OBG Management

It has been an incredible year for complex gynecology and minimally invasive gynecologic surgery (MIGS), with several outstanding new findings and reviews in 2023. The surgical community continues to push the envelope and emphasize the value of this specialty for women’s health.

Endometriosis and adenomyosis were at the center of several large cohort studies and systematic reviews that reassessed what we know about how to evaluate and treat these challenging diseases, including both surgical and nonsurgical approaches, with an emphasis on fertility-sparing modalities.^1-8 In addition, a focus on quality of life, patient-centered care, and racial biases allowed us to reflect on our own practice patterns and keep the patient at the center of care models.^9-13 Finally, there was a clear expansion in the use of technologies such as artificial intelligence (AI) and machine learning for care and novel minimally invasive tools.¹⁴

In this Update, we highlight and expand on how several particularly important developments are likely to make a difference in our clinical management.

New classification system for cesarean scar ectopic pregnancy with defined surgical guidance has 97% treatment success rate

Ban Y, Shen J, Wang X, et al. Cesarean scar ectopic pregnancy clinical classification system with recommended surgical strategy. Obstet Gynecol. 2023;141:927-936. doi:10.1097/AOG.0000000000005113

A large multiarmed study by Ban and colleagues used multivariable modeling to formulate and test a classification system and recommended surgical treatment strategies for patients with a cesarean scar ectopic pregnancy (CSP).¹⁵ In the study, 273 patients were included in the predictive modeling group, 118 in the internal validation group, and 564 within the model testing cohort. Classifications were based on 2 independent risk factors for intraoperative hemorrhage: anterior myometrial thickness and mean diameter of gestational sac (MSD).

Classification types

The 3 main CSP types were defined based on the anterior myometrial thickness at the cesarean section scar (type I, > 3 mm; type II, 1–3 mm; type III, ≤ 1 mm) and subtyped based on the MSD (type IIa, MSD ≤ 30 mm; type IIb, MSD > 30 mm; type IIIa, MSD ≤ 50 mm; type IIIb, MSD > 50 mm).

The subgroups were matched with recommended surgical strategy using expert opinion: Type I CSP was treated with suction dilation and aspiration (D&A) under ultrasound guidance, with or without hysteroscopy. Type IIa CSP was treated with suction D&A with hysteroscopy under ultrasound guidance. Type IIb CSP was treated with hysteroscopy with laparoscopic monitoring or excision, or transvaginal excision. Type IIIa CSP was treated with laparoscopic excision or transvaginal excision. Type IIIb CSP was treated with laparoscopic excision after uterine artery embolization or laparotomy (TABLE).¹⁵

obgm035120e05_update_table.jpg

Treatment outcomes

These guidelines were tested on a cohort of 564 patients between 2014 and 2022. Using these treatment guidelines, the overall treatment success rate was 97.5%; 85% of patients had a negative serum ß-human chorionic gonadotropin (ß-hCG) level within 3 weeks, and 95.2% of patients resumed menstrual cycles within 8 weeks. Successful treatment was defined as:

• complete resection of the products of conception
• no need to shift to a second-line surgical strategy
• no major complications
• no readmission for additional treatment
• serum ß-hCG levels that returned to normal within 4 weeks.

Continue to: Pre-op hormonal treatment of endometriosis found to be protective against post-op complications...

Pre-op hormonal treatment of endometriosis found to be protective against post-op complications

Casarin J, Ghezzi F, Mueller M, et al. Surgical outcomes and complications of laparoscopic hysterectomy for endometriosis: a multicentric cohort study. J Minim Invasive Gynecol. 2023;30:587-592. doi:1016/j.jmig.2023.03.018

In a large European multicenter retrospective cohort study, Casarin and colleagues evaluated perioperative complications during laparoscopic hysterectomy for endometriosis or adenomyosis in 995 patients treated from 2010 to 2020.²

Reported intraoperative data included the frequency of ureterolysis (26.8%), deep nodule resection (30%) and posterior adhesiolysis (38.9%), unilateral salpingo-oophorectomy (15.1%), bilateral salpingo-oophorectomy (26.8%), estimated blood loss (mean, 100 mL), and adverse events. Intraoperative complications occurred in 3% of cases (including bladder/bowel injury or need for transfusion).

Postoperative complications occurred in 13.8% of cases, and 9.3% had a major event, including vaginal cuff dehiscence, fever, abscess, and fistula.

Factors associated with postoperative complications

In a multivariate analysis, the authors found that increased operative time, younger age at surgery, previous surgery for endometriosis, and occurrence of intraoperative complications were associated with Clavien-Dindo score grade 2 or greater postoperative complications.

Medical treatment for endometriosis with estro-progestin or progestin medications, however, was found to be protective, with an odds ratio of 0.50 (95% confidence interval, 0.31–0.81).

Diaphragmatic endometriosis prevalence higher than previously reported

Pagano F, Schwander A, Vaineau C, et al. True prevalence of diaphragmatic endometriosis and its association with severe endometriosis: a call for awareness and investigation. J Minim Invasive Gynecol. 2023;30:329-334. doi:10.1016/j.jmig.2023.01.006

Pagano and colleagues conducted an impressive large prospective cohort study that included more than 1,300 patients with histologically proven endometriosis.¹ Each patient underwent a systematic evaluation and reporting of intraoperative findings, including bilateral evaluation for diaphragmatic endometriosis (DE).

Patients with DE had high rates of infertility and high-stage disease

In this cohort, 4.7% of patients were found to have diaphragmatic disease; 92.3% of these cases had DE involving the right diaphragm. Patients with DE had a higher rate of infertility than those without DE (nearly 50%), but otherwise they had no difference in typical endometriosis symptoms (dysmenorrhea, dyspareunia, dyschezia, dysuria). In this cohort, 27.4% had diaphragmatic symptoms (right shoulder pain, cough, cyclic dyspnea).

Patients found to have DE had higher rates of stage III/IV disease (78.4%), and the left pelvis was affected in more patients (73.8%).

A word on fertility-sparing treatments for adenomyosis

Several interesting and thoughtful studies were published on the fertility-sparing management of adenomyosis.^6-8 These included a comparison of fertility outcomes following excisional and nonexcisional therapies,⁶ a systematic review of the literature that compared recurrence rates following procedural and surgical treatments,⁸ and outcomes after use of a novel therapy (percutaneous microwave ablation) for the treatment of adenomyosis.⁷

Although our critical evaluation of these studies found that they are not robust enough to yet change our practice, we want to applaud the authors on their discerning questions and on taking the initial steps to answer critical questions, including:

• What is the best uterine-sparing method for treatment of diffuse adenomyosis?
• Are radiofrequency or microwave ablation procedures the future of adenomyosis care?
• How do we counsel patients about fertility potential following procedural treatments?

It has been an incredible year for complex gynecology and minimally invasive gynecologic surgery (MIGS), with several outstanding new findings and reviews in 2023. The surgical community continues to push the envelope and emphasize the value of this specialty for women’s health.

Endometriosis and adenomyosis were at the center of several large cohort studies and systematic reviews that reassessed what we know about how to evaluate and treat these challenging diseases, including both surgical and nonsurgical approaches, with an emphasis on fertility-sparing modalities.^1-8 In addition, a focus on quality of life, patient-centered care, and racial biases allowed us to reflect on our own practice patterns and keep the patient at the center of care models.^9-13 Finally, there was a clear expansion in the use of technologies such as artificial intelligence (AI) and machine learning for care and novel minimally invasive tools.¹⁴

In this Update, we highlight and expand on how several particularly important developments are likely to make a difference in our clinical management.

New classification system for cesarean scar ectopic pregnancy with defined surgical guidance has 97% treatment success rate

Ban Y, Shen J, Wang X, et al. Cesarean scar ectopic pregnancy clinical classification system with recommended surgical strategy. Obstet Gynecol. 2023;141:927-936. doi:10.1097/AOG.0000000000005113

A large multiarmed study by Ban and colleagues used multivariable modeling to formulate and test a classification system and recommended surgical treatment strategies for patients with a cesarean scar ectopic pregnancy (CSP).¹⁵ In the study, 273 patients were included in the predictive modeling group, 118 in the internal validation group, and 564 within the model testing cohort. Classifications were based on 2 independent risk factors for intraoperative hemorrhage: anterior myometrial thickness and mean diameter of gestational sac (MSD).

Classification types

The 3 main CSP types were defined based on the anterior myometrial thickness at the cesarean section scar (type I, > 3 mm; type II, 1–3 mm; type III, ≤ 1 mm) and subtyped based on the MSD (type IIa, MSD ≤ 30 mm; type IIb, MSD > 30 mm; type IIIa, MSD ≤ 50 mm; type IIIb, MSD > 50 mm).

The subgroups were matched with recommended surgical strategy using expert opinion: Type I CSP was treated with suction dilation and aspiration (D&A) under ultrasound guidance, with or without hysteroscopy. Type IIa CSP was treated with suction D&A with hysteroscopy under ultrasound guidance. Type IIb CSP was treated with hysteroscopy with laparoscopic monitoring or excision, or transvaginal excision. Type IIIa CSP was treated with laparoscopic excision or transvaginal excision. Type IIIb CSP was treated with laparoscopic excision after uterine artery embolization or laparotomy (TABLE).¹⁵

obgm035120e05_update_table.jpg

Treatment outcomes

These guidelines were tested on a cohort of 564 patients between 2014 and 2022. Using these treatment guidelines, the overall treatment success rate was 97.5%; 85% of patients had a negative serum ß-human chorionic gonadotropin (ß-hCG) level within 3 weeks, and 95.2% of patients resumed menstrual cycles within 8 weeks. Successful treatment was defined as:

• complete resection of the products of conception
• no need to shift to a second-line surgical strategy
• no major complications
• no readmission for additional treatment
• serum ß-hCG levels that returned to normal within 4 weeks.

Continue to: Pre-op hormonal treatment of endometriosis found to be protective against post-op complications...

Pre-op hormonal treatment of endometriosis found to be protective against post-op complications

Casarin J, Ghezzi F, Mueller M, et al. Surgical outcomes and complications of laparoscopic hysterectomy for endometriosis: a multicentric cohort study. J Minim Invasive Gynecol. 2023;30:587-592. doi:1016/j.jmig.2023.03.018

In a large European multicenter retrospective cohort study, Casarin and colleagues evaluated perioperative complications during laparoscopic hysterectomy for endometriosis or adenomyosis in 995 patients treated from 2010 to 2020.²

Reported intraoperative data included the frequency of ureterolysis (26.8%), deep nodule resection (30%) and posterior adhesiolysis (38.9%), unilateral salpingo-oophorectomy (15.1%), bilateral salpingo-oophorectomy (26.8%), estimated blood loss (mean, 100 mL), and adverse events. Intraoperative complications occurred in 3% of cases (including bladder/bowel injury or need for transfusion).

Postoperative complications occurred in 13.8% of cases, and 9.3% had a major event, including vaginal cuff dehiscence, fever, abscess, and fistula.

Factors associated with postoperative complications

In a multivariate analysis, the authors found that increased operative time, younger age at surgery, previous surgery for endometriosis, and occurrence of intraoperative complications were associated with Clavien-Dindo score grade 2 or greater postoperative complications.

Medical treatment for endometriosis with estro-progestin or progestin medications, however, was found to be protective, with an odds ratio of 0.50 (95% confidence interval, 0.31–0.81).

Diaphragmatic endometriosis prevalence higher than previously reported

Pagano F, Schwander A, Vaineau C, et al. True prevalence of diaphragmatic endometriosis and its association with severe endometriosis: a call for awareness and investigation. J Minim Invasive Gynecol. 2023;30:329-334. doi:10.1016/j.jmig.2023.01.006

Pagano and colleagues conducted an impressive large prospective cohort study that included more than 1,300 patients with histologically proven endometriosis.¹ Each patient underwent a systematic evaluation and reporting of intraoperative findings, including bilateral evaluation for diaphragmatic endometriosis (DE).

Patients with DE had high rates of infertility and high-stage disease

In this cohort, 4.7% of patients were found to have diaphragmatic disease; 92.3% of these cases had DE involving the right diaphragm. Patients with DE had a higher rate of infertility than those without DE (nearly 50%), but otherwise they had no difference in typical endometriosis symptoms (dysmenorrhea, dyspareunia, dyschezia, dysuria). In this cohort, 27.4% had diaphragmatic symptoms (right shoulder pain, cough, cyclic dyspnea).

Patients found to have DE had higher rates of stage III/IV disease (78.4%), and the left pelvis was affected in more patients (73.8%).

A word on fertility-sparing treatments for adenomyosis

Several interesting and thoughtful studies were published on the fertility-sparing management of adenomyosis.^6-8 These included a comparison of fertility outcomes following excisional and nonexcisional therapies,⁶ a systematic review of the literature that compared recurrence rates following procedural and surgical treatments,⁸ and outcomes after use of a novel therapy (percutaneous microwave ablation) for the treatment of adenomyosis.⁷

Although our critical evaluation of these studies found that they are not robust enough to yet change our practice, we want to applaud the authors on their discerning questions and on taking the initial steps to answer critical questions, including:

• What is the best uterine-sparing method for treatment of diffuse adenomyosis?
• Are radiofrequency or microwave ablation procedures the future of adenomyosis care?
• How do we counsel patients about fertility potential following procedural treatments?

