpopulations of individuals with low health literacy (92.6%; 95% CI, 92.1–93.0), adolescents aged 12–14 years (91.8%; 95% CI, 91.0–92.5%), and adolescents aged 15–17 years (91.9%; 95% CI, 91.4%–92.3%).

Research Q: When a pill was missed, did patients use backup contraception?

Study A: Yes, 97% of the time.

When including whether participants followed label instructions for mitigating behaviors when the pill was missed (eg, take a pill as soon as they remember, use backup contraception for 2 days after restarting the pill), adherence was 97.1% (95% CI, 97.0–97.2%). Most participants missed a single day of taking pills, and the most common reported reason for missing pills was issues with resupply as participants needed to get new packs from their enrolled research site, which should be less of a barrier when these pills are available over the counter.

Clinical implications of expanded access

Opportunities to expand access to effective contraception have become more critical in the increasingly restrictive environment for abortion care in the post-Dobbs era, and the availability of norgestrel to patients without prescription can advance contraceptive equity. Patients encounter many barriers to accessing prescription contraception, such as lack of insurance; difficulty with scheduling an appointment or getting to a clinic; not having a regular clinician or clinic; or health care providers requiring a visit, exam, or test prior to prescribing contraception.13,14 For patients who face these challenges, an alternative option is to use a nonprescription contraceptive, such as barrier or fertility awareness–based methods, which are typically associated with higher failure rates. With the introduction of norgestrel as a nonprescription contraceptive product, people can have direct access to a more effective contraceptive option.

A follow-up study of participants who had participated in the ACCESS actual-use study demonstrated that most (83%) would be likely to use the nonprescription method if available in the future for many reasons, including convenience, ease of access, ability to save time and money, not needing to visit a clinic, and flexibility of accessing the pills while traveling or having someone else get their pills for them.¹⁴ Furthermore, a nonprescription method could be beneficial for people who have concerns about privacy, such as adolescents or individuals affected by contraception sabotage (an act that can intentionally limit or prohibit a person's contraception access or use, ie, damaging condoms or hiding a person’s contraception method). This expansion of access can ultimately lead to a decrease in unintended pregnancies. In a model using the ACCESS actual-use data, about 1,500 to 34,000 unintended pregnancies would be prevented per year based on varying model parameters, with all scenarios demonstrating a benefit to nonprescription access to norgestrel.¹⁵

After norgestrel is available, where will patients be able to seek more information?

Patients who have questions or concerns about starting or taking norgestrel should talk to their clinician or a pharmacist for additional information (FIGURE 2). Examples of situations when additional clinical evaluation or counseling are recommended include:

• when a person is taking any medications with possible drug-drug interactions
• if a person is starting norgestrel after taking an emergency contraceptive in the last 5 days
• if there is a concern about pregnancy
• when there are any questions about adverse effects while taking norgestrel.

Bottom line

The nonprescription approval of norgestrel, a progestin-only pill, has the potential to greatly expand patient access to a safe and effective contraceptive method and advance contraceptive equity. The availability of informational materials for consumers about potential issues that may arise (for instance, changes in bleeding) will be important for initiation and continuation of this method. As this product is not yet available for purchase, several unknown factors remain, such as the cost and ease of accessibility in stores or online, that will ultimately determine its public health impact on unintended pregnancies. ●

Individuals spend close to half of their lives preventing, or planning for, pregnancy. As such, contraception plays a major role in patient-provider interactions. Contraception counseling and management is a common scenario encountered in the general gynecologist’s practice. Luckily, we have 2 evidence-based guidelines developed by the US Centers for Disease Control and Prevention (CDC) that support the provision of contraceptive care:

1. US Medical Eligibility for Contraceptive Use (US-MEC),¹ which provides guidance on which patients can safely use a method
2. US Selected Practice Recommendations for Contraceptive Use (US-SPR),² which provides method-specific guidance on how to use a method (including how to: initiate or start a method; manage adherence issues, such as a missed pill, etc; and manage common issues like breakthrough bleeding). 

Both of these guidelines are updated routinely and are publicly available online or for free, through smartphone applications.

While most contraceptive care is straightforward, there are circumstances that require additional consideration. In the concluding part of this series on contraceptive conundrums, we review 2 clinical cases, existing evidence to guide management decisions, and our recommendations.

CASE 1 Patient presents with hard-to-remove implant

A 44-year-old patient (G2P2) with a new diagnosis of estrogen and progesterone-receptor–positive breast cancer is undergoing her evaluation with her oncologist who recommends removal of her contraceptive implant, which has been in place for 2 years. She presents to your office for removal; however, the device is no longer palpable.

What are your next steps?

Conundrum 1. Should you attempt to remove it?

No, never attempt implant removal if you cannot palpate or localize it. Localization of the implant needs to occur prior to any attempt. However, we recommend checking the contra-lateral arm before sending the patient to obtain imaging, especially if you have no formal documentation regarding in which arm the implant was placed. The next step is identifying what type of implant the patient likely has so you can correctly interpret imaging studies.

Conundrum 2. What type of subdermal contraceptive device is it likely to be?

Currently, the only subdermal contraceptive device available for placement in the United States is the 68-mg etonogestrel implant, marketed with the brand name Nexplanon. This device was initially approved by the US Food and Drug Administration in 2001 and measures 4 cm in length by 2 mm in diameter. It is placed in the medial upper arm, about 8 cm proximal to the medial epicondyle and 3 cm posterior to the sulcus between the biceps and triceps muscles. (The implant should no longer be placed over the bicipital groove.) The implant is impregnated with 15 mg of barium sulfate, making it radiopaque and able to be seen on imaging modalities such as ultrasonography (10–18 mHz high frequency transducer) and x-ray (arm anteroposterior and lateral) for localization in cases in which the device becomes nonpalpable.³

Clinicians also may encounter devices which are no longer marketed in the United States, or which are only available in other countries, and thus should be aware of the appearance and imaging characteristics. It is important to let your imaging team know these characteristics as well:

• From 2006–2010, a 68-mg etonogestrel implant marketed under the name Implanon was available in the United States.⁴ It has the same dimensions and general placement recommendations as the Nexplanon etonogestrel device but is not able to be seen via imaging.
• A 2-arm, 75-mg levonorgestrel (LNG) device known as Jadelle (or, Norplant II; FIGURE 1) received FDA approval in 1996 and is currently only available overseas.⁵ It is also placed in the upper, inner arm in a V-shape using a single incision, and has dimensions similar to the etonogestrel implants.
• From 1990– 2002, the 6-rod device known as Norplant was available in the United States. Each rod measured 3.4 cm in length and contained 36 mg of LNG (FIGURE 2).

obgm03512034_edelman_fig1.jpg

obgm03512034_edelman_fig2.jpg

Continue to: How do you approach removal of a deep contraceptive implant?...

How do you approach removal of a deep contraceptive implant?

Clinicians who are not trained in deep or difficult implant removal should refer patients to a trained provider (eg, a complex family planning subspecialist), or if not available, partner with a health care practitioner that has expertise in the anatomy of the upper arm (eg, vascular surgery, orthopedics, or interventional radiology). A resource for finding a nearby trained provider is the Organon Information Center (1-877-467-5266). However, when these services are not readily available, consider the following 3-step approach to complex implant removal.

1. Be familiar with the anatomy of the upper arm (FIGURE 3). Nonpalpable implants may be close to or under the biceps or triceps fascia or be near critically important and fragile structures like the neurovascular bundle of the upper arm. Prior to attempting a difficult implant removal, ensure that you are well acquainted with critical structures in the upper arm. 
2. Locate the device. Prior to attempting removal, localize the device using either x-ray or ultrasonography, depending on local availability. Ultrasound offers the advantage of mapping the location in 3 dimensions, with the ability to map the device with skin markings immediately prior to removal. Typically, a highfrequency transducer (15- or 18-MHz) is used, such as for breast imaging, either in a clinician’s office or in coordination with radiology. If device removal is attempted the same day, the proximal, midportion, and distal aspects of the device should be marked with a skin pen, and it should be noted what position the arm is in when the device is marked (eg, arm flexed at elbow and externally rotated so that the wrist is parallel to the ear). 

obgm03512034_edelman_fig3.jpg

Rarely, if a device is not seen in the expected extremity, imaging of the contralateral arm or a chest x-ray can be undertaken to rule out mis-documented laterality or a migrated device. Lastly, if no device is seen, and the patient has no memory of device removal, you can obtain the patient’s etonogestrel levels. (Resource: Merck National Service Center, 1-877-888-4231.)

Removal procedure. For nonpalpable implants, strong consideration should be given to performing the procedure with ultrasonography guidance. Rarely, fluoroscopic guidance may be useful for orientation in challenging cases, which may require coordination with other services, such as interventional radiology.

Cleaning and anesthetizing the site is similar to routine removal of a palpable implant. A 2- to 3-mm skin incision is made, either at the distal end of the implant (if one end is amenable to traditional pop-out technique) or over the midportion of the device (if a clinician has experience using the “U” technique).⁶ The incision should be parallel to the long axis of the implant and not perpendicular, to facilitate extension of the incision if needed during the procedure. Straight or curved hemostat clamps can then be used for blunt dissection of the subcutaneous tissues and to grasp the end of the device. Experienced clinicians may have access to a modified vasectomy clamp (with a 2.2-mm aperture) to grasp around the device in the midportion (the “U” technique). Blunt and careful sharp dissection may be needed to free the implant from the surrounding fibrin sheath or if under the muscle fascia. At the conclusion, the device should be measured to ensure that it was completely removed (4 cm).

Indications for referral. Typically, referral to a complex family planning specialist or vascular surgeon is required for cases that involve dissection of the muscular fascia or where dissection would be in close proximity to critical neurologic or vascular structures.

CASE 1 Conclusion

Ultrasonography of the patient’s extremity demonstrated a 4-cm radiopaque implant in the deep subcutaneous tissues of the upper arm, above the fascia and overlying the triceps muscle. The patient was counseled on the risks, benefits, and alternatives to an ultrasound-guided removal, and she desired to move forward with a procedure under sedation. She was able to schedule this concurrently with her chest port placement with interventional radiology. The device was again mapped using high frequency ultrasound. Her arm was then prepped, anesthetized, and a 3-mm linear incision was made over the most superficial portion, the distal 1/3 of the length of the device. The subcutaneous tissues were dissected using a curved Hemostat, and the implant was grasped with the modified vasectomy clamp. Blunt and sharp dissection were then used to free the device from the surrounding capsule of scar tissue, and the device was removed intact.

CASE 2 Patient enquires about immediate IUD insertion

A 28-year-old patient (G1P0) arrives at your clinic for a contraceptive consultation. They report a condom break during intercourse 4 days ago. Prior to that they used condoms consistently with each act of intercourse. They have used combined hormonal contraceptive pills in the past but had difficulty remembering to take them consistently. The patient and their partner have been mutually monogamous for 6 months and have no plans for pregnancy. Last menstrual period was 12 days ago. Their cycles are regular but heavy and painful. They are interested in using a hormonal IUD for contraception and would love to get it today.

Continue to: Is same-day IUD an option?...

Yes. This patient needs EC given the recent condom break, but they are still eligible for having an IUD placed today if their pregnancy test is negative and after counseling of the potential risks and benefits. According to the US-SPR it is reasonable to insert an IUD at any time during the cycle as long as you are reasonably certain the patient is not pregnant.⁷

Options for EC are:

• 1.5-mg oral LNG pill
• 30-mg oral UPA pill
• copper IUD (cu-IUD).

