Women's Health

A more definitive picture of how some hormones and moisturizers can offer relief to women experiencing vaginal dryness or painful intercourse during menopause was published in a recent systematic review in Annals of Internal Medicine. However, researchers noted scant long-term data on the safety of these products.

Vaginal dryness and challenges with intercourse and urination are among the symptoms of genitourinary syndrome of menopause (GSM). Hormones such as vaginal estrogen, vaginal dehydroepiandrosterone (DHEA), or oral ospemifene are common treatments, along with moisturizers.

“The main finding is that commonly used therapies are likely to be effective for the common symptoms people have for GSM,” particularly vaginal dryness and painful intercourse, said Elisheva Danan, MD, MPH, a primary care physician and health services researcher at the Minneapolis VA Health Care System and assistant professor of medicine at the University of Minnesota Medical School in Minneapolis, who was the lead study author.

Many women might recognize hot flashes as connected to menopause, Dr. Danan said, as these tend to occur with the cessation of the menstrual cycle. However, genitourinary effects may not manifest until a few years later and worsen over time, when the connection to menopause is less clear.

“Women might not bring it up or think there’s a treatment that can work,” Dr. Danan said.

The systematic review may provide clinicians with more evidence of specific treatments to recommend. However, most of the trials included in the analysis studied treatment periods of 12 weeks or less, so the safety of long-term use is unclear.

“One question that hasn’t been answered yet in clinical trials is whether there could be a risk of uterine cancer with extended use of any of these treatments,” Dr. Danan said, because vaginal estrogen or ospemifene could stimulate growth of the uterine lining.

The studies Dr. Danan and colleagues found showed no increased risk for uterine cancer, but Dr, Danan noted that the maximum follow-up was 1 year, and study participants had a low risk for cancer to begin with. She advised that clinicians closely monitor women with risk factors if they use hormones to treat GSM indefinitely.
 

Forty-Six Randomized Controlled Trials, Many Open Questions

Dr. Danan and her colleagues conducted a systematic review of 46 randomized controlled trials, meant to inform an upcoming clinical practice guideline from the American Urological Association on treatment of GSM. Dr. Danan’s work was funded by the Patient-Centered Outcomes Research Institute.

Studies evaluated vaginal estrogen (22), other hormones such as vaginal oxytocin or vaginal testosterone (16), vaginal moisturizers (4), and multiple interventions (4).

Included trials lasted at least 8 weeks and included at least 20 postmenopausal women; most treatments lasted 12 weeks or less. Studies used varying definitions of GSM, and no head-to-head trials of different treatments were found.

Researchers used the Core Outcomes in Menopause (COMMA) framework, developed in 2021 to standardize outcomes research in menopause care and to understand treatment effectiveness. They applied this framework retroactively, as almost all the studies in the review were written before the COMMA framework existed.

Hormonal treatments were associated with reduced pain during intercourse and decreased vaginal dryness; moisturizers were linked to reduced dryness.

Vaginal estrogen did not reduce pain during intercourse as consistently as DHEA or oral ospemifene, per the review. Dr. Danan and her coauthors said this could be because the DHEA and ospemifene trials were larger and more uniformly conducted than those for vaginal estrogen. Even so, vaginal estrogen outperformed placebo at reducing painful intercourse.

But given the short timeframe of most studies and the differing definitions of GSM symptoms, Dr. Danan cautioned that all their conclusions have low certainty.

Few studies examined whether these treatments reduced vaginal itchiness or difficulties with urination. And the authors found no evidence for the benefit of oral DHEA, raloxifene, bazedoxifene, vaginal oxytocin, or vaginal testosterone for GSM treatment.

In an accompanying report, the researchers found no evidence for the benefits of treatments such as vaginal testosterone or vaginal laser therapy.

Stephanie Faubion, MD, MBA, medical director for the North American Menopause Society and director of the Mayo Clinic Center for Women’s Health, Rochester, Minnesota, wrote an accompanying editorial noting that the patients represented in the GSM treatment clinical trials were not diverse and that the exclusion criteria generally meant that women with cardiovascular challenges or cancer were not included.

“That’s one of the biggest questions — what is the safety in women with cardiovascular risk factors or history of a blood clot or history of a cancer? The data is just completely absent there,” Dr. Faubion said.
 

The Connection Between GSM and Urinary Tract Infections (UTIs)

“Genitourinary syndrome of menopause is not just a little bit of vaginal dryness that can be cured with moisturizers and lubricants, but the syndrome can lead to recurrent urinary tract infections, which are extremely harmful and dangerous to our patients and cost the healthcare system a lot of money,” said Rachel Rubin, MD, a urologist and sexual medicine specialist in Bethesda, Maryland.

Lubricants and moisturizers can all help with the symptoms of GSM, at least in the short term, Dr. Rubin noted. But only hormones can get to the root of the problem and reduce the risk for a recurrent UTI (rUTI), Dr. Rubin added, noting that the American Urological Association recommends the use of vaginal estrogen to reduce the risk for rUTIs and is developing the clinical practice guidelines for GSM.

Dr. Danan’s review did not address the association between UTIs and GSM, but Dr. Rubin said she sees the link in clinical practice.

“Recurrent urinary tract infections occur because of GSM, because of the lack of hormones to the tissue,” sometimes when a woman is in her 60s or 70s and thinks menopause is long over, Dr. Rubin said.

The reality is that women may need to take hormones for decades to reduce the risk for UTIs, another reason longer-term safety data are needed, Dr. Rubin said.

Dr. Danan, Dr. Faubion, and Dr. Rubin reported no relevant financial relationships.