It has been an incredible year for complex gynecology and minimally invasive gynecologic surgery (MIGS), with several outstanding new findings and reviews in 2023. The surgical community continues to push the envelope and emphasize the value of this specialty for women’s health.

Endometriosis and adenomyosis were at the center of several large cohort studies and systematic reviews that reassessed what we know about how to evaluate and treat these challenging diseases, including both surgical and nonsurgical approaches, with an emphasis on fertility-sparing modalities.^1-8 In addition, a focus on quality of life, patient-centered care, and racial biases allowed us to reflect on our own practice patterns and keep the patient at the center of care models.^9-13 Finally, there was a clear expansion in the use of technologies such as artificial intelligence (AI) and machine learning for care and novel minimally invasive tools.¹⁴

In this Update, we highlight and expand on how several particularly important developments are likely to make a difference in our clinical management.

New classification system for cesarean scar ectopic pregnancy with defined surgical guidance has 97% treatment success rate

Ban Y, Shen J, Wang X, et al. Cesarean scar ectopic pregnancy clinical classification system with recommended surgical strategy. Obstet Gynecol. 2023;141:927-936. doi:10.1097/AOG.0000000000005113

A large multiarmed study by Ban and colleagues used multivariable modeling to formulate and test a classification system and recommended surgical treatment strategies for patients with a cesarean scar ectopic pregnancy (CSP).¹⁵ In the study, 273 patients were included in the predictive modeling group, 118 in the internal validation group, and 564 within the model testing cohort. Classifications were based on 2 independent risk factors for intraoperative hemorrhage: anterior myometrial thickness and mean diameter of gestational sac (MSD).

Classification types

The 3 main CSP types were defined based on the anterior myometrial thickness at the cesarean section scar (type I, > 3 mm; type II, 1–3 mm; type III, ≤ 1 mm) and subtyped based on the MSD (type IIa, MSD ≤ 30 mm; type IIb, MSD > 30 mm; type IIIa, MSD ≤ 50 mm; type IIIb, MSD > 50 mm).

The subgroups were matched with recommended surgical strategy using expert opinion: Type I CSP was treated with suction dilation and aspiration (D&A) under ultrasound guidance, with or without hysteroscopy. Type IIa CSP was treated with suction D&A with hysteroscopy under ultrasound guidance. Type IIb CSP was treated with hysteroscopy with laparoscopic monitoring or excision, or transvaginal excision. Type IIIa CSP was treated with laparoscopic excision or transvaginal excision. Type IIIb CSP was treated with laparoscopic excision after uterine artery embolization or laparotomy (TABLE).¹⁵

obgm035120e05_update_table.jpg

Treatment outcomes

These guidelines were tested on a cohort of 564 patients between 2014 and 2022. Using these treatment guidelines, the overall treatment success rate was 97.5%; 85% of patients had a negative serum ß-human chorionic gonadotropin (ß-hCG) level within 3 weeks, and 95.2% of patients resumed menstrual cycles within 8 weeks. Successful treatment was defined as:

• complete resection of the products of conception
• no need to shift to a second-line surgical strategy
• no major complications
• no readmission for additional treatment
• serum ß-hCG levels that returned to normal within 4 weeks.

Continue to: Pre-op hormonal treatment of endometriosis found to be protective against post-op complications...

Pre-op hormonal treatment of endometriosis found to be protective against post-op complications

Casarin J, Ghezzi F, Mueller M, et al. Surgical outcomes and complications of laparoscopic hysterectomy for endometriosis: a multicentric cohort study. J Minim Invasive Gynecol. 2023;30:587-592. doi:1016/j.jmig.2023.03.018

In a large European multicenter retrospective cohort study, Casarin and colleagues evaluated perioperative complications during laparoscopic hysterectomy for endometriosis or adenomyosis in 995 patients treated from 2010 to 2020.²

Reported intraoperative data included the frequency of ureterolysis (26.8%), deep nodule resection (30%) and posterior adhesiolysis (38.9%), unilateral salpingo-oophorectomy (15.1%), bilateral salpingo-oophorectomy (26.8%), estimated blood loss (mean, 100 mL), and adverse events. Intraoperative complications occurred in 3% of cases (including bladder/bowel injury or need for transfusion).

Postoperative complications occurred in 13.8% of cases, and 9.3% had a major event, including vaginal cuff dehiscence, fever, abscess, and fistula.

Factors associated with postoperative complications

In a multivariate analysis, the authors found that increased operative time, younger age at surgery, previous surgery for endometriosis, and occurrence of intraoperative complications were associated with Clavien-Dindo score grade 2 or greater postoperative complications.

Medical treatment for endometriosis with estro-progestin or progestin medications, however, was found to be protective, with an odds ratio of 0.50 (95% confidence interval, 0.31–0.81).

Diaphragmatic endometriosis prevalence higher than previously reported

Pagano F, Schwander A, Vaineau C, et al. True prevalence of diaphragmatic endometriosis and its association with severe endometriosis: a call for awareness and investigation. J Minim Invasive Gynecol. 2023;30:329-334. doi:10.1016/j.jmig.2023.01.006

Pagano and colleagues conducted an impressive large prospective cohort study that included more than 1,300 patients with histologically proven endometriosis.¹ Each patient underwent a systematic evaluation and reporting of intraoperative findings, including bilateral evaluation for diaphragmatic endometriosis (DE).

Patients with DE had high rates of infertility and high-stage disease

In this cohort, 4.7% of patients were found to have diaphragmatic disease; 92.3% of these cases had DE involving the right diaphragm. Patients with DE had a higher rate of infertility than those without DE (nearly 50%), but otherwise they had no difference in typical endometriosis symptoms (dysmenorrhea, dyspareunia, dyschezia, dysuria). In this cohort, 27.4% had diaphragmatic symptoms (right shoulder pain, cough, cyclic dyspnea).

Patients found to have DE had higher rates of stage III/IV disease (78.4%), and the left pelvis was affected in more patients (73.8%).

A word on fertility-sparing treatments for adenomyosis

Several interesting and thoughtful studies were published on the fertility-sparing management of adenomyosis.^6-8 These included a comparison of fertility outcomes following excisional and nonexcisional therapies,⁶ a systematic review of the literature that compared recurrence rates following procedural and surgical treatments,⁸ and outcomes after use of a novel therapy (percutaneous microwave ablation) for the treatment of adenomyosis.⁷

Although our critical evaluation of these studies found that they are not robust enough to yet change our practice, we want to applaud the authors on their discerning questions and on taking the initial steps to answer critical questions, including:

• What is the best uterine-sparing method for treatment of diffuse adenomyosis?
• Are radiofrequency or microwave ablation procedures the future of adenomyosis care?
• How do we counsel patients about fertility potential following procedural treatments?

Dunne F, Newman C, Alvarez-Iglesia A, et al. Early metformin in gestational diabetes: a randomized clinical trial. JAMA. 2023;330:1547-1556. doi:10.1001/jama .2023.19869

EXPERT COMMENTARY

Gestational diabetes mellitus occurs in 4% to 7% of pregnancies, and the prevalence is likely to continue to increase given the rising rates of hypertension, obesity, advanced maternal age, and other medical comorbidities in pregnant persons in the United States.^1,2 Uncontrolled hyperglycemia in pregnancy is associated swith many adverse perinatal outcomes, including stillbirth, macrosomia, admission to the neonatal intensive care unit (NICU), development of hypertensive disorders, and cesarean deliveries. Hence, it is important to investigate and identify the optimal management of gestational diabetes.

Metformin, an oral biguanide, although studied for gestational diabetes treatment in phase 3 randomized clinical open-label trials, often is avoided in patients who are pregnant (with the exception of patients who have needle aversions, are financially unable to use insulin, or are unable to administer insulin safely).^1,2 Metformin is a highly effective first-line agent in the management of both prediabetes and type 2 diabetes, which begs us to question if there is a role for it in the management of gestational diabetes.

Details about the study

The study by Dunne and colleagues was a randomized controlled trial (RCT) conducted in a 1:1 parallel fashion at two institutions in Ireland from 2017–2022. The primary outcome assessed if treatment with metformin would reduce fasting blood glucose levels and the initiation of insulin among women diagnosed with gestational diabetes. A total of 510 participants enrolled in the study, with 268 receiving metformin (up to a maximum dose of 2,500 mg) at diagnosis and 267 receiving an identical placebo. Blood sugar levels were monitored 7 times a day, and medication adherence was assessed every 4 weeks.

Results. At 32 or 38 weeks’ gestation, 56.8% of patients in the metformin arm, and 63.7% of patients in the placebo arm required insulin or had fasting blood glucose levels above 5.1 mmol/L (91.8mg/dL), which was a statistically insignificant difference (P = .13). Although there was similarly no difference in the total amount of insulin used in each study group, the percentage of patients who required insulin initiation was decreased in the metformin arm (38.4% vs 51.1%; P = .004).

Study strengths and weaknesses

The authors conducted a well-designed double-blinded RCT—in both rural and tertiary care settings. Additionally, the study had an impressive 90% patient adherence rate for home blood glucose monitoring 7 times per day. The study arms were balanced for body mass index, as obesity is a known contributor to the development of gestational diabetes and response to insulin.

This study findings’ generalizability is limited across subpopulations given the lack of ethnic and racial diversity—the study population was 80% White. Additionally, utilization of the World Health Organization guidelines for diagnosing gestational diabetes, although adopted by most associations across the world, limits its application to areas of the world that use the National Diabetes Data Group or the Carpenter-Coustan diagnosis guidelines.^3,4 Furthermore, the diagnosis of gestational diabetes, which was based on 1 elevated value of a 2-hour glucose tolerance test, has limited scientific support, has not been proven to improve obstetric outcomes, and may increase health care costs when compared with the 2-step method.⁵ The criteria for insulin initiation in the trial was based on having 2 elevated measures of blood glucose during home glucose monitoring, a criteria that is much stricter than what is used in other countries or clinical practice. The trial authors concluded that use of metformin had a statistically significant reduction in neonates weighing > 4,000 g and > 90th% of weight, but they did not assess study group differences in neonatal skin fold thickness or anthropometric measurements, as reported in the Metformin in Gestational Diabetes trials.⁶ ●

Dunne F, Newman C, Alvarez-Iglesia A, et al. Early metformin in gestational diabetes: a randomized clinical trial. JAMA. 2023;330:1547-1556. doi:10.1001/jama .2023.19869

EXPERT COMMENTARY

Gestational diabetes mellitus occurs in 4% to 7% of pregnancies, and the prevalence is likely to continue to increase given the rising rates of hypertension, obesity, advanced maternal age, and other medical comorbidities in pregnant persons in the United States.^1,2 Uncontrolled hyperglycemia in pregnancy is associated swith many adverse perinatal outcomes, including stillbirth, macrosomia, admission to the neonatal intensive care unit (NICU), development of hypertensive disorders, and cesarean deliveries. Hence, it is important to investigate and identify the optimal management of gestational diabetes.

Metformin, an oral biguanide, although studied for gestational diabetes treatment in phase 3 randomized clinical open-label trials, often is avoided in patients who are pregnant (with the exception of patients who have needle aversions, are financially unable to use insulin, or are unable to administer insulin safely).^1,2 Metformin is a highly effective first-line agent in the management of both prediabetes and type 2 diabetes, which begs us to question if there is a role for it in the management of gestational diabetes.

Details about the study

The study by Dunne and colleagues was a randomized controlled trial (RCT) conducted in a 1:1 parallel fashion at two institutions in Ireland from 2017–2022. The primary outcome assessed if treatment with metformin would reduce fasting blood glucose levels and the initiation of insulin among women diagnosed with gestational diabetes. A total of 510 participants enrolled in the study, with 268 receiving metformin (up to a maximum dose of 2,500 mg) at diagnosis and 267 receiving an identical placebo. Blood sugar levels were monitored 7 times a day, and medication adherence was assessed every 4 weeks.

Results. At 32 or 38 weeks’ gestation, 56.8% of patients in the metformin arm, and 63.7% of patients in the placebo arm required insulin or had fasting blood glucose levels above 5.1 mmol/L (91.8mg/dL), which was a statistically insignificant difference (P = .13). Although there was similarly no difference in the total amount of insulin used in each study group, the percentage of patients who required insulin initiation was decreased in the metformin arm (38.4% vs 51.1%; P = .004).

Study strengths and weaknesses

The authors conducted a well-designed double-blinded RCT—in both rural and tertiary care settings. Additionally, the study had an impressive 90% patient adherence rate for home blood glucose monitoring 7 times per day. The study arms were balanced for body mass index, as obesity is a known contributor to the development of gestational diabetes and response to insulin.