If they are interested in the cu-IUD for long-term contraception, by having a cu-IUD placed they can get both their needs met—EC and an ongoing method of contraception. Any patient receiving EC, whether a pill or an IUD, should be counseled to repeat a home urine pregnancy test in 2 to 4 weeks.

Given the favorable non–contraceptive benefits associated with 52-mg LNG-IUDs, many clinicians and patients have advocated for additional evidence regarding the use of hormonal IUDs alone for EC.

What is the evidence concerning LNG-IUD placement as EC?

The 52-mg LNG-IUD has not been mechanistically proven to work as an EC, but growing evidence exists showing that it is safe for same-day or “quick start” placement even in a population seeking EC—if their pregnancy test result is negative at the time of presentation.

Turok and colleagues performed a noninferiority trial comparing 1-month pregnancy rates after placement of either an LNG-IUD or a cu-IUD for EC.⁸ This study concluded that the LNG-IUD (which resulted in 1 pregnancy in 317 users; pregnancy rate, 0.3%; 95% confidence interval [CI], 0.01–1.70) is noninferior to cu-IUD (0 pregnancies in 321 users; pregnancy rate, 0%; 95% CI, 0.0–1.1) for EC. Although encouraging, only a small percentage of the study population seeking EC who received an IUD were actually at high risk of pregnancy (eg, they were not mid-cycle or were recently using contraception), which is why it is difficult to determine if the LNG-IUD actually works mechanistically as an EC. More likely, the LNG-IUD helps prevent pregnancy due to its ongoing contraceptive effect.⁹ Ongoing acts of intercourse post–oral EC initiation without starting a method of contraception is one of the main reasons for EC failure, which is why starting a method immediately is so effective at preventing pregnancy.¹⁰

A systematic review conducted by Ramanadhan and colleagues concluded that Turok’s 2021 trial is the only relevant study specific to 52-mg LNG-IUD use as EC, but they also mention that its results are limited in the strength of its conclusions due to biases in randomization, including¹¹:

• the study groups were not balanced in that there was a 10% difference in reported use of contraception at last intercourse, which means that the LNG-IUD group had a lower baseline risk of pregnancy
• and a rare primary outcome (ie, pregnancy, which requires a larger sample size to know if the method works as an EC).

The review authors concluded that more studies are needed to further validate the effectiveness of using the 52-mg LNG-IUD as EC. Thus, for those at highest risk of pregnancy from recent unprotected sex and desiring a 52-mg IUD, it is probably best to continue combining oral EC with a 52-mg LNG-IUD and utilizing the LNG-IUD only as EC on a limited, case-by-case basis.

What we recommend

For anyone with a negative pregnancy test on the day of presentation, the studies mentioned further support the practice of same-day placement of a 52-mg LNG-IUD. However, those seeking EC who are at highest risk for an unplanned pregnancy (ie, the unprotected sex was mid-cycle), we recommend co-administering the LNG-IUD with oral LNG for EC.

CASE 2 Conclusion

After a conversation with the patient about all contraceptive options, through shared decision making the patient decided to take 1.5 mg of oral LNG and have a 52-mg LNG-IUD placed in the office today. They do not wish to be pregnant at this time and would choose termination if they became pregnant. They understood their pregnancy risk and opted to plan a urine pregnancy test at home in 2 weeks with a clear understanding that they should return to clinic immediately if the test is positive. ●

Individuals spend close to half of their lives preventing, or planning for, pregnancy. As such, contraception plays a major role in patient-provider interactions. Contraception counseling and management is a common scenario encountered in the general gynecologist’s practice. Luckily, we have 2 evidence-based guidelines developed by the US Centers for Disease Control and Prevention (CDC) that support the provision of contraceptive care:

1. US Medical Eligibility for Contraceptive Use (US-MEC),¹ which provides guidance on which patients can safely use a method
2. US Selected Practice Recommendations for Contraceptive Use (US-SPR),² which provides method-specific guidance on how to use a method (including how to: initiate or start a method; manage adherence issues, such as a missed pill, etc; and manage common issues like breakthrough bleeding). 

Both of these guidelines are updated routinely and are publicly available online or for free, through smartphone applications.

While most contraceptive care is straightforward, there are circumstances that require additional consideration. In the concluding part of this series on contraceptive conundrums, we review 2 clinical cases, existing evidence to guide management decisions, and our recommendations.

CASE 1 Patient presents with hard-to-remove implant

A 44-year-old patient (G2P2) with a new diagnosis of estrogen and progesterone-receptor–positive breast cancer is undergoing her evaluation with her oncologist who recommends removal of her contraceptive implant, which has been in place for 2 years. She presents to your office for removal; however, the device is no longer palpable.

What are your next steps?

Conundrum 1. Should you attempt to remove it?

No, never attempt implant removal if you cannot palpate or localize it. Localization of the implant needs to occur prior to any attempt. However, we recommend checking the contra-lateral arm before sending the patient to obtain imaging, especially if you have no formal documentation regarding in which arm the implant was placed. The next step is identifying what type of implant the patient likely has so you can correctly interpret imaging studies.

Conundrum 2. What type of subdermal contraceptive device is it likely to be?

Currently, the only subdermal contraceptive device available for placement in the United States is the 68-mg etonogestrel implant, marketed with the brand name Nexplanon. This device was initially approved by the US Food and Drug Administration in 2001 and measures 4 cm in length by 2 mm in diameter. It is placed in the medial upper arm, about 8 cm proximal to the medial epicondyle and 3 cm posterior to the sulcus between the biceps and triceps muscles. (The implant should no longer be placed over the bicipital groove.) The implant is impregnated with 15 mg of barium sulfate, making it radiopaque and able to be seen on imaging modalities such as ultrasonography (10–18 mHz high frequency transducer) and x-ray (arm anteroposterior and lateral) for localization in cases in which the device becomes nonpalpable.³

Clinicians also may encounter devices which are no longer marketed in the United States, or which are only available in other countries, and thus should be aware of the appearance and imaging characteristics. It is important to let your imaging team know these characteristics as well:

• From 2006–2010, a 68-mg etonogestrel implant marketed under the name Implanon was available in the United States.⁴ It has the same dimensions and general placement recommendations as the Nexplanon etonogestrel device but is not able to be seen via imaging.
• A 2-arm, 75-mg levonorgestrel (LNG) device known as Jadelle (or, Norplant II; FIGURE 1) received FDA approval in 1996 and is currently only available overseas.⁵ It is also placed in the upper, inner arm in a V-shape using a single incision, and has dimensions similar to the etonogestrel implants.
• From 1990– 2002, the 6-rod device known as Norplant was available in the United States. Each rod measured 3.4 cm in length and contained 36 mg of LNG (FIGURE 2).

obgm03512034_edelman_fig1.jpg

obgm03512034_edelman_fig2.jpg

Continue to: How do you approach removal of a deep contraceptive implant?...

How do you approach removal of a deep contraceptive implant?

Clinicians who are not trained in deep or difficult implant removal should refer patients to a trained provider (eg, a complex family planning subspecialist), or if not available, partner with a health care practitioner that has expertise in the anatomy of the upper arm (eg, vascular surgery, orthopedics, or interventional radiology). A resource for finding a nearby trained provider is the Organon Information Center (1-877-467-5266). However, when these services are not readily available, consider the following 3-step approach to complex implant removal.

1. Be familiar with the anatomy of the upper arm (FIGURE 3). Nonpalpable implants may be close to or under the biceps or triceps fascia or be near critically important and fragile structures like the neurovascular bundle of the upper arm. Prior to attempting a difficult implant removal, ensure that you are well acquainted with critical structures in the upper arm. 
2. Locate the device. Prior to attempting removal, localize the device using either x-ray or ultrasonography, depending on local availability. Ultrasound offers the advantage of mapping the location in 3 dimensions, with the ability to map the device with skin markings immediately prior to removal. Typically, a highfrequency transducer (15- or 18-MHz) is used, such as for breast imaging, either in a clinician’s office or in coordination with radiology. If device removal is attempted the same day, the proximal, midportion, and distal aspects of the device should be marked with a skin pen, and it should be noted what position the arm is in when the device is marked (eg, arm flexed at elbow and externally rotated so that the wrist is parallel to the ear). 

obgm03512034_edelman_fig3.jpg

Rarely, if a device is not seen in the expected extremity, imaging of the contralateral arm or a chest x-ray can be undertaken to rule out mis-documented laterality or a migrated device. Lastly, if no device is seen, and the patient has no memory of device removal, you can obtain the patient’s etonogestrel levels. (Resource: Merck National Service Center, 1-877-888-4231.)

Removal procedure. For nonpalpable implants, strong consideration should be given to performing the procedure with ultrasonography guidance. Rarely, fluoroscopic guidance may be useful for orientation in challenging cases, which may require coordination with other services, such as interventional radiology.

Cleaning and anesthetizing the site is similar to routine removal of a palpable implant. A 2- to 3-mm skin incision is made, either at the distal end of the implant (if one end is amenable to traditional pop-out technique) or over the midportion of the device (if a clinician has experience using the “U” technique).⁶ The incision should be parallel to the long axis of the implant and not perpendicular, to facilitate extension of the incision if needed during the procedure. Straight or curved hemostat clamps can then be used for blunt dissection of the subcutaneous tissues and to grasp the end of the device. Experienced clinicians may have access to a modified vasectomy clamp (with a 2.2-mm aperture) to grasp around the device in the midportion (the “U” technique). Blunt and careful sharp dissection may be needed to free the implant from the surrounding fibrin sheath or if under the muscle fascia. At the conclusion, the device should be measured to ensure that it was completely removed (4 cm).

Indications for referral. Typically, referral to a complex family planning specialist or vascular surgeon is required for cases that involve dissection of the muscular fascia or where dissection would be in close proximity to critical neurologic or vascular structures.

CASE 1 Conclusion

Ultrasonography of the patient’s extremity demonstrated a 4-cm radiopaque implant in the deep subcutaneous tissues of the upper arm, above the fascia and overlying the triceps muscle. The patient was counseled on the risks, benefits, and alternatives to an ultrasound-guided removal, and she desired to move forward with a procedure under sedation. She was able to schedule this concurrently with her chest port placement with interventional radiology. The device was again mapped using high frequency ultrasound. Her arm was then prepped, anesthetized, and a 3-mm linear incision was made over the most superficial portion, the distal 1/3 of the length of the device. The subcutaneous tissues were dissected using a curved Hemostat, and the implant was grasped with the modified vasectomy clamp. Blunt and sharp dissection were then used to free the device from the surrounding capsule of scar tissue, and the device was removed intact.

CASE 2 Patient enquires about immediate IUD insertion

A 28-year-old patient (G1P0) arrives at your clinic for a contraceptive consultation. They report a condom break during intercourse 4 days ago. Prior to that they used condoms consistently with each act of intercourse. They have used combined hormonal contraceptive pills in the past but had difficulty remembering to take them consistently. The patient and their partner have been mutually monogamous for 6 months and have no plans for pregnancy. Last menstrual period was 12 days ago. Their cycles are regular but heavy and painful. They are interested in using a hormonal IUD for contraception and would love to get it today.

Continue to: Is same-day IUD an option?...

