Gynecology

An ancient Chinese remedy for malaria could offer new hope to the 10% of reproductive-age women living with polycystic ovarian syndrome (PCOS), a poorly understood endocrine disorder that can cause hormonal imbalances, irregular periods, and cysts in the ovaries.

“PCOS is among the most common disorders of reproductive-age women,” said endocrinologist Andrea Dunaif, MD, a professor at the Icahn School of Medicine at Mount Sinai, New York City, who studies diabetes and women’s health. “It is a major risk factor for obesity, type 2 diabetes, and heart disease.” It’s also a leading cause of infertility.

Yet despite how common it is, PCOS has no Food and Drug Administration–approved treatments, though a few early-stage clinical trials are underway. Many women end up taking off-label medications such as oral contraceptives, insulin-sensitizing agents, and antiandrogens to help manage symptoms. Surgery can also be used to treat fertility problems associated with PCOS, though it may not work for everyone.

In a new study, a derivative of artemisinin — a molecule that comes from Artemisia plants, which have been used as far back as 1596 to treat malaria in China — helped relieve PCOS symptoms in rats and a small group of women.

Previously, the study’s lead researcher Qi-qun Tang, MD, PhD, had found that this derivative, called artemether, can increase thermogenesis, boosting metabolism. Dr. Tang and his team at Fudan University, Shanghai, China, wanted to see if it would help with PCOS, which is associated with metabolic problems such as insulin resistance.
 

What the Researchers Did

To simulate PCOS in rats, the team treated the rodents with insulin and human chorionic gonadotropin. Then, they tested artemether on the rats and found that it lowered androgen production in the ovaries.

“A common feature [of PCOS] is that the ovaries, and often the adrenal glands, make increased male hormones, nowhere near what a man makes but slightly above what a normal woman makes,” said Dr. Dunaif, who was not involved in the study.

Artemether “inhibits one of the steroidogenic enzymes, CYP11A1, which is important in the production of male hormones,” Dr. Tang said. It does this by increasing the enzyme’s interaction with a protein called LONP1, triggering the enzyme’s breakdown. Increased levels of LONP1 also appeared to suppress androgen production in the ovaries.

In a pilot clinical study of 19 women with PCOS, taking dihydroartemisinin — an approved drug used to treat malaria that contains active artemisinin derivatives — for 12 weeks substantially reduced serum testosterone and anti-Müllerian hormone levels (which are higher in women with PCOS). Using ultrasound, the researchers found that the antral follicle count (also higher than normal with PCOS) had been reduced. All participants had regular menstrual cycles during treatment. And no one reported significant side effects.

“Regular menstrual cycles suggest that there is ovulation, which can result in conception,” Dr. Dunaif said. Still, testing would be needed to confirm that cycles are ovulatory.

Lowering androgen levels “could improve a substantial portion of the symptoms of PCOS,” said Dr. Dunaif. But the research didn’t see an improvement in insulin sensitivity among the women, suggesting that targeting androgens may not help the metabolic symptoms.
 

What’s Next? 

A larger, placebo-controlled trial would still be needed to assess the drug’s efficacy, said Dr. Dunaif, pointing out that the human study did not have a placebo arm.

And unanswered questions remain. Are there any adrenal effects of the compound? “The enzymes that produce androgens are shared between the ovary and the adrenal [gland],” Dr. Dunaif said, but she pointed out that the study doesn’t address whether there is an adrenal benefit. It’s something to look at in future research.

Still, because artemisinin is an established drug, it may come to market faster than a new molecule would, she said. However, a pharmaceutical company would need to be willing to take on the drug. (Dr. Tang said several companies have already expressed interest.)

And while you can buy artemisinin on the Internet, Dr. Dunaif warned not to start taking it if you have PCOS. “I don’t think we’re at that point,” Dr. Dunaif said.

A version of this article first appeared on Medscape.com.

An ancient Chinese remedy for malaria could offer new hope to the 10% of reproductive-age women living with polycystic ovarian syndrome (PCOS), a poorly understood endocrine disorder that can cause hormonal imbalances, irregular periods, and cysts in the ovaries.

“PCOS is among the most common disorders of reproductive-age women,” said endocrinologist Andrea Dunaif, MD, a professor at the Icahn School of Medicine at Mount Sinai, New York City, who studies diabetes and women’s health. “It is a major risk factor for obesity, type 2 diabetes, and heart disease.” It’s also a leading cause of infertility.

Yet despite how common it is, PCOS has no Food and Drug Administration–approved treatments, though a few early-stage clinical trials are underway. Many women end up taking off-label medications such as oral contraceptives, insulin-sensitizing agents, and antiandrogens to help manage symptoms. Surgery can also be used to treat fertility problems associated with PCOS, though it may not work for everyone.

In a new study, a derivative of artemisinin — a molecule that comes from Artemisia plants, which have been used as far back as 1596 to treat malaria in China — helped relieve PCOS symptoms in rats and a small group of women.

Previously, the study’s lead researcher Qi-qun Tang, MD, PhD, had found that this derivative, called artemether, can increase thermogenesis, boosting metabolism. Dr. Tang and his team at Fudan University, Shanghai, China, wanted to see if it would help with PCOS, which is associated with metabolic problems such as insulin resistance.
 

What the Researchers Did

To simulate PCOS in rats, the team treated the rodents with insulin and human chorionic gonadotropin. Then, they tested artemether on the rats and found that it lowered androgen production in the ovaries.

“A common feature [of PCOS] is that the ovaries, and often the adrenal glands, make increased male hormones, nowhere near what a man makes but slightly above what a normal woman makes,” said Dr. Dunaif, who was not involved in the study.

Artemether “inhibits one of the steroidogenic enzymes, CYP11A1, which is important in the production of male hormones,” Dr. Tang said. It does this by increasing the enzyme’s interaction with a protein called LONP1, triggering the enzyme’s breakdown. Increased levels of LONP1 also appeared to suppress androgen production in the ovaries.

In a pilot clinical study of 19 women with PCOS, taking dihydroartemisinin — an approved drug used to treat malaria that contains active artemisinin derivatives — for 12 weeks substantially reduced serum testosterone and anti-Müllerian hormone levels (which are higher in women with PCOS). Using ultrasound, the researchers found that the antral follicle count (also higher than normal with PCOS) had been reduced. All participants had regular menstrual cycles during treatment. And no one reported significant side effects.

“Regular menstrual cycles suggest that there is ovulation, which can result in conception,” Dr. Dunaif said. Still, testing would be needed to confirm that cycles are ovulatory.

Lowering androgen levels “could improve a substantial portion of the symptoms of PCOS,” said Dr. Dunaif. But the research didn’t see an improvement in insulin sensitivity among the women, suggesting that targeting androgens may not help the metabolic symptoms.
 

What’s Next? 

A larger, placebo-controlled trial would still be needed to assess the drug’s efficacy, said Dr. Dunaif, pointing out that the human study did not have a placebo arm.

And unanswered questions remain. Are there any adrenal effects of the compound? “The enzymes that produce androgens are shared between the ovary and the adrenal [gland],” Dr. Dunaif said, but she pointed out that the study doesn’t address whether there is an adrenal benefit. It’s something to look at in future research.

Still, because artemisinin is an established drug, it may come to market faster than a new molecule would, she said. However, a pharmaceutical company would need to be willing to take on the drug. (Dr. Tang said several companies have already expressed interest.)

And while you can buy artemisinin on the Internet, Dr. Dunaif warned not to start taking it if you have PCOS. “I don’t think we’re at that point,” Dr. Dunaif said.

A version of this article first appeared on Medscape.com.

An ancient Chinese remedy for malaria could offer new hope to the 10% of reproductive-age women living with polycystic ovarian syndrome (PCOS), a poorly understood endocrine disorder that can cause hormonal imbalances, irregular periods, and cysts in the ovaries.

“PCOS is among the most common disorders of reproductive-age women,” said endocrinologist Andrea Dunaif, MD, a professor at the Icahn School of Medicine at Mount Sinai, New York City, who studies diabetes and women’s health. “It is a major risk factor for obesity, type 2 diabetes, and heart disease.” It’s also a leading cause of infertility.

Yet despite how common it is, PCOS has no Food and Drug Administration–approved treatments, though a few early-stage clinical trials are underway. Many women end up taking off-label medications such as oral contraceptives, insulin-sensitizing agents, and antiandrogens to help manage symptoms. Surgery can also be used to treat fertility problems associated with PCOS, though it may not work for everyone.

In a new study, a derivative of artemisinin — a molecule that comes from Artemisia plants, which have been used as far back as 1596 to treat malaria in China — helped relieve PCOS symptoms in rats and a small group of women.

Previously, the study’s lead researcher Qi-qun Tang, MD, PhD, had found that this derivative, called artemether, can increase thermogenesis, boosting metabolism. Dr. Tang and his team at Fudan University, Shanghai, China, wanted to see if it would help with PCOS, which is associated with metabolic problems such as insulin resistance.
 

What the Researchers Did

To simulate PCOS in rats, the team treated the rodents with insulin and human chorionic gonadotropin. Then, they tested artemether on the rats and found that it lowered androgen production in the ovaries.

“A common feature [of PCOS] is that the ovaries, and often the adrenal glands, make increased male hormones, nowhere near what a man makes but slightly above what a normal woman makes,” said Dr. Dunaif, who was not involved in the study.

Artemether “inhibits one of the steroidogenic enzymes, CYP11A1, which is important in the production of male hormones,” Dr. Tang said. It does this by increasing the enzyme’s interaction with a protein called LONP1, triggering the enzyme’s breakdown. Increased levels of LONP1 also appeared to suppress androgen production in the ovaries.

In a pilot clinical study of 19 women with PCOS, taking dihydroartemisinin — an approved drug used to treat malaria that contains active artemisinin derivatives — for 12 weeks substantially reduced serum testosterone and anti-Müllerian hormone levels (which are higher in women with PCOS). Using ultrasound, the researchers found that the antral follicle count (also higher than normal with PCOS) had been reduced. All participants had regular menstrual cycles during treatment. And no one reported significant side effects.

“Regular menstrual cycles suggest that there is ovulation, which can result in conception,” Dr. Dunaif said. Still, testing would be needed to confirm that cycles are ovulatory.

Lowering androgen levels “could improve a substantial portion of the symptoms of PCOS,” said Dr. Dunaif. But the research didn’t see an improvement in insulin sensitivity among the women, suggesting that targeting androgens may not help the metabolic symptoms.
 

What’s Next? 

A larger, placebo-controlled trial would still be needed to assess the drug’s efficacy, said Dr. Dunaif, pointing out that the human study did not have a placebo arm.

And unanswered questions remain. Are there any adrenal effects of the compound? “The enzymes that produce androgens are shared between the ovary and the adrenal [gland],” Dr. Dunaif said, but she pointed out that the study doesn’t address whether there is an adrenal benefit. It’s something to look at in future research.

Still, because artemisinin is an established drug, it may come to market faster than a new molecule would, she said. However, a pharmaceutical company would need to be willing to take on the drug. (Dr. Tang said several companies have already expressed interest.)

And while you can buy artemisinin on the Internet, Dr. Dunaif warned not to start taking it if you have PCOS. “I don’t think we’re at that point,” Dr. Dunaif said.

A version of this article first appeared on Medscape.com.

The US Food and Drug Administration has expanded the indication for durvalumab (Imfinzi, AstraZeneca) to include mismatch repair deficient (dMMR) newly diagnosed advanced or recurrent endometrial cancer in combination with carboplatin and paclitaxel followed by single-agent use for maintenance.

Originally approved in 2017, the programmed death ligand 1 inhibitor caries previously approved indications for non–small cell lung cancer, biliary tract cancer, and hepatocellular carcinoma.

Approval of the new indication was based on the phase 3 DUO-E trial, which included 95 women with newly diagnosed advanced or recurrent dMMR endometrial cancer. Patients were randomized to durvalumab 1120 mg or placebo with carboplatin plus paclitaxel every 3 weeks for a maximum of six cycles followed by durvalumab 1500 mg every 4 weeks until disease progression.

Median progression-free survival (PFS) was 7 months in the placebo arm but not reached in the durvalumab group. Overall survival outcomes were immature at the PFS analysis.

A quarter or more of durvalumab patients experienced peripheral neuropathy, musculoskeletal pain, nausea, alopecia, fatigue, abdominal pain, constipation, rash, diarrhea, vomiting, and cough.

The recommended treatment regimen for dMMR endometrial cancer in women who weigh ≥ 30 kg is 1120 mg with carboplatin plus paclitaxel every 3 weeks for six cycles, followed by single-agent durvalumab 1500 mg every 4 weeks.

The price of 2.4 mL of durvalumab at a concentration of 50 mg/mL is $1027, according to drugs.com.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration has expanded the indication for durvalumab (Imfinzi, AstraZeneca) to include mismatch repair deficient (dMMR) newly diagnosed advanced or recurrent endometrial cancer in combination with carboplatin and paclitaxel followed by single-agent use for maintenance.

Originally approved in 2017, the programmed death ligand 1 inhibitor caries previously approved indications for non–small cell lung cancer, biliary tract cancer, and hepatocellular carcinoma.

Approval of the new indication was based on the phase 3 DUO-E trial, which included 95 women with newly diagnosed advanced or recurrent dMMR endometrial cancer. Patients were randomized to durvalumab 1120 mg or placebo with carboplatin plus paclitaxel every 3 weeks for a maximum of six cycles followed by durvalumab 1500 mg every 4 weeks until disease progression.

Median progression-free survival (PFS) was 7 months in the placebo arm but not reached in the durvalumab group. Overall survival outcomes were immature at the PFS analysis.

A quarter or more of durvalumab patients experienced peripheral neuropathy, musculoskeletal pain, nausea, alopecia, fatigue, abdominal pain, constipation, rash, diarrhea, vomiting, and cough.

The recommended treatment regimen for dMMR endometrial cancer in women who weigh ≥ 30 kg is 1120 mg with carboplatin plus paclitaxel every 3 weeks for six cycles, followed by single-agent durvalumab 1500 mg every 4 weeks.

The price of 2.4 mL of durvalumab at a concentration of 50 mg/mL is $1027, according to drugs.com.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration has expanded the indication for durvalumab (Imfinzi, AstraZeneca) to include mismatch repair deficient (dMMR) newly diagnosed advanced or recurrent endometrial cancer in combination with carboplatin and paclitaxel followed by single-agent use for maintenance.

Originally approved in 2017, the programmed death ligand 1 inhibitor caries previously approved indications for non–small cell lung cancer, biliary tract cancer, and hepatocellular carcinoma.

Approval of the new indication was based on the phase 3 DUO-E trial, which included 95 women with newly diagnosed advanced or recurrent dMMR endometrial cancer. Patients were randomized to durvalumab 1120 mg or placebo with carboplatin plus paclitaxel every 3 weeks for a maximum of six cycles followed by durvalumab 1500 mg every 4 weeks until disease progression.

Median progression-free survival (PFS) was 7 months in the placebo arm but not reached in the durvalumab group. Overall survival outcomes were immature at the PFS analysis.

A quarter or more of durvalumab patients experienced peripheral neuropathy, musculoskeletal pain, nausea, alopecia, fatigue, abdominal pain, constipation, rash, diarrhea, vomiting, and cough.

The recommended treatment regimen for dMMR endometrial cancer in women who weigh ≥ 30 kg is 1120 mg with carboplatin plus paclitaxel every 3 weeks for six cycles, followed by single-agent durvalumab 1500 mg every 4 weeks.

The price of 2.4 mL of durvalumab at a concentration of 50 mg/mL is $1027, according to drugs.com.

A version of this article appeared on Medscape.com.

British Columbia (BC) could eliminate cervical cancer within the next 20 years if the province shifts from cytology to human papillomavirus (HPV)–based screening before the end of the decade, data suggested. To achieve this goal, the province will also need to reach historically underscreened, equity-seeking populations (ie, Black, indigenous, immigrant, LGBTQ, and disabled patients, and those with sexual trauma) through mailed self-screening HPV tests.

The adoption of both these strategies is essential, according to a modeling study that was published on June 3 in CMAJ, especially because the true impact of HPV vaccination has yet to be fully realized.

“In BC, we have a school-based program to increase vaccine coverage in boys and girls starting in grade 6,” study author Reka Pataky, PhD, a senior research health economist at the Canadian Centre for Applied Research in Cancer Control and BC Cancer in Vancouver, British Columbia, Canada, told this news organization. Dr. Pataky noted that this immunization program was launched in 2008 and that some of the initial cohorts haven›t yet reached the average age of diagnosis, which is between 30 and 59 years.

Three’s a Charm

The investigators undertook a modeling study to determine when and how BC might achieve the elimination of cervical cancer following a transition to HPV-based screening. Elimination was defined as an annual age-standardized incidence rate of < 4.0 per 100,000 women.

Modeling scenarios were developed using the Canadian Partnership Against Cancer’s priority targets, which include increasing HPV vaccination through school-based coverage from 70% to 90%, increasing the probability of ever receiving a screening test from 90% to 95%, increasing the rate of on-time screening from 70% to 90%, and improving follow-up to 95% for colposcopy (currently 88%) and HPV testing (currently 80%). Modeling simulated HPV transmission and the natural history of cervical cancer in the Canadian population and relied upon two reference scenarios: One using BC’s cytology-based screening at the time of analysis, and the other an HPV base-case scenario.

The researchers found that with the status quo (ie, cytology-based screening and no change to vaccination or screening participation rates), BC would not eliminate cervical cancer until 2045. Implementation of HPV-based screening at the current 70% participation rate would achieve elimination in 2034 and prevent 942 cases compared with cytology screening. Increasing the proportion of patients who were ever screened or increasing vaccination coverage would result in cervical cancer elimination by 2033. The time line would be shortened even further (to 2031) through a combination of three strategies (ie, improving recruitment, on-time screening, and follow-up compliance).

Low Incidence, Strained System

The incidence of cervical cancer in Canada is relatively low, accounting for 1.3% of all new female cancers and 1.1% of all female cancer deaths.