This study findings’ generalizability is limited across subpopulations given the lack of ethnic and racial diversity—the study population was 80% White. Additionally, utilization of the World Health Organization guidelines for diagnosing gestational diabetes, although adopted by most associations across the world, limits its application to areas of the world that use the National Diabetes Data Group or the Carpenter-Coustan diagnosis guidelines.^3,4 Furthermore, the diagnosis of gestational diabetes, which was based on 1 elevated value of a 2-hour glucose tolerance test, has limited scientific support, has not been proven to improve obstetric outcomes, and may increase health care costs when compared with the 2-step method.⁵ The criteria for insulin initiation in the trial was based on having 2 elevated measures of blood glucose during home glucose monitoring, a criteria that is much stricter than what is used in other countries or clinical practice. The trial authors concluded that use of metformin had a statistically significant reduction in neonates weighing > 4,000 g and > 90th% of weight, but they did not assess study group differences in neonatal skin fold thickness or anthropometric measurements, as reported in the Metformin in Gestational Diabetes trials.⁶ ●

Dunne F, Newman C, Alvarez-Iglesia A, et al. Early metformin in gestational diabetes: a randomized clinical trial. JAMA. 2023;330:1547-1556. doi:10.1001/jama .2023.19869

EXPERT COMMENTARY

Gestational diabetes mellitus occurs in 4% to 7% of pregnancies, and the prevalence is likely to continue to increase given the rising rates of hypertension, obesity, advanced maternal age, and other medical comorbidities in pregnant persons in the United States.^1,2 Uncontrolled hyperglycemia in pregnancy is associated swith many adverse perinatal outcomes, including stillbirth, macrosomia, admission to the neonatal intensive care unit (NICU), development of hypertensive disorders, and cesarean deliveries. Hence, it is important to investigate and identify the optimal management of gestational diabetes.

Metformin, an oral biguanide, although studied for gestational diabetes treatment in phase 3 randomized clinical open-label trials, often is avoided in patients who are pregnant (with the exception of patients who have needle aversions, are financially unable to use insulin, or are unable to administer insulin safely).^1,2 Metformin is a highly effective first-line agent in the management of both prediabetes and type 2 diabetes, which begs us to question if there is a role for it in the management of gestational diabetes.

Details about the study

The study by Dunne and colleagues was a randomized controlled trial (RCT) conducted in a 1:1 parallel fashion at two institutions in Ireland from 2017–2022. The primary outcome assessed if treatment with metformin would reduce fasting blood glucose levels and the initiation of insulin among women diagnosed with gestational diabetes. A total of 510 participants enrolled in the study, with 268 receiving metformin (up to a maximum dose of 2,500 mg) at diagnosis and 267 receiving an identical placebo. Blood sugar levels were monitored 7 times a day, and medication adherence was assessed every 4 weeks.

Results. At 32 or 38 weeks’ gestation, 56.8% of patients in the metformin arm, and 63.7% of patients in the placebo arm required insulin or had fasting blood glucose levels above 5.1 mmol/L (91.8mg/dL), which was a statistically insignificant difference (P = .13). Although there was similarly no difference in the total amount of insulin used in each study group, the percentage of patients who required insulin initiation was decreased in the metformin arm (38.4% vs 51.1%; P = .004).

Study strengths and weaknesses

The authors conducted a well-designed double-blinded RCT—in both rural and tertiary care settings. Additionally, the study had an impressive 90% patient adherence rate for home blood glucose monitoring 7 times per day. The study arms were balanced for body mass index, as obesity is a known contributor to the development of gestational diabetes and response to insulin.

This study findings’ generalizability is limited across subpopulations given the lack of ethnic and racial diversity—the study population was 80% White. Additionally, utilization of the World Health Organization guidelines for diagnosing gestational diabetes, although adopted by most associations across the world, limits its application to areas of the world that use the National Diabetes Data Group or the Carpenter-Coustan diagnosis guidelines.^3,4 Furthermore, the diagnosis of gestational diabetes, which was based on 1 elevated value of a 2-hour glucose tolerance test, has limited scientific support, has not been proven to improve obstetric outcomes, and may increase health care costs when compared with the 2-step method.⁵ The criteria for insulin initiation in the trial was based on having 2 elevated measures of blood glucose during home glucose monitoring, a criteria that is much stricter than what is used in other countries or clinical practice. The trial authors concluded that use of metformin had a statistically significant reduction in neonates weighing > 4,000 g and > 90th% of weight, but they did not assess study group differences in neonatal skin fold thickness or anthropometric measurements, as reported in the Metformin in Gestational Diabetes trials.⁶ ●

LUTECH LT-300 HD FOR COLPOSCOPY

obgm035120e03_productreview_fig1.jpg

Background. In March 1924, the colposcope was introduced to evaluate the portio of the cervix by Hans Hinselmann in Germany after years of work with the famous lens manufacturer Leitz.1 Although its adoption as a standard tool for evaluating lower genital tract neoplasia was protracted, today it sits as a cornerstone technology in gynecology, and every ObGyn provider has been trained to perform colposcopic exams that include visualizing the cervix, vagina, and vulva as well as taking biopsies. In December 2000, after 75 years of glass lens technology, Welch-Allyn (Skaneateles Falls, New York) introduced the first video colposcope, shepherding the field into the 21st century with only limited traction. Now, Lutech is entering the fray hoping to further nudge traditionalists into the digital age.

Design/Functionality. The Lutech LT-300 HD works off of a Sony Exmor CMOS (complementary metaloxide semiconductor) camera with 2.13 megapixels to provide high-definition optical magnification of 1-30X illuminated by a circular cool LED array that offers 3000 lx of white light with an adjustable green filter to allow for contrast at working distances between 5.1 and 15.7 inches. The colposcope comes with either a vertical stand or a swing arm stand and has both HDMI and USB 3.0 video output so that the system can be attached to either a stand-alone monitor or a computer (not included). The colposcope also comes in a standard definition configuration (LT-300 SD), but I did not trial that model because the price difference did not seem to justify the potentially lower resolution.

In my experience with its use, the Lutech LT-300 HD was pretty excellent. Being a man and a doctor, I refused the online training session that comes free with the colposcope, assuming I could figure it out on my own. My assumption was mostly true, but there were definitely some tips and tricks that would have made my life easier had I not been so stiff-necked. That said, the biggest adjustment is getting used to looking at a screen and not having to look through eyepieces. The picture output is great and, as a patient (or student) teaching tool, it is phenomenal. Also, because it is digital, the image capture features allow for image importation into notes (although it is clunky and requires work arounds when using Epic).

Innovation. From an innovation point of view, I am not sure that Lutech re-invented fire since, in essence, the LT-300 HD is a modified CMOS video camera. But the company did do a nice job bringing together a lot of existing technologies into a highly functional product. I would love to see better integration with some of the larger electronic medical records (EMRs), but I suspect the barriers lie with the EMR companies rather than with Lutech, so I am giving them a pass on that front.

Summary. At its core, a colposcope is simply a tool with which to obtain a magnified view of the cervix, vagina, and/or vulva. Prior to advent and proliferation of CMOS camera technology, the most readily available means of accomplishing this was to employ glass lenses. But that was then, and this is now; CMOS technology is just better, cheaper, and more versatile. I no longer turn my head to look over my shoulder while backing up my car—I use the back-up camera. My Kodak instamatic has given way to my iPhone. And now, my incredibly heavy, unwieldy Leisegang colposcope has been replaced by a light-weight camera on a stand that I can easily move from room to room. I won’t lie, though,…it still seems weird to not look through eyepieces and work the focus knobs, but I am happy with the change. My patients can now see what I am looking at and better understand their diagnosis (if they want), and my notes are prettier. Onward march of progress.

Reference

1. Fusco E, Padula F, Mancini E, et al. History of colposcopy: a brief biography of Hinselmann. J Prenat Med. 2008;2:19-23.

Continue to: DTR MEDICAL CERVICAL ROTATING BIOPSY PUNCH...

DTR MEDICAL CERVICAL ROTATING BIOPSY PUNCH

obgm035120e03_productreview_fig2.jpg

The single-use DTR Medical Cervical Rotating Biopsy Punch from Innovia Medical (Swansea, United Kingdom) “works great” and “is reasonably cost-effective to replace reusables.”

Background. Integral to every colposcopic examination is the potential need to biopsy abnormal appearing tissues. To accomplish this latter task, numerous punch-style biopsy devices have been developed in a variety of jaw shapes and styles, crafted from materials ranging from stainless steel to titanium to ceramic, with the ultimate goal the same—get a piece of tissue from the cervix as easily as possible.

Design/Functionality. DTR Medical Cervical Rotating Biopsy Punch is a single-use sterile device that comes packaged as 10 per box. It features Kevorkian-style “stronger than Titanium” jaws that yield a 3.0 mm x 7.5 mm sample attached to a metal shaft that can rotate 360°. The shaft inserts into a lightweight plastic pistol-grip style handle. From tip to handle, the device measures 36.5 cm (14.125 in).

In my experience with its use, the DTR Medical Cervical Rotating Biopsy Punch performed flawlessly. Its relatively low-profile jaws allowed for unobstructed access to biopsy sites and the ability to rotate the jaws was a big plus. The “stronger than Titanium” jaws consistently yielded the exact biopsies I wanted, like a knife going through butter.

Innovation. From an innovation standpoint, the DTR Medical Cervical Rotating Biopsy Punch is more of an engineering “duh” than “wow,” but it works great so who cares that it’s not a fusion reactor. That said, the innovative part from Innovia Medical is their ability to make such a high-quality biopsy device and sell it at a price that makes it reasonably cost-effective to replace reusables.

Summary. Whether it is a Tischler, Kevorkian, or Burke tip, the real question before any gynecologist uses the cervical biopsy device she/he/they has in her/his/ their hand is, will it cut? Because all reusable surgical instruments are in fact reusable, those edges that are designed to cut invariably become dull with reuse. And, unless they are meticulously maintained and routinely sharpened (spoiler alert, they never are), providers are not infrequently chagrinned by the gnawing rather than cutting that these instruments deliver. Thinking back, I could not remember the last time I had made an incision with a surgical scalpel blade that had previously been used then sharpened and re-sterilized. Then I did remember…never. Reflecting on this, I wondered why I was doing this with my cervical biopsy devices. While I really do not like the environmental waste created by single-use devices, reusable instruments that require re-processing do have an environmental impact and a significant cost. Considering this, I do not think that environmental reasons are enough of a barrier to justify using dull biopsy tools if it can be done cost-effectively with a minimal carbon footprint. All-in-all, I like this product, and I plan to use it. ●

LUTECH LT-300 HD FOR COLPOSCOPY

obgm035120e03_productreview_fig1.jpg

Background. In March 1924, the colposcope was introduced to evaluate the portio of the cervix by Hans Hinselmann in Germany after years of work with the famous lens manufacturer Leitz.1 Although its adoption as a standard tool for evaluating lower genital tract neoplasia was protracted, today it sits as a cornerstone technology in gynecology, and every ObGyn provider has been trained to perform colposcopic exams that include visualizing the cervix, vagina, and vulva as well as taking biopsies. In December 2000, after 75 years of glass lens technology, Welch-Allyn (Skaneateles Falls, New York) introduced the first video colposcope, shepherding the field into the 21st century with only limited traction. Now, Lutech is entering the fray hoping to further nudge traditionalists into the digital age.

Design/Functionality. The Lutech LT-300 HD works off of a Sony Exmor CMOS (complementary metaloxide semiconductor) camera with 2.13 megapixels to provide high-definition optical magnification of 1-30X illuminated by a circular cool LED array that offers 3000 lx of white light with an adjustable green filter to allow for contrast at working distances between 5.1 and 15.7 inches. The colposcope comes with either a vertical stand or a swing arm stand and has both HDMI and USB 3.0 video output so that the system can be attached to either a stand-alone monitor or a computer (not included). The colposcope also comes in a standard definition configuration (LT-300 SD), but I did not trial that model because the price difference did not seem to justify the potentially lower resolution.

In my experience with its use, the Lutech LT-300 HD was pretty excellent. Being a man and a doctor, I refused the online training session that comes free with the colposcope, assuming I could figure it out on my own. My assumption was mostly true, but there were definitely some tips and tricks that would have made my life easier had I not been so stiff-necked. That said, the biggest adjustment is getting used to looking at a screen and not having to look through eyepieces. The picture output is great and, as a patient (or student) teaching tool, it is phenomenal. Also, because it is digital, the image capture features allow for image importation into notes (although it is clunky and requires work arounds when using Epic).

Innovation. From an innovation point of view, I am not sure that Lutech re-invented fire since, in essence, the LT-300 HD is a modified CMOS video camera. But the company did do a nice job bringing together a lot of existing technologies into a highly functional product. I would love to see better integration with some of the larger electronic medical records (EMRs), but I suspect the barriers lie with the EMR companies rather than with Lutech, so I am giving them a pass on that front.

Summary. At its core, a colposcope is simply a tool with which to obtain a magnified view of the cervix, vagina, and/or vulva. Prior to advent and proliferation of CMOS camera technology, the most readily available means of accomplishing this was to employ glass lenses. But that was then, and this is now; CMOS technology is just better, cheaper, and more versatile. I no longer turn my head to look over my shoulder while backing up my car—I use the back-up camera. My Kodak instamatic has given way to my iPhone. And now, my incredibly heavy, unwieldy Leisegang colposcope has been replaced by a light-weight camera on a stand that I can easily move from room to room. I won’t lie, though,…it still seems weird to not look through eyepieces and work the focus knobs, but I am happy with the change. My patients can now see what I am looking at and better understand their diagnosis (if they want), and my notes are prettier. Onward march of progress.

Reference

1. Fusco E, Padula F, Mancini E, et al. History of colposcopy: a brief biography of Hinselmann. J Prenat Med. 2008;2:19-23.

Continue to: DTR MEDICAL CERVICAL ROTATING BIOPSY PUNCH...

DTR MEDICAL CERVICAL ROTATING BIOPSY PUNCH

obgm035120e03_productreview_fig2.jpg

The single-use DTR Medical Cervical Rotating Biopsy Punch from Innovia Medical (Swansea, United Kingdom) “works great” and “is reasonably cost-effective to replace reusables.”