Yes. This patient needs EC given the recent condom break, but they are still eligible for having an IUD placed today if their pregnancy test is negative and after counseling of the potential risks and benefits. According to the US-SPR it is reasonable to insert an IUD at any time during the cycle as long as you are reasonably certain the patient is not pregnant.⁷

Options for EC are:

• 1.5-mg oral LNG pill
• 30-mg oral UPA pill
• copper IUD (cu-IUD).

If they are interested in the cu-IUD for long-term contraception, by having a cu-IUD placed they can get both their needs met—EC and an ongoing method of contraception. Any patient receiving EC, whether a pill or an IUD, should be counseled to repeat a home urine pregnancy test in 2 to 4 weeks.

Given the favorable non–contraceptive benefits associated with 52-mg LNG-IUDs, many clinicians and patients have advocated for additional evidence regarding the use of hormonal IUDs alone for EC.

What is the evidence concerning LNG-IUD placement as EC?

The 52-mg LNG-IUD has not been mechanistically proven to work as an EC, but growing evidence exists showing that it is safe for same-day or “quick start” placement even in a population seeking EC—if their pregnancy test result is negative at the time of presentation.

Turok and colleagues performed a noninferiority trial comparing 1-month pregnancy rates after placement of either an LNG-IUD or a cu-IUD for EC.⁸ This study concluded that the LNG-IUD (which resulted in 1 pregnancy in 317 users; pregnancy rate, 0.3%; 95% confidence interval [CI], 0.01–1.70) is noninferior to cu-IUD (0 pregnancies in 321 users; pregnancy rate, 0%; 95% CI, 0.0–1.1) for EC. Although encouraging, only a small percentage of the study population seeking EC who received an IUD were actually at high risk of pregnancy (eg, they were not mid-cycle or were recently using contraception), which is why it is difficult to determine if the LNG-IUD actually works mechanistically as an EC. More likely, the LNG-IUD helps prevent pregnancy due to its ongoing contraceptive effect.⁹ Ongoing acts of intercourse post–oral EC initiation without starting a method of contraception is one of the main reasons for EC failure, which is why starting a method immediately is so effective at preventing pregnancy.¹⁰

A systematic review conducted by Ramanadhan and colleagues concluded that Turok’s 2021 trial is the only relevant study specific to 52-mg LNG-IUD use as EC, but they also mention that its results are limited in the strength of its conclusions due to biases in randomization, including¹¹:

• the study groups were not balanced in that there was a 10% difference in reported use of contraception at last intercourse, which means that the LNG-IUD group had a lower baseline risk of pregnancy
• and a rare primary outcome (ie, pregnancy, which requires a larger sample size to know if the method works as an EC).

The review authors concluded that more studies are needed to further validate the effectiveness of using the 52-mg LNG-IUD as EC. Thus, for those at highest risk of pregnancy from recent unprotected sex and desiring a 52-mg IUD, it is probably best to continue combining oral EC with a 52-mg LNG-IUD and utilizing the LNG-IUD only as EC on a limited, case-by-case basis.

What we recommend

For anyone with a negative pregnancy test on the day of presentation, the studies mentioned further support the practice of same-day placement of a 52-mg LNG-IUD. However, those seeking EC who are at highest risk for an unplanned pregnancy (ie, the unprotected sex was mid-cycle), we recommend co-administering the LNG-IUD with oral LNG for EC.

CASE 2 Conclusion

After a conversation with the patient about all contraceptive options, through shared decision making the patient decided to take 1.5 mg of oral LNG and have a 52-mg LNG-IUD placed in the office today. They do not wish to be pregnant at this time and would choose termination if they became pregnant. They understood their pregnancy risk and opted to plan a urine pregnancy test at home in 2 weeks with a clear understanding that they should return to clinic immediately if the test is positive. ●

Individuals spend close to half of their lives preventing, or planning for, pregnancy. As such, contraception plays a major role in patient-provider interactions. Contraception counseling and management is a common scenario encountered in the general gynecologist’s practice. Luckily, we have 2 evidence-based guidelines developed by the US Centers for Disease Control and Prevention (CDC) that support the provision of contraceptive care:

1. US Medical Eligibility for Contraceptive Use (US-MEC),¹ which provides guidance on which patients can safely use a method
2. US Selected Practice Recommendations for Contraceptive Use (US-SPR),² which provides method-specific guidance on how to use a method (including how to: initiate or start a method; manage adherence issues, such as a missed pill, etc; and manage common issues like breakthrough bleeding). 

Both of these guidelines are updated routinely and are publicly available online or for free, through smartphone applications.

While most contraceptive care is straightforward, there are circumstances that require additional consideration. In the concluding part of this series on contraceptive conundrums, we review 2 clinical cases, existing evidence to guide management decisions, and our recommendations.

CASE 1 Patient presents with hard-to-remove implant

A 44-year-old patient (G2P2) with a new diagnosis of estrogen and progesterone-receptor–positive breast cancer is undergoing her evaluation with her oncologist who recommends removal of her contraceptive implant, which has been in place for 2 years. She presents to your office for removal; however, the device is no longer palpable.

What are your next steps?

Conundrum 1. Should you attempt to remove it?

No, never attempt implant removal if you cannot palpate or localize it. Localization of the implant needs to occur prior to any attempt. However, we recommend checking the contra-lateral arm before sending the patient to obtain imaging, especially if you have no formal documentation regarding in which arm the implant was placed. The next step is identifying what type of implant the patient likely has so you can correctly interpret imaging studies.

Conundrum 2. What type of subdermal contraceptive device is it likely to be?

Currently, the only subdermal contraceptive device available for placement in the United States is the 68-mg etonogestrel implant, marketed with the brand name Nexplanon. This device was initially approved by the US Food and Drug Administration in 2001 and measures 4 cm in length by 2 mm in diameter. It is placed in the medial upper arm, about 8 cm proximal to the medial epicondyle and 3 cm posterior to the sulcus between the biceps and triceps muscles. (The implant should no longer be placed over the bicipital groove.) The implant is impregnated with 15 mg of barium sulfate, making it radiopaque and able to be seen on imaging modalities such as ultrasonography (10–18 mHz high frequency transducer) and x-ray (arm anteroposterior and lateral) for localization in cases in which the device becomes nonpalpable.³

Clinicians also may encounter devices which are no longer marketed in the United States, or which are only available in other countries, and thus should be aware of the appearance and imaging characteristics. It is important to let your imaging team know these characteristics as well:

• From 2006–2010, a 68-mg etonogestrel implant marketed under the name Implanon was available in the United States.⁴ It has the same dimensions and general placement recommendations as the Nexplanon etonogestrel device but is not able to be seen via imaging.
• A 2-arm, 75-mg levonorgestrel (LNG) device known as Jadelle (or, Norplant II; FIGURE 1) received FDA approval in 1996 and is currently only available overseas.⁵ It is also placed in the upper, inner arm in a V-shape using a single incision, and has dimensions similar to the etonogestrel implants.
• From 1990– 2002, the 6-rod device known as Norplant was available in the United States. Each rod measured 3.4 cm in length and contained 36 mg of LNG (FIGURE 2).

obgm03512034_edelman_fig1.jpg

obgm03512034_edelman_fig2.jpg

Continue to: How do you approach removal of a deep contraceptive implant?...

How do you approach removal of a deep contraceptive implant?

Clinicians who are not trained in deep or difficult implant removal should refer patients to a trained provider (eg, a complex family planning subspecialist), or if not available, partner with a health care practitioner that has expertise in the anatomy of the upper arm (eg, vascular surgery, orthopedics, or interventional radiology). A resource for finding a nearby trained provider is the Organon Information Center (1-877-467-5266). However, when these services are not readily available, consider the following 3-step approach to complex implant removal.

1. Be familiar with the anatomy of the upper arm (FIGURE 3). Nonpalpable implants may be close to or under the biceps or triceps fascia or be near critically important and fragile structures like the neurovascular bundle of the upper arm. Prior to attempting a difficult implant removal, ensure that you are well acquainted with critical structures in the upper arm. 
2. Locate the device. Prior to attempting removal, localize the device using either x-ray or ultrasonography, depending on local availability. Ultrasound offers the advantage of mapping the location in 3 dimensions, with the ability to map the device with skin markings immediately prior to removal. Typically, a highfrequency transducer (15- or 18-MHz) is used, such as for breast imaging, either in a clinician’s office or in coordination with radiology. If device removal is attempted the same day, the proximal, midportion, and distal aspects of the device should be marked with a skin pen, and it should be noted what position the arm is in when the device is marked (eg, arm flexed at elbow and externally rotated so that the wrist is parallel to the ear). 

obgm03512034_edelman_fig3.jpg

Rarely, if a device is not seen in the expected extremity, imaging of the contralateral arm or a chest x-ray can be undertaken to rule out mis-documented laterality or a migrated device. Lastly, if no device is seen, and the patient has no memory of device removal, you can obtain the patient’s etonogestrel levels. (Resource: Merck National Service Center, 1-877-888-4231.)

Removal procedure. For nonpalpable implants, strong consideration should be given to performing the procedure with ultrasonography guidance. Rarely, fluoroscopic guidance may be useful for orientation in challenging cases, which may require coordination with other services, such as interventional radiology.

Cleaning and anesthetizing the site is similar to routine removal of a palpable implant. A 2- to 3-mm skin incision is made, either at the distal end of the implant (if one end is amenable to traditional pop-out technique) or over the midportion of the device (if a clinician has experience using the “U” technique).⁶ The incision should be parallel to the long axis of the implant and not perpendicular, to facilitate extension of the incision if needed during the procedure. Straight or curved hemostat clamps can then be used for blunt dissection of the subcutaneous tissues and to grasp the end of the device. Experienced clinicians may have access to a modified vasectomy clamp (with a 2.2-mm aperture) to grasp around the device in the midportion (the “U” technique). Blunt and careful sharp dissection may be needed to free the implant from the surrounding fibrin sheath or if under the muscle fascia. At the conclusion, the device should be measured to ensure that it was completely removed (4 cm).

Indications for referral. Typically, referral to a complex family planning specialist or vascular surgeon is required for cases that involve dissection of the muscular fascia or where dissection would be in close proximity to critical neurologic or vascular structures.

CASE 1 Conclusion

Ultrasonography of the patient’s extremity demonstrated a 4-cm radiopaque implant in the deep subcutaneous tissues of the upper arm, above the fascia and overlying the triceps muscle. The patient was counseled on the risks, benefits, and alternatives to an ultrasound-guided removal, and she desired to move forward with a procedure under sedation. She was able to schedule this concurrently with her chest port placement with interventional radiology. The device was again mapped using high frequency ultrasound. Her arm was then prepped, anesthetized, and a 3-mm linear incision was made over the most superficial portion, the distal 1/3 of the length of the device. The subcutaneous tissues were dissected using a curved Hemostat, and the implant was grasped with the modified vasectomy clamp. Blunt and sharp dissection were then used to free the device from the surrounding capsule of scar tissue, and the device was removed intact.

CASE 2 Patient enquires about immediate IUD insertion

A 28-year-old patient (G1P0) arrives at your clinic for a contraceptive consultation. They report a condom break during intercourse 4 days ago. Prior to that they used condoms consistently with each act of intercourse. They have used combined hormonal contraceptive pills in the past but had difficulty remembering to take them consistently. The patient and their partner have been mutually monogamous for 6 months and have no plans for pregnancy. Last menstrual period was 12 days ago. Their cycles are regular but heavy and painful. They are interested in using a hormonal IUD for contraception and would love to get it today.

Continue to: Is same-day IUD an option?...