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

A more definitive picture of how some hormones and moisturizers can offer relief to women experiencing vaginal dryness or painful intercourse during menopause was published in a recent systematic review in Annals of Internal Medicine. However, researchers noted scant long-term data on the safety of these products.

Vaginal dryness and challenges with intercourse and urination are among the symptoms of genitourinary syndrome of menopause (GSM). Hormones such as vaginal estrogen, vaginal dehydroepiandrosterone (DHEA), or oral ospemifene are common treatments, along with moisturizers.

“The main finding is that commonly used therapies are likely to be effective for the common symptoms people have for GSM,” particularly vaginal dryness and painful intercourse, said Elisheva Danan, MD, MPH, a primary care physician and health services researcher at the Minneapolis VA Health Care System and assistant professor of medicine at the University of Minnesota Medical School in Minneapolis, who was the lead study author.

Many women might recognize hot flashes as connected to menopause, Dr. Danan said, as these tend to occur with the cessation of the menstrual cycle. However, genitourinary effects may not manifest until a few years later and worsen over time, when the connection to menopause is less clear.

“Women might not bring it up or think there’s a treatment that can work,” Dr. Danan said.

The systematic review may provide clinicians with more evidence of specific treatments to recommend. However, most of the trials included in the analysis studied treatment periods of 12 weeks or less, so the safety of long-term use is unclear.

“One question that hasn’t been answered yet in clinical trials is whether there could be a risk of uterine cancer with extended use of any of these treatments,” Dr. Danan said, because vaginal estrogen or ospemifene could stimulate growth of the uterine lining.

The studies Dr. Danan and colleagues found showed no increased risk for uterine cancer, but Dr, Danan noted that the maximum follow-up was 1 year, and study participants had a low risk for cancer to begin with. She advised that clinicians closely monitor women with risk factors if they use hormones to treat GSM indefinitely.
 

Forty-Six Randomized Controlled Trials, Many Open Questions

Dr. Danan and her colleagues conducted a systematic review of 46 randomized controlled trials, meant to inform an upcoming clinical practice guideline from the American Urological Association on treatment of GSM. Dr. Danan’s work was funded by the Patient-Centered Outcomes Research Institute.

Studies evaluated vaginal estrogen (22), other hormones such as vaginal oxytocin or vaginal testosterone (16), vaginal moisturizers (4), and multiple interventions (4).

Included trials lasted at least 8 weeks and included at least 20 postmenopausal women; most treatments lasted 12 weeks or less. Studies used varying definitions of GSM, and no head-to-head trials of different treatments were found.

Researchers used the Core Outcomes in Menopause (COMMA) framework, developed in 2021 to standardize outcomes research in menopause care and to understand treatment effectiveness. They applied this framework retroactively, as almost all the studies in the review were written before the COMMA framework existed.

Hormonal treatments were associated with reduced pain during intercourse and decreased vaginal dryness; moisturizers were linked to reduced dryness.

Vaginal estrogen did not reduce pain during intercourse as consistently as DHEA or oral ospemifene, per the review. Dr. Danan and her coauthors said this could be because the DHEA and ospemifene trials were larger and more uniformly conducted than those for vaginal estrogen. Even so, vaginal estrogen outperformed placebo at reducing painful intercourse.

But given the short timeframe of most studies and the differing definitions of GSM symptoms, Dr. Danan cautioned that all their conclusions have low certainty.

Few studies examined whether these treatments reduced vaginal itchiness or difficulties with urination. And the authors found no evidence for the benefit of oral DHEA, raloxifene, bazedoxifene, vaginal oxytocin, or vaginal testosterone for GSM treatment.

In an accompanying report, the researchers found no evidence for the benefits of treatments such as vaginal testosterone or vaginal laser therapy.

Stephanie Faubion, MD, MBA, medical director for the North American Menopause Society and director of the Mayo Clinic Center for Women’s Health, Rochester, Minnesota, wrote an accompanying editorial noting that the patients represented in the GSM treatment clinical trials were not diverse and that the exclusion criteria generally meant that women with cardiovascular challenges or cancer were not included.

“That’s one of the biggest questions — what is the safety in women with cardiovascular risk factors or history of a blood clot or history of a cancer? The data is just completely absent there,” Dr. Faubion said.
 

The Connection Between GSM and Urinary Tract Infections (UTIs)

“Genitourinary syndrome of menopause is not just a little bit of vaginal dryness that can be cured with moisturizers and lubricants, but the syndrome can lead to recurrent urinary tract infections, which are extremely harmful and dangerous to our patients and cost the healthcare system a lot of money,” said Rachel Rubin, MD, a urologist and sexual medicine specialist in Bethesda, Maryland.

Lubricants and moisturizers can all help with the symptoms of GSM, at least in the short term, Dr. Rubin noted. But only hormones can get to the root of the problem and reduce the risk for a recurrent UTI (rUTI), Dr. Rubin added, noting that the American Urological Association recommends the use of vaginal estrogen to reduce the risk for rUTIs and is developing the clinical practice guidelines for GSM.

Dr. Danan’s review did not address the association between UTIs and GSM, but Dr. Rubin said she sees the link in clinical practice.

“Recurrent urinary tract infections occur because of GSM, because of the lack of hormones to the tissue,” sometimes when a woman is in her 60s or 70s and thinks menopause is long over, Dr. Rubin said.

The reality is that women may need to take hormones for decades to reduce the risk for UTIs, another reason longer-term safety data are needed, Dr. Rubin said.

Dr. Danan, Dr. Faubion, and Dr. Rubin reported no relevant financial relationships.