Background. Integral to every colposcopic examination is the potential need to biopsy abnormal appearing tissues. To accomplish this latter task, numerous punch-style biopsy devices have been developed in a variety of jaw shapes and styles, crafted from materials ranging from stainless steel to titanium to ceramic, with the ultimate goal the same—get a piece of tissue from the cervix as easily as possible.

Design/Functionality. DTR Medical Cervical Rotating Biopsy Punch is a single-use sterile device that comes packaged as 10 per box. It features Kevorkian-style “stronger than Titanium” jaws that yield a 3.0 mm x 7.5 mm sample attached to a metal shaft that can rotate 360°. The shaft inserts into a lightweight plastic pistol-grip style handle. From tip to handle, the device measures 36.5 cm (14.125 in).

In my experience with its use, the DTR Medical Cervical Rotating Biopsy Punch performed flawlessly. Its relatively low-profile jaws allowed for unobstructed access to biopsy sites and the ability to rotate the jaws was a big plus. The “stronger than Titanium” jaws consistently yielded the exact biopsies I wanted, like a knife going through butter.

Innovation. From an innovation standpoint, the DTR Medical Cervical Rotating Biopsy Punch is more of an engineering “duh” than “wow,” but it works great so who cares that it’s not a fusion reactor. That said, the innovative part from Innovia Medical is their ability to make such a high-quality biopsy device and sell it at a price that makes it reasonably cost-effective to replace reusables.

Summary. Whether it is a Tischler, Kevorkian, or Burke tip, the real question before any gynecologist uses the cervical biopsy device she/he/they has in her/his/ their hand is, will it cut? Because all reusable surgical instruments are in fact reusable, those edges that are designed to cut invariably become dull with reuse. And, unless they are meticulously maintained and routinely sharpened (spoiler alert, they never are), providers are not infrequently chagrinned by the gnawing rather than cutting that these instruments deliver. Thinking back, I could not remember the last time I had made an incision with a surgical scalpel blade that had previously been used then sharpened and re-sterilized. Then I did remember…never. Reflecting on this, I wondered why I was doing this with my cervical biopsy devices. While I really do not like the environmental waste created by single-use devices, reusable instruments that require re-processing do have an environmental impact and a significant cost. Considering this, I do not think that environmental reasons are enough of a barrier to justify using dull biopsy tools if it can be done cost-effectively with a minimal carbon footprint. All-in-all, I like this product, and I plan to use it. ●

LUTECH LT-300 HD FOR COLPOSCOPY

obgm035120e03_productreview_fig1.jpg

Background. In March 1924, the colposcope was introduced to evaluate the portio of the cervix by Hans Hinselmann in Germany after years of work with the famous lens manufacturer Leitz.1 Although its adoption as a standard tool for evaluating lower genital tract neoplasia was protracted, today it sits as a cornerstone technology in gynecology, and every ObGyn provider has been trained to perform colposcopic exams that include visualizing the cervix, vagina, and vulva as well as taking biopsies. In December 2000, after 75 years of glass lens technology, Welch-Allyn (Skaneateles Falls, New York) introduced the first video colposcope, shepherding the field into the 21st century with only limited traction. Now, Lutech is entering the fray hoping to further nudge traditionalists into the digital age.

Design/Functionality. The Lutech LT-300 HD works off of a Sony Exmor CMOS (complementary metaloxide semiconductor) camera with 2.13 megapixels to provide high-definition optical magnification of 1-30X illuminated by a circular cool LED array that offers 3000 lx of white light with an adjustable green filter to allow for contrast at working distances between 5.1 and 15.7 inches. The colposcope comes with either a vertical stand or a swing arm stand and has both HDMI and USB 3.0 video output so that the system can be attached to either a stand-alone monitor or a computer (not included). The colposcope also comes in a standard definition configuration (LT-300 SD), but I did not trial that model because the price difference did not seem to justify the potentially lower resolution.

In my experience with its use, the Lutech LT-300 HD was pretty excellent. Being a man and a doctor, I refused the online training session that comes free with the colposcope, assuming I could figure it out on my own. My assumption was mostly true, but there were definitely some tips and tricks that would have made my life easier had I not been so stiff-necked. That said, the biggest adjustment is getting used to looking at a screen and not having to look through eyepieces. The picture output is great and, as a patient (or student) teaching tool, it is phenomenal. Also, because it is digital, the image capture features allow for image importation into notes (although it is clunky and requires work arounds when using Epic).

Innovation. From an innovation point of view, I am not sure that Lutech re-invented fire since, in essence, the LT-300 HD is a modified CMOS video camera. But the company did do a nice job bringing together a lot of existing technologies into a highly functional product. I would love to see better integration with some of the larger electronic medical records (EMRs), but I suspect the barriers lie with the EMR companies rather than with Lutech, so I am giving them a pass on that front.

Summary. At its core, a colposcope is simply a tool with which to obtain a magnified view of the cervix, vagina, and/or vulva. Prior to advent and proliferation of CMOS camera technology, the most readily available means of accomplishing this was to employ glass lenses. But that was then, and this is now; CMOS technology is just better, cheaper, and more versatile. I no longer turn my head to look over my shoulder while backing up my car—I use the back-up camera. My Kodak instamatic has given way to my iPhone. And now, my incredibly heavy, unwieldy Leisegang colposcope has been replaced by a light-weight camera on a stand that I can easily move from room to room. I won’t lie, though,…it still seems weird to not look through eyepieces and work the focus knobs, but I am happy with the change. My patients can now see what I am looking at and better understand their diagnosis (if they want), and my notes are prettier. Onward march of progress.

Reference

1. Fusco E, Padula F, Mancini E, et al. History of colposcopy: a brief biography of Hinselmann. J Prenat Med. 2008;2:19-23.

Continue to: DTR MEDICAL CERVICAL ROTATING BIOPSY PUNCH...

DTR MEDICAL CERVICAL ROTATING BIOPSY PUNCH

obgm035120e03_productreview_fig2.jpg

The single-use DTR Medical Cervical Rotating Biopsy Punch from Innovia Medical (Swansea, United Kingdom) “works great” and “is reasonably cost-effective to replace reusables.”

Background. Integral to every colposcopic examination is the potential need to biopsy abnormal appearing tissues. To accomplish this latter task, numerous punch-style biopsy devices have been developed in a variety of jaw shapes and styles, crafted from materials ranging from stainless steel to titanium to ceramic, with the ultimate goal the same—get a piece of tissue from the cervix as easily as possible.

Design/Functionality. DTR Medical Cervical Rotating Biopsy Punch is a single-use sterile device that comes packaged as 10 per box. It features Kevorkian-style “stronger than Titanium” jaws that yield a 3.0 mm x 7.5 mm sample attached to a metal shaft that can rotate 360°. The shaft inserts into a lightweight plastic pistol-grip style handle. From tip to handle, the device measures 36.5 cm (14.125 in).

In my experience with its use, the DTR Medical Cervical Rotating Biopsy Punch performed flawlessly. Its relatively low-profile jaws allowed for unobstructed access to biopsy sites and the ability to rotate the jaws was a big plus. The “stronger than Titanium” jaws consistently yielded the exact biopsies I wanted, like a knife going through butter.

Innovation. From an innovation standpoint, the DTR Medical Cervical Rotating Biopsy Punch is more of an engineering “duh” than “wow,” but it works great so who cares that it’s not a fusion reactor. That said, the innovative part from Innovia Medical is their ability to make such a high-quality biopsy device and sell it at a price that makes it reasonably cost-effective to replace reusables.

Summary. Whether it is a Tischler, Kevorkian, or Burke tip, the real question before any gynecologist uses the cervical biopsy device she/he/they has in her/his/ their hand is, will it cut? Because all reusable surgical instruments are in fact reusable, those edges that are designed to cut invariably become dull with reuse. And, unless they are meticulously maintained and routinely sharpened (spoiler alert, they never are), providers are not infrequently chagrinned by the gnawing rather than cutting that these instruments deliver. Thinking back, I could not remember the last time I had made an incision with a surgical scalpel blade that had previously been used then sharpened and re-sterilized. Then I did remember…never. Reflecting on this, I wondered why I was doing this with my cervical biopsy devices. While I really do not like the environmental waste created by single-use devices, reusable instruments that require re-processing do have an environmental impact and a significant cost. Considering this, I do not think that environmental reasons are enough of a barrier to justify using dull biopsy tools if it can be done cost-effectively with a minimal carbon footprint. All-in-all, I like this product, and I plan to use it. ●

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. ●

Evidence continues to show that the number of practicing ObGyns lags the growing and diverse US population of women.¹ Furthermore, approximately 1 in every 3 ObGyns will move usually once or twice every 10 years.² Knowing what to expect in being recruited requires a better understanding of your needs and capabilities and what they may be worth in real time. Some ObGyns elect to use a recruitment firm to begin their search to more objectively assess what is fair and equitable.

Understanding physician compensation involves many factors, such as patient composition, sources of reimbursement, impact of health care systems, and geography.³ Several sources report trends in annual physician compensation, most notably the American Medical Association, medical specialty organizations, and recruitment firms. Sources such as the Medical Group Management Association (MGMA), the American Medical Group Association (AMGA), and Medscape report total compensation.

Determining salaries for new positions

A standard and comprehensive benchmarking resource for salaries in new positions has been the annual review of physician and advanced practitioner recruiting incentives by AMN Healthcare (formerly Merritt Hawkins) Physician Solutions.⁴ This resource is used by hospitals, medical groups, academics, other health care systems, and others who track trends in physician supply, demand, and compensation. Their 2023 report considered starting salaries for more than 20 medical or surgical specialties.

Specialists’ revenue-generating potential is tracked by annual billings to commercial payers. The average annual billing by a full-time ObGyn ($3.8 million) is about the same as that of other specialties combined.⁵ As in the past, ObGyns are among the most consistently requested specialists in searches. In 2023, ObGyns were ranked the third most common physician specialists being recruited and tenth as the percentage of physicians per specialty (TABLE).⁴

obgm03512012_rayburn_table.jpg

Full-time salaries for ObGyns have remained within the middle third of all specialties. They consistently have been higher than primary care physicians’ salaries but remain among the lowest of the surgical specialties. This impression is reinforced by 2023 data shown in FIGURE 1.⁴ In the past, salaries remained flat compared with other surgical specialties. As with other specialties, starting salaries decreased during the peak 2020 and 2021 COVID-19 years. It is encouraging that averaged full-time salaries for recruiting ObGyns increased by 14.1% from 2020–2021 to 2021–2022 and by 10.5% from 2021–2022 to 2022–2023 (FIGURE 2).⁴

obgm03512012_rayburn_fig1.jpg

obgm03512012_rayburn_fig2.jpg

Special considerations

Incomes tended to be highest for ObGyns practicing in metropolitan areas with population sizes less than 1 million rather than in larger metropolitan areas.³ However, differences in reported incomes do not control for cost of living and other determinants of income (for example, surgeries, deliveries, patient care hours worked). Averaged salaries can vary regionally in the following order from highest to lowest: Midwest/Great Plains, West, Southwest, and Northeast and Southeast.⁴

Differences in starting salaries between male and female ObGyns are often not reported, although they are a very important consideration.^6,7 Both men and women desire “controllable lifestyles” with more flexibility and working in shifts. Sex-based differences in physician salary and compensation can be complex. Explanations may deal with the number of patients seen, number of procedures and surgeries performed, and frequency of after-hours duties. Women constitute most ObGyns, and their salary being at any lower end of the income spectrum may be partially explained by fewer desired work hours or less seniority.

Annual earnings can vary and are positively related to the number of working hours, being in the middle of one’s career (aged 42–51 years), working in a moderately large practice rather than in a solo or self-employed practice, and being board certified.³ A lower starting salary would be anticipated for a recent graduate. However, the resident going into a hard-to-fill position may be offered a higher salary than an experienced ObGyn who takes a relatively easy-to-fill position in a popular location. Practices would be more desirable in which patient volume is sufficient to invest in nonphysician clinicians and revenue-generating ancillary services that do not require costly layers of administration.

Information on physician salaries for new positions from individual recruiting or research firms can serve as a starting point for negotiation, although it may not entirely be representative. Sample sizes can be small, and information in some specialties may not separate salaries of physicians in academic versus nonacademic positions and generalists versus subspecialists. The information in this article reflects the average salaries offered to attract physicians to new practice settings rather than what they might earn and report on their tax return.

Continue to: Incentives...

Incentives

Negotiations involve incentives along with a starting salary. Signing bonuses, movingallowances, continuing education time and allowances, and medical education loan repayments are important incentives. Recent signing bonuses (average, $37,472) likely reflect efforts to bring physicians back to health care facilities post-COVID-19 or, more commonly, when candidates are considering multiple opportunities.⁴ It is important to clarify at the beginning any coverage for health insurance and professional liability insurance.

Relocation allowances are for those being recruited outside their current area of residence. The average continuing medical education allowance was $3,840 in 2023.⁴ Medical school debt is common, being approximately $200,000 at graduation for many. An educational loan repayment (average, $98,665) is typically an exchange for a commitment to stay in the community for a given period.