Yes. This patient needs EC given the recent condom break, but they are still eligible for having an IUD placed today if their pregnancy test is negative and after counseling of the potential risks and benefits. According to the US-SPR it is reasonable to insert an IUD at any time during the cycle as long as you are reasonably certain the patient is not pregnant.⁷

Options for EC are:

• 1.5-mg oral LNG pill
• 30-mg oral UPA pill
• copper IUD (cu-IUD).

If they are interested in the cu-IUD for long-term contraception, by having a cu-IUD placed they can get both their needs met—EC and an ongoing method of contraception. Any patient receiving EC, whether a pill or an IUD, should be counseled to repeat a home urine pregnancy test in 2 to 4 weeks.

Given the favorable non–contraceptive benefits associated with 52-mg LNG-IUDs, many clinicians and patients have advocated for additional evidence regarding the use of hormonal IUDs alone for EC.

What is the evidence concerning LNG-IUD placement as EC?

The 52-mg LNG-IUD has not been mechanistically proven to work as an EC, but growing evidence exists showing that it is safe for same-day or “quick start” placement even in a population seeking EC—if their pregnancy test result is negative at the time of presentation.

Turok and colleagues performed a noninferiority trial comparing 1-month pregnancy rates after placement of either an LNG-IUD or a cu-IUD for EC.⁸ This study concluded that the LNG-IUD (which resulted in 1 pregnancy in 317 users; pregnancy rate, 0.3%; 95% confidence interval [CI], 0.01–1.70) is noninferior to cu-IUD (0 pregnancies in 321 users; pregnancy rate, 0%; 95% CI, 0.0–1.1) for EC. Although encouraging, only a small percentage of the study population seeking EC who received an IUD were actually at high risk of pregnancy (eg, they were not mid-cycle or were recently using contraception), which is why it is difficult to determine if the LNG-IUD actually works mechanistically as an EC. More likely, the LNG-IUD helps prevent pregnancy due to its ongoing contraceptive effect.⁹ Ongoing acts of intercourse post–oral EC initiation without starting a method of contraception is one of the main reasons for EC failure, which is why starting a method immediately is so effective at preventing pregnancy.¹⁰

A systematic review conducted by Ramanadhan and colleagues concluded that Turok’s 2021 trial is the only relevant study specific to 52-mg LNG-IUD use as EC, but they also mention that its results are limited in the strength of its conclusions due to biases in randomization, including¹¹:

• the study groups were not balanced in that there was a 10% difference in reported use of contraception at last intercourse, which means that the LNG-IUD group had a lower baseline risk of pregnancy
• and a rare primary outcome (ie, pregnancy, which requires a larger sample size to know if the method works as an EC).

The review authors concluded that more studies are needed to further validate the effectiveness of using the 52-mg LNG-IUD as EC. Thus, for those at highest risk of pregnancy from recent unprotected sex and desiring a 52-mg IUD, it is probably best to continue combining oral EC with a 52-mg LNG-IUD and utilizing the LNG-IUD only as EC on a limited, case-by-case basis.

What we recommend

For anyone with a negative pregnancy test on the day of presentation, the studies mentioned further support the practice of same-day placement of a 52-mg LNG-IUD. However, those seeking EC who are at highest risk for an unplanned pregnancy (ie, the unprotected sex was mid-cycle), we recommend co-administering the LNG-IUD with oral LNG for EC.

CASE 2 Conclusion

After a conversation with the patient about all contraceptive options, through shared decision making the patient decided to take 1.5 mg of oral LNG and have a 52-mg LNG-IUD placed in the office today. They do not wish to be pregnant at this time and would choose termination if they became pregnant. They understood their pregnancy risk and opted to plan a urine pregnancy test at home in 2 weeks with a clear understanding that they should return to clinic immediately if the test is positive. ●

In a letter dated Nov. 30, 2023, the Food and Drug Administration informed isotretinoin manufacturers that they have 6 months to make five changes to existing iPLEDGE Risk Evaluation and Mitigation Strategy (REMS) requirements for the acne drug isotretinoin.

The development follows a March 2023 joint meeting of the FDA’s Drug Safety and Risk Management Advisory Committee and the Dermatologic and Ophthalmic Drugs Advisory Committee about iPLEDGE REMS requirements, which included feedback from patients and dermatologists and recommendations for changes to the REMS program, aimed at minimizing the burden of the program on patients, pharmacies, and prescribers while continuing to maintain safe use of the highly teratogenic drug for patients.

The five changes include the following:

• Remove the requirement that pregnancy tests must be performed in a specially certified (i.e., Clinical Laboratory Improvement Amendments [CLIA]) laboratory. In the opinion of John S. Barbieri, MD, MBA, director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital, Boston, this change “may make it easier to perform pregnancy tests in a clinic setting without needing to send the patient to a separate lab,” he said in an interview.
• Allow prescribers the option of using home pregnancy testing for their patients during and after isotretinoin treatment. Prescribers who rely on the patient to perform a home pregnancy test need to take steps to minimize patients falsifying the results of these tests. According to Dr. Barbieri, this means that two pregnancy tests prior to starting isotretinoin must be done in a lab or office setting. “However, all the pregnancy tests on therapy can be either in a medical setting or using a home pregnancy test,” he told this news organization. “This option facilitates the use of telemedicine so that patients would not need to come in; they can just share a pregnancy test with their name and date with their dermatologist.”
• Remove the waiting period requirement — also known as the “19-day lockout” — for patients if they do not obtain isotretinoin within the first 7-day prescription window. According to Dr. Barbieri, this change helps to ensure that patients can begin isotretinoin in a timely manner. “Insurance and pharmacy delays that are no fault of the patient can commonly cause missed initial window periods,” he said. “Allowing for immediate repeat of a pregnancy test to start a new window period, rather than requiring the patient to wait 19 more days, can ensure patient safety and pregnancy prevention without negatively impacting access.”
• Revise the pregnancy registry requirement to remove the objective to document the pregnancy and fetal outcomes for each pregnancy.
• Revise the requirement for prescribers to document patient counseling in patients who cannot become pregnant from monthly to only at enrollment. Dr. Barbieri characterized this change as “major” and said that it could eliminate the need for monthly visits for persons of non–childbearing potential. “This could substantially reduce logistical burdens for patients and reduce wait times to see a dermatologist,” he said.

Future changes to iPLEDGE that Dr. Barbieri would like to see include allowing for home pregnancy tests prior to starting therapy — particularly the test after the 30-day window period. “In addition, it would be good to be able to reduce the 30-day waiting period prior to therapy to something shorter,” such as 14 days, which would still “reliably exclude pregnancy, particularly for those on stable long-acting reversible contraception,” he said. There are also opportunities to improve the iPLEDGE website functionality and to ensure that the website is accessible to patients with limited English proficiency, he added.

[embed:render:related:node:262164]

He also recommended greater transparency by the Isotretinoin Products Manufacturers Group and inclusion of input from diverse stakeholders such as dermatologists, patients, and pharmacists.

Dr. Barbieri reported personal fees from Dexcel Pharma.

In a letter dated Nov. 30, 2023, the Food and Drug Administration informed isotretinoin manufacturers that they have 6 months to make five changes to existing iPLEDGE Risk Evaluation and Mitigation Strategy (REMS) requirements for the acne drug isotretinoin.

The development follows a March 2023 joint meeting of the FDA’s Drug Safety and Risk Management Advisory Committee and the Dermatologic and Ophthalmic Drugs Advisory Committee about iPLEDGE REMS requirements, which included feedback from patients and dermatologists and recommendations for changes to the REMS program, aimed at minimizing the burden of the program on patients, pharmacies, and prescribers while continuing to maintain safe use of the highly teratogenic drug for patients.

The five changes include the following:

• Remove the requirement that pregnancy tests must be performed in a specially certified (i.e., Clinical Laboratory Improvement Amendments [CLIA]) laboratory. In the opinion of John S. Barbieri, MD, MBA, director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital, Boston, this change “may make it easier to perform pregnancy tests in a clinic setting without needing to send the patient to a separate lab,” he said in an interview.
• Allow prescribers the option of using home pregnancy testing for their patients during and after isotretinoin treatment. Prescribers who rely on the patient to perform a home pregnancy test need to take steps to minimize patients falsifying the results of these tests. According to Dr. Barbieri, this means that two pregnancy tests prior to starting isotretinoin must be done in a lab or office setting. “However, all the pregnancy tests on therapy can be either in a medical setting or using a home pregnancy test,” he told this news organization. “This option facilitates the use of telemedicine so that patients would not need to come in; they can just share a pregnancy test with their name and date with their dermatologist.”
• Remove the waiting period requirement — also known as the “19-day lockout” — for patients if they do not obtain isotretinoin within the first 7-day prescription window. According to Dr. Barbieri, this change helps to ensure that patients can begin isotretinoin in a timely manner. “Insurance and pharmacy delays that are no fault of the patient can commonly cause missed initial window periods,” he said. “Allowing for immediate repeat of a pregnancy test to start a new window period, rather than requiring the patient to wait 19 more days, can ensure patient safety and pregnancy prevention without negatively impacting access.”
• Revise the pregnancy registry requirement to remove the objective to document the pregnancy and fetal outcomes for each pregnancy.
• Revise the requirement for prescribers to document patient counseling in patients who cannot become pregnant from monthly to only at enrollment. Dr. Barbieri characterized this change as “major” and said that it could eliminate the need for monthly visits for persons of non–childbearing potential. “This could substantially reduce logistical burdens for patients and reduce wait times to see a dermatologist,” he said.

Future changes to iPLEDGE that Dr. Barbieri would like to see include allowing for home pregnancy tests prior to starting therapy — particularly the test after the 30-day window period. “In addition, it would be good to be able to reduce the 30-day waiting period prior to therapy to something shorter,” such as 14 days, which would still “reliably exclude pregnancy, particularly for those on stable long-acting reversible contraception,” he said. There are also opportunities to improve the iPLEDGE website functionality and to ensure that the website is accessible to patients with limited English proficiency, he added.

[embed:render:related:node:262164]

He also recommended greater transparency by the Isotretinoin Products Manufacturers Group and inclusion of input from diverse stakeholders such as dermatologists, patients, and pharmacists.

Dr. Barbieri reported personal fees from Dexcel Pharma.

In a letter dated Nov. 30, 2023, the Food and Drug Administration informed isotretinoin manufacturers that they have 6 months to make five changes to existing iPLEDGE Risk Evaluation and Mitigation Strategy (REMS) requirements for the acne drug isotretinoin.

The development follows a March 2023 joint meeting of the FDA’s Drug Safety and Risk Management Advisory Committee and the Dermatologic and Ophthalmic Drugs Advisory Committee about iPLEDGE REMS requirements, which included feedback from patients and dermatologists and recommendations for changes to the REMS program, aimed at minimizing the burden of the program on patients, pharmacies, and prescribers while continuing to maintain safe use of the highly teratogenic drug for patients.