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

A more definitive picture of how some hormones and moisturizers can offer relief to women experiencing vaginal dryness or painful intercourse during menopause was published in a recent systematic review in Annals of Internal Medicine. However, researchers noted scant long-term data on the safety of these products.

Vaginal dryness and challenges with intercourse and urination are among the symptoms of genitourinary syndrome of menopause (GSM). Hormones such as vaginal estrogen, vaginal dehydroepiandrosterone (DHEA), or oral ospemifene are common treatments, along with moisturizers.

“The main finding is that commonly used therapies are likely to be effective for the common symptoms people have for GSM,” particularly vaginal dryness and painful intercourse, said Elisheva Danan, MD, MPH, a primary care physician and health services researcher at the Minneapolis VA Health Care System and assistant professor of medicine at the University of Minnesota Medical School in Minneapolis, who was the lead study author.

Many women might recognize hot flashes as connected to menopause, Dr. Danan said, as these tend to occur with the cessation of the menstrual cycle. However, genitourinary effects may not manifest until a few years later and worsen over time, when the connection to menopause is less clear.

“Women might not bring it up or think there’s a treatment that can work,” Dr. Danan said.

The systematic review may provide clinicians with more evidence of specific treatments to recommend. However, most of the trials included in the analysis studied treatment periods of 12 weeks or less, so the safety of long-term use is unclear.

“One question that hasn’t been answered yet in clinical trials is whether there could be a risk of uterine cancer with extended use of any of these treatments,” Dr. Danan said, because vaginal estrogen or ospemifene could stimulate growth of the uterine lining.

The studies Dr. Danan and colleagues found showed no increased risk for uterine cancer, but Dr, Danan noted that the maximum follow-up was 1 year, and study participants had a low risk for cancer to begin with. She advised that clinicians closely monitor women with risk factors if they use hormones to treat GSM indefinitely.
 

Forty-Six Randomized Controlled Trials, Many Open Questions

Dr. Danan and her colleagues conducted a systematic review of 46 randomized controlled trials, meant to inform an upcoming clinical practice guideline from the American Urological Association on treatment of GSM. Dr. Danan’s work was funded by the Patient-Centered Outcomes Research Institute.

Studies evaluated vaginal estrogen (22), other hormones such as vaginal oxytocin or vaginal testosterone (16), vaginal moisturizers (4), and multiple interventions (4).

Included trials lasted at least 8 weeks and included at least 20 postmenopausal women; most treatments lasted 12 weeks or less. Studies used varying definitions of GSM, and no head-to-head trials of different treatments were found.

Researchers used the Core Outcomes in Menopause (COMMA) framework, developed in 2021 to standardize outcomes research in menopause care and to understand treatment effectiveness. They applied this framework retroactively, as almost all the studies in the review were written before the COMMA framework existed.

Hormonal treatments were associated with reduced pain during intercourse and decreased vaginal dryness; moisturizers were linked to reduced dryness.

Vaginal estrogen did not reduce pain during intercourse as consistently as DHEA or oral ospemifene, per the review. Dr. Danan and her coauthors said this could be because the DHEA and ospemifene trials were larger and more uniformly conducted than those for vaginal estrogen. Even so, vaginal estrogen outperformed placebo at reducing painful intercourse.

But given the short timeframe of most studies and the differing definitions of GSM symptoms, Dr. Danan cautioned that all their conclusions have low certainty.

Few studies examined whether these treatments reduced vaginal itchiness or difficulties with urination. And the authors found no evidence for the benefit of oral DHEA, raloxifene, bazedoxifene, vaginal oxytocin, or vaginal testosterone for GSM treatment.

In an accompanying report, the researchers found no evidence for the benefits of treatments such as vaginal testosterone or vaginal laser therapy.

Stephanie Faubion, MD, MBA, medical director for the North American Menopause Society and director of the Mayo Clinic Center for Women’s Health, Rochester, Minnesota, wrote an accompanying editorial noting that the patients represented in the GSM treatment clinical trials were not diverse and that the exclusion criteria generally meant that women with cardiovascular challenges or cancer were not included.

“That’s one of the biggest questions — what is the safety in women with cardiovascular risk factors or history of a blood clot or history of a cancer? The data is just completely absent there,” Dr. Faubion said.
 

The Connection Between GSM and Urinary Tract Infections (UTIs)

“Genitourinary syndrome of menopause is not just a little bit of vaginal dryness that can be cured with moisturizers and lubricants, but the syndrome can lead to recurrent urinary tract infections, which are extremely harmful and dangerous to our patients and cost the healthcare system a lot of money,” said Rachel Rubin, MD, a urologist and sexual medicine specialist in Bethesda, Maryland.

Lubricants and moisturizers can all help with the symptoms of GSM, at least in the short term, Dr. Rubin noted. But only hormones can get to the root of the problem and reduce the risk for a recurrent UTI (rUTI), Dr. Rubin added, noting that the American Urological Association recommends the use of vaginal estrogen to reduce the risk for rUTIs and is developing the clinical practice guidelines for GSM.

Dr. Danan’s review did not address the association between UTIs and GSM, but Dr. Rubin said she sees the link in clinical practice.

“Recurrent urinary tract infections occur because of GSM, because of the lack of hormones to the tissue,” sometimes when a woman is in her 60s or 70s and thinks menopause is long over, Dr. Rubin said.

The reality is that women may need to take hormones for decades to reduce the risk for UTIs, another reason longer-term safety data are needed, Dr. Rubin said.

Dr. Danan, Dr. Faubion, and Dr. Rubin reported no relevant financial relationships.