Starting employment contracts with hospitals or large medical groups often feature a production bonus to reward additional clinical work performed or an adherence to quality protocol or guidelines, rather than income guarantees alone. Metrics are usually volume driven (for example, relative value units, net collections, gross billings, patients seen). Initiatives by payers and health care organizations have included quality metrics, such as high patient satisfaction scores, low morbidity rates, and low readmission rates. Production-based formulas are straightforward, while use of quality-based formulas (up to 14% of total compensation) can be less clear to define.⁴ ●

Evidence continues to show that the number of practicing ObGyns lags the growing and diverse US population of women.¹ Furthermore, approximately 1 in every 3 ObGyns will move usually once or twice every 10 years.² Knowing what to expect in being recruited requires a better understanding of your needs and capabilities and what they may be worth in real time. Some ObGyns elect to use a recruitment firm to begin their search to more objectively assess what is fair and equitable.

Understanding physician compensation involves many factors, such as patient composition, sources of reimbursement, impact of health care systems, and geography.³ Several sources report trends in annual physician compensation, most notably the American Medical Association, medical specialty organizations, and recruitment firms. Sources such as the Medical Group Management Association (MGMA), the American Medical Group Association (AMGA), and Medscape report total compensation.

Determining salaries for new positions

A standard and comprehensive benchmarking resource for salaries in new positions has been the annual review of physician and advanced practitioner recruiting incentives by AMN Healthcare (formerly Merritt Hawkins) Physician Solutions.⁴ This resource is used by hospitals, medical groups, academics, other health care systems, and others who track trends in physician supply, demand, and compensation. Their 2023 report considered starting salaries for more than 20 medical or surgical specialties.

Specialists’ revenue-generating potential is tracked by annual billings to commercial payers. The average annual billing by a full-time ObGyn ($3.8 million) is about the same as that of other specialties combined.⁵ As in the past, ObGyns are among the most consistently requested specialists in searches. In 2023, ObGyns were ranked the third most common physician specialists being recruited and tenth as the percentage of physicians per specialty (TABLE).⁴

obgm03512012_rayburn_table.jpg

Full-time salaries for ObGyns have remained within the middle third of all specialties. They consistently have been higher than primary care physicians’ salaries but remain among the lowest of the surgical specialties. This impression is reinforced by 2023 data shown in FIGURE 1.⁴ In the past, salaries remained flat compared with other surgical specialties. As with other specialties, starting salaries decreased during the peak 2020 and 2021 COVID-19 years. It is encouraging that averaged full-time salaries for recruiting ObGyns increased by 14.1% from 2020–2021 to 2021–2022 and by 10.5% from 2021–2022 to 2022–2023 (FIGURE 2).⁴

obgm03512012_rayburn_fig1.jpg

obgm03512012_rayburn_fig2.jpg

Special considerations

Incomes tended to be highest for ObGyns practicing in metropolitan areas with population sizes less than 1 million rather than in larger metropolitan areas.³ However, differences in reported incomes do not control for cost of living and other determinants of income (for example, surgeries, deliveries, patient care hours worked). Averaged salaries can vary regionally in the following order from highest to lowest: Midwest/Great Plains, West, Southwest, and Northeast and Southeast.⁴

Differences in starting salaries between male and female ObGyns are often not reported, although they are a very important consideration.^6,7 Both men and women desire “controllable lifestyles” with more flexibility and working in shifts. Sex-based differences in physician salary and compensation can be complex. Explanations may deal with the number of patients seen, number of procedures and surgeries performed, and frequency of after-hours duties. Women constitute most ObGyns, and their salary being at any lower end of the income spectrum may be partially explained by fewer desired work hours or less seniority.

Annual earnings can vary and are positively related to the number of working hours, being in the middle of one’s career (aged 42–51 years), working in a moderately large practice rather than in a solo or self-employed practice, and being board certified.³ A lower starting salary would be anticipated for a recent graduate. However, the resident going into a hard-to-fill position may be offered a higher salary than an experienced ObGyn who takes a relatively easy-to-fill position in a popular location. Practices would be more desirable in which patient volume is sufficient to invest in nonphysician clinicians and revenue-generating ancillary services that do not require costly layers of administration.

Information on physician salaries for new positions from individual recruiting or research firms can serve as a starting point for negotiation, although it may not entirely be representative. Sample sizes can be small, and information in some specialties may not separate salaries of physicians in academic versus nonacademic positions and generalists versus subspecialists. The information in this article reflects the average salaries offered to attract physicians to new practice settings rather than what they might earn and report on their tax return.

Continue to: Incentives...

Incentives

Negotiations involve incentives along with a starting salary. Signing bonuses, movingallowances, continuing education time and allowances, and medical education loan repayments are important incentives. Recent signing bonuses (average, $37,472) likely reflect efforts to bring physicians back to health care facilities post-COVID-19 or, more commonly, when candidates are considering multiple opportunities.⁴ It is important to clarify at the beginning any coverage for health insurance and professional liability insurance.

Relocation allowances are for those being recruited outside their current area of residence. The average continuing medical education allowance was $3,840 in 2023.⁴ Medical school debt is common, being approximately $200,000 at graduation for many. An educational loan repayment (average, $98,665) is typically an exchange for a commitment to stay in the community for a given period.

Starting employment contracts with hospitals or large medical groups often feature a production bonus to reward additional clinical work performed or an adherence to quality protocol or guidelines, rather than income guarantees alone. Metrics are usually volume driven (for example, relative value units, net collections, gross billings, patients seen). Initiatives by payers and health care organizations have included quality metrics, such as high patient satisfaction scores, low morbidity rates, and low readmission rates. Production-based formulas are straightforward, while use of quality-based formulas (up to 14% of total compensation) can be less clear to define.⁴ ●

Evidence continues to show that the number of practicing ObGyns lags the growing and diverse US population of women.¹ Furthermore, approximately 1 in every 3 ObGyns will move usually once or twice every 10 years.² Knowing what to expect in being recruited requires a better understanding of your needs and capabilities and what they may be worth in real time. Some ObGyns elect to use a recruitment firm to begin their search to more objectively assess what is fair and equitable.

Understanding physician compensation involves many factors, such as patient composition, sources of reimbursement, impact of health care systems, and geography.³ Several sources report trends in annual physician compensation, most notably the American Medical Association, medical specialty organizations, and recruitment firms. Sources such as the Medical Group Management Association (MGMA), the American Medical Group Association (AMGA), and Medscape report total compensation.

Determining salaries for new positions

A standard and comprehensive benchmarking resource for salaries in new positions has been the annual review of physician and advanced practitioner recruiting incentives by AMN Healthcare (formerly Merritt Hawkins) Physician Solutions.⁴ This resource is used by hospitals, medical groups, academics, other health care systems, and others who track trends in physician supply, demand, and compensation. Their 2023 report considered starting salaries for more than 20 medical or surgical specialties.

Specialists’ revenue-generating potential is tracked by annual billings to commercial payers. The average annual billing by a full-time ObGyn ($3.8 million) is about the same as that of other specialties combined.⁵ As in the past, ObGyns are among the most consistently requested specialists in searches. In 2023, ObGyns were ranked the third most common physician specialists being recruited and tenth as the percentage of physicians per specialty (TABLE).⁴

obgm03512012_rayburn_table.jpg

Full-time salaries for ObGyns have remained within the middle third of all specialties. They consistently have been higher than primary care physicians’ salaries but remain among the lowest of the surgical specialties. This impression is reinforced by 2023 data shown in FIGURE 1.⁴ In the past, salaries remained flat compared with other surgical specialties. As with other specialties, starting salaries decreased during the peak 2020 and 2021 COVID-19 years. It is encouraging that averaged full-time salaries for recruiting ObGyns increased by 14.1% from 2020–2021 to 2021–2022 and by 10.5% from 2021–2022 to 2022–2023 (FIGURE 2).⁴

obgm03512012_rayburn_fig1.jpg

obgm03512012_rayburn_fig2.jpg

Special considerations

Incomes tended to be highest for ObGyns practicing in metropolitan areas with population sizes less than 1 million rather than in larger metropolitan areas.³ However, differences in reported incomes do not control for cost of living and other determinants of income (for example, surgeries, deliveries, patient care hours worked). Averaged salaries can vary regionally in the following order from highest to lowest: Midwest/Great Plains, West, Southwest, and Northeast and Southeast.⁴

Differences in starting salaries between male and female ObGyns are often not reported, although they are a very important consideration.^6,7 Both men and women desire “controllable lifestyles” with more flexibility and working in shifts. Sex-based differences in physician salary and compensation can be complex. Explanations may deal with the number of patients seen, number of procedures and surgeries performed, and frequency of after-hours duties. Women constitute most ObGyns, and their salary being at any lower end of the income spectrum may be partially explained by fewer desired work hours or less seniority.

Annual earnings can vary and are positively related to the number of working hours, being in the middle of one’s career (aged 42–51 years), working in a moderately large practice rather than in a solo or self-employed practice, and being board certified.³ A lower starting salary would be anticipated for a recent graduate. However, the resident going into a hard-to-fill position may be offered a higher salary than an experienced ObGyn who takes a relatively easy-to-fill position in a popular location. Practices would be more desirable in which patient volume is sufficient to invest in nonphysician clinicians and revenue-generating ancillary services that do not require costly layers of administration.

Information on physician salaries for new positions from individual recruiting or research firms can serve as a starting point for negotiation, although it may not entirely be representative. Sample sizes can be small, and information in some specialties may not separate salaries of physicians in academic versus nonacademic positions and generalists versus subspecialists. The information in this article reflects the average salaries offered to attract physicians to new practice settings rather than what they might earn and report on their tax return.

Continue to: Incentives...

Incentives

Negotiations involve incentives along with a starting salary. Signing bonuses, movingallowances, continuing education time and allowances, and medical education loan repayments are important incentives. Recent signing bonuses (average, $37,472) likely reflect efforts to bring physicians back to health care facilities post-COVID-19 or, more commonly, when candidates are considering multiple opportunities.⁴ It is important to clarify at the beginning any coverage for health insurance and professional liability insurance.

Relocation allowances are for those being recruited outside their current area of residence. The average continuing medical education allowance was $3,840 in 2023.⁴ Medical school debt is common, being approximately $200,000 at graduation for many. An educational loan repayment (average, $98,665) is typically an exchange for a commitment to stay in the community for a given period.

Starting employment contracts with hospitals or large medical groups often feature a production bonus to reward additional clinical work performed or an adherence to quality protocol or guidelines, rather than income guarantees alone. Metrics are usually volume driven (for example, relative value units, net collections, gross billings, patients seen). Initiatives by payers and health care organizations have included quality metrics, such as high patient satisfaction scores, low morbidity rates, and low readmission rates. Production-based formulas are straightforward, while use of quality-based formulas (up to 14% of total compensation) can be less clear to define.⁴ ●

Breast cancer represents the most commonly diagnosed cancer in the nation.¹ However, unlike other cancers, most breast cancers are identified at stage I and have a 90% survival rate 5-year prognosis.² These outcomes are attributable to various factors, one of the most significant being screening mammography—a largely accessible, highly sensitive and specific screening tool.³ Data demonstrate that malignant tumors detected on screening mammography have more favorable profiles in tumor size and nodal status compared with symptomatic breast cancers,⁴ which make it critical for early diagnosis. Most importantly, the research overwhelmingly demonstrates that screening mammography decreases breast cancer–related mortality.^5-7

The USPSTF big change: Mammography starting at age 40 for all recommended

Despite the general accessibility and mortality benefits of screening mammography (in light of the high lifetime 12% prevalence of breast cancer in the United States⁸), recommendations still conflict across medical societies regarding optimal timing and frequency.^9-12 Previously, the US Preventive Services Task Force (USPSTF) recommended that screening mammography should occur at age 50 biennially and that screening between ages 40 and 49 should be an individualized decision.^13,14 In the draft recommendation statement issued on May 9, 2023, however, the USPSTF now recommends screening every other year starting at age 40 to decrease the risk of dying from breast cancer.¹⁵

This change represents a critically important shift. The new guidance:

• acknowledges the increasing incidence of early-onset breast cancer
• reinforces a national consciousness toward screening mammography in decreasing mortality,17 even among a younger age group for whom the perception of risk may be lower.

The USPSTF statement represents a significant change in how patients should be counseled. Practitioners now have more direct guidance that is concordant with what other national medical organizations offer or recommend, including the American College of Obstetricians and Gynecologists (ACOG), the American College of Radiology (ACR), and the National Comprehensive Cancer Network (NCCN).

However, while the USPSTF statement can and should encourage health care practitioners to initiate mammography earlier than prior recommendations, ongoing discussion regarding the optimal screening interval is warranted. The USPSTF recommendations state that mammography should be performed biennially. While the age at initiation represents a step in the right direction, this recommended screening interval should be reevaluated.

Annual vs biennial screening?

The debate between annual and biennial screening mammography is not new. While many randomized trials on screening mammography have evaluated such factors as breast cancer mortality by age or rate of false positives,¹⁸ fewer trials have evaluated the optimal screening interval.