“The reason that we have such low rates is because we have organized screening programs,” explained Rachel Kupets, MD, associate professor of gynecologic oncology at the University of Toronto and Sunnybrook Hospital, Toronto. She was not involved in the study.

“We’re starting to see what happens when the system gets strained with lower participation rates. I am starting to see a lot more women with invasive cervical cancer. They’re younger, and their cancers are less curable and less treatable,” she said.

Difficulties with access, interest, and education have contributed to low cervical screening rates among equity-seeking populations, according to Dr. Pataky and Dr. Kupets.

“Self-screening is another tool that can incrementally benefit those folks who wouldn’t otherwise undergo screening or don’t want an invasive test,” said Dr. Kupets. It can also play an increasing role, while current access to primary care services in Canada is at an all-time low. Community outreach through centers, mobile coaches, and nursing stations might help ensure participation by at-risk populations. These measures also could boost follow-up for and education about positive results, said Dr. Kupets.

In a related editorial, Shannon Charlebois, MD, medical editor of CMAJ, and Sarah Kean, MD, assistant professor of gynecologic oncology at the University of Manitoba in Winnipeg, Manitoba, Canada, emphasized the need for mailed HPV self-screening kits to be paid for and integrated into provincial cervical cancer screening programs across Canada to support earlier cervical cancer detection and lower invasive cancer rates.

Dr. Pataky concurred. “There have been discussions about making the big transition from traditional cytology to implementing HPV self-screening,” she said. “We have really effective tools for preventing cervical cancer, and it’s important to not lose sight of that goal.”

The study was funded by the National Institutes of Health. Dr. Pataky and Dr. Kupets reported no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

British Columbia (BC) could eliminate cervical cancer within the next 20 years if the province shifts from cytology to human papillomavirus (HPV)–based screening before the end of the decade, data suggested. To achieve this goal, the province will also need to reach historically underscreened, equity-seeking populations (ie, Black, indigenous, immigrant, LGBTQ, and disabled patients, and those with sexual trauma) through mailed self-screening HPV tests.

The adoption of both these strategies is essential, according to a modeling study that was published on June 3 in CMAJ, especially because the true impact of HPV vaccination has yet to be fully realized.

“In BC, we have a school-based program to increase vaccine coverage in boys and girls starting in grade 6,” study author Reka Pataky, PhD, a senior research health economist at the Canadian Centre for Applied Research in Cancer Control and BC Cancer in Vancouver, British Columbia, Canada, told this news organization. Dr. Pataky noted that this immunization program was launched in 2008 and that some of the initial cohorts haven›t yet reached the average age of diagnosis, which is between 30 and 59 years.

Three’s a Charm

The investigators undertook a modeling study to determine when and how BC might achieve the elimination of cervical cancer following a transition to HPV-based screening. Elimination was defined as an annual age-standardized incidence rate of < 4.0 per 100,000 women.

Modeling scenarios were developed using the Canadian Partnership Against Cancer’s priority targets, which include increasing HPV vaccination through school-based coverage from 70% to 90%, increasing the probability of ever receiving a screening test from 90% to 95%, increasing the rate of on-time screening from 70% to 90%, and improving follow-up to 95% for colposcopy (currently 88%) and HPV testing (currently 80%). Modeling simulated HPV transmission and the natural history of cervical cancer in the Canadian population and relied upon two reference scenarios: One using BC’s cytology-based screening at the time of analysis, and the other an HPV base-case scenario.

The researchers found that with the status quo (ie, cytology-based screening and no change to vaccination or screening participation rates), BC would not eliminate cervical cancer until 2045. Implementation of HPV-based screening at the current 70% participation rate would achieve elimination in 2034 and prevent 942 cases compared with cytology screening. Increasing the proportion of patients who were ever screened or increasing vaccination coverage would result in cervical cancer elimination by 2033. The time line would be shortened even further (to 2031) through a combination of three strategies (ie, improving recruitment, on-time screening, and follow-up compliance).

Low Incidence, Strained System

The incidence of cervical cancer in Canada is relatively low, accounting for 1.3% of all new female cancers and 1.1% of all female cancer deaths.

“The reason that we have such low rates is because we have organized screening programs,” explained Rachel Kupets, MD, associate professor of gynecologic oncology at the University of Toronto and Sunnybrook Hospital, Toronto. She was not involved in the study.

“We’re starting to see what happens when the system gets strained with lower participation rates. I am starting to see a lot more women with invasive cervical cancer. They’re younger, and their cancers are less curable and less treatable,” she said.

Difficulties with access, interest, and education have contributed to low cervical screening rates among equity-seeking populations, according to Dr. Pataky and Dr. Kupets.

“Self-screening is another tool that can incrementally benefit those folks who wouldn’t otherwise undergo screening or don’t want an invasive test,” said Dr. Kupets. It can also play an increasing role, while current access to primary care services in Canada is at an all-time low. Community outreach through centers, mobile coaches, and nursing stations might help ensure participation by at-risk populations. These measures also could boost follow-up for and education about positive results, said Dr. Kupets.

In a related editorial, Shannon Charlebois, MD, medical editor of CMAJ, and Sarah Kean, MD, assistant professor of gynecologic oncology at the University of Manitoba in Winnipeg, Manitoba, Canada, emphasized the need for mailed HPV self-screening kits to be paid for and integrated into provincial cervical cancer screening programs across Canada to support earlier cervical cancer detection and lower invasive cancer rates.

Dr. Pataky concurred. “There have been discussions about making the big transition from traditional cytology to implementing HPV self-screening,” she said. “We have really effective tools for preventing cervical cancer, and it’s important to not lose sight of that goal.”

The study was funded by the National Institutes of Health. Dr. Pataky and Dr. Kupets reported no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

British Columbia (BC) could eliminate cervical cancer within the next 20 years if the province shifts from cytology to human papillomavirus (HPV)–based screening before the end of the decade, data suggested. To achieve this goal, the province will also need to reach historically underscreened, equity-seeking populations (ie, Black, indigenous, immigrant, LGBTQ, and disabled patients, and those with sexual trauma) through mailed self-screening HPV tests.

The adoption of both these strategies is essential, according to a modeling study that was published on June 3 in CMAJ, especially because the true impact of HPV vaccination has yet to be fully realized.

“In BC, we have a school-based program to increase vaccine coverage in boys and girls starting in grade 6,” study author Reka Pataky, PhD, a senior research health economist at the Canadian Centre for Applied Research in Cancer Control and BC Cancer in Vancouver, British Columbia, Canada, told this news organization. Dr. Pataky noted that this immunization program was launched in 2008 and that some of the initial cohorts haven›t yet reached the average age of diagnosis, which is between 30 and 59 years.

Three’s a Charm

The investigators undertook a modeling study to determine when and how BC might achieve the elimination of cervical cancer following a transition to HPV-based screening. Elimination was defined as an annual age-standardized incidence rate of < 4.0 per 100,000 women.

Modeling scenarios were developed using the Canadian Partnership Against Cancer’s priority targets, which include increasing HPV vaccination through school-based coverage from 70% to 90%, increasing the probability of ever receiving a screening test from 90% to 95%, increasing the rate of on-time screening from 70% to 90%, and improving follow-up to 95% for colposcopy (currently 88%) and HPV testing (currently 80%). Modeling simulated HPV transmission and the natural history of cervical cancer in the Canadian population and relied upon two reference scenarios: One using BC’s cytology-based screening at the time of analysis, and the other an HPV base-case scenario.

The researchers found that with the status quo (ie, cytology-based screening and no change to vaccination or screening participation rates), BC would not eliminate cervical cancer until 2045. Implementation of HPV-based screening at the current 70% participation rate would achieve elimination in 2034 and prevent 942 cases compared with cytology screening. Increasing the proportion of patients who were ever screened or increasing vaccination coverage would result in cervical cancer elimination by 2033. The time line would be shortened even further (to 2031) through a combination of three strategies (ie, improving recruitment, on-time screening, and follow-up compliance).

Low Incidence, Strained System

The incidence of cervical cancer in Canada is relatively low, accounting for 1.3% of all new female cancers and 1.1% of all female cancer deaths.

“The reason that we have such low rates is because we have organized screening programs,” explained Rachel Kupets, MD, associate professor of gynecologic oncology at the University of Toronto and Sunnybrook Hospital, Toronto. She was not involved in the study.

“We’re starting to see what happens when the system gets strained with lower participation rates. I am starting to see a lot more women with invasive cervical cancer. They’re younger, and their cancers are less curable and less treatable,” she said.

Difficulties with access, interest, and education have contributed to low cervical screening rates among equity-seeking populations, according to Dr. Pataky and Dr. Kupets.

“Self-screening is another tool that can incrementally benefit those folks who wouldn’t otherwise undergo screening or don’t want an invasive test,” said Dr. Kupets. It can also play an increasing role, while current access to primary care services in Canada is at an all-time low. Community outreach through centers, mobile coaches, and nursing stations might help ensure participation by at-risk populations. These measures also could boost follow-up for and education about positive results, said Dr. Kupets.

In a related editorial, Shannon Charlebois, MD, medical editor of CMAJ, and Sarah Kean, MD, assistant professor of gynecologic oncology at the University of Manitoba in Winnipeg, Manitoba, Canada, emphasized the need for mailed HPV self-screening kits to be paid for and integrated into provincial cervical cancer screening programs across Canada to support earlier cervical cancer detection and lower invasive cancer rates.

Dr. Pataky concurred. “There have been discussions about making the big transition from traditional cytology to implementing HPV self-screening,” she said. “We have really effective tools for preventing cervical cancer, and it’s important to not lose sight of that goal.”

The study was funded by the National Institutes of Health. Dr. Pataky and Dr. Kupets reported no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

Two decades after the landmark Women’s Health Initiative (WHI) changed the way clinicians thought about hormone therapy and cancer, new findings suggest this national health study is "the gift that keeps on giving."

Follow-up from two of the WHI’s randomized trials have found that estrogen alone in women with prior hysterectomy significantly increased ovarian cancer incidence and mortality in postmenopausal women. Estrogen and progesterone together, meanwhile, did not increase ovarian cancer risk, and significantly reduced the risk of endometrial cancer. Rowan T. Chlebowski, MD, PhD, of The Lundquist Institute in Torrance, California, presented these results from the latest WHI findings, at the annual meeting of the American Society of Clinical Oncology in Chicago.

Dr. Chlebowski and his colleagues conducted an analysis from two randomized, placebo-controlled trials, which between 1993 and 1998 enrolled nearly 28,000 postmenopausal women aged 50-79 years without prior cancer from 40 centers across the United States. (The full WHI effort involved a total cohort of 161,000 patients, and included an observational study and two other non-drug trials.)

In one of the hormone therapy trials, 17,000 women with a uterus at baseline were randomized to combined equine estrogen plus medroxyprogesterone acetate, or placebo. In the other trial, about 11,000 women with prior hysterectomy were randomized to daily estrogen alone or placebo. Both trials were stopped early: the estrogen-only trial due to an increased stroke risk, and the combined therapy trial due to findings of increased breast cancer and cardiovascular risk.

Mean exposure to hormone therapy was 5.6 years for the combined therapy trial and 7.2 years for estrogen alone trial.
 

Ovarian Cancer Incidence Doubles with Estrogen

At 20 years’ follow up, with mortality information available for nearly the full cohort, Dr. Chlebowski and his colleagues could determine that ovarian cancer incidence doubled among women who had taken estrogen alone (hazard ratio = 2.04; 95% CI 1.14-3.65; P = .01), a difference that reached statistical significance at 12 years’ follow up. Ovarian cancer mortality was also significantly increased (HR = 2.79 95% CI 1.30-5.99, P = .006). Absolute numbers were small, however, with 35 cases of ovarian cancer compared with 17 in the placebo group.

Combined therapy recipients saw no increased risk for ovarian cancer and significantly lower endometrial cancer incidence (106 cases vs. 140 HR = 0.72; 95% CI, 0.56-0.92; P = .01).

Conjugated equine estrogen, Dr. Chlebowski said during his presentation at the meeting, “was introduced in US clinical practice in 1943 and used for over half a century, yet the question about hormone therapy’s influence on endometrial and ovarian cancer remains unsettled. Endometrial cancer and ovarian cancer are the fourth and fifth leading causes of cancer deaths in women ... and there’s some discordant findings from observational studies.”

Care of Ovarian Cancer Survivors Should Change

The new findings should prompt practice and guideline changes regarding the use of estrogen alone in ovarian cancer survivors, Dr. Chlebowski said.

In an interview, oncologist Eleonora Teplinsky, MD, of Valley-Mount Sinai Comprehensive Cancer Care in Paramus, New Jersey, said that apart from this subgroup of ovarian cancer survivors, the findings would not likely have much impact on how clinicians and patients approach hormone replacement therapy today.

“Twenty years ago the Women’s Health Initiative showed that hormone replacement therapy increases breast cancer risk, and everyone stopped taking HRT. And now people pushing back on it and saying wait a second – it was the estrogen plus progesterone that increased breast cancer, not estrogen alone. And now we’ve got these newer [estrogen] formulations.

“Yes, there’s a little bit of an increased risk [for ovarian cancer]. Patients should be aware. They should know the symptoms of ovarian cancer. But if they have indications and have been recommended HRT, this is not something that we would advise them against because of this very slightly increased risk,” Dr. Teplinsky said.

Oncologist Allison Kurian, MD of Stanford University in Stanford, California, who specializes in breast cancer, also noted that the duration of hormone treatment, treatment timing relative to age of menopause onset, and commonly used estrogen preparations had indeed changed since the time the WHI trials were conducted, making it harder to generalize the findings to current practice. Nonetheless, she argued, they still have real significance.

“WHI is an incredibly complex but also incredibly valuable resource,” said Dr. Kurian, who has conducted studies using WHI data. “The first big results came out in 2002, and we’re still learning from it. These are randomized trials, which offer the strongest form of scientific evidence that exists. So whenever we see results from this study, we have to take note of them,” she said.

Because the WHI trials had shown combined therapy, not estrogen alone, to be associated with breast cancer risk, clinicians have felt reassured over the years about using estrogen alone.

“You can’t give it to a person unless they have their uterus removed, because we know it will cause uterine cancer if the uterus is in place. But if the uterus is removed, the feeling was that you can give estrogen alone. I think the new piece that is going to get everyone’s attention is this signal for ovarian cancer.”

Something else the new findings show, Dr. Kurian said, is that WHI is “the gift that keeps on giving,” even after decades. “Some of the participants had a relatively short-term exposure to HRT. They took a medication for just a little while. But you didn’t see the effects until you followed people 12 years. So we’re now going to be a little more worried about ovarian cancer in this setting than we used to be. And that’s going to be something we’re all going to keep an eye on and think twice about in terms of talking to patients.”

These results help demonstrate what happens when a society invests in science on a national scale, Dr. Kurian said. “Here we have a really long-term, incredibly informative study that keeps generating knowledge to help women.”

When the WHI began, it “really was the first time that people decided it was important to systematically study women at midlife. It was a remarkable thing then that society got mobilized to do this, and we’re still seeing the benefits.”

Dr. Chlebowski disclosed receiving consulting or advisory fees from Pfizer. Dr. Teplinsky and Dr. Kurian disclosed no financial conflicts of interest.

Two decades after the landmark Women’s Health Initiative (WHI) changed the way clinicians thought about hormone therapy and cancer, new findings suggest this national health study is "the gift that keeps on giving."

Follow-up from two of the WHI’s randomized trials have found that estrogen alone in women with prior hysterectomy significantly increased ovarian cancer incidence and mortality in postmenopausal women. Estrogen and progesterone together, meanwhile, did not increase ovarian cancer risk, and significantly reduced the risk of endometrial cancer. Rowan T. Chlebowski, MD, PhD, of The Lundquist Institute in Torrance, California, presented these results from the latest WHI findings, at the annual meeting of the American Society of Clinical Oncology in Chicago.

Dr. Chlebowski and his colleagues conducted an analysis from two randomized, placebo-controlled trials, which between 1993 and 1998 enrolled nearly 28,000 postmenopausal women aged 50-79 years without prior cancer from 40 centers across the United States. (The full WHI effort involved a total cohort of 161,000 patients, and included an observational study and two other non-drug trials.)

In one of the hormone therapy trials, 17,000 women with a uterus at baseline were randomized to combined equine estrogen plus medroxyprogesterone acetate, or placebo. In the other trial, about 11,000 women with prior hysterectomy were randomized to daily estrogen alone or placebo. Both trials were stopped early: the estrogen-only trial due to an increased stroke risk, and the combined therapy trial due to findings of increased breast cancer and cardiovascular risk.

Mean exposure to hormone therapy was 5.6 years for the combined therapy trial and 7.2 years for estrogen alone trial.
 

Ovarian Cancer Incidence Doubles with Estrogen

At 20 years’ follow up, with mortality information available for nearly the full cohort, Dr. Chlebowski and his colleagues could determine that ovarian cancer incidence doubled among women who had taken estrogen alone (hazard ratio = 2.04; 95% CI 1.14-3.65; P = .01), a difference that reached statistical significance at 12 years’ follow up. Ovarian cancer mortality was also significantly increased (HR = 2.79 95% CI 1.30-5.99, P = .006). Absolute numbers were small, however, with 35 cases of ovarian cancer compared with 17 in the placebo group.

Combined therapy recipients saw no increased risk for ovarian cancer and significantly lower endometrial cancer incidence (106 cases vs. 140 HR = 0.72; 95% CI, 0.56-0.92; P = .01).

Conjugated equine estrogen, Dr. Chlebowski said during his presentation at the meeting, “was introduced in US clinical practice in 1943 and used for over half a century, yet the question about hormone therapy’s influence on endometrial and ovarian cancer remains unsettled. Endometrial cancer and ovarian cancer are the fourth and fifth leading causes of cancer deaths in women ... and there’s some discordant findings from observational studies.”

Care of Ovarian Cancer Survivors Should Change

The new findings should prompt practice and guideline changes regarding the use of estrogen alone in ovarian cancer survivors, Dr. Chlebowski said.

In an interview, oncologist Eleonora Teplinsky, MD, of Valley-Mount Sinai Comprehensive Cancer Care in Paramus, New Jersey, said that apart from this subgroup of ovarian cancer survivors, the findings would not likely have much impact on how clinicians and patients approach hormone replacement therapy today.