The five changes include the following:

• Remove the requirement that pregnancy tests must be performed in a specially certified (i.e., Clinical Laboratory Improvement Amendments [CLIA]) laboratory. In the opinion of John S. Barbieri, MD, MBA, director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital, Boston, this change “may make it easier to perform pregnancy tests in a clinic setting without needing to send the patient to a separate lab,” he said in an interview.
• Allow prescribers the option of using home pregnancy testing for their patients during and after isotretinoin treatment. Prescribers who rely on the patient to perform a home pregnancy test need to take steps to minimize patients falsifying the results of these tests. According to Dr. Barbieri, this means that two pregnancy tests prior to starting isotretinoin must be done in a lab or office setting. “However, all the pregnancy tests on therapy can be either in a medical setting or using a home pregnancy test,” he told this news organization. “This option facilitates the use of telemedicine so that patients would not need to come in; they can just share a pregnancy test with their name and date with their dermatologist.”
• Remove the waiting period requirement — also known as the “19-day lockout” — for patients if they do not obtain isotretinoin within the first 7-day prescription window. According to Dr. Barbieri, this change helps to ensure that patients can begin isotretinoin in a timely manner. “Insurance and pharmacy delays that are no fault of the patient can commonly cause missed initial window periods,” he said. “Allowing for immediate repeat of a pregnancy test to start a new window period, rather than requiring the patient to wait 19 more days, can ensure patient safety and pregnancy prevention without negatively impacting access.”
• Revise the pregnancy registry requirement to remove the objective to document the pregnancy and fetal outcomes for each pregnancy.
• Revise the requirement for prescribers to document patient counseling in patients who cannot become pregnant from monthly to only at enrollment. Dr. Barbieri characterized this change as “major” and said that it could eliminate the need for monthly visits for persons of non–childbearing potential. “This could substantially reduce logistical burdens for patients and reduce wait times to see a dermatologist,” he said.

Future changes to iPLEDGE that Dr. Barbieri would like to see include allowing for home pregnancy tests prior to starting therapy — particularly the test after the 30-day window period. “In addition, it would be good to be able to reduce the 30-day waiting period prior to therapy to something shorter,” such as 14 days, which would still “reliably exclude pregnancy, particularly for those on stable long-acting reversible contraception,” he said. There are also opportunities to improve the iPLEDGE website functionality and to ensure that the website is accessible to patients with limited English proficiency, he added.

[embed:render:related:node:262164]

He also recommended greater transparency by the Isotretinoin Products Manufacturers Group and inclusion of input from diverse stakeholders such as dermatologists, patients, and pharmacists.

Dr. Barbieri reported personal fees from Dexcel Pharma.

Meaidi A, Mascolo A, Sessa M, et al. Venous thromboembolism with use of hormonal contraception and non-steroidal anti-inflammatory drugs: nationwide cohort study. BMJ. 2023;382:e074450. doi:10.1136/bmj-2022-074450

EXPERT COMMENTARY

Combination (estrogen plus progestin) hormonal contraceptives as well as non–aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) increase the risk of VTE events, including lower extremity clots and pulmonary embolism. Taking contraceptives formulated with ethinyl estradiol increases hepatic production of clotting factors on a dose-related basis. Newer progestins, including desogestrel and drospirenone, also may contribute to an elevated VTE risk, although this association is controversial.¹ NSAIDs promote platelet aggregation, thereby activating the clotting system and formation of clots. Although studies that assessed the association between NSAID use and thrombosis have focused on arterial clots, a substantial literature suggests that NSAIDs, including older NSAIDs (such as ibuprofen, diclofenac, and naproxen), also increase VTE risk.²

Although combination contraceptives (oral contraceptives, patches, vaginal rings) and NSAIDs are both commonly used by reproductive-age women, little data have assessed the impact of concomitant use of these medications on VTE risk. Accordingly, investigators in Denmark, using national databases, conducted a retrospective cohort study to assess the impact that independent as well as concomitant use of these medications have on VTE risk.

Details of the study

Meaidi and colleagues included in the cohort reproductive-age women living in Denmark between 1996 and 2017 with no history of thrombosis, thrombophilia, cancer, tubal sterilization, hysterectomy, bilateral oophorectomy, or infertility treatment. National prescription data were used to assess exposure to hormonal contraception.

The investigators classified hormonal contraception into 3 VTE risk categories:

1. high risk—estrogen-progestin patches and vaginal rings; oral contraceptives containing 50 µg of ethinyl estradiol; or the progestins desogestrel, drospirenone, gestodene, or cyproterone (with the latter 2 progestins not available in the United States)
2. medium risk—all other combination oral contraceptives, including those formulated with the progestins norethindrone, norethindrone acetate, norgestrel, and levonorgestrel, as well as depot medroxyprogesterone acetate
3. low/no risk—progestin-only pills, implants, and progestin-containing intrauterine devices (IUDs).

Because in Denmark NSAIDs are prescribed as a single package containing no more than 30 tablets, time exposed to non–aspirin NSAIDs was assumed to last 1 week from the prescription date.

The authors considered first-time diagnoses of lower limb venous thrombosis or pulmonary embolism that were made in hospitals to represent VTE. They also constructed a subgroup of VTE patients in whom the diagnosis was either confirmed with imaging or followed by prescription of an anticoagulant.

To address potential confounding, the authors adjusted their analysis based on age, calendar year, educational attainment, occurrence of pregnancy, surgery, hypertension, diabetes, polycystic ovary syndrome, endometriosis, migraine, systemic connective tissue diseases, inflammatory polyarthropathies, and use of tranexamic acid (a medication that may increase VTE risk). They also censored (temporarily excluded women from analysis) episodes associated with a transiently elevated risk of VTE: pregnancy and 6 months following delivery, 12 weeks after other pregnancy terminations, 8 weeks following any surgery involving hospital admission, and 8 weeks following prescription of tranexamic acid.

Continue to: VTEs associated with risk category of hormonal contraception used...

Results. The overall cohort included more than 2 million women who were followed for a median of 10 years. During 21.0 million person-years, 8,710 VTE events were diagnosed; almost one-third of these were pulmonary embolisms, with the remainder diagnosed as lower extremity VTE. Of these 8,710 women diagnosed with VTE, 7,043 (81%) were confirmed with either diagnostic imaging or prescription of an anticoagulant. Unfortunately, 228 women (2.6%) died within 30 days of the diagnosis of VTE.

The investigators identified concomitant use of hormonal contraception and NSAIDs in more than 500,000 women. Among women with such concomitant use, 58% were using contraceptives that were high risk while 23% used medium-risk and 19% used low/no-risk contraceptives. Ibuprofen (60%) was the most commonly used NSAID, followed by diclofenac (20%) and naproxen (6%). Between 97% and 98% of high-risk and medium-risk contraceptives were combination pills; 89% of low/no-risk contraceptives were progestin IUDs.

Compared with nonuse of both hormonal contraceptives and NSAIDs, incidence rate ratios of VTE adjusted for age, calendar year, and education were 8.1 (95% confidence interval [CI], 6.9–9.6) for use of NSAIDs only, 4.2 (95% CI, 4.0–4.4) for use of high-risk contraceptives only, 3.0 (95% CI, 2.8–3.2) for medium-risk contraceptive use, and 1.1 (95% CI, 1.0–1.3) for use of low/no-risk hormonal contraception. Risk of VTE was approximately twice as high with the use of diclofenac only compared with the risks associated with ibuprofen or naproxen use only.

With respect to concomitant use of NSAIDs and hormonal contraception, incidence rate ratios of VTE were 50.6 (95% CI, 44.2–57.8), 26.1 (95% CI, 19.6–34.7), and 5.7 (95% CI, 3.3–10.1), respectively, with use of high-risk, medium-risk, and low/no-risk hormonal contraceptives. Adjusting for time updated information on occurrences of migraine, connective tissue disorder, inflammatory polyarthropathies, endometriosis, polycystic ovary syndrome, hypertension, and diabetes did not materially affect these associations.

When analysis was limited to women without these occurring conditions, rate ratios were somewhat higher (5.7 and 4.1) for use of high-risk and medium-risk contraceptives only. Incidence rate ratios in this subcohort of healthier women were substantially higher for NSAID use only (15.0), and 111.7, 43.2, and 13.0, respectively, for concomitant use of NSAIDs with high-risk, medium-risk, and low/no-risk contraceptives. In this analysis of healthier women, diclofenac continued to be associated with substantially higher risks of VTE than ibuprofen or naproxen. When the stricter definition of VTE (confirmed cases) was used, adjusted rate ratios remained similar.

Absolute risks of VTE

Although some of the elevated rate ratios noted in this study might appear alarming, it is important to keep in mind that the baseline incidence of VTE in healthy reproductive-age women is low. Accordingly, as the authors pointed out, even among women who used NSAIDs concomitantly with high-risk combination hormonal contraceptives, the absolute risk of VTE was 2/10,000.

Study strengths and limitations

Strengths of this analysis by Meaidi and colleagues include the use of large, essentially all-inclusive national registries. In addition, nationwide Danish registry data that indicate a diagnosis of VTE have been found to have a high positive predictive value.³ Another strength is the large number of potentially confounding factors that the authors controlled for.

One potential limitation of their analysis is that the use of only prescribed NSAIDs was considered. Fortunately, however, the prevalence of over-the-counter ibuprofen use in Denmark is not high enough to materially affect the authors’ findings.⁴ Another potential limitation was that information on smoking and body mass index was not available for most of the women included in the study cohort. The authors countered this limitation by pointing out that, in Denmark, smoking and obesity are highly correlated with educational status, and that all analyses were adjusted for educational status. ●

Meaidi A, Mascolo A, Sessa M, et al. Venous thromboembolism with use of hormonal contraception and non-steroidal anti-inflammatory drugs: nationwide cohort study. BMJ. 2023;382:e074450. doi:10.1136/bmj-2022-074450

EXPERT COMMENTARY

Combination (estrogen plus progestin) hormonal contraceptives as well as non–aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) increase the risk of VTE events, including lower extremity clots and pulmonary embolism. Taking contraceptives formulated with ethinyl estradiol increases hepatic production of clotting factors on a dose-related basis. Newer progestins, including desogestrel and drospirenone, also may contribute to an elevated VTE risk, although this association is controversial.¹ NSAIDs promote platelet aggregation, thereby activating the clotting system and formation of clots. Although studies that assessed the association between NSAID use and thrombosis have focused on arterial clots, a substantial literature suggests that NSAIDs, including older NSAIDs (such as ibuprofen, diclofenac, and naproxen), also increase VTE risk.²

Although combination contraceptives (oral contraceptives, patches, vaginal rings) and NSAIDs are both commonly used by reproductive-age women, little data have assessed the impact of concomitant use of these medications on VTE risk. Accordingly, investigators in Denmark, using national databases, conducted a retrospective cohort study to assess the impact that independent as well as concomitant use of these medications have on VTE risk.

Details of the study

Meaidi and colleagues included in the cohort reproductive-age women living in Denmark between 1996 and 2017 with no history of thrombosis, thrombophilia, cancer, tubal sterilization, hysterectomy, bilateral oophorectomy, or infertility treatment. National prescription data were used to assess exposure to hormonal contraception.

The investigators classified hormonal contraception into 3 VTE risk categories:

1. high risk—estrogen-progestin patches and vaginal rings; oral contraceptives containing 50 µg of ethinyl estradiol; or the progestins desogestrel, drospirenone, gestodene, or cyproterone (with the latter 2 progestins not available in the United States)
2. medium risk—all other combination oral contraceptives, including those formulated with the progestins norethindrone, norethindrone acetate, norgestrel, and levonorgestrel, as well as depot medroxyprogesterone acetate
3. low/no risk—progestin-only pills, implants, and progestin-containing intrauterine devices (IUDs).

Because in Denmark NSAIDs are prescribed as a single package containing no more than 30 tablets, time exposed to non–aspirin NSAIDs was assumed to last 1 week from the prescription date.