One randomized trial from the United Kingdom evaluated 99,389 people aged 50 to 62 from 1989 to 1996 who underwent annual screening (study arm) versus 3 years later (control).¹⁹ Findings demonstrated a significantly smaller tumor size in the study arm (P=.05) as well as an increased total cancer detection rate. However, the authors concluded that shortening the screening interval (from 3 years) would not yield a statistically significant decrease in mortality.¹⁹

In a randomized trial from Finland, researchers screened those aged older than 50 at biennial intervals and those aged younger than 50 at either annual or triennial intervals.²⁰ Results demonstrated that, among those aged 40 to 49, the frequency of stage I cancers was not significantly different from screen-detected cancers, interval cancers, or cancers detected outside of screening (50%, 42%, and 44%, respectively; P=.73). Furthermore, there was a greater likelihood of interval cancers among those aged 40 to 49 at 1-year (27%) and 3-year (39%) screening intervals compared with those aged older than 50 screened biennially (18%; P=.08 and P=.0009, respectively).²⁰

These randomized trials, however, have been scrutinized because of factors such as discrepancies in screening intervals by country as well as substantial improvements made in screening mammography since the time these trials were conducted.⁵ Due to the dearth of more contemporary randomized controlled trials accounting for more up-to-date training and technology, most of the more recent data has been largely observational, retrospective, or used modeling.²¹ The TABLE outlines some of the major studies on this topic.

obgm03512043_pleasant_table.jpg

False-positive results, biopsy rates. The arguments against more frequent screening include the possibility of false positives that require callbacks and biopsies, which may be more frequent among those who undergo annual mammography.²² A systematic review from the Breast Cancer Surveillance Consortium demonstrated a 61.3% annual (confidence interval [CI], 59.4%–63.1%) versus 41.6% biennial (CI, 40.6%–42.5%) false-positive rate, resulting in a 7% (CI, 6.1%–7.8%) versus 4.8% (CI, 4.4–5.2%) rate of biopsy, respectively.²³ This false-positive rate, however, also may be increased in younger patients aged 40 to 49 and in those with dense breasts.^22,24 These callbacks and biopsies could induce significant patient stress, pain, and anxiety, as well as carry financial implications related to subsequent diagnostic imaging.

Overdiagnosis. There is also the risk of overdiagnosis, in which an indolent breast cancer that otherwise would not grow or progress to become symptomatic is identified. This could lead to overtreatment. While the exact incidence of overdiagnosis is unclear (due to recommendations for universal treatment of ductal carcinoma in situ), some data suggest that overdiagnosis could be decreased with biennial screening.²⁵

While discomfort could also be a barrier, it may not necessarily be prohibitive for some to continue with future screening mammograms.²² Further, increased radiation with annual mammography is a concern. However, modeling studies have shown that the mortality benefit for annual mammography starting at age 40 outweighs (by 60-fold) the mortality risk from a radiation-induced breast cancer.²⁶

Benefit from biennial screening

Some research suggests overall benefit from biennial screening. One study that used Cancer Intervention and Surveillance Modeling Network (CISNET) breast cancer microsimulation was adapted to measure the incidence, mortality, and life-years gained for Canadian patients.²⁷ This model demonstrated that mortality reduction was linked to greater lifetime screens for breast cancer, but this applied primarily to patients aged 50 and older. Overall, a larger impact was observed by initiating screening at age 40 than by decreasing screening intervals.²⁷

Using modeling, Mandelblatt and colleagues demonstrated that biennial screening could capture most of the benefit of annual screening with less harm.²⁸ In another study in 2016, Mandelblatt and colleagues used updated and revised versions of these simulation models and maintained that biennial screening upheld 79.8% to 81.3% of the benefits of annual screening mammography but with fewer overdiagnoses and false-positive results.²⁵ The authors concluded that while biennial screening is equally effective for average-risk populations, there should be an evaluation of benefits and harms based on the clinical scenario (suggesting that annual screening for those at age 40 who carried elevated risk was similar to biennial screening for average-risk patients starting at age 50).²⁵

Another study that served to inform the European Commission Initiative on Breast Cancer recommendations evaluated randomized controlled trials and observational and modeling studies that assessed breast screening intervals.²⁹ The authors concluded that each screening interval has risks and benefits, with data suggesting more benefit with biennial screening for people aged 50 to 69 years and more possible harm with annual screening in younger people (aged 45–49).²⁹

Continue to: Benefit from annual screening...

However, these data conflict with other studies that demonstrate the benefit of annual compared with biennial screening mammography. One large retrospective review of prospectively collected data evaluated outcome differences based on mammography frequency.³⁰ For those undergoing annual versus biennial screening, the median tumor size was 11 mm (versus 15 mm), the percentage of lymph node metastasis was 14% (versus 24%), and cancer stage II or higher was 17% (versus 29%). The study overall demonstrated that annual screening resulted in lower recall rates (P<.0001) and detection of smaller tumors that carried a more favorable prognosis (P<.04).³⁰

Another observational study from 2004 that assessed data from 7 different mammography registries nationwide noted that, among those aged 40 to 49, patients who underwent biennial screening had an increased likelihood of late-stage disease compared with those with annual screening (28% vs 21%, respectively; odds ratio [OR], 1.35; 95% CI, 1.01–1.81), although this discrepancy was not observed in people aged 50 or older.³¹

A study that critiqued the previous 2012 version of the USPSTF guidelines used CISNET modeling, which demonstrated a 39.6% mortality reduction with annual screening for those aged 40 to 84 versus 23.2% for biennial screening for those aged 50 to 74.⁵

More recent data also reflect these findings. A retrospective cohort study that evaluated patients aged 40 to 84 diagnosed with breast cancer found that those who previously underwent annual versus biennial screening mammography had lower incidences of late-stage diagnoses (24.0% vs 43.8%, respectively; P=.02), fewer interval cancers (10.5% vs 37.5%; P<.001), and smaller mean (SD) tumor diameter (1.4 [1.2] cm vs 1.8 [1.6] cm; P=.04).²¹ Postmenopausal patients in this cohort also demonstrated similar findings when comparing mammogram frequency. Although not significant, biennial (or greater) frequency of screening mammography also resulted in an increased likelihood of axillary lymph node dissection and chemotherapy.

Similarly, authors of another large prospective cohort study concluded that breast cancers diagnosed in premenopausal patients were more likely to be larger with less favorable prognostic characteristics (tumor size >15 mm, relative risk [RR], 1.21 [95% CI, 1.07–1.37]; P=.002); any less favorable prognostic characteristics (RR, 1.11 [95% CI, 1.00–1.22]; P=.047), and higher stage (stage IIB or higher, RR, 1.28 [95% CI, 1.01–1.63]; P=.04) for those who underwent biennial screening compared with breast cancers diagnosed by annual screening.³² However, this trend was not observed in postmenopausal patients not taking hormone therapy.³²

Some international studies also show more favorable outcomes with annual screening mammography. A Swedish study evaluated mammography screening intervals of 21 months compared with 18 or 12 months in patients aged 40 to 49.³³ Data showed an improved effectiveness of 1.6% to 9.8% for interval cancers and 2.9% to 17.4% for both interval and screening-detected cancers by reducing the screening frequency to 12 months, with authors suggesting a further reduction in breast cancer–related mortality rates for this age group.³³

Results from another descriptive study from Europe also showed increasing interval breast cancer rates with increasing screening intervals.³⁴ After a negative screen, the interval cancer rates and regional ranges for 0 to less than 12 months, 12 to less than 24 months, and 24 to less than 36 months per 1,000 screened were 0.55 (0.43–0.76), 1.13 (0.92–1.47), and 1.22 (0.93–1.57), respectively.³⁴

Finally, a study conducted in Canada evaluated interval breast cancers among people with dense breasts screened between 2008 and 2010.³⁵ Those with screening programs with policies that offered annual screening reported fewer interval cancers (interval cancer rate, 0.89 per 1,000; 95% CI, 0.67–1.11) compared with those who had policies that used biennial screening (interval cancer rate, 1.45 per 1,000 [annualized]; 95% CI, 1.19–1.72), which was 63% higher (P=.002). For those for whom radiologists recommended screening, interval cancer was lower for annual (0.93 per 1,000; 95% CI, 0.71–1.16) versus biennial screening (1.70 per 1,000 [annualized]; 95% CI, 0.70–2.71) (P=.061).³⁵

Continue to: Black patients have a worse breast cancer prognosis...

Black patients have a worse breast cancer prognosis

Additional consideration should be given to populations with worse survival outcomes at baseline for whom screening mammography could play a significant role. In particular, Black people have similar rates of breast cancer compared with White people (127.8 cases per 100,000 vs 133.7 cases per 100,000, respectively) but have a 40% increased breast cancer–related mortality.⁸ The USPSTF recognizes this disparity and mentions it in their recommendations, encouraging health care clinicians to engage in shared decision making with Black patients and asserting that more research is needed on screening mammography in Black communities.¹⁵

While the age modification to the new guidelines better addresses the disparities that impact the Black community (such as increased likelihood of early-onset breast cancer³⁶ and increased rate of breast cancer diagnosis at first mammogram³⁷), the next obvious question is: Can groups with higher breast cancer mortality such as Black communities afford to undergo mammography every 2 years (as opposed to every year)?

Although some data specifically have evaluated the age of initiation and frequency of screening mammography among Black patients,^38,39 little data have specifically assessed outcomes for annual versus biennial screening among Black people. Despite these research gaps, risk factors among the Black community should be considered. There is an increased risk of triple-negative breast cancer that can contribute to higher mortality among Black communities.⁴⁰ Black people also tend to be diagnosed with more aggressive subtypes overall,^41,42 are more likely to have dense breasts,^43,44 have a higher likelihood of advanced stages at the time of diagnosis compared with White people,^8,45 and have a greater chance of diagnosis of a second primary or contralateral breast cancer^46-48—all risk factors that support the importance of regular and early-screening mammography.

How I counsel my patients

As Director of the Cancer Genetics and Breast Health Clinic, I am a gynecologist who primarily evaluates patients at increased risk for breast cancer (and other cancers). As an initial step, I strongly encourage all patients (especially Black patients and those of Ashkenazi Jewish ancestry as per the American College of Radiology recommendations⁹) to undergo risk assessment at age 25 to determine if they may be at increased risk for breast cancer. This first step may include genetic testing if the patient meets NCCN testing criteria based on personal or family history. If results are positive for a germline pathogenic variant, the timing and nature of breast screening would be based on NCCN recommendations for that particular variant (with possible modification of age of initiation based on family history). If testing is negative, lifetime risk assessment would then be performed using risk calculators—such as Tyrer-Cuzick—to determine if the patient meets criteria for intensive surveillance with supplemental breast magnetic resonance imaging. If the patient is subsequently determined to be at average risk after these assessments, I recommend they undergo screening mammography annually starting at age 40. However, it must be recognized that risk may change over time. A patient’s risk can continue to be assessed over a lifetime—with changing family history, personal risk factors, and new discoveries in genetics.

Summary

Ultimately, it is reassuring that the USPSTF guidelines have been updated to be concordant with other national medical society recommendations. They reflect the increasing nationwide trends that clearly demonstrate the high overall prevalence of breast cancer as well as the increasing incidence of early-onset breast cancer.

The updated guidelines, however, do not reflect the entirety of breast cancer trends in this country. With breast cancer being the most commonly diagnosed cancer in the United States, it is imperative to consider the data that demonstrate improved prognostics with annual compared with biennial mammography. Furthermore, the guidelines only begin to explore the disparities that Black patients face regarding breast cancer–related mortality. The risks of younger age at diagnosis, greater likelihood of aggressive subtypes, increased risk of second primary and contralateral breast cancer, and later stage at diagnosis must be seriously evaluated when counseling this patient population.

While the USPSTF recommendations for age at initiation reflect national statistics, recommendations by the ACR and NCCN more appropriately recognize that the benefits of annual screening outweigh the potential risks. Annual screening frequency should be adopted when counseling patients, particularly for the Black community. ●

Breast cancer represents the most commonly diagnosed cancer in the nation.¹ However, unlike other cancers, most breast cancers are identified at stage I and have a 90% survival rate 5-year prognosis.² These outcomes are attributable to various factors, one of the most significant being screening mammography—a largely accessible, highly sensitive and specific screening tool.³ Data demonstrate that malignant tumors detected on screening mammography have more favorable profiles in tumor size and nodal status compared with symptomatic breast cancers,⁴ which make it critical for early diagnosis. Most importantly, the research overwhelmingly demonstrates that screening mammography decreases breast cancer–related mortality.^5-7

The USPSTF big change: Mammography starting at age 40 for all recommended

Despite the general accessibility and mortality benefits of screening mammography (in light of the high lifetime 12% prevalence of breast cancer in the United States⁸), recommendations still conflict across medical societies regarding optimal timing and frequency.^9-12 Previously, the US Preventive Services Task Force (USPSTF) recommended that screening mammography should occur at age 50 biennially and that screening between ages 40 and 49 should be an individualized decision.^13,14 In the draft recommendation statement issued on May 9, 2023, however, the USPSTF now recommends screening every other year starting at age 40 to decrease the risk of dying from breast cancer.¹⁵

This change represents a critically important shift. The new guidance:

• acknowledges the increasing incidence of early-onset breast cancer
• reinforces a national consciousness toward screening mammography in decreasing mortality,17 even among a younger age group for whom the perception of risk may be lower.

The USPSTF statement represents a significant change in how patients should be counseled. Practitioners now have more direct guidance that is concordant with what other national medical organizations offer or recommend, including the American College of Obstetricians and Gynecologists (ACOG), the American College of Radiology (ACR), and the National Comprehensive Cancer Network (NCCN).