“Twenty years ago the Women’s Health Initiative showed that hormone replacement therapy increases breast cancer risk, and everyone stopped taking HRT. And now people pushing back on it and saying wait a second – it was the estrogen plus progesterone that increased breast cancer, not estrogen alone. And now we’ve got these newer [estrogen] formulations.

“Yes, there’s a little bit of an increased risk [for ovarian cancer]. Patients should be aware. They should know the symptoms of ovarian cancer. But if they have indications and have been recommended HRT, this is not something that we would advise them against because of this very slightly increased risk,” Dr. Teplinsky said.

Oncologist Allison Kurian, MD of Stanford University in Stanford, California, who specializes in breast cancer, also noted that the duration of hormone treatment, treatment timing relative to age of menopause onset, and commonly used estrogen preparations had indeed changed since the time the WHI trials were conducted, making it harder to generalize the findings to current practice. Nonetheless, she argued, they still have real significance.

“WHI is an incredibly complex but also incredibly valuable resource,” said Dr. Kurian, who has conducted studies using WHI data. “The first big results came out in 2002, and we’re still learning from it. These are randomized trials, which offer the strongest form of scientific evidence that exists. So whenever we see results from this study, we have to take note of them,” she said.

Because the WHI trials had shown combined therapy, not estrogen alone, to be associated with breast cancer risk, clinicians have felt reassured over the years about using estrogen alone.

“You can’t give it to a person unless they have their uterus removed, because we know it will cause uterine cancer if the uterus is in place. But if the uterus is removed, the feeling was that you can give estrogen alone. I think the new piece that is going to get everyone’s attention is this signal for ovarian cancer.”

Something else the new findings show, Dr. Kurian said, is that WHI is “the gift that keeps on giving,” even after decades. “Some of the participants had a relatively short-term exposure to HRT. They took a medication for just a little while. But you didn’t see the effects until you followed people 12 years. So we’re now going to be a little more worried about ovarian cancer in this setting than we used to be. And that’s going to be something we’re all going to keep an eye on and think twice about in terms of talking to patients.”

These results help demonstrate what happens when a society invests in science on a national scale, Dr. Kurian said. “Here we have a really long-term, incredibly informative study that keeps generating knowledge to help women.”

When the WHI began, it “really was the first time that people decided it was important to systematically study women at midlife. It was a remarkable thing then that society got mobilized to do this, and we’re still seeing the benefits.”

Dr. Chlebowski disclosed receiving consulting or advisory fees from Pfizer. Dr. Teplinsky and Dr. Kurian disclosed no financial conflicts of interest.

Two decades after the landmark Women’s Health Initiative (WHI) changed the way clinicians thought about hormone therapy and cancer, new findings suggest this national health study is "the gift that keeps on giving."

Follow-up from two of the WHI’s randomized trials have found that estrogen alone in women with prior hysterectomy significantly increased ovarian cancer incidence and mortality in postmenopausal women. Estrogen and progesterone together, meanwhile, did not increase ovarian cancer risk, and significantly reduced the risk of endometrial cancer. Rowan T. Chlebowski, MD, PhD, of The Lundquist Institute in Torrance, California, presented these results from the latest WHI findings, at the annual meeting of the American Society of Clinical Oncology in Chicago.

Dr. Chlebowski and his colleagues conducted an analysis from two randomized, placebo-controlled trials, which between 1993 and 1998 enrolled nearly 28,000 postmenopausal women aged 50-79 years without prior cancer from 40 centers across the United States. (The full WHI effort involved a total cohort of 161,000 patients, and included an observational study and two other non-drug trials.)

In one of the hormone therapy trials, 17,000 women with a uterus at baseline were randomized to combined equine estrogen plus medroxyprogesterone acetate, or placebo. In the other trial, about 11,000 women with prior hysterectomy were randomized to daily estrogen alone or placebo. Both trials were stopped early: the estrogen-only trial due to an increased stroke risk, and the combined therapy trial due to findings of increased breast cancer and cardiovascular risk.

Mean exposure to hormone therapy was 5.6 years for the combined therapy trial and 7.2 years for estrogen alone trial.
 

Ovarian Cancer Incidence Doubles with Estrogen

At 20 years’ follow up, with mortality information available for nearly the full cohort, Dr. Chlebowski and his colleagues could determine that ovarian cancer incidence doubled among women who had taken estrogen alone (hazard ratio = 2.04; 95% CI 1.14-3.65; P = .01), a difference that reached statistical significance at 12 years’ follow up. Ovarian cancer mortality was also significantly increased (HR = 2.79 95% CI 1.30-5.99, P = .006). Absolute numbers were small, however, with 35 cases of ovarian cancer compared with 17 in the placebo group.

Combined therapy recipients saw no increased risk for ovarian cancer and significantly lower endometrial cancer incidence (106 cases vs. 140 HR = 0.72; 95% CI, 0.56-0.92; P = .01).

Conjugated equine estrogen, Dr. Chlebowski said during his presentation at the meeting, “was introduced in US clinical practice in 1943 and used for over half a century, yet the question about hormone therapy’s influence on endometrial and ovarian cancer remains unsettled. Endometrial cancer and ovarian cancer are the fourth and fifth leading causes of cancer deaths in women ... and there’s some discordant findings from observational studies.”

Care of Ovarian Cancer Survivors Should Change

The new findings should prompt practice and guideline changes regarding the use of estrogen alone in ovarian cancer survivors, Dr. Chlebowski said.

In an interview, oncologist Eleonora Teplinsky, MD, of Valley-Mount Sinai Comprehensive Cancer Care in Paramus, New Jersey, said that apart from this subgroup of ovarian cancer survivors, the findings would not likely have much impact on how clinicians and patients approach hormone replacement therapy today.

“Twenty years ago the Women’s Health Initiative showed that hormone replacement therapy increases breast cancer risk, and everyone stopped taking HRT. And now people pushing back on it and saying wait a second – it was the estrogen plus progesterone that increased breast cancer, not estrogen alone. And now we’ve got these newer [estrogen] formulations.

“Yes, there’s a little bit of an increased risk [for ovarian cancer]. Patients should be aware. They should know the symptoms of ovarian cancer. But if they have indications and have been recommended HRT, this is not something that we would advise them against because of this very slightly increased risk,” Dr. Teplinsky said.

Oncologist Allison Kurian, MD of Stanford University in Stanford, California, who specializes in breast cancer, also noted that the duration of hormone treatment, treatment timing relative to age of menopause onset, and commonly used estrogen preparations had indeed changed since the time the WHI trials were conducted, making it harder to generalize the findings to current practice. Nonetheless, she argued, they still have real significance.

“WHI is an incredibly complex but also incredibly valuable resource,” said Dr. Kurian, who has conducted studies using WHI data. “The first big results came out in 2002, and we’re still learning from it. These are randomized trials, which offer the strongest form of scientific evidence that exists. So whenever we see results from this study, we have to take note of them,” she said.

Because the WHI trials had shown combined therapy, not estrogen alone, to be associated with breast cancer risk, clinicians have felt reassured over the years about using estrogen alone.

“You can’t give it to a person unless they have their uterus removed, because we know it will cause uterine cancer if the uterus is in place. But if the uterus is removed, the feeling was that you can give estrogen alone. I think the new piece that is going to get everyone’s attention is this signal for ovarian cancer.”

Something else the new findings show, Dr. Kurian said, is that WHI is “the gift that keeps on giving,” even after decades. “Some of the participants had a relatively short-term exposure to HRT. They took a medication for just a little while. But you didn’t see the effects until you followed people 12 years. So we’re now going to be a little more worried about ovarian cancer in this setting than we used to be. And that’s going to be something we’re all going to keep an eye on and think twice about in terms of talking to patients.”

These results help demonstrate what happens when a society invests in science on a national scale, Dr. Kurian said. “Here we have a really long-term, incredibly informative study that keeps generating knowledge to help women.”

When the WHI began, it “really was the first time that people decided it was important to systematically study women at midlife. It was a remarkable thing then that society got mobilized to do this, and we’re still seeing the benefits.”

Dr. Chlebowski disclosed receiving consulting or advisory fees from Pfizer. Dr. Teplinsky and Dr. Kurian disclosed no financial conflicts of interest.

Vaccination against human papillomavirus (HPV) is an effective way to prevent HPV infection and cancers typically caused by HPV, including cervical cancer and head and neck cancers, new research showed.

The analysis, featured at a press briefing ahead of the presentation at the American Society of Clinical Oncology (ASCO) 2024 annual meeting, notably found that men who received the HPV vaccine had a 56% lower risk for head and neck cancers.

“We’ve known for a long time that having the HPV vaccine can prevent the development of HPV infection, yes, but importantly, cancer,” primarily cervical cancer, said briefing moderator and ASCO president Lynn Schuchter, MD, Abramson Cancer Center, University of Pennsylvania, Philadelphia. “This is a really important study that extends the information about the impact.”

Using the US TriNetX database, lead investigator Jefferson DeKloe, BS, a research fellow with Thomas Jefferson University, Philadelphia, and colleagues created a matched cohort of 760,540 HPV-vaccinated and unvaccinated men and 945,999 HPV-vaccinated and unvaccinated women.

HPV-vaccinated men had a 54% lower risk for all HPV-related cancers (odds ratio [OR], 0.46; P < .001) and a 56% lower risk for head and neck cancers (OR, 0.44; P < .001) than unvaccinated men. There were not enough cases of anal and penile cancers for analysis.

HPV-vaccinated women had a 27% lower risk for all HPV-related cancers (OR, 0.73; P < .05), a 54% lower risk for cervical cancer (OR, 0.46; P < .05), and a 33% lower risk for head and neck cancers (OR, 0.67; 95% CI, 0.42-1.08) than HPV-unvaccinated women, but this finding was not significant. There were not enough cases of anal cancers for analysis, and the odds of developing vulvar or vaginal cancer was not significantly different in HPV-vaccinated vs unvaccinated women.

Vaccinated women, however, were less likely than unvaccinated women to develop high-grade squamous intraepithelial lesions (OR, 0.44), cervical carcinoma in situ (OR, 0.42), or abnormal Pap findings (OR, 0.87), and were less likely to undergo cone biopsy and loop electrosurgical excision (OR, 0.45).

“This study really highlights the importance of getting the HPV vaccine,” Dr. Schuchter said at the briefing.

“HPV vaccination is cancer prevention,” Glenn Hanna, MD, with Dana-Farber Cancer Institute, Boston, said in an ASCO statement.

Still, HPV vaccination rates in the United States remain relatively low. According to the National Cancer Institute, in 2022, only about 58% of adolescents aged 13-15 years had received two or three doses of HPV vaccine as recommended.

“The goal,” Dr. Schuchter said at the briefing, “is that younger girls and young boys get vaccinated to prevent development of HPV infection, and that should decrease the risk of cancer, which is what we’ve seen.”

Mr. DeKloe agreed and highlighted the importance of improving vaccination rates. “Identifying effective interventions that increase HPV vaccination rates is critical in reducing undue cancer burden in the United States,” Mr. DeKloe said in a statement.

The study had no funding source. Mr. DeKloe had no relevant disclosures. Dr. Hanna has disclosed relationships with Bicara Therapeutics, Bristol Myers Squibb, Coherus BioSciences, and others. Dr. Schuchter had no relevant disclosures.

A version of this article appeared on Medscape.com .

Vaccination against human papillomavirus (HPV) is an effective way to prevent HPV infection and cancers typically caused by HPV, including cervical cancer and head and neck cancers, new research showed.

The analysis, featured at a press briefing ahead of the presentation at the American Society of Clinical Oncology (ASCO) 2024 annual meeting, notably found that men who received the HPV vaccine had a 56% lower risk for head and neck cancers.

“We’ve known for a long time that having the HPV vaccine can prevent the development of HPV infection, yes, but importantly, cancer,” primarily cervical cancer, said briefing moderator and ASCO president Lynn Schuchter, MD, Abramson Cancer Center, University of Pennsylvania, Philadelphia. “This is a really important study that extends the information about the impact.”

Using the US TriNetX database, lead investigator Jefferson DeKloe, BS, a research fellow with Thomas Jefferson University, Philadelphia, and colleagues created a matched cohort of 760,540 HPV-vaccinated and unvaccinated men and 945,999 HPV-vaccinated and unvaccinated women.

HPV-vaccinated men had a 54% lower risk for all HPV-related cancers (odds ratio [OR], 0.46; P < .001) and a 56% lower risk for head and neck cancers (OR, 0.44; P < .001) than unvaccinated men. There were not enough cases of anal and penile cancers for analysis.

HPV-vaccinated women had a 27% lower risk for all HPV-related cancers (OR, 0.73; P < .05), a 54% lower risk for cervical cancer (OR, 0.46; P < .05), and a 33% lower risk for head and neck cancers (OR, 0.67; 95% CI, 0.42-1.08) than HPV-unvaccinated women, but this finding was not significant. There were not enough cases of anal cancers for analysis, and the odds of developing vulvar or vaginal cancer was not significantly different in HPV-vaccinated vs unvaccinated women.

Vaccinated women, however, were less likely than unvaccinated women to develop high-grade squamous intraepithelial lesions (OR, 0.44), cervical carcinoma in situ (OR, 0.42), or abnormal Pap findings (OR, 0.87), and were less likely to undergo cone biopsy and loop electrosurgical excision (OR, 0.45).

“This study really highlights the importance of getting the HPV vaccine,” Dr. Schuchter said at the briefing.

“HPV vaccination is cancer prevention,” Glenn Hanna, MD, with Dana-Farber Cancer Institute, Boston, said in an ASCO statement.

Still, HPV vaccination rates in the United States remain relatively low. According to the National Cancer Institute, in 2022, only about 58% of adolescents aged 13-15 years had received two or three doses of HPV vaccine as recommended.

“The goal,” Dr. Schuchter said at the briefing, “is that younger girls and young boys get vaccinated to prevent development of HPV infection, and that should decrease the risk of cancer, which is what we’ve seen.”

Mr. DeKloe agreed and highlighted the importance of improving vaccination rates. “Identifying effective interventions that increase HPV vaccination rates is critical in reducing undue cancer burden in the United States,” Mr. DeKloe said in a statement.

The study had no funding source. Mr. DeKloe had no relevant disclosures. Dr. Hanna has disclosed relationships with Bicara Therapeutics, Bristol Myers Squibb, Coherus BioSciences, and others. Dr. Schuchter had no relevant disclosures.

A version of this article appeared on Medscape.com .

Vaccination against human papillomavirus (HPV) is an effective way to prevent HPV infection and cancers typically caused by HPV, including cervical cancer and head and neck cancers, new research showed.

The analysis, featured at a press briefing ahead of the presentation at the American Society of Clinical Oncology (ASCO) 2024 annual meeting, notably found that men who received the HPV vaccine had a 56% lower risk for head and neck cancers.

“We’ve known for a long time that having the HPV vaccine can prevent the development of HPV infection, yes, but importantly, cancer,” primarily cervical cancer, said briefing moderator and ASCO president Lynn Schuchter, MD, Abramson Cancer Center, University of Pennsylvania, Philadelphia. “This is a really important study that extends the information about the impact.”

Using the US TriNetX database, lead investigator Jefferson DeKloe, BS, a research fellow with Thomas Jefferson University, Philadelphia, and colleagues created a matched cohort of 760,540 HPV-vaccinated and unvaccinated men and 945,999 HPV-vaccinated and unvaccinated women.

HPV-vaccinated men had a 54% lower risk for all HPV-related cancers (odds ratio [OR], 0.46; P < .001) and a 56% lower risk for head and neck cancers (OR, 0.44; P < .001) than unvaccinated men. There were not enough cases of anal and penile cancers for analysis.

HPV-vaccinated women had a 27% lower risk for all HPV-related cancers (OR, 0.73; P < .05), a 54% lower risk for cervical cancer (OR, 0.46; P < .05), and a 33% lower risk for head and neck cancers (OR, 0.67; 95% CI, 0.42-1.08) than HPV-unvaccinated women, but this finding was not significant. There were not enough cases of anal cancers for analysis, and the odds of developing vulvar or vaginal cancer was not significantly different in HPV-vaccinated vs unvaccinated women.

Vaccinated women, however, were less likely than unvaccinated women to develop high-grade squamous intraepithelial lesions (OR, 0.44), cervical carcinoma in situ (OR, 0.42), or abnormal Pap findings (OR, 0.87), and were less likely to undergo cone biopsy and loop electrosurgical excision (OR, 0.45).

“This study really highlights the importance of getting the HPV vaccine,” Dr. Schuchter said at the briefing.

“HPV vaccination is cancer prevention,” Glenn Hanna, MD, with Dana-Farber Cancer Institute, Boston, said in an ASCO statement.

Still, HPV vaccination rates in the United States remain relatively low. According to the National Cancer Institute, in 2022, only about 58% of adolescents aged 13-15 years had received two or three doses of HPV vaccine as recommended.

“The goal,” Dr. Schuchter said at the briefing, “is that younger girls and young boys get vaccinated to prevent development of HPV infection, and that should decrease the risk of cancer, which is what we’ve seen.”

Mr. DeKloe agreed and highlighted the importance of improving vaccination rates. “Identifying effective interventions that increase HPV vaccination rates is critical in reducing undue cancer burden in the United States,” Mr. DeKloe said in a statement.

The study had no funding source. Mr. DeKloe had no relevant disclosures. Dr. Hanna has disclosed relationships with Bicara Therapeutics, Bristol Myers Squibb, Coherus BioSciences, and others. Dr. Schuchter had no relevant disclosures.

A version of this article appeared on Medscape.com .

TOPLINE:

Vaginal estrogen therapy does not increase the risk for recurrence in women with hormone receptor (HR)–negative breast cancer or in those with HR–positive tumors concurrently treated with tamoxifen but should be avoided in aromatase inhibitor users, a French study suggested.