The authors considered first-time diagnoses of lower limb venous thrombosis or pulmonary embolism that were made in hospitals to represent VTE. They also constructed a subgroup of VTE patients in whom the diagnosis was either confirmed with imaging or followed by prescription of an anticoagulant.

To address potential confounding, the authors adjusted their analysis based on age, calendar year, educational attainment, occurrence of pregnancy, surgery, hypertension, diabetes, polycystic ovary syndrome, endometriosis, migraine, systemic connective tissue diseases, inflammatory polyarthropathies, and use of tranexamic acid (a medication that may increase VTE risk). They also censored (temporarily excluded women from analysis) episodes associated with a transiently elevated risk of VTE: pregnancy and 6 months following delivery, 12 weeks after other pregnancy terminations, 8 weeks following any surgery involving hospital admission, and 8 weeks following prescription of tranexamic acid.

Continue to: VTEs associated with risk category of hormonal contraception used...

Results. The overall cohort included more than 2 million women who were followed for a median of 10 years. During 21.0 million person-years, 8,710 VTE events were diagnosed; almost one-third of these were pulmonary embolisms, with the remainder diagnosed as lower extremity VTE. Of these 8,710 women diagnosed with VTE, 7,043 (81%) were confirmed with either diagnostic imaging or prescription of an anticoagulant. Unfortunately, 228 women (2.6%) died within 30 days of the diagnosis of VTE.

The investigators identified concomitant use of hormonal contraception and NSAIDs in more than 500,000 women. Among women with such concomitant use, 58% were using contraceptives that were high risk while 23% used medium-risk and 19% used low/no-risk contraceptives. Ibuprofen (60%) was the most commonly used NSAID, followed by diclofenac (20%) and naproxen (6%). Between 97% and 98% of high-risk and medium-risk contraceptives were combination pills; 89% of low/no-risk contraceptives were progestin IUDs.

Compared with nonuse of both hormonal contraceptives and NSAIDs, incidence rate ratios of VTE adjusted for age, calendar year, and education were 8.1 (95% confidence interval [CI], 6.9–9.6) for use of NSAIDs only, 4.2 (95% CI, 4.0–4.4) for use of high-risk contraceptives only, 3.0 (95% CI, 2.8–3.2) for medium-risk contraceptive use, and 1.1 (95% CI, 1.0–1.3) for use of low/no-risk hormonal contraception. Risk of VTE was approximately twice as high with the use of diclofenac only compared with the risks associated with ibuprofen or naproxen use only.

With respect to concomitant use of NSAIDs and hormonal contraception, incidence rate ratios of VTE were 50.6 (95% CI, 44.2–57.8), 26.1 (95% CI, 19.6–34.7), and 5.7 (95% CI, 3.3–10.1), respectively, with use of high-risk, medium-risk, and low/no-risk hormonal contraceptives. Adjusting for time updated information on occurrences of migraine, connective tissue disorder, inflammatory polyarthropathies, endometriosis, polycystic ovary syndrome, hypertension, and diabetes did not materially affect these associations.

When analysis was limited to women without these occurring conditions, rate ratios were somewhat higher (5.7 and 4.1) for use of high-risk and medium-risk contraceptives only. Incidence rate ratios in this subcohort of healthier women were substantially higher for NSAID use only (15.0), and 111.7, 43.2, and 13.0, respectively, for concomitant use of NSAIDs with high-risk, medium-risk, and low/no-risk contraceptives. In this analysis of healthier women, diclofenac continued to be associated with substantially higher risks of VTE than ibuprofen or naproxen. When the stricter definition of VTE (confirmed cases) was used, adjusted rate ratios remained similar.

Absolute risks of VTE

Although some of the elevated rate ratios noted in this study might appear alarming, it is important to keep in mind that the baseline incidence of VTE in healthy reproductive-age women is low. Accordingly, as the authors pointed out, even among women who used NSAIDs concomitantly with high-risk combination hormonal contraceptives, the absolute risk of VTE was 2/10,000.

Study strengths and limitations

Strengths of this analysis by Meaidi and colleagues include the use of large, essentially all-inclusive national registries. In addition, nationwide Danish registry data that indicate a diagnosis of VTE have been found to have a high positive predictive value.³ Another strength is the large number of potentially confounding factors that the authors controlled for.

One potential limitation of their analysis is that the use of only prescribed NSAIDs was considered. Fortunately, however, the prevalence of over-the-counter ibuprofen use in Denmark is not high enough to materially affect the authors’ findings.⁴ Another potential limitation was that information on smoking and body mass index was not available for most of the women included in the study cohort. The authors countered this limitation by pointing out that, in Denmark, smoking and obesity are highly correlated with educational status, and that all analyses were adjusted for educational status. ●

Meaidi A, Mascolo A, Sessa M, et al. Venous thromboembolism with use of hormonal contraception and non-steroidal anti-inflammatory drugs: nationwide cohort study. BMJ. 2023;382:e074450. doi:10.1136/bmj-2022-074450

EXPERT COMMENTARY

Combination (estrogen plus progestin) hormonal contraceptives as well as non–aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) increase the risk of VTE events, including lower extremity clots and pulmonary embolism. Taking contraceptives formulated with ethinyl estradiol increases hepatic production of clotting factors on a dose-related basis. Newer progestins, including desogestrel and drospirenone, also may contribute to an elevated VTE risk, although this association is controversial.¹ NSAIDs promote platelet aggregation, thereby activating the clotting system and formation of clots. Although studies that assessed the association between NSAID use and thrombosis have focused on arterial clots, a substantial literature suggests that NSAIDs, including older NSAIDs (such as ibuprofen, diclofenac, and naproxen), also increase VTE risk.²

Although combination contraceptives (oral contraceptives, patches, vaginal rings) and NSAIDs are both commonly used by reproductive-age women, little data have assessed the impact of concomitant use of these medications on VTE risk. Accordingly, investigators in Denmark, using national databases, conducted a retrospective cohort study to assess the impact that independent as well as concomitant use of these medications have on VTE risk.

Details of the study

Meaidi and colleagues included in the cohort reproductive-age women living in Denmark between 1996 and 2017 with no history of thrombosis, thrombophilia, cancer, tubal sterilization, hysterectomy, bilateral oophorectomy, or infertility treatment. National prescription data were used to assess exposure to hormonal contraception.

The investigators classified hormonal contraception into 3 VTE risk categories:

1. high risk—estrogen-progestin patches and vaginal rings; oral contraceptives containing 50 µg of ethinyl estradiol; or the progestins desogestrel, drospirenone, gestodene, or cyproterone (with the latter 2 progestins not available in the United States)
2. medium risk—all other combination oral contraceptives, including those formulated with the progestins norethindrone, norethindrone acetate, norgestrel, and levonorgestrel, as well as depot medroxyprogesterone acetate
3. low/no risk—progestin-only pills, implants, and progestin-containing intrauterine devices (IUDs).

Because in Denmark NSAIDs are prescribed as a single package containing no more than 30 tablets, time exposed to non–aspirin NSAIDs was assumed to last 1 week from the prescription date.

The authors considered first-time diagnoses of lower limb venous thrombosis or pulmonary embolism that were made in hospitals to represent VTE. They also constructed a subgroup of VTE patients in whom the diagnosis was either confirmed with imaging or followed by prescription of an anticoagulant.

To address potential confounding, the authors adjusted their analysis based on age, calendar year, educational attainment, occurrence of pregnancy, surgery, hypertension, diabetes, polycystic ovary syndrome, endometriosis, migraine, systemic connective tissue diseases, inflammatory polyarthropathies, and use of tranexamic acid (a medication that may increase VTE risk). They also censored (temporarily excluded women from analysis) episodes associated with a transiently elevated risk of VTE: pregnancy and 6 months following delivery, 12 weeks after other pregnancy terminations, 8 weeks following any surgery involving hospital admission, and 8 weeks following prescription of tranexamic acid.

Continue to: VTEs associated with risk category of hormonal contraception used...

Results. The overall cohort included more than 2 million women who were followed for a median of 10 years. During 21.0 million person-years, 8,710 VTE events were diagnosed; almost one-third of these were pulmonary embolisms, with the remainder diagnosed as lower extremity VTE. Of these 8,710 women diagnosed with VTE, 7,043 (81%) were confirmed with either diagnostic imaging or prescription of an anticoagulant. Unfortunately, 228 women (2.6%) died within 30 days of the diagnosis of VTE.

The investigators identified concomitant use of hormonal contraception and NSAIDs in more than 500,000 women. Among women with such concomitant use, 58% were using contraceptives that were high risk while 23% used medium-risk and 19% used low/no-risk contraceptives. Ibuprofen (60%) was the most commonly used NSAID, followed by diclofenac (20%) and naproxen (6%). Between 97% and 98% of high-risk and medium-risk contraceptives were combination pills; 89% of low/no-risk contraceptives were progestin IUDs.

Compared with nonuse of both hormonal contraceptives and NSAIDs, incidence rate ratios of VTE adjusted for age, calendar year, and education were 8.1 (95% confidence interval [CI], 6.9–9.6) for use of NSAIDs only, 4.2 (95% CI, 4.0–4.4) for use of high-risk contraceptives only, 3.0 (95% CI, 2.8–3.2) for medium-risk contraceptive use, and 1.1 (95% CI, 1.0–1.3) for use of low/no-risk hormonal contraception. Risk of VTE was approximately twice as high with the use of diclofenac only compared with the risks associated with ibuprofen or naproxen use only.

With respect to concomitant use of NSAIDs and hormonal contraception, incidence rate ratios of VTE were 50.6 (95% CI, 44.2–57.8), 26.1 (95% CI, 19.6–34.7), and 5.7 (95% CI, 3.3–10.1), respectively, with use of high-risk, medium-risk, and low/no-risk hormonal contraceptives. Adjusting for time updated information on occurrences of migraine, connective tissue disorder, inflammatory polyarthropathies, endometriosis, polycystic ovary syndrome, hypertension, and diabetes did not materially affect these associations.

When analysis was limited to women without these occurring conditions, rate ratios were somewhat higher (5.7 and 4.1) for use of high-risk and medium-risk contraceptives only. Incidence rate ratios in this subcohort of healthier women were substantially higher for NSAID use only (15.0), and 111.7, 43.2, and 13.0, respectively, for concomitant use of NSAIDs with high-risk, medium-risk, and low/no-risk contraceptives. In this analysis of healthier women, diclofenac continued to be associated with substantially higher risks of VTE than ibuprofen or naproxen. When the stricter definition of VTE (confirmed cases) was used, adjusted rate ratios remained similar.

Absolute risks of VTE

Although some of the elevated rate ratios noted in this study might appear alarming, it is important to keep in mind that the baseline incidence of VTE in healthy reproductive-age women is low. Accordingly, as the authors pointed out, even among women who used NSAIDs concomitantly with high-risk combination hormonal contraceptives, the absolute risk of VTE was 2/10,000.

Study strengths and limitations

Strengths of this analysis by Meaidi and colleagues include the use of large, essentially all-inclusive national registries. In addition, nationwide Danish registry data that indicate a diagnosis of VTE have been found to have a high positive predictive value.³ Another strength is the large number of potentially confounding factors that the authors controlled for.