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

Elinzanetant, the selective antagonist of neurokinin 1 and 3 receptors, led to rapid improvement in the frequency of vasomotor symptoms and significant improvements in the severity of symptoms, sleep disturbances, and menopause-related quality of life in two phase 3 studies. Researchers led by JoAnn V. Pinkerton, MD, from the University of Virginia Health in Charlottesville, reported their findings, which resulted from the randomized OASIS 1 and 2 studies, in JAMA.

“Women experience a variety of symptoms during their menopausal transition, including vasomotor symptoms ... and sleep disturbances, reported by up to 80% and 60%, respectively,” wrote the researchers. “Menopausal symptoms can negatively impact quality of life, reducing the capacity for daily activities and work productivity, and may be associated with long-term negative health outcomes such as cardiovascular events, depressive symptoms, cognitive decline, and other adverse brain outcomes.” The researchers also noted that some therapeutic options are available, including hormone replacement therapy and, in some countries, paroxetine, a selective serotonin reuptake inhibitor.

The Italian Ministry of Health’s menopause website points out that the transition generally occurs between ages 45 and 55 years. This huge hormonal change has consequences for women’s health. Ministry experts explain that diet and hormone replacement therapy (which should be taken under medical supervision) can prevent or counteract these consequences.

“Many women have contraindications, have tolerability issues leading to discontinuation, or prefer not to take these treatments,” wrote Dr. Pinkerton and colleagues, who evaluated the efficacy and tolerability of elinzanetant, a nonhormonal alternative treatment in development. The two double-blind, randomized, phase 3 studies (OASIS 1 and 2) included postmenopausal participants between ages 40 and 65 years with moderate to severe vasomotor symptoms who were treated with elinzanetant (OASIS 1, n = 199; OASIS 2, n = 200) or placebo (OASIS 1, n = 197; OASIS 2, n = 200).

After 4 weeks of treatment, 62.8% of participants in the OASIS 1 study and 62.2% in the OASIS 2 study reported at least a 50% reduction in the frequency of vasomotor symptoms (29.2% and 32.3% in the respective placebo groups). Improvements increased by week 12, with 71.4% and 74.7% of women in the elinzanetant group achieving this reduction (42.0% and 48.3% in the respective placebo groups). Women who took the medication also reported a reduction in the severity of vasomotor symptoms and improvements in sleep and menopause-related quality of life, with no significant tolerability and safety issues. “Elinzanetant has the potential to provide a well-tolerated and efficacious nonhormonal treatment option to address the unmet health needs of many menopausal individuals with moderate to severe vasomotor symptoms,” the authors concluded.

“With the discovery of nonhormonal treatment options targeting the neurons responsible for vasomotor symptoms, menopause care should advance on this solid scientific footing to benefit affected individuals,” wrote Stephanie S. Faubion, MD, and Chrisandra L. Shufelt, MD, who are affiliated with the Mayo Clinic in Rochester, Minnesota, and Jacksonville, Florida, in an accompanying editorial.

This story was translated from Univadis Italy using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Elinzanetant, the selective antagonist of neurokinin 1 and 3 receptors, led to rapid improvement in the frequency of vasomotor symptoms and significant improvements in the severity of symptoms, sleep disturbances, and menopause-related quality of life in two phase 3 studies. Researchers led by JoAnn V. Pinkerton, MD, from the University of Virginia Health in Charlottesville, reported their findings, which resulted from the randomized OASIS 1 and 2 studies, in JAMA.

“Women experience a variety of symptoms during their menopausal transition, including vasomotor symptoms ... and sleep disturbances, reported by up to 80% and 60%, respectively,” wrote the researchers. “Menopausal symptoms can negatively impact quality of life, reducing the capacity for daily activities and work productivity, and may be associated with long-term negative health outcomes such as cardiovascular events, depressive symptoms, cognitive decline, and other adverse brain outcomes.” The researchers also noted that some therapeutic options are available, including hormone replacement therapy and, in some countries, paroxetine, a selective serotonin reuptake inhibitor.

The Italian Ministry of Health’s menopause website points out that the transition generally occurs between ages 45 and 55 years. This huge hormonal change has consequences for women’s health. Ministry experts explain that diet and hormone replacement therapy (which should be taken under medical supervision) can prevent or counteract these consequences.

“Many women have contraindications, have tolerability issues leading to discontinuation, or prefer not to take these treatments,” wrote Dr. Pinkerton and colleagues, who evaluated the efficacy and tolerability of elinzanetant, a nonhormonal alternative treatment in development. The two double-blind, randomized, phase 3 studies (OASIS 1 and 2) included postmenopausal participants between ages 40 and 65 years with moderate to severe vasomotor symptoms who were treated with elinzanetant (OASIS 1, n = 199; OASIS 2, n = 200) or placebo (OASIS 1, n = 197; OASIS 2, n = 200).

After 4 weeks of treatment, 62.8% of participants in the OASIS 1 study and 62.2% in the OASIS 2 study reported at least a 50% reduction in the frequency of vasomotor symptoms (29.2% and 32.3% in the respective placebo groups). Improvements increased by week 12, with 71.4% and 74.7% of women in the elinzanetant group achieving this reduction (42.0% and 48.3% in the respective placebo groups). Women who took the medication also reported a reduction in the severity of vasomotor symptoms and improvements in sleep and menopause-related quality of life, with no significant tolerability and safety issues. “Elinzanetant has the potential to provide a well-tolerated and efficacious nonhormonal treatment option to address the unmet health needs of many menopausal individuals with moderate to severe vasomotor symptoms,” the authors concluded.