METHODOLOGY:

• Survivors of breast cancer often experience genitourinary symptoms due to declining estrogen levels. Vaginal estrogen therapies, including estriol and promestriene (3-propyl ethyl, 17B-methyl estradiol), can prevent these symptoms, but the effect on breast cancer outcomes remains uncertain.
• Researchers used French insurance claims data to emulate a target trial assessing the effect of initiating vaginal estrogen therapy — any molecule, promestriene, or estriol — on disease-free survival in survivors of breast cancer.
• Patients included in the study had a median age of 54 years; 85% were HR-positive, and 15% were HR–negative. The researchers conducted subgroup analyses based on HR status and endocrine therapy regimen.

TAKEAWAY:

• Among 134,942 unique patients, 1739 started vaginal estrogen therapy — 56%, promestriene; 34%, estriol; and 10%, both. 
• Initiation of vaginal estrogen therapy led to a modest decrease in disease-free survival in patients with HR–positive tumors (−2.1 percentage point at 5 years), particularly in those concurrently treated with an aromatase inhibitor (−3.0 percentage points).
• No decrease in disease-free survival was observed in patients with HR–negative tumors or in those treated with tamoxifen.
• In aromatase inhibitor users, starting estriol led to a “more severe and premature” decrease in disease-free survival (−4.2 percentage point after 3 years) compared with initiating promestriene (1.0 percentage point difference at 3 years).

IN PRACTICE:

“This study addresses a very important survivorship issue — sexual dysfunction in cancer patients — which is associated with anxiety and depression and should be considered a crucial component of survivorship care,” said study discussant Matteo Lambertini, MD, PhD, with University of Genova, Genova, Italy.

Our results suggest that using vaginal estrogen therapy “is safe in individuals with HR-negative tumors and in those concurrently treated with tamoxifen,” said study presenter Elise Dumas, PhD, with Institut Curie, Paris, France. For breast cancer survivors treated with aromatase inhibitors, vaginal estrogen therapy should be avoided as much as possible, but promestriene is preferred over estriol in this subgroup of patients.

SOURCE:

The research (Abstract 268MO) was presented at the European Society for Medical Oncology Breast Cancer 2024 Annual Congress on May 17, 2024.

LIMITATIONS:

No limitations were discussed in the presentation.

DISCLOSURES:

Funding was provided by Monoprix and the French National Cancer Institute. Dumas declared no conflicts of interest. Lambertini has financial relationships with various pharmaceutical companies including Roche, Novartis, AstraZeneca, Lilly, Exact Sciences, Pfizer, and others.

A version of this article first appeared on Medscape.com.

TOPLINE:

Vaginal estrogen therapy does not increase the risk for recurrence in women with hormone receptor (HR)–negative breast cancer or in those with HR–positive tumors concurrently treated with tamoxifen but should be avoided in aromatase inhibitor users, a French study suggested.

METHODOLOGY:

• Survivors of breast cancer often experience genitourinary symptoms due to declining estrogen levels. Vaginal estrogen therapies, including estriol and promestriene (3-propyl ethyl, 17B-methyl estradiol), can prevent these symptoms, but the effect on breast cancer outcomes remains uncertain.
• Researchers used French insurance claims data to emulate a target trial assessing the effect of initiating vaginal estrogen therapy — any molecule, promestriene, or estriol — on disease-free survival in survivors of breast cancer.
• Patients included in the study had a median age of 54 years; 85% were HR-positive, and 15% were HR–negative. The researchers conducted subgroup analyses based on HR status and endocrine therapy regimen.

TAKEAWAY:

• Among 134,942 unique patients, 1739 started vaginal estrogen therapy — 56%, promestriene; 34%, estriol; and 10%, both. 
• Initiation of vaginal estrogen therapy led to a modest decrease in disease-free survival in patients with HR–positive tumors (−2.1 percentage point at 5 years), particularly in those concurrently treated with an aromatase inhibitor (−3.0 percentage points).
• No decrease in disease-free survival was observed in patients with HR–negative tumors or in those treated with tamoxifen.
• In aromatase inhibitor users, starting estriol led to a “more severe and premature” decrease in disease-free survival (−4.2 percentage point after 3 years) compared with initiating promestriene (1.0 percentage point difference at 3 years).

IN PRACTICE:

“This study addresses a very important survivorship issue — sexual dysfunction in cancer patients — which is associated with anxiety and depression and should be considered a crucial component of survivorship care,” said study discussant Matteo Lambertini, MD, PhD, with University of Genova, Genova, Italy.

Our results suggest that using vaginal estrogen therapy “is safe in individuals with HR-negative tumors and in those concurrently treated with tamoxifen,” said study presenter Elise Dumas, PhD, with Institut Curie, Paris, France. For breast cancer survivors treated with aromatase inhibitors, vaginal estrogen therapy should be avoided as much as possible, but promestriene is preferred over estriol in this subgroup of patients.

SOURCE:

The research (Abstract 268MO) was presented at the European Society for Medical Oncology Breast Cancer 2024 Annual Congress on May 17, 2024.

LIMITATIONS:

No limitations were discussed in the presentation.

DISCLOSURES:

Funding was provided by Monoprix and the French National Cancer Institute. Dumas declared no conflicts of interest. Lambertini has financial relationships with various pharmaceutical companies including Roche, Novartis, AstraZeneca, Lilly, Exact Sciences, Pfizer, and others.

A version of this article first appeared on Medscape.com.

TOPLINE:

Vaginal estrogen therapy does not increase the risk for recurrence in women with hormone receptor (HR)–negative breast cancer or in those with HR–positive tumors concurrently treated with tamoxifen but should be avoided in aromatase inhibitor users, a French study suggested.

METHODOLOGY:

• Survivors of breast cancer often experience genitourinary symptoms due to declining estrogen levels. Vaginal estrogen therapies, including estriol and promestriene (3-propyl ethyl, 17B-methyl estradiol), can prevent these symptoms, but the effect on breast cancer outcomes remains uncertain.
• Researchers used French insurance claims data to emulate a target trial assessing the effect of initiating vaginal estrogen therapy — any molecule, promestriene, or estriol — on disease-free survival in survivors of breast cancer.
• Patients included in the study had a median age of 54 years; 85% were HR-positive, and 15% were HR–negative. The researchers conducted subgroup analyses based on HR status and endocrine therapy regimen.

TAKEAWAY:

• Among 134,942 unique patients, 1739 started vaginal estrogen therapy — 56%, promestriene; 34%, estriol; and 10%, both. 
• Initiation of vaginal estrogen therapy led to a modest decrease in disease-free survival in patients with HR–positive tumors (−2.1 percentage point at 5 years), particularly in those concurrently treated with an aromatase inhibitor (−3.0 percentage points).
• No decrease in disease-free survival was observed in patients with HR–negative tumors or in those treated with tamoxifen.
• In aromatase inhibitor users, starting estriol led to a “more severe and premature” decrease in disease-free survival (−4.2 percentage point after 3 years) compared with initiating promestriene (1.0 percentage point difference at 3 years).

IN PRACTICE:

“This study addresses a very important survivorship issue — sexual dysfunction in cancer patients — which is associated with anxiety and depression and should be considered a crucial component of survivorship care,” said study discussant Matteo Lambertini, MD, PhD, with University of Genova, Genova, Italy.

Our results suggest that using vaginal estrogen therapy “is safe in individuals with HR-negative tumors and in those concurrently treated with tamoxifen,” said study presenter Elise Dumas, PhD, with Institut Curie, Paris, France. For breast cancer survivors treated with aromatase inhibitors, vaginal estrogen therapy should be avoided as much as possible, but promestriene is preferred over estriol in this subgroup of patients.

SOURCE:

The research (Abstract 268MO) was presented at the European Society for Medical Oncology Breast Cancer 2024 Annual Congress on May 17, 2024.

LIMITATIONS:

No limitations were discussed in the presentation.

DISCLOSURES:

Funding was provided by Monoprix and the French National Cancer Institute. Dumas declared no conflicts of interest. Lambertini has financial relationships with various pharmaceutical companies including Roche, Novartis, AstraZeneca, Lilly, Exact Sciences, Pfizer, and others.

A version of this article first appeared on Medscape.com.

SAN FRANCISCO — An estimated two out of five adult women in the United States have obesity, and given the potential challenges of losing pregnancy weight postpartum or staving off the weight gain associated with menopause, women are likely to be receptive toward weight management help from their ob.gyns. A whole new armamentarium of anti-obesity medications has become available in the past decade, providing physicians and patients with more treatment options.

Ob.gyns. are therefore well-poised to offer counseling and treatment for obesity management for their patients, Johanna G. Finkle, MD, clinical assistant professor of obstetrics and gynecology and a weight management specialist at the University of Kansas Heath System, told attendees at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. Dr. Finkle provided an extensive overview of what ob.gyns. need to know if they are interested in prescribing anti-obesity medications or simply providing their patients with information about the available drugs.

Kitila S. Heyward, MD, an ob.gyn. at Atrium Health in Monroe, North Carolina, who attended the talk, tries to prescribe anti-obesity medications but has run into roadblocks that Dr. Finkle’s talk helped her understand how to overcome.

“I thought it was very helpful because [I] and one of my midwives, in practice, have been trying to get things prescribed, and we can’t figure out the loopholes,” Dr. Heyward said. “Also, the failure rates are really helpful to us so that we know how to counsel people.”

Even for clinicians who aren’t prescribing these medications, Dr. Heyward said the talk was illuminating. “It offered a better understanding of the medications that your patients are on and how it can affect things like birth control, management of surgery, pregnancy, and things along those lines from a clinical day-by-day standpoint,” she said.
 

Starting With the Basics

Dr. Finkle began by emphasizing the importance of using patient-first language in discussing obesity, which means using terms such as “weight, excess weight, overweight, body mass index,” and “affected by obesity” instead of “obese, morbidly obese, heaviness, or large.” She also cited the Obesity Medicine Association’s definition of obesity: “a chronic, relapsing and treatable multifactorial, neurobehavioral disease, wherein an increase in body fat promotes adipose tissue dysfunction and abnormal fat mass physical forces, resulting in adverse metabolic, biomechanical, and psychosocial health consequences.”

Though Dr. Finkle acknowledged the limitations of relying on BMI for defining obesity, it remains the standard tool in current practice, with a BMI of 25-29.9 defining overweight and a BMI of 30 or greater defining obesity. Other diagnostic criteria for obesity in women, however, include a percentage body fat over 32% or a waist circumference of more than 35 inches.

“Women are at risk for weight gain through their entire lifespan” Dr. Finkle said, and in women with polycystic ovarian syndrome, 60%-80% have pre-obesity or obesity. In menopause, the triple threat of decreased estrogen, decreased activity, and changes in diet all contribute to obesity risk and no evidence suggests that hormone therapy can prevent weight gain.

Healthy nutrition, physical activity, and behavioral modification remain key pillars of weight management, but interventions such as surgery or medications are also important tools, she said.

“One size does not fit all in terms of treatment,” Dr. Finkle said. ”When I talk to a patient, I think about other medical complications that I can treat with these medications.”

Women for whom anti-obesity medications may be indicated are those with a BMI of 30 or greater, and those with a BMI of at least 27 along with at least one obesity-related comorbidity, such as hypertension, high cholesterol, diabetes, or sleep apnea. The goal of treating obesity with medication is at least a 5%-10% reduction of body weight.
 

Three Pharmacotherapy Categories

Dr. Finkle reviewed three basic categories of anti-obesity medications: Food and Drug Administration–approved short-term and long-term medications and then off-label drugs that can also aid in healthy weight loss. Short-term options include phentermine, diethylpropion, phendimetrazine, and benzphetamine. Long-term options include orlistat, phentermine/topiramate ER, naltrexone HCl/bupropion HCl ER, and the three GLP-1 receptor agonist drugs, liraglutide, semaglutide, and tirzepatide.

The short-term medications are stimulants that increase satiety, but adverse effects can include tachycardia, hypertension, insomnia, dry mouth, constipation, and diarrhea.

These medications are contraindicated for anyone with uncontrolled hypertension, hyperthyroidism, cardiovascular disease, MAOI use, glaucoma, or history of substance use. The goal is a 5% weight loss in 3 months, and 3 months is the maximum prescribing term.

Then Dr. Finkle reviewed the side effects and contraindications for the oral long-term medications. Orlistat, which can aid in up to 5% weight loss, can result in oily stools and fecal incontinence and is contraindicated for people with chronic malabsorption or cholestasis.

Phentermine/topiramate ER, which can aid in up to 10% weight loss, can result in hypertension, paresthesia, or constipation, and is contraindicated for those with glaucoma, hyperthyroidism, and kidney stones. After the starting dose of 3.75 mg/23 mg, Dr. Finkle increases patients’ dose every 2 weeks, ”but if they’re not tolerating it, if they’re having significant side effects, or they’re losing weight, you do not increase the medication.”

Side effects of naltrexone HCl/bupropion HCl ER, which can lead to 5%-6% weight loss, can include hypertension, suicidal ideation, and glaucoma, and it’s contraindicated in those taking opioids or with a history of seizures or anorexia.
 

The GLP-1 Receptor Agonists

Next Dr. Finkle discussed the newest but most effective medications, the GLP-1 agonists liraglutide, semaglutide, and tirzepatide. The main contraindications for these drugs are a personal or family history of medullary thyroid cancer, multiple endocrine neoplasia type II syndrome, or any hypersensitivity to this drug class. The two main serious risks are pancreatitis — a 1% risk — and gallstones. Though Dr. Finkle included suicidal ideation as a potential risk of these drugs, the most recent evidence suggests there is no link between suicidal ideation and GLP-1 agonists. The most common side effects are nausea, vomiting, diarrhea, constipation, dyspepsia, and an increased heart rate, though these eventually resolve.

“We always start low with these medications,” Dr. Finkle said, and then titrate the dose up each week, “but if they are having awful side effects, just stay on that dose longer.”

The mechanisms of all three drugs for treating obesity are similar; they work to curb central satiety and slow gastric emptying, though they also have additional mechanisms with benefits for blood glucose levels and for the liver and heart.

• Liraglutide, the first of these drugs approved, is a daily subcutaneous injection that starts at a dose of 0.6 mg and goes up to 3 mg. Patients should lose 4% of weight in 16 weeks or else they are non-responders, Dr. Finkle said.
• Semaglutide, a GLP-1 agonist given as a weekly subcutaneous injection, starts at a dose of 0.25 mg and goes up to 2.4 mg; patients should expect a 5% weight loss in 16 weeks if they are responders. Long term, however, patients lose up to an average 15% of body weight with semaglutide; a third of patients lost more than 20% of body weight in clinical trials, compared with 7%-8% body weight loss with liraglutide. An additional benefit of semaglutide is a 20% reduction in risk of cardiovascular disease.
• Tirzepatide is a combined GLP-1 and GIP agonist, also delivered as a weekly subcutaneous injection, that should result in an estimated 5% weight loss in 16 weeks for responders. But tirzepatide is the most effective of the three, with 91% of patients losing at least 5% body weight and more than half of patients (56%) losing at least 20%.

The big drawbacks to the GLP-1 agonists, however, are their high cost, common lack of insurance coverage, and continued shortages. Dr. Finkle recommended using manufacturer coupons, comparison shopping on Good Rx, and appealing prior authorization requirements to help patients pay for the GLP-1 agonists.

“Drug availability is my second problem. There’s not enough drug,” she said, and her patients often have to call around to different pharmacies to find out which ones are carrying the drug and at what doses. She will sometimes switch their doses as needed based on availability.

It’s also important for physicians to be aware of guidance from the American Society of Anesthesiologists regarding GLP-1 agonist use prior to surgery because of their slowed gastric-emptying mechanism. To reduce the risk of aspiration, patients undergoing general anesthesia should not take liraglutide on the day of surgery, and semaglutide and tirzepatide should be held for 1 week prior to the procedure. New research in JAMA Surgery, however, suggests holding these medications for longer than a week may be wiser.
 

Getting Patients Started

All the short-term and long-term medications are contraindicated during pregnancy and breastfeeding, Dr. Finkle said. Animal studies with GLP-1 agonists suggest adverse fetal effects when used during pregnancy, but the limited data in human studies so far have not shown a risk of major malformations. Dr. Finkle said the recommendations for now are to stop all GLP-1 receptor agonist drugs 2 months before patients attempt to become pregnant and not to begin them again until after they are no longer breastfeeding.

Finally, Dr. Finkle reviewed off-label medications that can result in modest weight loss, including topiramate, phentermine (not to be used for longer than 12 weeks), bupropion, naltrexone, and metformin. Metformin is likely to result in only 2% weight loss, but it may enhance the effects of GLP-1s, she said.

For ob.gyns. who want to get their patients started on one of these medications, Dr. Finkle first recommends asking patients if it’s okay to discuss their weight. ”Studies show that if you just ask permission to discuss someone’s weight, they go on to lose weight and lose more than someone who has never been asked,” Dr. Finkle said. Then she takes a history.

”When I see a patient, I ask, ‘Tell me why you’re here today,’ ” Dr. Finkle said.

This gives me a lot of insight as to why they’re coming in and it helps me understand where they’re at in terms of other things, such as depression or anxiety with weight, and it helps me to tailor my treatment.”

A full medical history is important for learning about potential contraindications or picking medications that might help with other conditions, such as topiramate for migraines. Finally, Dr. Finkle advises a lab screening with a comprehensive metabolic panel, lipid panel, HbA1c, and vitamin D.

“The [comprehensive metabolic panel] allows me to know about creatinine and liver function,” she said. If these are elevated, she will still prescribe GLP-1s but will monitor the values more closely. “Then I discuss options with the patient. They may be eligible for bariatric surgery or medications. We talk about lifestyle behavioral management, and then I go through the medications and we set goals.”

Goals include nutrition and exercise; start modest and have them work their way up by doing activities they enjoy. In addition, patients taking GLP-1s need to eat enough protein — 80 to 100 grams a day, though she starts them at 60 grams — and do regular muscle strengthening since they can lose muscle mass.

Indications for referral to an obesity medicine specialist are a history of gastric bypass/sleeve surgery, having type 2 diabetes, having an eating disorder, or having failed one of these anti-obesity medications.