One potential limitation of their analysis is that the use of only prescribed NSAIDs was considered. Fortunately, however, the prevalence of over-the-counter ibuprofen use in Denmark is not high enough to materially affect the authors’ findings.⁴ Another potential limitation was that information on smoking and body mass index was not available for most of the women included in the study cohort. The authors countered this limitation by pointing out that, in Denmark, smoking and obesity are highly correlated with educational status, and that all analyses were adjusted for educational status. ●

Individuals spend close to half of their lives preventing, or planning for, pregnancy. As such, contraception plays a major role in patient-provider interactions. Contraception counseling and management is a common scenario encountered in the general gynecologist’s practice. Luckily, we have two evidence-based guidelines developed by the US Centers for Disease Control and Prevention (CDC) that support the provision of contraceptive care:

1. US Medical Eligibility for Contraceptive Use (US-MEC),¹ which provides guidance on which patients can safely use a method
2. US Selected Practice Recommendations for Contraceptive Use (US-SPR),² which provides method-specific guidance on how to use a method (including how to: initiate or start a method; manage adherence issues, such as a missed pill, etc; and manage common issues like breakthrough bleeding). Both of these guidelines are updated routinely and are publicly available online or for free, through smartphone applications.

While most contraceptive care is straightforward, there are circumstances that require additional consideration. In this 3-part series we review 3 clinical cases, existing evidence to guide management decisions, and our recommendations. In part 1, we focus on restarting hormonal contraception after ulipristal acetate administration. In parts 2 and 3, we will discuss removal of a nonpalpable contraceptive implant and the consideration of a levonorgestrel-releasing intrauterine device (LNG-IUD) for emergency contraception.

CASE Meeting emergency and follow-up contraception needs

A 27-year-old woman (G0) presents to you after having unprotected intercourse 4 days ago. She does not formally track her menstrual cycles and is unsure when her last menstrual period was. She is not using contraception but is interested in starting a method. After counseling, she elects to take a dose of oral ulipristal acetate (UPA; Ella) now for emergency contraception and would like to start a combined oral contraceptive (COC) pill moving forward.

How soon after taking UPA should you tell her to start the combined hormonal pill?

Effectiveness of hormonal contraception following UPA

UPA does not appear to decrease the efficacy of COCs when started around the same time. However, immediately starting a hormonal contraceptive can decrease the effectiveness of UPA, and as such, it is recommended to take UPA and then abstain or use a backup method for 7 days before initiating a hormonal contraceptive method.¹ By obtaining some additional information from your patient and with the use of shared decision making, though, your patient may be able to start their contraceptive method earlier than 5 days after UPA.

What is UPA

UPA is a progesterone receptor modulator used for emergency contraception intenhded to prevent pregnancy after unprotected intercourse or contraceptive failure.³ It works by delaying follicular rupture at least 5 days, if taken before the peak of the luteinizing hormone (LH) surge. If taken after that timeframe, it does not work. Since UPA competes for the progesterone receptor, there is a concern that the effectiveness of UPA may be decreased if a progestin-containing form of contraception is started immediately after taking UPA, or vice versa.⁴ Several studies have now specifically looked at the interaction between UPA and progestin-containing contraceptives, including at how UPA is impacted by the contraceptive method, and conversely, how the contraceptive method is impacted by UPA.^5-8

Data on types of hormonal contraception. Brache and colleagues demonstrated that UPA users who started a desogestrel progestin-only pill (DSG POP) the next day had higher rates of ovulation within 5 days of taking UPA (45%), compared with those who the next day started a placebo pill (3%).⁶ This type of progestin-only pill is not available in the United States.

A study by Edelman and colleagues demonstrated similar findings in those starting a COC pill containing estrogen and progestin. When taking a COC two days after UPA use, more participants had evidence of follicular rupture in less than 5 days.⁵ It should be noted that these studies focused on ovulation, which—while necessary for conception to occur—is a surrogate biomarker for pregnancy risk. Additional studies have looked at the impact of UPA on the COC and have not found that UPA impacts ovulation suppression of the COC with its initiation or use.⁸

Considering unprotected intercourse and UPA timing. Of course, the risk of pregnancy is reliant on cycle timing plus the presence of viable sperm in the reproductive tract. Sperm have been shown to only be viable in the reproductive tract for 5 days, which could result in fertilization and subsequent pregnancy. Longevity of an egg is much shorter, at 12 to 24 hours after ovulation. For this patient, her exposure was 4 days ago, but sperm are only viable for approximately 5 days—she could consider taking the UPA now and then starting a COC earlier than 5 days since she only needs an extra day or two of protection from the UPA from the sperm in her reproductive tract. Your patient’s involvement in this decision making is paramount, as only they can prioritize their desire to avoid pregnancy from their recent act of unprotected intercourse versus their immediate needs for starting their method of contraception. It is important that individuals abstain from sexual activity or use an additional back-up method during the first 7 days of starting their method of contraception.

Continue to: Counseling considerations for the case patient...

For a patient planning to start or resume a hormonal contraceptive method after taking UPA, the waiting period recommended by the CDC (5 days) is most beneficial for patients who are uncertain about their menstrual cycle timing in relation to the act of unprotected intercourse that already occurred and need to prioritize maximum effectiveness of emergency contraception.

Patients with unsure cycle-sex timing planning to self-start or resume a short-term hormonal contraceptive method (eg, pills, patches, or rings), should be counseled to wait 5 days after the most recent act of unprotected sex, before taking their hormonal contraceptive method.⁷ Patients with unsure cycle-sex timing planning to use provider-dependent hormonal contraceptive methods (eg, those requiring a prescription, including a progestin-contraceptive implant or depot medroxyprogesterone acetate) should also be counseled to wait. Timing of levonorgestrel and copper intrauterine devices are addressed in part 3 of this series.

However, if your patient has a good understanding of their menstrual cycle, and the primary concern is exposure from subsequent sexual encounters and not the recent unprotected intercourse, it is advisable to provide UPA and immediately initiate a contraceptive method. One of the primary reasons for emergency contraception failure is that its effectiveness is limited to the most recent act of unprotected sexual intercourse and does not extend to subsequent acts throughout the month.

For these patients with sure cycle-sex timing who are planning to start or resume short-or long-term contraceptive methods, and whose primary concern is to prevent pregnancy risk from subsequent sexual encounters, immediately initiating a contraceptive method is advisable. For provider-dependent methods, we must weigh the risk of unintended pregnancy from the act of intercourse that already occurred (and the potential to increase that risk by initiating a method that could compromise UPA efficacy) versus the future risk of pregnancy if the patient cannot return for a contraception visit.⁷

In short, starting the contraceptive method at the time of UPA use can be considered after shared decision making with the patient and understanding what their primary concerns are.

Important point

Counsel on using backup barrier contraception after UPA

Oral emergency contraception only covers that one act of unprotected intercourse and does not continue to protect a patient from pregnancy for the rest of their cycle. When taken before ovulation, UPA works by delaying follicular development and rupture for at least 5 days. Patients who continue to have unprotected intercourse after taking UPA are at a high risk of an unintended pregnancy from this ‘stalled’ follicle that will eventually ovulate. Follicular maturation resumes after UPA’s effects wane, and the patient is primed for ovulation (and therefore unintended pregnancy) if ongoing unprotected intercourse occurs for the rest of their cycle.

Therefore, it is important to counsel patients on the need, if they do not desire a pregnancy, to abstain or start a method of contraception.

Final question

What about starting or resuming non–hormonal contraceptive methods?

Non-hormonal contraceptive methods can be started immediately with UPA use.¹

CASE Resolved

After shared decision making, the patient decides to start using the COC pill. You prescribe her both UPA for emergency contraception and a combined hormonal contraceptive pill. Given her unsure cycle-sex timing, she expresses to you that her most important priority is preventing unintended pregnancy. You counsel her to set a reminder on her phone to start taking the pill 5 days from her most recent act of unprotected intercourse. You also counsel her to use a back-up barrier method of contraception for 7 days after starting her COC pill. ●

obgm035011016_edelman_fig.jpg

Individuals spend close to half of their lives preventing, or planning for, pregnancy. As such, contraception plays a major role in patient-provider interactions. Contraception counseling and management is a common scenario encountered in the general gynecologist’s practice. Luckily, we have two evidence-based guidelines developed by the US Centers for Disease Control and Prevention (CDC) that support the provision of contraceptive care:

1. US Medical Eligibility for Contraceptive Use (US-MEC),¹ which provides guidance on which patients can safely use a method
2. US Selected Practice Recommendations for Contraceptive Use (US-SPR),² which provides method-specific guidance on how to use a method (including how to: initiate or start a method; manage adherence issues, such as a missed pill, etc; and manage common issues like breakthrough bleeding). Both of these guidelines are updated routinely and are publicly available online or for free, through smartphone applications.

While most contraceptive care is straightforward, there are circumstances that require additional consideration. In this 3-part series we review 3 clinical cases, existing evidence to guide management decisions, and our recommendations. In part 1, we focus on restarting hormonal contraception after ulipristal acetate administration. In parts 2 and 3, we will discuss removal of a nonpalpable contraceptive implant and the consideration of a levonorgestrel-releasing intrauterine device (LNG-IUD) for emergency contraception.

CASE Meeting emergency and follow-up contraception needs

A 27-year-old woman (G0) presents to you after having unprotected intercourse 4 days ago. She does not formally track her menstrual cycles and is unsure when her last menstrual period was. She is not using contraception but is interested in starting a method. After counseling, she elects to take a dose of oral ulipristal acetate (UPA; Ella) now for emergency contraception and would like to start a combined oral contraceptive (COC) pill moving forward.

How soon after taking UPA should you tell her to start the combined hormonal pill?

Effectiveness of hormonal contraception following UPA

UPA does not appear to decrease the efficacy of COCs when started around the same time. However, immediately starting a hormonal contraceptive can decrease the effectiveness of UPA, and as such, it is recommended to take UPA and then abstain or use a backup method for 7 days before initiating a hormonal contraceptive method.¹ By obtaining some additional information from your patient and with the use of shared decision making, though, your patient may be able to start their contraceptive method earlier than 5 days after UPA.

What is UPA

UPA is a progesterone receptor modulator used for emergency contraception intenhded to prevent pregnancy after unprotected intercourse or contraceptive failure.³ It works by delaying follicular rupture at least 5 days, if taken before the peak of the luteinizing hormone (LH) surge. If taken after that timeframe, it does not work. Since UPA competes for the progesterone receptor, there is a concern that the effectiveness of UPA may be decreased if a progestin-containing form of contraception is started immediately after taking UPA, or vice versa.⁴ Several studies have now specifically looked at the interaction between UPA and progestin-containing contraceptives, including at how UPA is impacted by the contraceptive method, and conversely, how the contraceptive method is impacted by UPA.^5-8

Data on types of hormonal contraception. Brache and colleagues demonstrated that UPA users who started a desogestrel progestin-only pill (DSG POP) the next day had higher rates of ovulation within 5 days of taking UPA (45%), compared with those who the next day started a placebo pill (3%).⁶ This type of progestin-only pill is not available in the United States.