“With the discovery of nonhormonal treatment options targeting the neurons responsible for vasomotor symptoms, menopause care should advance on this solid scientific footing to benefit affected individuals,” wrote Stephanie S. Faubion, MD, and Chrisandra L. Shufelt, MD, who are affiliated with the Mayo Clinic in Rochester, Minnesota, and Jacksonville, Florida, in an accompanying editorial.

This story was translated from Univadis Italy using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Elinzanetant, the selective antagonist of neurokinin 1 and 3 receptors, led to rapid improvement in the frequency of vasomotor symptoms and significant improvements in the severity of symptoms, sleep disturbances, and menopause-related quality of life in two phase 3 studies. Researchers led by JoAnn V. Pinkerton, MD, from the University of Virginia Health in Charlottesville, reported their findings, which resulted from the randomized OASIS 1 and 2 studies, in JAMA.

“Women experience a variety of symptoms during their menopausal transition, including vasomotor symptoms ... and sleep disturbances, reported by up to 80% and 60%, respectively,” wrote the researchers. “Menopausal symptoms can negatively impact quality of life, reducing the capacity for daily activities and work productivity, and may be associated with long-term negative health outcomes such as cardiovascular events, depressive symptoms, cognitive decline, and other adverse brain outcomes.” The researchers also noted that some therapeutic options are available, including hormone replacement therapy and, in some countries, paroxetine, a selective serotonin reuptake inhibitor.

The Italian Ministry of Health’s menopause website points out that the transition generally occurs between ages 45 and 55 years. This huge hormonal change has consequences for women’s health. Ministry experts explain that diet and hormone replacement therapy (which should be taken under medical supervision) can prevent or counteract these consequences.

“Many women have contraindications, have tolerability issues leading to discontinuation, or prefer not to take these treatments,” wrote Dr. Pinkerton and colleagues, who evaluated the efficacy and tolerability of elinzanetant, a nonhormonal alternative treatment in development. The two double-blind, randomized, phase 3 studies (OASIS 1 and 2) included postmenopausal participants between ages 40 and 65 years with moderate to severe vasomotor symptoms who were treated with elinzanetant (OASIS 1, n = 199; OASIS 2, n = 200) or placebo (OASIS 1, n = 197; OASIS 2, n = 200).

After 4 weeks of treatment, 62.8% of participants in the OASIS 1 study and 62.2% in the OASIS 2 study reported at least a 50% reduction in the frequency of vasomotor symptoms (29.2% and 32.3% in the respective placebo groups). Improvements increased by week 12, with 71.4% and 74.7% of women in the elinzanetant group achieving this reduction (42.0% and 48.3% in the respective placebo groups). Women who took the medication also reported a reduction in the severity of vasomotor symptoms and improvements in sleep and menopause-related quality of life, with no significant tolerability and safety issues. “Elinzanetant has the potential to provide a well-tolerated and efficacious nonhormonal treatment option to address the unmet health needs of many menopausal individuals with moderate to severe vasomotor symptoms,” the authors concluded.

“With the discovery of nonhormonal treatment options targeting the neurons responsible for vasomotor symptoms, menopause care should advance on this solid scientific footing to benefit affected individuals,” wrote Stephanie S. Faubion, MD, and Chrisandra L. Shufelt, MD, who are affiliated with the Mayo Clinic in Rochester, Minnesota, and Jacksonville, Florida, in an accompanying editorial.

This story was translated from Univadis Italy using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Hormone therapy (HT) can help women manage menopause symptoms into their 80s and the reasons are varied, according to a retrospective analysis being presented at the annual meeting of The Menopause Society.

“It’s important to know that this is a preselected group of women who had no contraindications to continuing their hormone therapy,” senior author Wendy Wolfman, MD, director of the Menopause Clinic and The Premature Ovarian Insufficiency Clinic at Mount Sinai Hospital in Toronto, Ontario, Canada, said in an interview. “They had the initiation of hormone therapy closer to menopause and carried on their hormones. We followed them for a long time and basically saw no real concerns about taking the hormones and the patients did very well. It’s important to emphasize this was not the new initiation of hormone therapy in elderly women.”

She said that, in her large tertiary referral center, “I still see patients who are referred who are told that they have to stop their hormones after 5 years based on a false assumption. Everybody ages at different rates and everybody has different risk factors.”

About 70%-80% of women experience menopause symptoms that restrict quality of life and productivity, the authors noted. HT has consistently been the most effective means for managing many of the side effects, especially hot flashes.

Hot flashes last on average 7-11 years. But they continue in up to 40% of women in their 60s and 10%-15% in their 70s, the authors wrote. 

The analysis included more than 100 women in Canada older than 65 who continue to use HT and explored the motivations of the women to use them.

The average age of the women was 71 and nearly 8% were age 80 or older. The mean age for starting HT was 52 years and the women continued HT for an average 18 years, though 42% used it regularly for more than 20 years. Most of the women (nearly 88%) used a transdermal form of estrogen; only 12% used oral estrogen pills. Fewer than 5% of participants used synthetic progestins.

Controlling hot flashes was the No. 1 reason the women continued HT beyond age 65 (55%), followed by a desire for a better quality of life (29%), and to reduce chronic pain and arthritis symptoms (7%).

Some adverse effects were reported – postmenopausal bleeding was the most common – but no strokes, myocardial infarctions, or uterine cancers were documented.

More than one fourth (26.4%) of the women tried stopping HT once, but 87% reported that the return of hot flashes was the main reason to restart HT.