Finally, Dr. Finkle reviewed medications that can cause weight gain: medroxyprogesterone acetate for birth control; beta blockers for hypertension or migraine; the antidepressants amitriptyline, paroxetine, venlafaxine, and trazodone; the mood stabilizers gabapentin, lithium, valproate, and carbamazepine; and diphenhydramine and zolpidem for sleep.

No external funding was used for the talk. Dr. Finkle and Dr. Heyward had no disclosures.

SAN FRANCISCO — An estimated two out of five adult women in the United States have obesity, and given the potential challenges of losing pregnancy weight postpartum or staving off the weight gain associated with menopause, women are likely to be receptive toward weight management help from their ob.gyns. A whole new armamentarium of anti-obesity medications has become available in the past decade, providing physicians and patients with more treatment options.

Ob.gyns. are therefore well-poised to offer counseling and treatment for obesity management for their patients, Johanna G. Finkle, MD, clinical assistant professor of obstetrics and gynecology and a weight management specialist at the University of Kansas Heath System, told attendees at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. Dr. Finkle provided an extensive overview of what ob.gyns. need to know if they are interested in prescribing anti-obesity medications or simply providing their patients with information about the available drugs.

Kitila S. Heyward, MD, an ob.gyn. at Atrium Health in Monroe, North Carolina, who attended the talk, tries to prescribe anti-obesity medications but has run into roadblocks that Dr. Finkle’s talk helped her understand how to overcome.

“I thought it was very helpful because [I] and one of my midwives, in practice, have been trying to get things prescribed, and we can’t figure out the loopholes,” Dr. Heyward said. “Also, the failure rates are really helpful to us so that we know how to counsel people.”

Even for clinicians who aren’t prescribing these medications, Dr. Heyward said the talk was illuminating. “It offered a better understanding of the medications that your patients are on and how it can affect things like birth control, management of surgery, pregnancy, and things along those lines from a clinical day-by-day standpoint,” she said.
 

Starting With the Basics

Dr. Finkle began by emphasizing the importance of using patient-first language in discussing obesity, which means using terms such as “weight, excess weight, overweight, body mass index,” and “affected by obesity” instead of “obese, morbidly obese, heaviness, or large.” She also cited the Obesity Medicine Association’s definition of obesity: “a chronic, relapsing and treatable multifactorial, neurobehavioral disease, wherein an increase in body fat promotes adipose tissue dysfunction and abnormal fat mass physical forces, resulting in adverse metabolic, biomechanical, and psychosocial health consequences.”

Though Dr. Finkle acknowledged the limitations of relying on BMI for defining obesity, it remains the standard tool in current practice, with a BMI of 25-29.9 defining overweight and a BMI of 30 or greater defining obesity. Other diagnostic criteria for obesity in women, however, include a percentage body fat over 32% or a waist circumference of more than 35 inches.

“Women are at risk for weight gain through their entire lifespan” Dr. Finkle said, and in women with polycystic ovarian syndrome, 60%-80% have pre-obesity or obesity. In menopause, the triple threat of decreased estrogen, decreased activity, and changes in diet all contribute to obesity risk and no evidence suggests that hormone therapy can prevent weight gain.

Healthy nutrition, physical activity, and behavioral modification remain key pillars of weight management, but interventions such as surgery or medications are also important tools, she said.

“One size does not fit all in terms of treatment,” Dr. Finkle said. ”When I talk to a patient, I think about other medical complications that I can treat with these medications.”

Women for whom anti-obesity medications may be indicated are those with a BMI of 30 or greater, and those with a BMI of at least 27 along with at least one obesity-related comorbidity, such as hypertension, high cholesterol, diabetes, or sleep apnea. The goal of treating obesity with medication is at least a 5%-10% reduction of body weight.
 

Three Pharmacotherapy Categories

Dr. Finkle reviewed three basic categories of anti-obesity medications: Food and Drug Administration–approved short-term and long-term medications and then off-label drugs that can also aid in healthy weight loss. Short-term options include phentermine, diethylpropion, phendimetrazine, and benzphetamine. Long-term options include orlistat, phentermine/topiramate ER, naltrexone HCl/bupropion HCl ER, and the three GLP-1 receptor agonist drugs, liraglutide, semaglutide, and tirzepatide.

The short-term medications are stimulants that increase satiety, but adverse effects can include tachycardia, hypertension, insomnia, dry mouth, constipation, and diarrhea.

These medications are contraindicated for anyone with uncontrolled hypertension, hyperthyroidism, cardiovascular disease, MAOI use, glaucoma, or history of substance use. The goal is a 5% weight loss in 3 months, and 3 months is the maximum prescribing term.

Then Dr. Finkle reviewed the side effects and contraindications for the oral long-term medications. Orlistat, which can aid in up to 5% weight loss, can result in oily stools and fecal incontinence and is contraindicated for people with chronic malabsorption or cholestasis.

Phentermine/topiramate ER, which can aid in up to 10% weight loss, can result in hypertension, paresthesia, or constipation, and is contraindicated for those with glaucoma, hyperthyroidism, and kidney stones. After the starting dose of 3.75 mg/23 mg, Dr. Finkle increases patients’ dose every 2 weeks, ”but if they’re not tolerating it, if they’re having significant side effects, or they’re losing weight, you do not increase the medication.”

Side effects of naltrexone HCl/bupropion HCl ER, which can lead to 5%-6% weight loss, can include hypertension, suicidal ideation, and glaucoma, and it’s contraindicated in those taking opioids or with a history of seizures or anorexia.
 

The GLP-1 Receptor Agonists

Next Dr. Finkle discussed the newest but most effective medications, the GLP-1 agonists liraglutide, semaglutide, and tirzepatide. The main contraindications for these drugs are a personal or family history of medullary thyroid cancer, multiple endocrine neoplasia type II syndrome, or any hypersensitivity to this drug class. The two main serious risks are pancreatitis — a 1% risk — and gallstones. Though Dr. Finkle included suicidal ideation as a potential risk of these drugs, the most recent evidence suggests there is no link between suicidal ideation and GLP-1 agonists. The most common side effects are nausea, vomiting, diarrhea, constipation, dyspepsia, and an increased heart rate, though these eventually resolve.

“We always start low with these medications,” Dr. Finkle said, and then titrate the dose up each week, “but if they are having awful side effects, just stay on that dose longer.”

The mechanisms of all three drugs for treating obesity are similar; they work to curb central satiety and slow gastric emptying, though they also have additional mechanisms with benefits for blood glucose levels and for the liver and heart.

• Liraglutide, the first of these drugs approved, is a daily subcutaneous injection that starts at a dose of 0.6 mg and goes up to 3 mg. Patients should lose 4% of weight in 16 weeks or else they are non-responders, Dr. Finkle said.
• Semaglutide, a GLP-1 agonist given as a weekly subcutaneous injection, starts at a dose of 0.25 mg and goes up to 2.4 mg; patients should expect a 5% weight loss in 16 weeks if they are responders. Long term, however, patients lose up to an average 15% of body weight with semaglutide; a third of patients lost more than 20% of body weight in clinical trials, compared with 7%-8% body weight loss with liraglutide. An additional benefit of semaglutide is a 20% reduction in risk of cardiovascular disease.
• Tirzepatide is a combined GLP-1 and GIP agonist, also delivered as a weekly subcutaneous injection, that should result in an estimated 5% weight loss in 16 weeks for responders. But tirzepatide is the most effective of the three, with 91% of patients losing at least 5% body weight and more than half of patients (56%) losing at least 20%.

The big drawbacks to the GLP-1 agonists, however, are their high cost, common lack of insurance coverage, and continued shortages. Dr. Finkle recommended using manufacturer coupons, comparison shopping on Good Rx, and appealing prior authorization requirements to help patients pay for the GLP-1 agonists.

“Drug availability is my second problem. There’s not enough drug,” she said, and her patients often have to call around to different pharmacies to find out which ones are carrying the drug and at what doses. She will sometimes switch their doses as needed based on availability.

It’s also important for physicians to be aware of guidance from the American Society of Anesthesiologists regarding GLP-1 agonist use prior to surgery because of their slowed gastric-emptying mechanism. To reduce the risk of aspiration, patients undergoing general anesthesia should not take liraglutide on the day of surgery, and semaglutide and tirzepatide should be held for 1 week prior to the procedure. New research in JAMA Surgery, however, suggests holding these medications for longer than a week may be wiser.
 

Getting Patients Started

All the short-term and long-term medications are contraindicated during pregnancy and breastfeeding, Dr. Finkle said. Animal studies with GLP-1 agonists suggest adverse fetal effects when used during pregnancy, but the limited data in human studies so far have not shown a risk of major malformations. Dr. Finkle said the recommendations for now are to stop all GLP-1 receptor agonist drugs 2 months before patients attempt to become pregnant and not to begin them again until after they are no longer breastfeeding.

Finally, Dr. Finkle reviewed off-label medications that can result in modest weight loss, including topiramate, phentermine (not to be used for longer than 12 weeks), bupropion, naltrexone, and metformin. Metformin is likely to result in only 2% weight loss, but it may enhance the effects of GLP-1s, she said.

For ob.gyns. who want to get their patients started on one of these medications, Dr. Finkle first recommends asking patients if it’s okay to discuss their weight. ”Studies show that if you just ask permission to discuss someone’s weight, they go on to lose weight and lose more than someone who has never been asked,” Dr. Finkle said. Then she takes a history.

”When I see a patient, I ask, ‘Tell me why you’re here today,’ ” Dr. Finkle said.

This gives me a lot of insight as to why they’re coming in and it helps me understand where they’re at in terms of other things, such as depression or anxiety with weight, and it helps me to tailor my treatment.”

A full medical history is important for learning about potential contraindications or picking medications that might help with other conditions, such as topiramate for migraines. Finally, Dr. Finkle advises a lab screening with a comprehensive metabolic panel, lipid panel, HbA1c, and vitamin D.

“The [comprehensive metabolic panel] allows me to know about creatinine and liver function,” she said. If these are elevated, she will still prescribe GLP-1s but will monitor the values more closely. “Then I discuss options with the patient. They may be eligible for bariatric surgery or medications. We talk about lifestyle behavioral management, and then I go through the medications and we set goals.”

Goals include nutrition and exercise; start modest and have them work their way up by doing activities they enjoy. In addition, patients taking GLP-1s need to eat enough protein — 80 to 100 grams a day, though she starts them at 60 grams — and do regular muscle strengthening since they can lose muscle mass.

Indications for referral to an obesity medicine specialist are a history of gastric bypass/sleeve surgery, having type 2 diabetes, having an eating disorder, or having failed one of these anti-obesity medications.

Finally, Dr. Finkle reviewed medications that can cause weight gain: medroxyprogesterone acetate for birth control; beta blockers for hypertension or migraine; the antidepressants amitriptyline, paroxetine, venlafaxine, and trazodone; the mood stabilizers gabapentin, lithium, valproate, and carbamazepine; and diphenhydramine and zolpidem for sleep.

No external funding was used for the talk. Dr. Finkle and Dr. Heyward had no disclosures.

SAN FRANCISCO — An estimated two out of five adult women in the United States have obesity, and given the potential challenges of losing pregnancy weight postpartum or staving off the weight gain associated with menopause, women are likely to be receptive toward weight management help from their ob.gyns. A whole new armamentarium of anti-obesity medications has become available in the past decade, providing physicians and patients with more treatment options.

Ob.gyns. are therefore well-poised to offer counseling and treatment for obesity management for their patients, Johanna G. Finkle, MD, clinical assistant professor of obstetrics and gynecology and a weight management specialist at the University of Kansas Heath System, told attendees at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. Dr. Finkle provided an extensive overview of what ob.gyns. need to know if they are interested in prescribing anti-obesity medications or simply providing their patients with information about the available drugs.

Kitila S. Heyward, MD, an ob.gyn. at Atrium Health in Monroe, North Carolina, who attended the talk, tries to prescribe anti-obesity medications but has run into roadblocks that Dr. Finkle’s talk helped her understand how to overcome.

“I thought it was very helpful because [I] and one of my midwives, in practice, have been trying to get things prescribed, and we can’t figure out the loopholes,” Dr. Heyward said. “Also, the failure rates are really helpful to us so that we know how to counsel people.”

Even for clinicians who aren’t prescribing these medications, Dr. Heyward said the talk was illuminating. “It offered a better understanding of the medications that your patients are on and how it can affect things like birth control, management of surgery, pregnancy, and things along those lines from a clinical day-by-day standpoint,” she said.
 

Starting With the Basics

Dr. Finkle began by emphasizing the importance of using patient-first language in discussing obesity, which means using terms such as “weight, excess weight, overweight, body mass index,” and “affected by obesity” instead of “obese, morbidly obese, heaviness, or large.” She also cited the Obesity Medicine Association’s definition of obesity: “a chronic, relapsing and treatable multifactorial, neurobehavioral disease, wherein an increase in body fat promotes adipose tissue dysfunction and abnormal fat mass physical forces, resulting in adverse metabolic, biomechanical, and psychosocial health consequences.”

Though Dr. Finkle acknowledged the limitations of relying on BMI for defining obesity, it remains the standard tool in current practice, with a BMI of 25-29.9 defining overweight and a BMI of 30 or greater defining obesity. Other diagnostic criteria for obesity in women, however, include a percentage body fat over 32% or a waist circumference of more than 35 inches.

“Women are at risk for weight gain through their entire lifespan” Dr. Finkle said, and in women with polycystic ovarian syndrome, 60%-80% have pre-obesity or obesity. In menopause, the triple threat of decreased estrogen, decreased activity, and changes in diet all contribute to obesity risk and no evidence suggests that hormone therapy can prevent weight gain.

Healthy nutrition, physical activity, and behavioral modification remain key pillars of weight management, but interventions such as surgery or medications are also important tools, she said.

“One size does not fit all in terms of treatment,” Dr. Finkle said. ”When I talk to a patient, I think about other medical complications that I can treat with these medications.”

Women for whom anti-obesity medications may be indicated are those with a BMI of 30 or greater, and those with a BMI of at least 27 along with at least one obesity-related comorbidity, such as hypertension, high cholesterol, diabetes, or sleep apnea. The goal of treating obesity with medication is at least a 5%-10% reduction of body weight.
 

Three Pharmacotherapy Categories

Dr. Finkle reviewed three basic categories of anti-obesity medications: Food and Drug Administration–approved short-term and long-term medications and then off-label drugs that can also aid in healthy weight loss. Short-term options include phentermine, diethylpropion, phendimetrazine, and benzphetamine. Long-term options include orlistat, phentermine/topiramate ER, naltrexone HCl/bupropion HCl ER, and the three GLP-1 receptor agonist drugs, liraglutide, semaglutide, and tirzepatide.

The short-term medications are stimulants that increase satiety, but adverse effects can include tachycardia, hypertension, insomnia, dry mouth, constipation, and diarrhea.

These medications are contraindicated for anyone with uncontrolled hypertension, hyperthyroidism, cardiovascular disease, MAOI use, glaucoma, or history of substance use. The goal is a 5% weight loss in 3 months, and 3 months is the maximum prescribing term.

Then Dr. Finkle reviewed the side effects and contraindications for the oral long-term medications. Orlistat, which can aid in up to 5% weight loss, can result in oily stools and fecal incontinence and is contraindicated for people with chronic malabsorption or cholestasis.

Phentermine/topiramate ER, which can aid in up to 10% weight loss, can result in hypertension, paresthesia, or constipation, and is contraindicated for those with glaucoma, hyperthyroidism, and kidney stones. After the starting dose of 3.75 mg/23 mg, Dr. Finkle increases patients’ dose every 2 weeks, ”but if they’re not tolerating it, if they’re having significant side effects, or they’re losing weight, you do not increase the medication.”

Side effects of naltrexone HCl/bupropion HCl ER, which can lead to 5%-6% weight loss, can include hypertension, suicidal ideation, and glaucoma, and it’s contraindicated in those taking opioids or with a history of seizures or anorexia.
 

The GLP-1 Receptor Agonists

Next Dr. Finkle discussed the newest but most effective medications, the GLP-1 agonists liraglutide, semaglutide, and tirzepatide. The main contraindications for these drugs are a personal or family history of medullary thyroid cancer, multiple endocrine neoplasia type II syndrome, or any hypersensitivity to this drug class. The two main serious risks are pancreatitis — a 1% risk — and gallstones. Though Dr. Finkle included suicidal ideation as a potential risk of these drugs, the most recent evidence suggests there is no link between suicidal ideation and GLP-1 agonists. The most common side effects are nausea, vomiting, diarrhea, constipation, dyspepsia, and an increased heart rate, though these eventually resolve.

“We always start low with these medications,” Dr. Finkle said, and then titrate the dose up each week, “but if they are having awful side effects, just stay on that dose longer.”

The mechanisms of all three drugs for treating obesity are similar; they work to curb central satiety and slow gastric emptying, though they also have additional mechanisms with benefits for blood glucose levels and for the liver and heart.

• Liraglutide, the first of these drugs approved, is a daily subcutaneous injection that starts at a dose of 0.6 mg and goes up to 3 mg. Patients should lose 4% of weight in 16 weeks or else they are non-responders, Dr. Finkle said.
• Semaglutide, a GLP-1 agonist given as a weekly subcutaneous injection, starts at a dose of 0.25 mg and goes up to 2.4 mg; patients should expect a 5% weight loss in 16 weeks if they are responders. Long term, however, patients lose up to an average 15% of body weight with semaglutide; a third of patients lost more than 20% of body weight in clinical trials, compared with 7%-8% body weight loss with liraglutide. An additional benefit of semaglutide is a 20% reduction in risk of cardiovascular disease.
• Tirzepatide is a combined GLP-1 and GIP agonist, also delivered as a weekly subcutaneous injection, that should result in an estimated 5% weight loss in 16 weeks for responders. But tirzepatide is the most effective of the three, with 91% of patients losing at least 5% body weight and more than half of patients (56%) losing at least 20%.

The big drawbacks to the GLP-1 agonists, however, are their high cost, common lack of insurance coverage, and continued shortages. Dr. Finkle recommended using manufacturer coupons, comparison shopping on Good Rx, and appealing prior authorization requirements to help patients pay for the GLP-1 agonists.