However, while the USPSTF statement can and should encourage health care practitioners to initiate mammography earlier than prior recommendations, ongoing discussion regarding the optimal screening interval is warranted. The USPSTF recommendations state that mammography should be performed biennially. While the age at initiation represents a step in the right direction, this recommended screening interval should be reevaluated.

Annual vs biennial screening?

The debate between annual and biennial screening mammography is not new. While many randomized trials on screening mammography have evaluated such factors as breast cancer mortality by age or rate of false positives,¹⁸ fewer trials have evaluated the optimal screening interval.

One randomized trial from the United Kingdom evaluated 99,389 people aged 50 to 62 from 1989 to 1996 who underwent annual screening (study arm) versus 3 years later (control).¹⁹ Findings demonstrated a significantly smaller tumor size in the study arm (P=.05) as well as an increased total cancer detection rate. However, the authors concluded that shortening the screening interval (from 3 years) would not yield a statistically significant decrease in mortality.¹⁹

In a randomized trial from Finland, researchers screened those aged older than 50 at biennial intervals and those aged younger than 50 at either annual or triennial intervals.²⁰ Results demonstrated that, among those aged 40 to 49, the frequency of stage I cancers was not significantly different from screen-detected cancers, interval cancers, or cancers detected outside of screening (50%, 42%, and 44%, respectively; P=.73). Furthermore, there was a greater likelihood of interval cancers among those aged 40 to 49 at 1-year (27%) and 3-year (39%) screening intervals compared with those aged older than 50 screened biennially (18%; P=.08 and P=.0009, respectively).²⁰

These randomized trials, however, have been scrutinized because of factors such as discrepancies in screening intervals by country as well as substantial improvements made in screening mammography since the time these trials were conducted.⁵ Due to the dearth of more contemporary randomized controlled trials accounting for more up-to-date training and technology, most of the more recent data has been largely observational, retrospective, or used modeling.²¹ The TABLE outlines some of the major studies on this topic.

obgm03512043_pleasant_table.jpg

False-positive results, biopsy rates. The arguments against more frequent screening include the possibility of false positives that require callbacks and biopsies, which may be more frequent among those who undergo annual mammography.²² A systematic review from the Breast Cancer Surveillance Consortium demonstrated a 61.3% annual (confidence interval [CI], 59.4%–63.1%) versus 41.6% biennial (CI, 40.6%–42.5%) false-positive rate, resulting in a 7% (CI, 6.1%–7.8%) versus 4.8% (CI, 4.4–5.2%) rate of biopsy, respectively.²³ This false-positive rate, however, also may be increased in younger patients aged 40 to 49 and in those with dense breasts.^22,24 These callbacks and biopsies could induce significant patient stress, pain, and anxiety, as well as carry financial implications related to subsequent diagnostic imaging.

Overdiagnosis. There is also the risk of overdiagnosis, in which an indolent breast cancer that otherwise would not grow or progress to become symptomatic is identified. This could lead to overtreatment. While the exact incidence of overdiagnosis is unclear (due to recommendations for universal treatment of ductal carcinoma in situ), some data suggest that overdiagnosis could be decreased with biennial screening.²⁵

While discomfort could also be a barrier, it may not necessarily be prohibitive for some to continue with future screening mammograms.²² Further, increased radiation with annual mammography is a concern. However, modeling studies have shown that the mortality benefit for annual mammography starting at age 40 outweighs (by 60-fold) the mortality risk from a radiation-induced breast cancer.²⁶

Benefit from biennial screening

Some research suggests overall benefit from biennial screening. One study that used Cancer Intervention and Surveillance Modeling Network (CISNET) breast cancer microsimulation was adapted to measure the incidence, mortality, and life-years gained for Canadian patients.²⁷ This model demonstrated that mortality reduction was linked to greater lifetime screens for breast cancer, but this applied primarily to patients aged 50 and older. Overall, a larger impact was observed by initiating screening at age 40 than by decreasing screening intervals.²⁷

Using modeling, Mandelblatt and colleagues demonstrated that biennial screening could capture most of the benefit of annual screening with less harm.²⁸ In another study in 2016, Mandelblatt and colleagues used updated and revised versions of these simulation models and maintained that biennial screening upheld 79.8% to 81.3% of the benefits of annual screening mammography but with fewer overdiagnoses and false-positive results.²⁵ The authors concluded that while biennial screening is equally effective for average-risk populations, there should be an evaluation of benefits and harms based on the clinical scenario (suggesting that annual screening for those at age 40 who carried elevated risk was similar to biennial screening for average-risk patients starting at age 50).²⁵

Another study that served to inform the European Commission Initiative on Breast Cancer recommendations evaluated randomized controlled trials and observational and modeling studies that assessed breast screening intervals.²⁹ The authors concluded that each screening interval has risks and benefits, with data suggesting more benefit with biennial screening for people aged 50 to 69 years and more possible harm with annual screening in younger people (aged 45–49).²⁹

Continue to: Benefit from annual screening...

However, these data conflict with other studies that demonstrate the benefit of annual compared with biennial screening mammography. One large retrospective review of prospectively collected data evaluated outcome differences based on mammography frequency.³⁰ For those undergoing annual versus biennial screening, the median tumor size was 11 mm (versus 15 mm), the percentage of lymph node metastasis was 14% (versus 24%), and cancer stage II or higher was 17% (versus 29%). The study overall demonstrated that annual screening resulted in lower recall rates (P<.0001) and detection of smaller tumors that carried a more favorable prognosis (P<.04).³⁰

Another observational study from 2004 that assessed data from 7 different mammography registries nationwide noted that, among those aged 40 to 49, patients who underwent biennial screening had an increased likelihood of late-stage disease compared with those with annual screening (28% vs 21%, respectively; odds ratio [OR], 1.35; 95% CI, 1.01–1.81), although this discrepancy was not observed in people aged 50 or older.³¹

A study that critiqued the previous 2012 version of the USPSTF guidelines used CISNET modeling, which demonstrated a 39.6% mortality reduction with annual screening for those aged 40 to 84 versus 23.2% for biennial screening for those aged 50 to 74.⁵

More recent data also reflect these findings. A retrospective cohort study that evaluated patients aged 40 to 84 diagnosed with breast cancer found that those who previously underwent annual versus biennial screening mammography had lower incidences of late-stage diagnoses (24.0% vs 43.8%, respectively; P=.02), fewer interval cancers (10.5% vs 37.5%; P<.001), and smaller mean (SD) tumor diameter (1.4 [1.2] cm vs 1.8 [1.6] cm; P=.04).²¹ Postmenopausal patients in this cohort also demonstrated similar findings when comparing mammogram frequency. Although not significant, biennial (or greater) frequency of screening mammography also resulted in an increased likelihood of axillary lymph node dissection and chemotherapy.

Similarly, authors of another large prospective cohort study concluded that breast cancers diagnosed in premenopausal patients were more likely to be larger with less favorable prognostic characteristics (tumor size >15 mm, relative risk [RR], 1.21 [95% CI, 1.07–1.37]; P=.002); any less favorable prognostic characteristics (RR, 1.11 [95% CI, 1.00–1.22]; P=.047), and higher stage (stage IIB or higher, RR, 1.28 [95% CI, 1.01–1.63]; P=.04) for those who underwent biennial screening compared with breast cancers diagnosed by annual screening.³² However, this trend was not observed in postmenopausal patients not taking hormone therapy.³²

Some international studies also show more favorable outcomes with annual screening mammography. A Swedish study evaluated mammography screening intervals of 21 months compared with 18 or 12 months in patients aged 40 to 49.³³ Data showed an improved effectiveness of 1.6% to 9.8% for interval cancers and 2.9% to 17.4% for both interval and screening-detected cancers by reducing the screening frequency to 12 months, with authors suggesting a further reduction in breast cancer–related mortality rates for this age group.³³

Results from another descriptive study from Europe also showed increasing interval breast cancer rates with increasing screening intervals.³⁴ After a negative screen, the interval cancer rates and regional ranges for 0 to less than 12 months, 12 to less than 24 months, and 24 to less than 36 months per 1,000 screened were 0.55 (0.43–0.76), 1.13 (0.92–1.47), and 1.22 (0.93–1.57), respectively.³⁴

Finally, a study conducted in Canada evaluated interval breast cancers among people with dense breasts screened between 2008 and 2010.³⁵ Those with screening programs with policies that offered annual screening reported fewer interval cancers (interval cancer rate, 0.89 per 1,000; 95% CI, 0.67–1.11) compared with those who had policies that used biennial screening (interval cancer rate, 1.45 per 1,000 [annualized]; 95% CI, 1.19–1.72), which was 63% higher (P=.002). For those for whom radiologists recommended screening, interval cancer was lower for annual (0.93 per 1,000; 95% CI, 0.71–1.16) versus biennial screening (1.70 per 1,000 [annualized]; 95% CI, 0.70–2.71) (P=.061).³⁵

Continue to: Black patients have a worse breast cancer prognosis...

Black patients have a worse breast cancer prognosis

Additional consideration should be given to populations with worse survival outcomes at baseline for whom screening mammography could play a significant role. In particular, Black people have similar rates of breast cancer compared with White people (127.8 cases per 100,000 vs 133.7 cases per 100,000, respectively) but have a 40% increased breast cancer–related mortality.⁸ The USPSTF recognizes this disparity and mentions it in their recommendations, encouraging health care clinicians to engage in shared decision making with Black patients and asserting that more research is needed on screening mammography in Black communities.¹⁵

While the age modification to the new guidelines better addresses the disparities that impact the Black community (such as increased likelihood of early-onset breast cancer³⁶ and increased rate of breast cancer diagnosis at first mammogram³⁷), the next obvious question is: Can groups with higher breast cancer mortality such as Black communities afford to undergo mammography every 2 years (as opposed to every year)?

Although some data specifically have evaluated the age of initiation and frequency of screening mammography among Black patients,^38,39 little data have specifically assessed outcomes for annual versus biennial screening among Black people. Despite these research gaps, risk factors among the Black community should be considered. There is an increased risk of triple-negative breast cancer that can contribute to higher mortality among Black communities.⁴⁰ Black people also tend to be diagnosed with more aggressive subtypes overall,^41,42 are more likely to have dense breasts,^43,44 have a higher likelihood of advanced stages at the time of diagnosis compared with White people,^8,45 and have a greater chance of diagnosis of a second primary or contralateral breast cancer^46-48—all risk factors that support the importance of regular and early-screening mammography.

How I counsel my patients

As Director of the Cancer Genetics and Breast Health Clinic, I am a gynecologist who primarily evaluates patients at increased risk for breast cancer (and other cancers). As an initial step, I strongly encourage all patients (especially Black patients and those of Ashkenazi Jewish ancestry as per the American College of Radiology recommendations⁹) to undergo risk assessment at age 25 to determine if they may be at increased risk for breast cancer. This first step may include genetic testing if the patient meets NCCN testing criteria based on personal or family history. If results are positive for a germline pathogenic variant, the timing and nature of breast screening would be based on NCCN recommendations for that particular variant (with possible modification of age of initiation based on family history). If testing is negative, lifetime risk assessment would then be performed using risk calculators—such as Tyrer-Cuzick—to determine if the patient meets criteria for intensive surveillance with supplemental breast magnetic resonance imaging. If the patient is subsequently determined to be at average risk after these assessments, I recommend they undergo screening mammography annually starting at age 40. However, it must be recognized that risk may change over time. A patient’s risk can continue to be assessed over a lifetime—with changing family history, personal risk factors, and new discoveries in genetics.

Summary

Ultimately, it is reassuring that the USPSTF guidelines have been updated to be concordant with other national medical society recommendations. They reflect the increasing nationwide trends that clearly demonstrate the high overall prevalence of breast cancer as well as the increasing incidence of early-onset breast cancer.

The updated guidelines, however, do not reflect the entirety of breast cancer trends in this country. With breast cancer being the most commonly diagnosed cancer in the United States, it is imperative to consider the data that demonstrate improved prognostics with annual compared with biennial mammography. Furthermore, the guidelines only begin to explore the disparities that Black patients face regarding breast cancer–related mortality. The risks of younger age at diagnosis, greater likelihood of aggressive subtypes, increased risk of second primary and contralateral breast cancer, and later stage at diagnosis must be seriously evaluated when counseling this patient population.

While the USPSTF recommendations for age at initiation reflect national statistics, recommendations by the ACR and NCCN more appropriately recognize that the benefits of annual screening outweigh the potential risks. Annual screening frequency should be adopted when counseling patients, particularly for the Black community. ●

Breast cancer represents the most commonly diagnosed cancer in the nation.¹ However, unlike other cancers, most breast cancers are identified at stage I and have a 90% survival rate 5-year prognosis.² These outcomes are attributable to various factors, one of the most significant being screening mammography—a largely accessible, highly sensitive and specific screening tool.³ Data demonstrate that malignant tumors detected on screening mammography have more favorable profiles in tumor size and nodal status compared with symptomatic breast cancers,⁴ which make it critical for early diagnosis. Most importantly, the research overwhelmingly demonstrates that screening mammography decreases breast cancer–related mortality.^5-7

The USPSTF big change: Mammography starting at age 40 for all recommended

Despite the general accessibility and mortality benefits of screening mammography (in light of the high lifetime 12% prevalence of breast cancer in the United States⁸), recommendations still conflict across medical societies regarding optimal timing and frequency.^9-12 Previously, the US Preventive Services Task Force (USPSTF) recommended that screening mammography should occur at age 50 biennially and that screening between ages 40 and 49 should be an individualized decision.^13,14 In the draft recommendation statement issued on May 9, 2023, however, the USPSTF now recommends screening every other year starting at age 40 to decrease the risk of dying from breast cancer.¹⁵

This change represents a critically important shift. The new guidance:

• acknowledges the increasing incidence of early-onset breast cancer
• reinforces a national consciousness toward screening mammography in decreasing mortality,17 even among a younger age group for whom the perception of risk may be lower.