In addition, “many women choose to continue hormone therapy long term for relief of nonvasomotor symptoms, preservation of bone density, and a desire to benefit from potential long-term cardiovascular protection,” said Lauren F. Streicher, MD, Professor of Obstetrics and Gynecology at Feinberg School of Medicine at Northwestern University in Chicago, who was not part of the research.

In 2022, The Menopause Society position statement on hormone therapy acknowledged that, on an individual basis, it is appropriate for women to continue hormone therapy long term with counseling on benefits and risks.

“However, few studies have evaluated the outcomes of using hormone therapy for more than 10 years, and individual motivation for doing so,” Dr. Streicher said. She pointed to a study that analyzed the insurance records of more than 10 million women who continued their HT past the age of 65 and reassuringly found that there were significant risk reductions in all-cause mortality, breast cancer, lung cancer, colorectal cancer, heart failure, venous thromboembolism, atrial fibrillation, acute myocardial infarction, and dementia. In that study, however, the reasons women chose to continue hormone therapy were not specified. 

“In this retrospective Canadian study,” she noted, “the outcomes were again reassuring, with no increase in strokes, myocardial infarctions, or uterine cancers. The reasons cited for continuing hormone therapy were not just to treat ongoing vasomotor symptoms, but also other menopause symptoms such as musculoskeletal aches and pains, and overall quality of life.

Dr. Streicher said that, while long-term longitudinal studies are needed to make definitive recommendations, “It is reassuring that women who choose to extend hormone therapy can safely do so. It is irresponsible, cruel, and nonsensical to continue to make blanket statements that hormone therapy should be discontinued based on age or years of use and commit women to enduring symptoms and depriving them of possible long-term benefits.”

Dr. Streicher gives lectures for Midi Health and owns Sermonix stock. Dr. Wolfman has been on the advisory boards for many pharmaceutical companies. She is the past president of the Canadian Menopause Society and is on the board of the International Menopause Society.

Hormone therapy (HT) can help women manage menopause symptoms into their 80s and the reasons are varied, according to a retrospective analysis being presented at the annual meeting of The Menopause Society.

“It’s important to know that this is a preselected group of women who had no contraindications to continuing their hormone therapy,” senior author Wendy Wolfman, MD, director of the Menopause Clinic and The Premature Ovarian Insufficiency Clinic at Mount Sinai Hospital in Toronto, Ontario, Canada, said in an interview. “They had the initiation of hormone therapy closer to menopause and carried on their hormones. We followed them for a long time and basically saw no real concerns about taking the hormones and the patients did very well. It’s important to emphasize this was not the new initiation of hormone therapy in elderly women.”

She said that, in her large tertiary referral center, “I still see patients who are referred who are told that they have to stop their hormones after 5 years based on a false assumption. Everybody ages at different rates and everybody has different risk factors.”

About 70%-80% of women experience menopause symptoms that restrict quality of life and productivity, the authors noted. HT has consistently been the most effective means for managing many of the side effects, especially hot flashes.

Hot flashes last on average 7-11 years. But they continue in up to 40% of women in their 60s and 10%-15% in their 70s, the authors wrote. 

The analysis included more than 100 women in Canada older than 65 who continue to use HT and explored the motivations of the women to use them.

The average age of the women was 71 and nearly 8% were age 80 or older. The mean age for starting HT was 52 years and the women continued HT for an average 18 years, though 42% used it regularly for more than 20 years. Most of the women (nearly 88%) used a transdermal form of estrogen; only 12% used oral estrogen pills. Fewer than 5% of participants used synthetic progestins.

Controlling hot flashes was the No. 1 reason the women continued HT beyond age 65 (55%), followed by a desire for a better quality of life (29%), and to reduce chronic pain and arthritis symptoms (7%).

Some adverse effects were reported – postmenopausal bleeding was the most common – but no strokes, myocardial infarctions, or uterine cancers were documented.

More than one fourth (26.4%) of the women tried stopping HT once, but 87% reported that the return of hot flashes was the main reason to restart HT.

In addition, “many women choose to continue hormone therapy long term for relief of nonvasomotor symptoms, preservation of bone density, and a desire to benefit from potential long-term cardiovascular protection,” said Lauren F. Streicher, MD, Professor of Obstetrics and Gynecology at Feinberg School of Medicine at Northwestern University in Chicago, who was not part of the research.

In 2022, The Menopause Society position statement on hormone therapy acknowledged that, on an individual basis, it is appropriate for women to continue hormone therapy long term with counseling on benefits and risks.

“However, few studies have evaluated the outcomes of using hormone therapy for more than 10 years, and individual motivation for doing so,” Dr. Streicher said. She pointed to a study that analyzed the insurance records of more than 10 million women who continued their HT past the age of 65 and reassuringly found that there were significant risk reductions in all-cause mortality, breast cancer, lung cancer, colorectal cancer, heart failure, venous thromboembolism, atrial fibrillation, acute myocardial infarction, and dementia. In that study, however, the reasons women chose to continue hormone therapy were not specified. 

“In this retrospective Canadian study,” she noted, “the outcomes were again reassuring, with no increase in strokes, myocardial infarctions, or uterine cancers. The reasons cited for continuing hormone therapy were not just to treat ongoing vasomotor symptoms, but also other menopause symptoms such as musculoskeletal aches and pains, and overall quality of life.

Dr. Streicher said that, while long-term longitudinal studies are needed to make definitive recommendations, “It is reassuring that women who choose to extend hormone therapy can safely do so. It is irresponsible, cruel, and nonsensical to continue to make blanket statements that hormone therapy should be discontinued based on age or years of use and commit women to enduring symptoms and depriving them of possible long-term benefits.”