“Drug availability is my second problem. There’s not enough drug,” she said, and her patients often have to call around to different pharmacies to find out which ones are carrying the drug and at what doses. She will sometimes switch their doses as needed based on availability.

It’s also important for physicians to be aware of guidance from the American Society of Anesthesiologists regarding GLP-1 agonist use prior to surgery because of their slowed gastric-emptying mechanism. To reduce the risk of aspiration, patients undergoing general anesthesia should not take liraglutide on the day of surgery, and semaglutide and tirzepatide should be held for 1 week prior to the procedure. New research in JAMA Surgery, however, suggests holding these medications for longer than a week may be wiser.
 

Getting Patients Started

All the short-term and long-term medications are contraindicated during pregnancy and breastfeeding, Dr. Finkle said. Animal studies with GLP-1 agonists suggest adverse fetal effects when used during pregnancy, but the limited data in human studies so far have not shown a risk of major malformations. Dr. Finkle said the recommendations for now are to stop all GLP-1 receptor agonist drugs 2 months before patients attempt to become pregnant and not to begin them again until after they are no longer breastfeeding.

Finally, Dr. Finkle reviewed off-label medications that can result in modest weight loss, including topiramate, phentermine (not to be used for longer than 12 weeks), bupropion, naltrexone, and metformin. Metformin is likely to result in only 2% weight loss, but it may enhance the effects of GLP-1s, she said.

For ob.gyns. who want to get their patients started on one of these medications, Dr. Finkle first recommends asking patients if it’s okay to discuss their weight. ”Studies show that if you just ask permission to discuss someone’s weight, they go on to lose weight and lose more than someone who has never been asked,” Dr. Finkle said. Then she takes a history.

”When I see a patient, I ask, ‘Tell me why you’re here today,’ ” Dr. Finkle said.

This gives me a lot of insight as to why they’re coming in and it helps me understand where they’re at in terms of other things, such as depression or anxiety with weight, and it helps me to tailor my treatment.”

A full medical history is important for learning about potential contraindications or picking medications that might help with other conditions, such as topiramate for migraines. Finally, Dr. Finkle advises a lab screening with a comprehensive metabolic panel, lipid panel, HbA1c, and vitamin D.

“The [comprehensive metabolic panel] allows me to know about creatinine and liver function,” she said. If these are elevated, she will still prescribe GLP-1s but will monitor the values more closely. “Then I discuss options with the patient. They may be eligible for bariatric surgery or medications. We talk about lifestyle behavioral management, and then I go through the medications and we set goals.”

Goals include nutrition and exercise; start modest and have them work their way up by doing activities they enjoy. In addition, patients taking GLP-1s need to eat enough protein — 80 to 100 grams a day, though she starts them at 60 grams — and do regular muscle strengthening since they can lose muscle mass.

Indications for referral to an obesity medicine specialist are a history of gastric bypass/sleeve surgery, having type 2 diabetes, having an eating disorder, or having failed one of these anti-obesity medications.

Finally, Dr. Finkle reviewed medications that can cause weight gain: medroxyprogesterone acetate for birth control; beta blockers for hypertension or migraine; the antidepressants amitriptyline, paroxetine, venlafaxine, and trazodone; the mood stabilizers gabapentin, lithium, valproate, and carbamazepine; and diphenhydramine and zolpidem for sleep.

No external funding was used for the talk. Dr. Finkle and Dr. Heyward had no disclosures.

For breast cancer survivors harboring BRCA1/2 gene mutations, the prospect of future pregnancy often raises concerns because of limited data on the safety of assisted reproductive techniques (ART) in this population. However, results from a large international study presented at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress provide reassuring evidence that ART, such as in vitro fertilization, can be safely used by BRCA1/2 mutation carriers previously treated for breast cancer.

“Our primary aim was to evaluate the safety profile of ART in this high-risk population by comparing maternal and fetal outcomes between those who conceived spontaneously versus those using ART,” explained Matteo Lambertini, MD, PhD, during his talk at the conference. “We found no statistically significant differences in pregnancy complications or fetal abnormalities.” Dr. Lambertini is an associate professor and medical oncologist at the University of Genova and IRCCS Policlinico San Martino Hospital, Genova, Italy.
 

Unmet Fertility Needs for Women With Breast Cancer

With the rising rates of early-onset breast cancer and improved survival outcomes with new therapies, the number of long-term breast cancer survivors is increasing. Fertility preservation and future reproductive choices are important considerations for young patients with breast cancer, especially for high-risk patients carrying pathogenic BRCA1/2 mutations. During his talk, Dr. Lambertini explained that defects in DNA damage repair due to BRCA1/2 mutations, in addition to chemotherapy after breast cancer diagnosis, can lead to premature menopause.

According to Dr. Lambertini, physicians face challenges in counseling these patients regarding the potential risks and benefits of pursuing pregnancy after cancer treatment because of the limited evidence available on the safety of ART in BRCA1/2 mutation carriers.

“Clinicians have to counsel BRCA carriers based on very limited data about the safety of pursuing pregnancy with ART after a breast cancer diagnosis,” he said during his presentation.
 

Study Design and Patient Population

The retrospective cohort study pooled data from 78 centers worldwide to explore ART outcomes in BRCA1/2 mutation carriers. The analysis included 4732 women diagnosed with stage I-III breast cancer at age 40 years or younger, all harboring a pathogenic BRCA1 or BRCA2 variant.

Among these high-risk patients, 543 became pregnant after completing cancer treatment; of these, 436 conceived naturally and 107 used ART. In the ART group, 45.5% underwent oocyte or embryo cryopreservation at breast cancer diagnosis, 33.3% underwent ovarian stimulation for in vitro fertilization after cancer treatment, and 21.2% underwent embryo transfer following oocyte donation.

Dr. Janice Tsang, MD, a clinical oncology specialist and assistant professor at the University of Hong Kong who was not involved in this study, highlighted that this is the largest study focusing on ART safety in young patients with BRCA1/2 mutations. “With over 500 BRCA1/2 mutation carriers studied across nearly 80 sites, the cohort analysis had sufficient statistical power and global representation to detect potential safety signals with ART utilization, unlike prior smaller studies,” she said. Dr. Tsang, a clinical oncology specialist and assistant professor at the University of Hong Kong who was not involved in this study, served as a discussant, providing her expert opinion on the findings presented by Dr. Lambertini.
 

No Increased Risks for Pregnancy and Fetal Outcomes

Although women using ART had slightly higher miscarriage rates (11.3% versus 8.8%) and lower rates of induced abortion (0.9% versus 8.3%) than women with spontaneous conceptions, the analysis revealed no statistically significant differences in the frequency of pregnancy complications, delivery complications, or congenital abnormalities between those who received ART and those who conceived naturally.

Dr. Lambertini explained that variations in baseline characteristics, such as age, may have contributed to differences in miscarriage rates.

“Patients in the ART group tended to be older at the time of conception, with a median age of 37.1 years, compared with 34.3 years in the spontaneous pregnancy group,” he said, during his presentation. Women in the ART group also more frequently had hormone receptor–positive breast cancer (43.4% versus 30.8%) and longer median time from diagnosis to conception (4.2 versus 3.3 years).
 

No Adverse Effects on Breast Cancer Prognosis

At a median follow-up of 5.2 years from conception, there was no detrimental effect of ART on disease-free survival for carriers of pathogenic BRCA1/2 variants who were treated for breast cancer. The ART group showed 13 (13.1%) recurrence events, compared with 118 (27.1%) recurrences in the spontaneous pregnancy group (adjusted hazard ratio, 0.72; 95% CI, 0.38-1.33; P = .147).

“The risk of cancer recurrence was comparable between those using and not using ART to become pregnant after their breast cancer diagnosis and treatment, and the small number of recurrence events in the ART group mostly involved locoregional recurrences,” Dr. Lambertini noted during his talk.

Moreover, breast cancer–specific survival and overall survival appeared to be similar between the two groups, although the small number of deaths precluded the conduction of formal analysis.

“These survival data suggest that utilizing ART does not appear to negatively impact the prognosis or course of the underlying breast cancer,” Dr. Lambertini said during the discussion.
 

Clinical Implications and Future Work

According to Dr. Lambertini, these results are incredibly valuable for clinicians counseling young breast cancer survivors with pathogenic BRCA1/2 mutations who wish to have biological children.

“Given the interest of patients in having their own family and for some of them in avoiding the transmission of the BRCA1/2 pathogenic variants, our results are critical in improving the oncofertility counseling of young women with breast cancer,” said Dr. Lambertini during his presentation. “We can reassure patients that pursuing ART does not appear to worsen their cancer prognosis or compromise pregnancy outcomes compared to spontaneous conceptions.”

During her discussion session, Dr. Tsang echoed the clinical implications of these findings, emphasizing that, by incorporating this evidence into clinical practice, healthcare providers can better support patients in making informed choices regarding fertility preservation and family planning after cancer treatment.

“Though this study is [retrospective] with a relatively small number, these real-world findings make a major contribution to our limited evidence base on ART safety for cancer survivors carrying BRCA1/2 mutations,” she said.

She cautioned, however, that there remain several unanswered questions and uncertainties. “We need prospective data with a larger sample size to confirm the safety of ART in this population, as well as studies to assess whether different types of ART have different safety profiles.”

Dr. Lambertini concluded his talk by saying, “While waiting for prospective studies to confirm our results, fertility preservation at diagnosis of early breast cancer should be offered to all women interested in future fertility, including BRCA carriers.”

Dr. Lambertini reported financial relationships with Roche, AstraZeneca, Lilly, Novartis, Pfizer, Exact Sciences, MSD, Seagen, Gilead, Pierre Fabre, and Menarini (consulting or advisory roles); Takeda, Roche, Lilly, Novartis, Pfizer, AstraZeneca, Sandoz, Ipsen, Libbs, Knight, Dalichi Sankyo, Gilead, Menarini (honoraria); Gilead, Daiichi Sankyo, and Roche (travel support); and Gilead (research funding to the institution). Dr. Tsang reported financial relationships with AstraZeneca, Amgen, Daichi Sankyo, Eisai, Gilead, Lilly, Lucence, Novartis, Pfizer, and Veracyte (honoraria); De Novo (consulting or advisory roles); and Pfizer (grant panel reviewer).

For breast cancer survivors harboring BRCA1/2 gene mutations, the prospect of future pregnancy often raises concerns because of limited data on the safety of assisted reproductive techniques (ART) in this population. However, results from a large international study presented at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress provide reassuring evidence that ART, such as in vitro fertilization, can be safely used by BRCA1/2 mutation carriers previously treated for breast cancer.

“Our primary aim was to evaluate the safety profile of ART in this high-risk population by comparing maternal and fetal outcomes between those who conceived spontaneously versus those using ART,” explained Matteo Lambertini, MD, PhD, during his talk at the conference. “We found no statistically significant differences in pregnancy complications or fetal abnormalities.” Dr. Lambertini is an associate professor and medical oncologist at the University of Genova and IRCCS Policlinico San Martino Hospital, Genova, Italy.
 

Unmet Fertility Needs for Women With Breast Cancer

With the rising rates of early-onset breast cancer and improved survival outcomes with new therapies, the number of long-term breast cancer survivors is increasing. Fertility preservation and future reproductive choices are important considerations for young patients with breast cancer, especially for high-risk patients carrying pathogenic BRCA1/2 mutations. During his talk, Dr. Lambertini explained that defects in DNA damage repair due to BRCA1/2 mutations, in addition to chemotherapy after breast cancer diagnosis, can lead to premature menopause.

According to Dr. Lambertini, physicians face challenges in counseling these patients regarding the potential risks and benefits of pursuing pregnancy after cancer treatment because of the limited evidence available on the safety of ART in BRCA1/2 mutation carriers.

“Clinicians have to counsel BRCA carriers based on very limited data about the safety of pursuing pregnancy with ART after a breast cancer diagnosis,” he said during his presentation.
 

Study Design and Patient Population

The retrospective cohort study pooled data from 78 centers worldwide to explore ART outcomes in BRCA1/2 mutation carriers. The analysis included 4732 women diagnosed with stage I-III breast cancer at age 40 years or younger, all harboring a pathogenic BRCA1 or BRCA2 variant.

Among these high-risk patients, 543 became pregnant after completing cancer treatment; of these, 436 conceived naturally and 107 used ART. In the ART group, 45.5% underwent oocyte or embryo cryopreservation at breast cancer diagnosis, 33.3% underwent ovarian stimulation for in vitro fertilization after cancer treatment, and 21.2% underwent embryo transfer following oocyte donation.

Dr. Janice Tsang, MD, a clinical oncology specialist and assistant professor at the University of Hong Kong who was not involved in this study, highlighted that this is the largest study focusing on ART safety in young patients with BRCA1/2 mutations. “With over 500 BRCA1/2 mutation carriers studied across nearly 80 sites, the cohort analysis had sufficient statistical power and global representation to detect potential safety signals with ART utilization, unlike prior smaller studies,” she said. Dr. Tsang, a clinical oncology specialist and assistant professor at the University of Hong Kong who was not involved in this study, served as a discussant, providing her expert opinion on the findings presented by Dr. Lambertini.
 

No Increased Risks for Pregnancy and Fetal Outcomes

Although women using ART had slightly higher miscarriage rates (11.3% versus 8.8%) and lower rates of induced abortion (0.9% versus 8.3%) than women with spontaneous conceptions, the analysis revealed no statistically significant differences in the frequency of pregnancy complications, delivery complications, or congenital abnormalities between those who received ART and those who conceived naturally.

Dr. Lambertini explained that variations in baseline characteristics, such as age, may have contributed to differences in miscarriage rates.

“Patients in the ART group tended to be older at the time of conception, with a median age of 37.1 years, compared with 34.3 years in the spontaneous pregnancy group,” he said, during his presentation. Women in the ART group also more frequently had hormone receptor–positive breast cancer (43.4% versus 30.8%) and longer median time from diagnosis to conception (4.2 versus 3.3 years).
 

No Adverse Effects on Breast Cancer Prognosis

At a median follow-up of 5.2 years from conception, there was no detrimental effect of ART on disease-free survival for carriers of pathogenic BRCA1/2 variants who were treated for breast cancer. The ART group showed 13 (13.1%) recurrence events, compared with 118 (27.1%) recurrences in the spontaneous pregnancy group (adjusted hazard ratio, 0.72; 95% CI, 0.38-1.33; P = .147).

“The risk of cancer recurrence was comparable between those using and not using ART to become pregnant after their breast cancer diagnosis and treatment, and the small number of recurrence events in the ART group mostly involved locoregional recurrences,” Dr. Lambertini noted during his talk.

Moreover, breast cancer–specific survival and overall survival appeared to be similar between the two groups, although the small number of deaths precluded the conduction of formal analysis.

“These survival data suggest that utilizing ART does not appear to negatively impact the prognosis or course of the underlying breast cancer,” Dr. Lambertini said during the discussion.
 

Clinical Implications and Future Work

According to Dr. Lambertini, these results are incredibly valuable for clinicians counseling young breast cancer survivors with pathogenic BRCA1/2 mutations who wish to have biological children.

“Given the interest of patients in having their own family and for some of them in avoiding the transmission of the BRCA1/2 pathogenic variants, our results are critical in improving the oncofertility counseling of young women with breast cancer,” said Dr. Lambertini during his presentation. “We can reassure patients that pursuing ART does not appear to worsen their cancer prognosis or compromise pregnancy outcomes compared to spontaneous conceptions.”

During her discussion session, Dr. Tsang echoed the clinical implications of these findings, emphasizing that, by incorporating this evidence into clinical practice, healthcare providers can better support patients in making informed choices regarding fertility preservation and family planning after cancer treatment.

“Though this study is [retrospective] with a relatively small number, these real-world findings make a major contribution to our limited evidence base on ART safety for cancer survivors carrying BRCA1/2 mutations,” she said.

She cautioned, however, that there remain several unanswered questions and uncertainties. “We need prospective data with a larger sample size to confirm the safety of ART in this population, as well as studies to assess whether different types of ART have different safety profiles.”

Dr. Lambertini concluded his talk by saying, “While waiting for prospective studies to confirm our results, fertility preservation at diagnosis of early breast cancer should be offered to all women interested in future fertility, including BRCA carriers.”

Dr. Lambertini reported financial relationships with Roche, AstraZeneca, Lilly, Novartis, Pfizer, Exact Sciences, MSD, Seagen, Gilead, Pierre Fabre, and Menarini (consulting or advisory roles); Takeda, Roche, Lilly, Novartis, Pfizer, AstraZeneca, Sandoz, Ipsen, Libbs, Knight, Dalichi Sankyo, Gilead, Menarini (honoraria); Gilead, Daiichi Sankyo, and Roche (travel support); and Gilead (research funding to the institution). Dr. Tsang reported financial relationships with AstraZeneca, Amgen, Daichi Sankyo, Eisai, Gilead, Lilly, Lucence, Novartis, Pfizer, and Veracyte (honoraria); De Novo (consulting or advisory roles); and Pfizer (grant panel reviewer).

For breast cancer survivors harboring BRCA1/2 gene mutations, the prospect of future pregnancy often raises concerns because of limited data on the safety of assisted reproductive techniques (ART) in this population. However, results from a large international study presented at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress provide reassuring evidence that ART, such as in vitro fertilization, can be safely used by BRCA1/2 mutation carriers previously treated for breast cancer.

“Our primary aim was to evaluate the safety profile of ART in this high-risk population by comparing maternal and fetal outcomes between those who conceived spontaneously versus those using ART,” explained Matteo Lambertini, MD, PhD, during his talk at the conference. “We found no statistically significant differences in pregnancy complications or fetal abnormalities.” Dr. Lambertini is an associate professor and medical oncologist at the University of Genova and IRCCS Policlinico San Martino Hospital, Genova, Italy.
 

Unmet Fertility Needs for Women With Breast Cancer

With the rising rates of early-onset breast cancer and improved survival outcomes with new therapies, the number of long-term breast cancer survivors is increasing. Fertility preservation and future reproductive choices are important considerations for young patients with breast cancer, especially for high-risk patients carrying pathogenic BRCA1/2 mutations. During his talk, Dr. Lambertini explained that defects in DNA damage repair due to BRCA1/2 mutations, in addition to chemotherapy after breast cancer diagnosis, can lead to premature menopause.