The USPSTF statement represents a significant change in how patients should be counseled. Practitioners now have more direct guidance that is concordant with what other national medical organizations offer or recommend, including the American College of Obstetricians and Gynecologists (ACOG), the American College of Radiology (ACR), and the National Comprehensive Cancer Network (NCCN).

However, while the USPSTF statement can and should encourage health care practitioners to initiate mammography earlier than prior recommendations, ongoing discussion regarding the optimal screening interval is warranted. The USPSTF recommendations state that mammography should be performed biennially. While the age at initiation represents a step in the right direction, this recommended screening interval should be reevaluated.

Annual vs biennial screening?

The debate between annual and biennial screening mammography is not new. While many randomized trials on screening mammography have evaluated such factors as breast cancer mortality by age or rate of false positives,¹⁸ fewer trials have evaluated the optimal screening interval.

One randomized trial from the United Kingdom evaluated 99,389 people aged 50 to 62 from 1989 to 1996 who underwent annual screening (study arm) versus 3 years later (control).¹⁹ Findings demonstrated a significantly smaller tumor size in the study arm (P=.05) as well as an increased total cancer detection rate. However, the authors concluded that shortening the screening interval (from 3 years) would not yield a statistically significant decrease in mortality.¹⁹

In a randomized trial from Finland, researchers screened those aged older than 50 at biennial intervals and those aged younger than 50 at either annual or triennial intervals.²⁰ Results demonstrated that, among those aged 40 to 49, the frequency of stage I cancers was not significantly different from screen-detected cancers, interval cancers, or cancers detected outside of screening (50%, 42%, and 44%, respectively; P=.73). Furthermore, there was a greater likelihood of interval cancers among those aged 40 to 49 at 1-year (27%) and 3-year (39%) screening intervals compared with those aged older than 50 screened biennially (18%; P=.08 and P=.0009, respectively).²⁰

These randomized trials, however, have been scrutinized because of factors such as discrepancies in screening intervals by country as well as substantial improvements made in screening mammography since the time these trials were conducted.⁵ Due to the dearth of more contemporary randomized controlled trials accounting for more up-to-date training and technology, most of the more recent data has been largely observational, retrospective, or used modeling.²¹ The TABLE outlines some of the major studies on this topic.

obgm03512043_pleasant_table.jpg

False-positive results, biopsy rates. The arguments against more frequent screening include the possibility of false positives that require callbacks and biopsies, which may be more frequent among those who undergo annual mammography.²² A systematic review from the Breast Cancer Surveillance Consortium demonstrated a 61.3% annual (confidence interval [CI], 59.4%–63.1%) versus 41.6% biennial (CI, 40.6%–42.5%) false-positive rate, resulting in a 7% (CI, 6.1%–7.8%) versus 4.8% (CI, 4.4–5.2%) rate of biopsy, respectively.²³ This false-positive rate, however, also may be increased in younger patients aged 40 to 49 and in those with dense breasts.^22,24 These callbacks and biopsies could induce significant patient stress, pain, and anxiety, as well as carry financial implications related to subsequent diagnostic imaging.

Overdiagnosis. There is also the risk of overdiagnosis, in which an indolent breast cancer that otherwise would not grow or progress to become symptomatic is identified. This could lead to overtreatment. While the exact incidence of overdiagnosis is unclear (due to recommendations for universal treatment of ductal carcinoma in situ), some data suggest that overdiagnosis could be decreased with biennial screening.²⁵

While discomfort could also be a barrier, it may not necessarily be prohibitive for some to continue with future screening mammograms.²² Further, increased radiation with annual mammography is a concern. However, modeling studies have shown that the mortality benefit for annual mammography starting at age 40 outweighs (by 60-fold) the mortality risk from a radiation-induced breast cancer.²⁶

Benefit from biennial screening

Some research suggests overall benefit from biennial screening. One study that used Cancer Intervention and Surveillance Modeling Network (CISNET) breast cancer microsimulation was adapted to measure the incidence, mortality, and life-years gained for Canadian patients.²⁷ This model demonstrated that mortality reduction was linked to greater lifetime screens for breast cancer, but this applied primarily to patients aged 50 and older. Overall, a larger impact was observed by initiating screening at age 40 than by decreasing screening intervals.²⁷

Using modeling, Mandelblatt and colleagues demonstrated that biennial screening could capture most of the benefit of annual screening with less harm.²⁸ In another study in 2016, Mandelblatt and colleagues used updated and revised versions of these simulation models and maintained that biennial screening upheld 79.8% to 81.3% of the benefits of annual screening mammography but with fewer overdiagnoses and false-positive results.²⁵ The authors concluded that while biennial screening is equally effective for average-risk populations, there should be an evaluation of benefits and harms based on the clinical scenario (suggesting that annual screening for those at age 40 who carried elevated risk was similar to biennial screening for average-risk patients starting at age 50).²⁵

Another study that served to inform the European Commission Initiative on Breast Cancer recommendations evaluated randomized controlled trials and observational and modeling studies that assessed breast screening intervals.²⁹ The authors concluded that each screening interval has risks and benefits, with data suggesting more benefit with biennial screening for people aged 50 to 69 years and more possible harm with annual screening in younger people (aged 45–49).²⁹

Continue to: Benefit from annual screening...

However, these data conflict with other studies that demonstrate the benefit of annual compared with biennial screening mammography. One large retrospective review of prospectively collected data evaluated outcome differences based on mammography frequency.³⁰ For those undergoing annual versus biennial screening, the median tumor size was 11 mm (versus 15 mm), the percentage of lymph node metastasis was 14% (versus 24%), and cancer stage II or higher was 17% (versus 29%). The study overall demonstrated that annual screening resulted in lower recall rates (P<.0001) and detection of smaller tumors that carried a more favorable prognosis (P<.04).³⁰

Another observational study from 2004 that assessed data from 7 different mammography registries nationwide noted that, among those aged 40 to 49, patients who underwent biennial screening had an increased likelihood of late-stage disease compared with those with annual screening (28% vs 21%, respectively; odds ratio [OR], 1.35; 95% CI, 1.01–1.81), although this discrepancy was not observed in people aged 50 or older.³¹

A study that critiqued the previous 2012 version of the USPSTF guidelines used CISNET modeling, which demonstrated a 39.6% mortality reduction with annual screening for those aged 40 to 84 versus 23.2% for biennial screening for those aged 50 to 74.⁵

More recent data also reflect these findings. A retrospective cohort study that evaluated patients aged 40 to 84 diagnosed with breast cancer found that those who previously underwent annual versus biennial screening mammography had lower incidences of late-stage diagnoses (24.0% vs 43.8%, respectively; P=.02), fewer interval cancers (10.5% vs 37.5%; P<.001), and smaller mean (SD) tumor diameter (1.4 [1.2] cm vs 1.8 [1.6] cm; P=.04).²¹ Postmenopausal patients in this cohort also demonstrated similar findings when comparing mammogram frequency. Although not significant, biennial (or greater) frequency of screening mammography also resulted in an increased likelihood of axillary lymph node dissection and chemotherapy.

Similarly, authors of another large prospective cohort study concluded that breast cancers diagnosed in premenopausal patients were more likely to be larger with less favorable prognostic characteristics (tumor size >15 mm, relative risk [RR], 1.21 [95% CI, 1.07–1.37]; P=.002); any less favorable prognostic characteristics (RR, 1.11 [95% CI, 1.00–1.22]; P=.047), and higher stage (stage IIB or higher, RR, 1.28 [95% CI, 1.01–1.63]; P=.04) for those who underwent biennial screening compared with breast cancers diagnosed by annual screening.³² However, this trend was not observed in postmenopausal patients not taking hormone therapy.³²

Some international studies also show more favorable outcomes with annual screening mammography. A Swedish study evaluated mammography screening intervals of 21 months compared with 18 or 12 months in patients aged 40 to 49.³³ Data showed an improved effectiveness of 1.6% to 9.8% for interval cancers and 2.9% to 17.4% for both interval and screening-detected cancers by reducing the screening frequency to 12 months, with authors suggesting a further reduction in breast cancer–related mortality rates for this age group.³³

Results from another descriptive study from Europe also showed increasing interval breast cancer rates with increasing screening intervals.³⁴ After a negative screen, the interval cancer rates and regional ranges for 0 to less than 12 months, 12 to less than 24 months, and 24 to less than 36 months per 1,000 screened were 0.55 (0.43–0.76), 1.13 (0.92–1.47), and 1.22 (0.93–1.57), respectively.³⁴

Finally, a study conducted in Canada evaluated interval breast cancers among people with dense breasts screened between 2008 and 2010.³⁵ Those with screening programs with policies that offered annual screening reported fewer interval cancers (interval cancer rate, 0.89 per 1,000; 95% CI, 0.67–1.11) compared with those who had policies that used biennial screening (interval cancer rate, 1.45 per 1,000 [annualized]; 95% CI, 1.19–1.72), which was 63% higher (P=.002). For those for whom radiologists recommended screening, interval cancer was lower for annual (0.93 per 1,000; 95% CI, 0.71–1.16) versus biennial screening (1.70 per 1,000 [annualized]; 95% CI, 0.70–2.71) (P=.061).³⁵

Continue to: Black patients have a worse breast cancer prognosis...

Black patients have a worse breast cancer prognosis

Additional consideration should be given to populations with worse survival outcomes at baseline for whom screening mammography could play a significant role. In particular, Black people have similar rates of breast cancer compared with White people (127.8 cases per 100,000 vs 133.7 cases per 100,000, respectively) but have a 40% increased breast cancer–related mortality.⁸ The USPSTF recognizes this disparity and mentions it in their recommendations, encouraging health care clinicians to engage in shared decision making with Black patients and asserting that more research is needed on screening mammography in Black communities.¹⁵

While the age modification to the new guidelines better addresses the disparities that impact the Black community (such as increased likelihood of early-onset breast cancer³⁶ and increased rate of breast cancer diagnosis at first mammogram³⁷), the next obvious question is: Can groups with higher breast cancer mortality such as Black communities afford to undergo mammography every 2 years (as opposed to every year)?

Although some data specifically have evaluated the age of initiation and frequency of screening mammography among Black patients,^38,39 little data have specifically assessed outcomes for annual versus biennial screening among Black people. Despite these research gaps, risk factors among the Black community should be considered. There is an increased risk of triple-negative breast cancer that can contribute to higher mortality among Black communities.⁴⁰ Black people also tend to be diagnosed with more aggressive subtypes overall,^41,42 are more likely to have dense breasts,^43,44 have a higher likelihood of advanced stages at the time of diagnosis compared with White people,^8,45 and have a greater chance of diagnosis of a second primary or contralateral breast cancer^46-48—all risk factors that support the importance of regular and early-screening mammography.

How I counsel my patients

As Director of the Cancer Genetics and Breast Health Clinic, I am a gynecologist who primarily evaluates patients at increased risk for breast cancer (and other cancers). As an initial step, I strongly encourage all patients (especially Black patients and those of Ashkenazi Jewish ancestry as per the American College of Radiology recommendations⁹) to undergo risk assessment at age 25 to determine if they may be at increased risk for breast cancer. This first step may include genetic testing if the patient meets NCCN testing criteria based on personal or family history. If results are positive for a germline pathogenic variant, the timing and nature of breast screening would be based on NCCN recommendations for that particular variant (with possible modification of age of initiation based on family history). If testing is negative, lifetime risk assessment would then be performed using risk calculators—such as Tyrer-Cuzick—to determine if the patient meets criteria for intensive surveillance with supplemental breast magnetic resonance imaging. If the patient is subsequently determined to be at average risk after these assessments, I recommend they undergo screening mammography annually starting at age 40. However, it must be recognized that risk may change over time. A patient’s risk can continue to be assessed over a lifetime—with changing family history, personal risk factors, and new discoveries in genetics.

Summary

Ultimately, it is reassuring that the USPSTF guidelines have been updated to be concordant with other national medical society recommendations. They reflect the increasing nationwide trends that clearly demonstrate the high overall prevalence of breast cancer as well as the increasing incidence of early-onset breast cancer.

The updated guidelines, however, do not reflect the entirety of breast cancer trends in this country. With breast cancer being the most commonly diagnosed cancer in the United States, it is imperative to consider the data that demonstrate improved prognostics with annual compared with biennial mammography. Furthermore, the guidelines only begin to explore the disparities that Black patients face regarding breast cancer–related mortality. The risks of younger age at diagnosis, greater likelihood of aggressive subtypes, increased risk of second primary and contralateral breast cancer, and later stage at diagnosis must be seriously evaluated when counseling this patient population.

While the USPSTF recommendations for age at initiation reflect national statistics, recommendations by the ACR and NCCN more appropriately recognize that the benefits of annual screening outweigh the potential risks. Annual screening frequency should be adopted when counseling patients, particularly for the Black community. ●