Dr. Streicher gives lectures for Midi Health and owns Sermonix stock. Dr. Wolfman has been on the advisory boards for many pharmaceutical companies. She is the past president of the Canadian Menopause Society and is on the board of the International Menopause Society.

Hormone therapy (HT) can help women manage menopause symptoms into their 80s and the reasons are varied, according to a retrospective analysis being presented at the annual meeting of The Menopause Society.

“It’s important to know that this is a preselected group of women who had no contraindications to continuing their hormone therapy,” senior author Wendy Wolfman, MD, director of the Menopause Clinic and The Premature Ovarian Insufficiency Clinic at Mount Sinai Hospital in Toronto, Ontario, Canada, said in an interview. “They had the initiation of hormone therapy closer to menopause and carried on their hormones. We followed them for a long time and basically saw no real concerns about taking the hormones and the patients did very well. It’s important to emphasize this was not the new initiation of hormone therapy in elderly women.”

She said that, in her large tertiary referral center, “I still see patients who are referred who are told that they have to stop their hormones after 5 years based on a false assumption. Everybody ages at different rates and everybody has different risk factors.”

About 70%-80% of women experience menopause symptoms that restrict quality of life and productivity, the authors noted. HT has consistently been the most effective means for managing many of the side effects, especially hot flashes.

Hot flashes last on average 7-11 years. But they continue in up to 40% of women in their 60s and 10%-15% in their 70s, the authors wrote. 

The analysis included more than 100 women in Canada older than 65 who continue to use HT and explored the motivations of the women to use them.

The average age of the women was 71 and nearly 8% were age 80 or older. The mean age for starting HT was 52 years and the women continued HT for an average 18 years, though 42% used it regularly for more than 20 years. Most of the women (nearly 88%) used a transdermal form of estrogen; only 12% used oral estrogen pills. Fewer than 5% of participants used synthetic progestins.

Controlling hot flashes was the No. 1 reason the women continued HT beyond age 65 (55%), followed by a desire for a better quality of life (29%), and to reduce chronic pain and arthritis symptoms (7%).

Some adverse effects were reported – postmenopausal bleeding was the most common – but no strokes, myocardial infarctions, or uterine cancers were documented.

More than one fourth (26.4%) of the women tried stopping HT once, but 87% reported that the return of hot flashes was the main reason to restart HT.

In addition, “many women choose to continue hormone therapy long term for relief of nonvasomotor symptoms, preservation of bone density, and a desire to benefit from potential long-term cardiovascular protection,” said Lauren F. Streicher, MD, Professor of Obstetrics and Gynecology at Feinberg School of Medicine at Northwestern University in Chicago, who was not part of the research.

In 2022, The Menopause Society position statement on hormone therapy acknowledged that, on an individual basis, it is appropriate for women to continue hormone therapy long term with counseling on benefits and risks.

“However, few studies have evaluated the outcomes of using hormone therapy for more than 10 years, and individual motivation for doing so,” Dr. Streicher said. She pointed to a study that analyzed the insurance records of more than 10 million women who continued their HT past the age of 65 and reassuringly found that there were significant risk reductions in all-cause mortality, breast cancer, lung cancer, colorectal cancer, heart failure, venous thromboembolism, atrial fibrillation, acute myocardial infarction, and dementia. In that study, however, the reasons women chose to continue hormone therapy were not specified. 

“In this retrospective Canadian study,” she noted, “the outcomes were again reassuring, with no increase in strokes, myocardial infarctions, or uterine cancers. The reasons cited for continuing hormone therapy were not just to treat ongoing vasomotor symptoms, but also other menopause symptoms such as musculoskeletal aches and pains, and overall quality of life.

Dr. Streicher said that, while long-term longitudinal studies are needed to make definitive recommendations, “It is reassuring that women who choose to extend hormone therapy can safely do so. It is irresponsible, cruel, and nonsensical to continue to make blanket statements that hormone therapy should be discontinued based on age or years of use and commit women to enduring symptoms and depriving them of possible long-term benefits.”

Dr. Streicher gives lectures for Midi Health and owns Sermonix stock. Dr. Wolfman has been on the advisory boards for many pharmaceutical companies. She is the past president of the Canadian Menopause Society and is on the board of the International Menopause Society.

TOPLINE:

The use of menopausal hormone therapy (MHT) increases breast cancer risk in women with a strong family history of breast cancer. These women have a striking cumulative risk of developing breast cancer (age, 50-80 years) of 22.4%, according to a new modelling study of UK women.

METHODOLOGY:

This was a modeling study integrating two data-sets of UK women: the BOADICEA dataset of age-specific breast cancer risk with family history and the Collaborative Group on Hormonal Factors in Breast Cancer, which covers relative risk for breast cancer with different types and durations of MHT.

Four different breast cancer family history profiles were:

• “Average” family history of breast cancer has unknown affected family members;
• “Modest” family history comprises a single first-degree relative with breast cancer at the age of 60 years.
• “Intermediate” family history comprises a single first-degree relative who developed breast cancer at the age of 40 years.
• “Strong” family history comprises two first-degree relatives who developed breast cancer at the age of 50 years.

TAKEAWAY:

• The lowest risk category: “Average” family history with no MHT use has a cumulative breast cancer risk (age, 50-80 years) of 9.8% and a risk of dying from breast cancer of 1.7%. These risks rise with 5 years’ exposure to MHT (age, 50-55 years) to 11.0% and 1.8%, respectively.
• The highest risk category: “Strong” family history with no MHT use has a cumulative breast cancer risk (age, 50-80 years) of 19.6% and a risk of dying from breast cancer of 3.2%. These risks rise with 5 years’ exposure to MHT (age, 50-55 years) to 22.4% and 3.5%, respectively.