According to Dr. Lambertini, physicians face challenges in counseling these patients regarding the potential risks and benefits of pursuing pregnancy after cancer treatment because of the limited evidence available on the safety of ART in BRCA1/2 mutation carriers.

“Clinicians have to counsel BRCA carriers based on very limited data about the safety of pursuing pregnancy with ART after a breast cancer diagnosis,” he said during his presentation.
 

Study Design and Patient Population

The retrospective cohort study pooled data from 78 centers worldwide to explore ART outcomes in BRCA1/2 mutation carriers. The analysis included 4732 women diagnosed with stage I-III breast cancer at age 40 years or younger, all harboring a pathogenic BRCA1 or BRCA2 variant.

Among these high-risk patients, 543 became pregnant after completing cancer treatment; of these, 436 conceived naturally and 107 used ART. In the ART group, 45.5% underwent oocyte or embryo cryopreservation at breast cancer diagnosis, 33.3% underwent ovarian stimulation for in vitro fertilization after cancer treatment, and 21.2% underwent embryo transfer following oocyte donation.

Dr. Janice Tsang, MD, a clinical oncology specialist and assistant professor at the University of Hong Kong who was not involved in this study, highlighted that this is the largest study focusing on ART safety in young patients with BRCA1/2 mutations. “With over 500 BRCA1/2 mutation carriers studied across nearly 80 sites, the cohort analysis had sufficient statistical power and global representation to detect potential safety signals with ART utilization, unlike prior smaller studies,” she said. Dr. Tsang, a clinical oncology specialist and assistant professor at the University of Hong Kong who was not involved in this study, served as a discussant, providing her expert opinion on the findings presented by Dr. Lambertini.
 

No Increased Risks for Pregnancy and Fetal Outcomes

Although women using ART had slightly higher miscarriage rates (11.3% versus 8.8%) and lower rates of induced abortion (0.9% versus 8.3%) than women with spontaneous conceptions, the analysis revealed no statistically significant differences in the frequency of pregnancy complications, delivery complications, or congenital abnormalities between those who received ART and those who conceived naturally.

Dr. Lambertini explained that variations in baseline characteristics, such as age, may have contributed to differences in miscarriage rates.

“Patients in the ART group tended to be older at the time of conception, with a median age of 37.1 years, compared with 34.3 years in the spontaneous pregnancy group,” he said, during his presentation. Women in the ART group also more frequently had hormone receptor–positive breast cancer (43.4% versus 30.8%) and longer median time from diagnosis to conception (4.2 versus 3.3 years).
 

No Adverse Effects on Breast Cancer Prognosis

At a median follow-up of 5.2 years from conception, there was no detrimental effect of ART on disease-free survival for carriers of pathogenic BRCA1/2 variants who were treated for breast cancer. The ART group showed 13 (13.1%) recurrence events, compared with 118 (27.1%) recurrences in the spontaneous pregnancy group (adjusted hazard ratio, 0.72; 95% CI, 0.38-1.33; P = .147).

“The risk of cancer recurrence was comparable between those using and not using ART to become pregnant after their breast cancer diagnosis and treatment, and the small number of recurrence events in the ART group mostly involved locoregional recurrences,” Dr. Lambertini noted during his talk.

Moreover, breast cancer–specific survival and overall survival appeared to be similar between the two groups, although the small number of deaths precluded the conduction of formal analysis.

“These survival data suggest that utilizing ART does not appear to negatively impact the prognosis or course of the underlying breast cancer,” Dr. Lambertini said during the discussion.
 

Clinical Implications and Future Work

According to Dr. Lambertini, these results are incredibly valuable for clinicians counseling young breast cancer survivors with pathogenic BRCA1/2 mutations who wish to have biological children.

“Given the interest of patients in having their own family and for some of them in avoiding the transmission of the BRCA1/2 pathogenic variants, our results are critical in improving the oncofertility counseling of young women with breast cancer,” said Dr. Lambertini during his presentation. “We can reassure patients that pursuing ART does not appear to worsen their cancer prognosis or compromise pregnancy outcomes compared to spontaneous conceptions.”

During her discussion session, Dr. Tsang echoed the clinical implications of these findings, emphasizing that, by incorporating this evidence into clinical practice, healthcare providers can better support patients in making informed choices regarding fertility preservation and family planning after cancer treatment.

“Though this study is [retrospective] with a relatively small number, these real-world findings make a major contribution to our limited evidence base on ART safety for cancer survivors carrying BRCA1/2 mutations,” she said.

She cautioned, however, that there remain several unanswered questions and uncertainties. “We need prospective data with a larger sample size to confirm the safety of ART in this population, as well as studies to assess whether different types of ART have different safety profiles.”

Dr. Lambertini concluded his talk by saying, “While waiting for prospective studies to confirm our results, fertility preservation at diagnosis of early breast cancer should be offered to all women interested in future fertility, including BRCA carriers.”

Dr. Lambertini reported financial relationships with Roche, AstraZeneca, Lilly, Novartis, Pfizer, Exact Sciences, MSD, Seagen, Gilead, Pierre Fabre, and Menarini (consulting or advisory roles); Takeda, Roche, Lilly, Novartis, Pfizer, AstraZeneca, Sandoz, Ipsen, Libbs, Knight, Dalichi Sankyo, Gilead, Menarini (honoraria); Gilead, Daiichi Sankyo, and Roche (travel support); and Gilead (research funding to the institution). Dr. Tsang reported financial relationships with AstraZeneca, Amgen, Daichi Sankyo, Eisai, Gilead, Lilly, Lucence, Novartis, Pfizer, and Veracyte (honoraria); De Novo (consulting or advisory roles); and Pfizer (grant panel reviewer).

Charles Powell, MD, said he sometimes has a hard time persuading patients to start on low-dose vaginal estrogen, which can help prevent urinary tract infections and ease other symptoms of menopause.

Many women fear taking these vaginal products because of what Dr. Powell considers excessively strong warnings about the risk for cancer and cardiovascular disease linked to daily estrogen pills that were issued in the early 2000s.

He is advocating for the US Food and Drug Administration (FDA) to remove the boxed warning on low-dose estrogen. His efforts are separate from his roles as an associate professor of urology at the Indiana University School of Medicine, and as a member of the American Urological Association (AUA), Dr. Powell said.

In his quest to find out how to change labeling, Dr. Powell has gained a quick education about drug regulation. He has enlisted Representative Jim Baird (R-IN) and Senator Mike Braun (R-IN) to contact the FDA on his behalf, while congressional staff guided him through the hurdles of getting the warning label changed. For instance, a manufacturer of low-dose estrogen may need to become involved.

“You don’t learn this in med school,” Dr. Powell said in an interview.

With this work, Dr. Powell is wading into a long-standing argument between the FDA and some clinicians and researchers about the potential harms of low-dose estrogen.

He is doing so at a time of increased interest in understanding genitourinary syndrome of menopause (GSM), a term coined a decade ago by the International Society for the Study of Women’s Sexual Health and the North American Menopause Society to cover “a constellation of conditions” related to urogenital atrophy.

Symptoms of GSM include vaginal dryness and burning and recurrent urinary tract infections.

The federal government in 2022 began a project budgeted with nearly $1 million to review evidence on treatments, including vaginal and low-dose estrogen. The aim is to eventually help the AUA develop clinical guidelines for addressing GSM.

In addition, a bipartisan Senate bill introduced in May calls for authorizing $125 million over 5 years for the National Institutes of Health (NIH) to fund research on menopause. Senator Patty Murray (D-WA), the lead sponsor of the bill, is a longtime advocate for women’s health and serves as chairwoman for the Senate Appropriations Committee, which largely sets the NIH budget.

“The bottom line is, for too long, menopause has been overlooked, underinvested in and left behind,” Sen. Murray said during a May 2 press conference. “It is well past time to stop treating menopause like some kind of secret and start treating it like the major mainstream public health issue it is.”

Evidence Demands

Increased federal funding for menopause research could help efforts to change the warning label on low-dose estrogen, according to JoAnn Manson, MD, chief of preventive medicine at Brigham and Women’s Hospital in Boston.

Dr. Manson was a leader of the Women’s Health Initiative (WHI), a major federally funded research project launched in 1991 to investigate if hormone therapy and diet could protect older women from chronic diseases related to aging.

Before the WHI, clinicians prescribed hormones to prevent cardiovascular disease, based on evidence from earlier research.

But in 2002, a WHI trial that compared estrogen-progestin tablets with placebo was halted early because of disturbing findings, including an association with higher risk for breast cancer and cardiovascular disease.

Compared with placebo, for every 10,000 women taking estrogen plus progestin annually, incidences of cardiovascular disease, stroke, pulmonary embolism, and invasive breast cancer were seven to eight times higher.

In January 2003, the FDA announced it would put a boxed warning about cardiovascular risk and cancer risk on estrogen products, reflecting the WHI finding.

The agency at the time said clinicians should work with patients to assess risks and benefits of these products to manage the effects of menopause.

But more news on the potential harms of estrogen followed in 2004: A WHI study comparing estrogen-only pills with placebo produced signals of a small increased risk for stroke, although it also indicated no excess risk for breast cancer for at least 6.8 years of use.

Dr. Manson and the North American Menopause Society in 2016 filed a petition with the FDA to remove the boxed warning that appears on the front of low-dose estrogen products. The group wanted the information on risks moved to the usual warning section of the label.

Two years later, the FDA rejected the petition, citing the absence of “well-controlled studies,” to prove low-dose topical estrogen poses less risk to women than the high-dose pills studied in the WHI.

The FDA told this news organization that it stands by the decisions in its rejection of the petition.

Persuading the FDA to revise the labels on low-dose estrogen products likely will require evidence from randomized, large-scale studies, Dr. Manson said. The agency has not been satisfied to date with findings from other kinds of studies, including observational research.

“Once that evidence is available that the benefit-risk profile is different for different formulations and the evidence is compelling and definitive, that warning should change,” Dr. Manson told this news organization.

But the warning continues to have a chilling effect on patient willingness to use low-dose vaginal estrogen, even with the FDA’s continued endorsement of estrogen for menopause symptoms, clinicians told this news organization.

Risa Kagan, MD, a gynecologist at Sutter Health in Berkeley, California, said in many cases her patients’ partners also need to be reassured. Dr. Kagan said she still sees women who have had to discontinue sexual intercourse because of pain. In some cases, the patients will bring the medicine home only to find that the warnings frighten their spouses.

“The spouse says, ‘Oh my God, I don’t want you to get dementia, to get breast cancer, it’s not worth it, so let’s keep doing outercourse’,” meaning sexual relations without penetration, Dr. Kagan said.

Difficult Messaging

From the initial unveiling of disappointing WHI results, clinicians and researchers have stressed that women could continue using estrogen products for managing symptoms of menopause, even while advising strongly against their continued use with the intention of preventing heart disease.

Newly published findings from follow-ups of WHI participants may give clinicians and patients even more confidence for the use of estrogen products in early menopause.

According to the study, which Dr. Manson coauthored, younger women have a low risk for cardiovascular disease and other associated conditions when taking hormone therapy. Risks attributed to these drugs were less than one additional adverse event per 1000 women annually. This population may also derive significant quality-of-life benefits for symptom relief.

Dr. Manson told this news organization that estrogen in lower doses and delivered through the skin as a patch or gel may further reduce risks.

“The WHI findings should never be used as a reason to deny hormone therapy to women in early menopause with bothersome menopausal symptoms,” Dr. Manson said. “Many women are good candidates for treatment and, in shared decision-making with their clinicians, should be able to receive appropriate and personalized healthcare for their needs.”

But the current FDA warning label makes it difficult to help women understand the risk and benefits of low-dose estrogen, according to Stephanie Faubion, MD, MBA, medical director at the North American Menopause Society and director of Mayo Clinic’s Center for Women’s Health in Jacksonville, Florida.

Clinicians now must set aside time to explain the warnings to women when they prescribe low-dose estrogen, Dr. Faubion said.

“The package insert is going to look scary: I prepare women for that because otherwise they often won’t even fill it or use it.”
 

A version of this article appeared on Medscape.com .

Charles Powell, MD, said he sometimes has a hard time persuading patients to start on low-dose vaginal estrogen, which can help prevent urinary tract infections and ease other symptoms of menopause.

Many women fear taking these vaginal products because of what Dr. Powell considers excessively strong warnings about the risk for cancer and cardiovascular disease linked to daily estrogen pills that were issued in the early 2000s.

He is advocating for the US Food and Drug Administration (FDA) to remove the boxed warning on low-dose estrogen. His efforts are separate from his roles as an associate professor of urology at the Indiana University School of Medicine, and as a member of the American Urological Association (AUA), Dr. Powell said.

In his quest to find out how to change labeling, Dr. Powell has gained a quick education about drug regulation. He has enlisted Representative Jim Baird (R-IN) and Senator Mike Braun (R-IN) to contact the FDA on his behalf, while congressional staff guided him through the hurdles of getting the warning label changed. For instance, a manufacturer of low-dose estrogen may need to become involved.

“You don’t learn this in med school,” Dr. Powell said in an interview.

With this work, Dr. Powell is wading into a long-standing argument between the FDA and some clinicians and researchers about the potential harms of low-dose estrogen.

He is doing so at a time of increased interest in understanding genitourinary syndrome of menopause (GSM), a term coined a decade ago by the International Society for the Study of Women’s Sexual Health and the North American Menopause Society to cover “a constellation of conditions” related to urogenital atrophy.

Symptoms of GSM include vaginal dryness and burning and recurrent urinary tract infections.

The federal government in 2022 began a project budgeted with nearly $1 million to review evidence on treatments, including vaginal and low-dose estrogen. The aim is to eventually help the AUA develop clinical guidelines for addressing GSM.

In addition, a bipartisan Senate bill introduced in May calls for authorizing $125 million over 5 years for the National Institutes of Health (NIH) to fund research on menopause. Senator Patty Murray (D-WA), the lead sponsor of the bill, is a longtime advocate for women’s health and serves as chairwoman for the Senate Appropriations Committee, which largely sets the NIH budget.

“The bottom line is, for too long, menopause has been overlooked, underinvested in and left behind,” Sen. Murray said during a May 2 press conference. “It is well past time to stop treating menopause like some kind of secret and start treating it like the major mainstream public health issue it is.”

Evidence Demands

Increased federal funding for menopause research could help efforts to change the warning label on low-dose estrogen, according to JoAnn Manson, MD, chief of preventive medicine at Brigham and Women’s Hospital in Boston.

Dr. Manson was a leader of the Women’s Health Initiative (WHI), a major federally funded research project launched in 1991 to investigate if hormone therapy and diet could protect older women from chronic diseases related to aging.

Before the WHI, clinicians prescribed hormones to prevent cardiovascular disease, based on evidence from earlier research.

But in 2002, a WHI trial that compared estrogen-progestin tablets with placebo was halted early because of disturbing findings, including an association with higher risk for breast cancer and cardiovascular disease.

Compared with placebo, for every 10,000 women taking estrogen plus progestin annually, incidences of cardiovascular disease, stroke, pulmonary embolism, and invasive breast cancer were seven to eight times higher.

In January 2003, the FDA announced it would put a boxed warning about cardiovascular risk and cancer risk on estrogen products, reflecting the WHI finding.

The agency at the time said clinicians should work with patients to assess risks and benefits of these products to manage the effects of menopause.

But more news on the potential harms of estrogen followed in 2004: A WHI study comparing estrogen-only pills with placebo produced signals of a small increased risk for stroke, although it also indicated no excess risk for breast cancer for at least 6.8 years of use.

Dr. Manson and the North American Menopause Society in 2016 filed a petition with the FDA to remove the boxed warning that appears on the front of low-dose estrogen products. The group wanted the information on risks moved to the usual warning section of the label.

Two years later, the FDA rejected the petition, citing the absence of “well-controlled studies,” to prove low-dose topical estrogen poses less risk to women than the high-dose pills studied in the WHI.

The FDA told this news organization that it stands by the decisions in its rejection of the petition.

Persuading the FDA to revise the labels on low-dose estrogen products likely will require evidence from randomized, large-scale studies, Dr. Manson said. The agency has not been satisfied to date with findings from other kinds of studies, including observational research.

“Once that evidence is available that the benefit-risk profile is different for different formulations and the evidence is compelling and definitive, that warning should change,” Dr. Manson told this news organization.

But the warning continues to have a chilling effect on patient willingness to use low-dose vaginal estrogen, even with the FDA’s continued endorsement of estrogen for menopause symptoms, clinicians told this news organization.

Risa Kagan, MD, a gynecologist at Sutter Health in Berkeley, California, said in many cases her patients’ partners also need to be reassured. Dr. Kagan said she still sees women who have had to discontinue sexual intercourse because of pain. In some cases, the patients will bring the medicine home only to find that the warnings frighten their spouses.

“The spouse says, ‘Oh my God, I don’t want you to get dementia, to get breast cancer, it’s not worth it, so let’s keep doing outercourse’,” meaning sexual relations without penetration, Dr. Kagan said.

Difficult Messaging

From the initial unveiling of disappointing WHI results, clinicians and researchers have stressed that women could continue using estrogen products for managing symptoms of menopause, even while advising strongly against their continued use with the intention of preventing heart disease.

Newly published findings from follow-ups of WHI participants may give clinicians and patients even more confidence for the use of estrogen products in early menopause.

According to the study, which Dr. Manson coauthored, younger women have a low risk for cardiovascular disease and other associated conditions when taking hormone therapy. Risks attributed to these drugs were less than one additional adverse event per 1000 women annually. This population may also derive significant quality-of-life benefits for symptom relief.

Dr. Manson told this news organization that estrogen in lower doses and delivered through the skin as a patch or gel may further reduce risks.

“The WHI findings should never be used as a reason to deny hormone therapy to women in early menopause with bothersome menopausal symptoms,” Dr. Manson said. “Many women are good candidates for treatment and, in shared decision-making with their clinicians, should be able to receive appropriate and personalized healthcare for their needs.”