A study by Edelman and colleagues demonstrated similar findings in those starting a COC pill containing estrogen and progestin. When taking a COC two days after UPA use, more participants had evidence of follicular rupture in less than 5 days.⁵ It should be noted that these studies focused on ovulation, which—while necessary for conception to occur—is a surrogate biomarker for pregnancy risk. Additional studies have looked at the impact of UPA on the COC and have not found that UPA impacts ovulation suppression of the COC with its initiation or use.⁸

Considering unprotected intercourse and UPA timing. Of course, the risk of pregnancy is reliant on cycle timing plus the presence of viable sperm in the reproductive tract. Sperm have been shown to only be viable in the reproductive tract for 5 days, which could result in fertilization and subsequent pregnancy. Longevity of an egg is much shorter, at 12 to 24 hours after ovulation. For this patient, her exposure was 4 days ago, but sperm are only viable for approximately 5 days—she could consider taking the UPA now and then starting a COC earlier than 5 days since she only needs an extra day or two of protection from the UPA from the sperm in her reproductive tract. Your patient’s involvement in this decision making is paramount, as only they can prioritize their desire to avoid pregnancy from their recent act of unprotected intercourse versus their immediate needs for starting their method of contraception. It is important that individuals abstain from sexual activity or use an additional back-up method during the first 7 days of starting their method of contraception.

Continue to: Counseling considerations for the case patient...

For a patient planning to start or resume a hormonal contraceptive method after taking UPA, the waiting period recommended by the CDC (5 days) is most beneficial for patients who are uncertain about their menstrual cycle timing in relation to the act of unprotected intercourse that already occurred and need to prioritize maximum effectiveness of emergency contraception.

Patients with unsure cycle-sex timing planning to self-start or resume a short-term hormonal contraceptive method (eg, pills, patches, or rings), should be counseled to wait 5 days after the most recent act of unprotected sex, before taking their hormonal contraceptive method.⁷ Patients with unsure cycle-sex timing planning to use provider-dependent hormonal contraceptive methods (eg, those requiring a prescription, including a progestin-contraceptive implant or depot medroxyprogesterone acetate) should also be counseled to wait. Timing of levonorgestrel and copper intrauterine devices are addressed in part 3 of this series.

However, if your patient has a good understanding of their menstrual cycle, and the primary concern is exposure from subsequent sexual encounters and not the recent unprotected intercourse, it is advisable to provide UPA and immediately initiate a contraceptive method. One of the primary reasons for emergency contraception failure is that its effectiveness is limited to the most recent act of unprotected sexual intercourse and does not extend to subsequent acts throughout the month.

For these patients with sure cycle-sex timing who are planning to start or resume short-or long-term contraceptive methods, and whose primary concern is to prevent pregnancy risk from subsequent sexual encounters, immediately initiating a contraceptive method is advisable. For provider-dependent methods, we must weigh the risk of unintended pregnancy from the act of intercourse that already occurred (and the potential to increase that risk by initiating a method that could compromise UPA efficacy) versus the future risk of pregnancy if the patient cannot return for a contraception visit.⁷

In short, starting the contraceptive method at the time of UPA use can be considered after shared decision making with the patient and understanding what their primary concerns are.

Important point

Counsel on using backup barrier contraception after UPA

Oral emergency contraception only covers that one act of unprotected intercourse and does not continue to protect a patient from pregnancy for the rest of their cycle. When taken before ovulation, UPA works by delaying follicular development and rupture for at least 5 days. Patients who continue to have unprotected intercourse after taking UPA are at a high risk of an unintended pregnancy from this ‘stalled’ follicle that will eventually ovulate. Follicular maturation resumes after UPA’s effects wane, and the patient is primed for ovulation (and therefore unintended pregnancy) if ongoing unprotected intercourse occurs for the rest of their cycle.

Therefore, it is important to counsel patients on the need, if they do not desire a pregnancy, to abstain or start a method of contraception.

Final question

What about starting or resuming non–hormonal contraceptive methods?

Non-hormonal contraceptive methods can be started immediately with UPA use.¹

CASE Resolved

After shared decision making, the patient decides to start using the COC pill. You prescribe her both UPA for emergency contraception and a combined hormonal contraceptive pill. Given her unsure cycle-sex timing, she expresses to you that her most important priority is preventing unintended pregnancy. You counsel her to set a reminder on her phone to start taking the pill 5 days from her most recent act of unprotected intercourse. You also counsel her to use a back-up barrier method of contraception for 7 days after starting her COC pill. ●

obgm035011016_edelman_fig.jpg

Individuals spend close to half of their lives preventing, or planning for, pregnancy. As such, contraception plays a major role in patient-provider interactions. Contraception counseling and management is a common scenario encountered in the general gynecologist’s practice. Luckily, we have two evidence-based guidelines developed by the US Centers for Disease Control and Prevention (CDC) that support the provision of contraceptive care:

1. US Medical Eligibility for Contraceptive Use (US-MEC),¹ which provides guidance on which patients can safely use a method
2. US Selected Practice Recommendations for Contraceptive Use (US-SPR),² which provides method-specific guidance on how to use a method (including how to: initiate or start a method; manage adherence issues, such as a missed pill, etc; and manage common issues like breakthrough bleeding). Both of these guidelines are updated routinely and are publicly available online or for free, through smartphone applications.

While most contraceptive care is straightforward, there are circumstances that require additional consideration. In this 3-part series we review 3 clinical cases, existing evidence to guide management decisions, and our recommendations. In part 1, we focus on restarting hormonal contraception after ulipristal acetate administration. In parts 2 and 3, we will discuss removal of a nonpalpable contraceptive implant and the consideration of a levonorgestrel-releasing intrauterine device (LNG-IUD) for emergency contraception.

CASE Meeting emergency and follow-up contraception needs

A 27-year-old woman (G0) presents to you after having unprotected intercourse 4 days ago. She does not formally track her menstrual cycles and is unsure when her last menstrual period was. She is not using contraception but is interested in starting a method. After counseling, she elects to take a dose of oral ulipristal acetate (UPA; Ella) now for emergency contraception and would like to start a combined oral contraceptive (COC) pill moving forward.

How soon after taking UPA should you tell her to start the combined hormonal pill?

Effectiveness of hormonal contraception following UPA

UPA does not appear to decrease the efficacy of COCs when started around the same time. However, immediately starting a hormonal contraceptive can decrease the effectiveness of UPA, and as such, it is recommended to take UPA and then abstain or use a backup method for 7 days before initiating a hormonal contraceptive method.¹ By obtaining some additional information from your patient and with the use of shared decision making, though, your patient may be able to start their contraceptive method earlier than 5 days after UPA.

What is UPA

UPA is a progesterone receptor modulator used for emergency contraception intenhded to prevent pregnancy after unprotected intercourse or contraceptive failure.³ It works by delaying follicular rupture at least 5 days, if taken before the peak of the luteinizing hormone (LH) surge. If taken after that timeframe, it does not work. Since UPA competes for the progesterone receptor, there is a concern that the effectiveness of UPA may be decreased if a progestin-containing form of contraception is started immediately after taking UPA, or vice versa.⁴ Several studies have now specifically looked at the interaction between UPA and progestin-containing contraceptives, including at how UPA is impacted by the contraceptive method, and conversely, how the contraceptive method is impacted by UPA.^5-8

Data on types of hormonal contraception. Brache and colleagues demonstrated that UPA users who started a desogestrel progestin-only pill (DSG POP) the next day had higher rates of ovulation within 5 days of taking UPA (45%), compared with those who the next day started a placebo pill (3%).⁶ This type of progestin-only pill is not available in the United States.

A study by Edelman and colleagues demonstrated similar findings in those starting a COC pill containing estrogen and progestin. When taking a COC two days after UPA use, more participants had evidence of follicular rupture in less than 5 days.⁵ It should be noted that these studies focused on ovulation, which—while necessary for conception to occur—is a surrogate biomarker for pregnancy risk. Additional studies have looked at the impact of UPA on the COC and have not found that UPA impacts ovulation suppression of the COC with its initiation or use.⁸

Considering unprotected intercourse and UPA timing. Of course, the risk of pregnancy is reliant on cycle timing plus the presence of viable sperm in the reproductive tract. Sperm have been shown to only be viable in the reproductive tract for 5 days, which could result in fertilization and subsequent pregnancy. Longevity of an egg is much shorter, at 12 to 24 hours after ovulation. For this patient, her exposure was 4 days ago, but sperm are only viable for approximately 5 days—she could consider taking the UPA now and then starting a COC earlier than 5 days since she only needs an extra day or two of protection from the UPA from the sperm in her reproductive tract. Your patient’s involvement in this decision making is paramount, as only they can prioritize their desire to avoid pregnancy from their recent act of unprotected intercourse versus their immediate needs for starting their method of contraception. It is important that individuals abstain from sexual activity or use an additional back-up method during the first 7 days of starting their method of contraception.

Continue to: Counseling considerations for the case patient...

For a patient planning to start or resume a hormonal contraceptive method after taking UPA, the waiting period recommended by the CDC (5 days) is most beneficial for patients who are uncertain about their menstrual cycle timing in relation to the act of unprotected intercourse that already occurred and need to prioritize maximum effectiveness of emergency contraception.

Patients with unsure cycle-sex timing planning to self-start or resume a short-term hormonal contraceptive method (eg, pills, patches, or rings), should be counseled to wait 5 days after the most recent act of unprotected sex, before taking their hormonal contraceptive method.⁷ Patients with unsure cycle-sex timing planning to use provider-dependent hormonal contraceptive methods (eg, those requiring a prescription, including a progestin-contraceptive implant or depot medroxyprogesterone acetate) should also be counseled to wait. Timing of levonorgestrel and copper intrauterine devices are addressed in part 3 of this series.

However, if your patient has a good understanding of their menstrual cycle, and the primary concern is exposure from subsequent sexual encounters and not the recent unprotected intercourse, it is advisable to provide UPA and immediately initiate a contraceptive method. One of the primary reasons for emergency contraception failure is that its effectiveness is limited to the most recent act of unprotected sexual intercourse and does not extend to subsequent acts throughout the month.

For these patients with sure cycle-sex timing who are planning to start or resume short-or long-term contraceptive methods, and whose primary concern is to prevent pregnancy risk from subsequent sexual encounters, immediately initiating a contraceptive method is advisable. For provider-dependent methods, we must weigh the risk of unintended pregnancy from the act of intercourse that already occurred (and the potential to increase that risk by initiating a method that could compromise UPA efficacy) versus the future risk of pregnancy if the patient cannot return for a contraception visit.⁷

In short, starting the contraceptive method at the time of UPA use can be considered after shared decision making with the patient and understanding what their primary concerns are.

Important point

Counsel on using backup barrier contraception after UPA

Oral emergency contraception only covers that one act of unprotected intercourse and does not continue to protect a patient from pregnancy for the rest of their cycle. When taken before ovulation, UPA works by delaying follicular development and rupture for at least 5 days. Patients who continue to have unprotected intercourse after taking UPA are at a high risk of an unintended pregnancy from this ‘stalled’ follicle that will eventually ovulate. Follicular maturation resumes after UPA’s effects wane, and the patient is primed for ovulation (and therefore unintended pregnancy) if ongoing unprotected intercourse occurs for the rest of their cycle.

Therefore, it is important to counsel patients on the need, if they do not desire a pregnancy, to abstain or start a method of contraception.

Final question

What about starting or resuming non–hormonal contraceptive methods?

Non-hormonal contraceptive methods can be started immediately with UPA use.¹

CASE Resolved

After shared decision making, the patient decides to start using the COC pill. You prescribe her both UPA for emergency contraception and a combined hormonal contraceptive pill. Given her unsure cycle-sex timing, she expresses to you that her most important priority is preventing unintended pregnancy. You counsel her to set a reminder on her phone to start taking the pill 5 days from her most recent act of unprotected intercourse. You also counsel her to use a back-up barrier method of contraception for 7 days after starting her COC pill. ●

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