But the current FDA warning label makes it difficult to help women understand the risk and benefits of low-dose estrogen, according to Stephanie Faubion, MD, MBA, medical director at the North American Menopause Society and director of Mayo Clinic’s Center for Women’s Health in Jacksonville, Florida.

Clinicians now must set aside time to explain the warnings to women when they prescribe low-dose estrogen, Dr. Faubion said.

“The package insert is going to look scary: I prepare women for that because otherwise they often won’t even fill it or use it.”
 

A version of this article appeared on Medscape.com .

Charles Powell, MD, said he sometimes has a hard time persuading patients to start on low-dose vaginal estrogen, which can help prevent urinary tract infections and ease other symptoms of menopause.

Many women fear taking these vaginal products because of what Dr. Powell considers excessively strong warnings about the risk for cancer and cardiovascular disease linked to daily estrogen pills that were issued in the early 2000s.

He is advocating for the US Food and Drug Administration (FDA) to remove the boxed warning on low-dose estrogen. His efforts are separate from his roles as an associate professor of urology at the Indiana University School of Medicine, and as a member of the American Urological Association (AUA), Dr. Powell said.

In his quest to find out how to change labeling, Dr. Powell has gained a quick education about drug regulation. He has enlisted Representative Jim Baird (R-IN) and Senator Mike Braun (R-IN) to contact the FDA on his behalf, while congressional staff guided him through the hurdles of getting the warning label changed. For instance, a manufacturer of low-dose estrogen may need to become involved.

“You don’t learn this in med school,” Dr. Powell said in an interview.

With this work, Dr. Powell is wading into a long-standing argument between the FDA and some clinicians and researchers about the potential harms of low-dose estrogen.

He is doing so at a time of increased interest in understanding genitourinary syndrome of menopause (GSM), a term coined a decade ago by the International Society for the Study of Women’s Sexual Health and the North American Menopause Society to cover “a constellation of conditions” related to urogenital atrophy.

Symptoms of GSM include vaginal dryness and burning and recurrent urinary tract infections.

The federal government in 2022 began a project budgeted with nearly $1 million to review evidence on treatments, including vaginal and low-dose estrogen. The aim is to eventually help the AUA develop clinical guidelines for addressing GSM.

In addition, a bipartisan Senate bill introduced in May calls for authorizing $125 million over 5 years for the National Institutes of Health (NIH) to fund research on menopause. Senator Patty Murray (D-WA), the lead sponsor of the bill, is a longtime advocate for women’s health and serves as chairwoman for the Senate Appropriations Committee, which largely sets the NIH budget.

“The bottom line is, for too long, menopause has been overlooked, underinvested in and left behind,” Sen. Murray said during a May 2 press conference. “It is well past time to stop treating menopause like some kind of secret and start treating it like the major mainstream public health issue it is.”

Evidence Demands

Increased federal funding for menopause research could help efforts to change the warning label on low-dose estrogen, according to JoAnn Manson, MD, chief of preventive medicine at Brigham and Women’s Hospital in Boston.

Dr. Manson was a leader of the Women’s Health Initiative (WHI), a major federally funded research project launched in 1991 to investigate if hormone therapy and diet could protect older women from chronic diseases related to aging.

Before the WHI, clinicians prescribed hormones to prevent cardiovascular disease, based on evidence from earlier research.

But in 2002, a WHI trial that compared estrogen-progestin tablets with placebo was halted early because of disturbing findings, including an association with higher risk for breast cancer and cardiovascular disease.

Compared with placebo, for every 10,000 women taking estrogen plus progestin annually, incidences of cardiovascular disease, stroke, pulmonary embolism, and invasive breast cancer were seven to eight times higher.

In January 2003, the FDA announced it would put a boxed warning about cardiovascular risk and cancer risk on estrogen products, reflecting the WHI finding.

The agency at the time said clinicians should work with patients to assess risks and benefits of these products to manage the effects of menopause.

But more news on the potential harms of estrogen followed in 2004: A WHI study comparing estrogen-only pills with placebo produced signals of a small increased risk for stroke, although it also indicated no excess risk for breast cancer for at least 6.8 years of use.

Dr. Manson and the North American Menopause Society in 2016 filed a petition with the FDA to remove the boxed warning that appears on the front of low-dose estrogen products. The group wanted the information on risks moved to the usual warning section of the label.

Two years later, the FDA rejected the petition, citing the absence of “well-controlled studies,” to prove low-dose topical estrogen poses less risk to women than the high-dose pills studied in the WHI.

The FDA told this news organization that it stands by the decisions in its rejection of the petition.

Persuading the FDA to revise the labels on low-dose estrogen products likely will require evidence from randomized, large-scale studies, Dr. Manson said. The agency has not been satisfied to date with findings from other kinds of studies, including observational research.

“Once that evidence is available that the benefit-risk profile is different for different formulations and the evidence is compelling and definitive, that warning should change,” Dr. Manson told this news organization.

But the warning continues to have a chilling effect on patient willingness to use low-dose vaginal estrogen, even with the FDA’s continued endorsement of estrogen for menopause symptoms, clinicians told this news organization.

Risa Kagan, MD, a gynecologist at Sutter Health in Berkeley, California, said in many cases her patients’ partners also need to be reassured. Dr. Kagan said she still sees women who have had to discontinue sexual intercourse because of pain. In some cases, the patients will bring the medicine home only to find that the warnings frighten their spouses.

“The spouse says, ‘Oh my God, I don’t want you to get dementia, to get breast cancer, it’s not worth it, so let’s keep doing outercourse’,” meaning sexual relations without penetration, Dr. Kagan said.

Difficult Messaging

From the initial unveiling of disappointing WHI results, clinicians and researchers have stressed that women could continue using estrogen products for managing symptoms of menopause, even while advising strongly against their continued use with the intention of preventing heart disease.

Newly published findings from follow-ups of WHI participants may give clinicians and patients even more confidence for the use of estrogen products in early menopause.

According to the study, which Dr. Manson coauthored, younger women have a low risk for cardiovascular disease and other associated conditions when taking hormone therapy. Risks attributed to these drugs were less than one additional adverse event per 1000 women annually. This population may also derive significant quality-of-life benefits for symptom relief.

Dr. Manson told this news organization that estrogen in lower doses and delivered through the skin as a patch or gel may further reduce risks.

“The WHI findings should never be used as a reason to deny hormone therapy to women in early menopause with bothersome menopausal symptoms,” Dr. Manson said. “Many women are good candidates for treatment and, in shared decision-making with their clinicians, should be able to receive appropriate and personalized healthcare for their needs.”

But the current FDA warning label makes it difficult to help women understand the risk and benefits of low-dose estrogen, according to Stephanie Faubion, MD, MBA, medical director at the North American Menopause Society and director of Mayo Clinic’s Center for Women’s Health in Jacksonville, Florida.

Clinicians now must set aside time to explain the warnings to women when they prescribe low-dose estrogen, Dr. Faubion said.

“The package insert is going to look scary: I prepare women for that because otherwise they often won’t even fill it or use it.”
 

A version of this article appeared on Medscape.com .

TOPLINE:

A hypofractionated intensity-modulated radiotherapy (IMRT) may be safe and well-tolerated in women with cervical cancer undergoing pelvic irradiation with concurrent chemotherapy following surgical resection, results from the phase 2 POHIM-CCRT trial suggested.

METHODOLOGY:

• To date, no studies have assessed the treatment outcomes and toxic effects of hypofractionated IMRT following radical hysterectomy in patients with cervical cancer undergoing curative radiotherapy.
• The team analyzed outcomes from 79 patients undergoing hypofractionated IMRT for cervical cancer after radical hysterectomy and pelvic lymph node dissection.
• Patients were a median age of 48; 29.5% had stage IB to IIA disease, another 29.5% had stage IIB disease, and 41% had stage III disease. Patients also had at least one of the following criteria following radical hysterectomy and pelvic lymph node dissection: lymph node metastasis (39.7%), parametrial invasion (54.4%), and positive resection margin (5.1%).
• The prescribed dose to the planning target volume was 40 Gy, delivered in 16 fractions to the whole pelvis, with any type of IMRT permitted. Overall, 71 patients also underwent concurrent weekly cisplatin (40 mg/m² of body surface area for three cycles), and eight received fluorouracil (1000 mg/m² on days 1-5) with cisplatin (60 mg/m² for two cycles).
• The primary endpoint was the incidence of acute grade 3 or higher gastrointestinal tract, genitourinary, and hematologic toxic effects during radiotherapy or within 3 months of completing radiotherapy.

TAKEAWAY:

• After radiotherapy, only two patients (2.5%) experienced acute grade 3 or higher toxic effects. One was hospitalized for enterocolitis on the last day of radiotherapy and developed grade 3 anemia 3 months after completing radiotherapy; the other experienced hematologic toxic effects and also developed grade 3 anemia 3 months after completing radiotherapy.
• No patients experienced late grade 3 or higher toxic effects.
• When assessing toxic effects of any grade, acute and late gastrointestinal tract toxicities occurred in 76% and 31.6% of patients, respectively; acute and late genitourinary toxicities, all grade 1, occurred in 19% and 24.1% of patients, respectively; and hematologic toxicities occurred in 29.1% and 6.3% of patients, respectively.
• Overall, at 3 years, 79.3% of patients were disease-free and 98% were alive. After a median follow-up of 43 months, 16 patients (20.3%) experienced disease recurrence, four of whom were salvaged and three of whom died.

IN PRACTICE:

“This nonrandomized controlled trial is the first prospective trial, to our knowledge, to show acceptable acute toxic effects of hypofractionated IMRT for cervical cancer in a postoperative concurrent chemoradiotherapy setting,” the authors said, adding that the rate of grade 3 or higher acute toxic effects of 2.5% reported in this study was “substantially lower than our initial hypothesis of less than 15%.”

However , in an accompanying editorial, Mark E. Bernard, MD, of the University of Kentucky College of Medicine, Lexington, highlighted caveats to the study design and raised two core questions: “Should acute toxic effects be the primary endpoint of a single-group, phase 2 study using hypofractionation with fewer cycles of concurrent chemotherapy? Should the primary endpoint rather have been a cancer control endpoint, such as disease-free survival, overall survival, or local control?”

Still, Dr. Bernard wrote, “This trial does help lay the foundation for future pelvic hypofractionated trials with concurrent chemotherapy, especially for gynecological malignant tumors.”

SOURCE:

The research, led by Won Park, MD, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea, was published in JAMA Oncology.

LIMITATIONS:

The trial is a single-arm study, with a short follow-up time. In the editorial, Bernard listed several limitations, including the fact that patients received fewer cycles of concurrent chemotherapy than what’s typically given in this population.

DISCLOSURES:

No funding or relevant financial relationships were declared.

A version of this article appeared on Medscape.com.

TOPLINE:

A hypofractionated intensity-modulated radiotherapy (IMRT) may be safe and well-tolerated in women with cervical cancer undergoing pelvic irradiation with concurrent chemotherapy following surgical resection, results from the phase 2 POHIM-CCRT trial suggested.

METHODOLOGY:

• To date, no studies have assessed the treatment outcomes and toxic effects of hypofractionated IMRT following radical hysterectomy in patients with cervical cancer undergoing curative radiotherapy.
• The team analyzed outcomes from 79 patients undergoing hypofractionated IMRT for cervical cancer after radical hysterectomy and pelvic lymph node dissection.
• Patients were a median age of 48; 29.5% had stage IB to IIA disease, another 29.5% had stage IIB disease, and 41% had stage III disease. Patients also had at least one of the following criteria following radical hysterectomy and pelvic lymph node dissection: lymph node metastasis (39.7%), parametrial invasion (54.4%), and positive resection margin (5.1%).
• The prescribed dose to the planning target volume was 40 Gy, delivered in 16 fractions to the whole pelvis, with any type of IMRT permitted. Overall, 71 patients also underwent concurrent weekly cisplatin (40 mg/m² of body surface area for three cycles), and eight received fluorouracil (1000 mg/m² on days 1-5) with cisplatin (60 mg/m² for two cycles).
• The primary endpoint was the incidence of acute grade 3 or higher gastrointestinal tract, genitourinary, and hematologic toxic effects during radiotherapy or within 3 months of completing radiotherapy.

TAKEAWAY:

• After radiotherapy, only two patients (2.5%) experienced acute grade 3 or higher toxic effects. One was hospitalized for enterocolitis on the last day of radiotherapy and developed grade 3 anemia 3 months after completing radiotherapy; the other experienced hematologic toxic effects and also developed grade 3 anemia 3 months after completing radiotherapy.
• No patients experienced late grade 3 or higher toxic effects.
• When assessing toxic effects of any grade, acute and late gastrointestinal tract toxicities occurred in 76% and 31.6% of patients, respectively; acute and late genitourinary toxicities, all grade 1, occurred in 19% and 24.1% of patients, respectively; and hematologic toxicities occurred in 29.1% and 6.3% of patients, respectively.
• Overall, at 3 years, 79.3% of patients were disease-free and 98% were alive. After a median follow-up of 43 months, 16 patients (20.3%) experienced disease recurrence, four of whom were salvaged and three of whom died.

IN PRACTICE:

“This nonrandomized controlled trial is the first prospective trial, to our knowledge, to show acceptable acute toxic effects of hypofractionated IMRT for cervical cancer in a postoperative concurrent chemoradiotherapy setting,” the authors said, adding that the rate of grade 3 or higher acute toxic effects of 2.5% reported in this study was “substantially lower than our initial hypothesis of less than 15%.”

However , in an accompanying editorial, Mark E. Bernard, MD, of the University of Kentucky College of Medicine, Lexington, highlighted caveats to the study design and raised two core questions: “Should acute toxic effects be the primary endpoint of a single-group, phase 2 study using hypofractionation with fewer cycles of concurrent chemotherapy? Should the primary endpoint rather have been a cancer control endpoint, such as disease-free survival, overall survival, or local control?”

Still, Dr. Bernard wrote, “This trial does help lay the foundation for future pelvic hypofractionated trials with concurrent chemotherapy, especially for gynecological malignant tumors.”

SOURCE:

The research, led by Won Park, MD, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea, was published in JAMA Oncology.

LIMITATIONS:

The trial is a single-arm study, with a short follow-up time. In the editorial, Bernard listed several limitations, including the fact that patients received fewer cycles of concurrent chemotherapy than what’s typically given in this population.

DISCLOSURES:

No funding or relevant financial relationships were declared.

A version of this article appeared on Medscape.com.

TOPLINE:

A hypofractionated intensity-modulated radiotherapy (IMRT) may be safe and well-tolerated in women with cervical cancer undergoing pelvic irradiation with concurrent chemotherapy following surgical resection, results from the phase 2 POHIM-CCRT trial suggested.

METHODOLOGY:

• To date, no studies have assessed the treatment outcomes and toxic effects of hypofractionated IMRT following radical hysterectomy in patients with cervical cancer undergoing curative radiotherapy.
• The team analyzed outcomes from 79 patients undergoing hypofractionated IMRT for cervical cancer after radical hysterectomy and pelvic lymph node dissection.
• Patients were a median age of 48; 29.5% had stage IB to IIA disease, another 29.5% had stage IIB disease, and 41% had stage III disease. Patients also had at least one of the following criteria following radical hysterectomy and pelvic lymph node dissection: lymph node metastasis (39.7%), parametrial invasion (54.4%), and positive resection margin (5.1%).
• The prescribed dose to the planning target volume was 40 Gy, delivered in 16 fractions to the whole pelvis, with any type of IMRT permitted. Overall, 71 patients also underwent concurrent weekly cisplatin (40 mg/m² of body surface area for three cycles), and eight received fluorouracil (1000 mg/m² on days 1-5) with cisplatin (60 mg/m² for two cycles).
• The primary endpoint was the incidence of acute grade 3 or higher gastrointestinal tract, genitourinary, and hematologic toxic effects during radiotherapy or within 3 months of completing radiotherapy.

TAKEAWAY:

• After radiotherapy, only two patients (2.5%) experienced acute grade 3 or higher toxic effects. One was hospitalized for enterocolitis on the last day of radiotherapy and developed grade 3 anemia 3 months after completing radiotherapy; the other experienced hematologic toxic effects and also developed grade 3 anemia 3 months after completing radiotherapy.
• No patients experienced late grade 3 or higher toxic effects.
• When assessing toxic effects of any grade, acute and late gastrointestinal tract toxicities occurred in 76% and 31.6% of patients, respectively; acute and late genitourinary toxicities, all grade 1, occurred in 19% and 24.1% of patients, respectively; and hematologic toxicities occurred in 29.1% and 6.3% of patients, respectively.
• Overall, at 3 years, 79.3% of patients were disease-free and 98% were alive. After a median follow-up of 43 months, 16 patients (20.3%) experienced disease recurrence, four of whom were salvaged and three of whom died.

IN PRACTICE:

“This nonrandomized controlled trial is the first prospective trial, to our knowledge, to show acceptable acute toxic effects of hypofractionated IMRT for cervical cancer in a postoperative concurrent chemoradiotherapy setting,” the authors said, adding that the rate of grade 3 or higher acute toxic effects of 2.5% reported in this study was “substantially lower than our initial hypothesis of less than 15%.”

However , in an accompanying editorial, Mark E. Bernard, MD, of the University of Kentucky College of Medicine, Lexington, highlighted caveats to the study design and raised two core questions: “Should acute toxic effects be the primary endpoint of a single-group, phase 2 study using hypofractionation with fewer cycles of concurrent chemotherapy? Should the primary endpoint rather have been a cancer control endpoint, such as disease-free survival, overall survival, or local control?”

Still, Dr. Bernard wrote, “This trial does help lay the foundation for future pelvic hypofractionated trials with concurrent chemotherapy, especially for gynecological malignant tumors.”

SOURCE:

The research, led by Won Park, MD, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea, was published in JAMA Oncology.

LIMITATIONS:

The trial is a single-arm study, with a short follow-up time. In the editorial, Bernard listed several limitations, including the fact that patients received fewer cycles of concurrent chemotherapy than what’s typically given in this population.

DISCLOSURES:

No funding or relevant financial relationships were declared.

A version of this article appeared on Medscape.com.