IN PRACTICE:

The authors concluded that, “These integrated data will enable more accurate estimates of absolute and attributable risk associated with MHT exposure for women with a family history of breast cancer, informing shared decision-making.”

SOURCE:

The lead author is Catherine Huntley of the Institute of Cancer Research, London, England. The study appeared in the British Journal of General Practice.

LIMITATIONS:

Limitations included modeling study that did not directly measure individuals with combined risks.

DISCLOSURES:

The study was funded by several sources including Cancer Research UK. The authors reported no conflicts of interest.

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

TOPLINE:

The use of menopausal hormone therapy (MHT) increases breast cancer risk in women with a strong family history of breast cancer. These women have a striking cumulative risk of developing breast cancer (age, 50-80 years) of 22.4%, according to a new modelling study of UK women.

METHODOLOGY:

This was a modeling study integrating two data-sets of UK women: the BOADICEA dataset of age-specific breast cancer risk with family history and the Collaborative Group on Hormonal Factors in Breast Cancer, which covers relative risk for breast cancer with different types and durations of MHT.

Four different breast cancer family history profiles were:

• “Average” family history of breast cancer has unknown affected family members;
• “Modest” family history comprises a single first-degree relative with breast cancer at the age of 60 years.
• “Intermediate” family history comprises a single first-degree relative who developed breast cancer at the age of 40 years.
• “Strong” family history comprises two first-degree relatives who developed breast cancer at the age of 50 years.

TAKEAWAY:

• The lowest risk category: “Average” family history with no MHT use has a cumulative breast cancer risk (age, 50-80 years) of 9.8% and a risk of dying from breast cancer of 1.7%. These risks rise with 5 years’ exposure to MHT (age, 50-55 years) to 11.0% and 1.8%, respectively.
• The highest risk category: “Strong” family history with no MHT use has a cumulative breast cancer risk (age, 50-80 years) of 19.6% and a risk of dying from breast cancer of 3.2%. These risks rise with 5 years’ exposure to MHT (age, 50-55 years) to 22.4% and 3.5%, respectively.

IN PRACTICE:

The authors concluded that, “These integrated data will enable more accurate estimates of absolute and attributable risk associated with MHT exposure for women with a family history of breast cancer, informing shared decision-making.”

SOURCE:

The lead author is Catherine Huntley of the Institute of Cancer Research, London, England. The study appeared in the British Journal of General Practice.

LIMITATIONS:

Limitations included modeling study that did not directly measure individuals with combined risks.

DISCLOSURES:

The study was funded by several sources including Cancer Research UK. The authors reported no conflicts of interest.

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

TOPLINE:

The use of menopausal hormone therapy (MHT) increases breast cancer risk in women with a strong family history of breast cancer. These women have a striking cumulative risk of developing breast cancer (age, 50-80 years) of 22.4%, according to a new modelling study of UK women.

METHODOLOGY:

This was a modeling study integrating two data-sets of UK women: the BOADICEA dataset of age-specific breast cancer risk with family history and the Collaborative Group on Hormonal Factors in Breast Cancer, which covers relative risk for breast cancer with different types and durations of MHT.

Four different breast cancer family history profiles were:

• “Average” family history of breast cancer has unknown affected family members;
• “Modest” family history comprises a single first-degree relative with breast cancer at the age of 60 years.
• “Intermediate” family history comprises a single first-degree relative who developed breast cancer at the age of 40 years.
• “Strong” family history comprises two first-degree relatives who developed breast cancer at the age of 50 years.

TAKEAWAY:

• The lowest risk category: “Average” family history with no MHT use has a cumulative breast cancer risk (age, 50-80 years) of 9.8% and a risk of dying from breast cancer of 1.7%. These risks rise with 5 years’ exposure to MHT (age, 50-55 years) to 11.0% and 1.8%, respectively.
• The highest risk category: “Strong” family history with no MHT use has a cumulative breast cancer risk (age, 50-80 years) of 19.6% and a risk of dying from breast cancer of 3.2%. These risks rise with 5 years’ exposure to MHT (age, 50-55 years) to 22.4% and 3.5%, respectively.

IN PRACTICE:

The authors concluded that, “These integrated data will enable more accurate estimates of absolute and attributable risk associated with MHT exposure for women with a family history of breast cancer, informing shared decision-making.”

SOURCE:

The lead author is Catherine Huntley of the Institute of Cancer Research, London, England. The study appeared in the British Journal of General Practice.

LIMITATIONS:

Limitations included modeling study that did not directly measure individuals with combined risks.

DISCLOSURES:

The study was funded by several sources including Cancer Research UK. The authors reported no conflicts of interest.

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

TOPLINE:

Hormone-modulating therapy for breast cancer may protect older women from Alzheimer’s disease and related dementias, although the protective effect varies by age and race, with the greatest benefit seen in younger Black women.

METHODOLOGY:

• Hormone-modulating therapy is widely used to treat hormone receptor–positive breast cancer, but the cognitive effects of the treatment, including a potential link to dementia, remain unclear.
• To investigate, researchers used the SEER-Medicare linked database to identify women aged 65 years or older with breast cancer who did and did not receive hormone-modulating therapy within 3 years following their diagnosis.
• The researchers excluded women with preexisting Alzheimer’s disease/dementia diagnoses or those who had received hormone-modulating therapy before their breast cancer diagnosis.
• Analyses were adjusted for demographic, sociocultural, and clinical variables, and subgroup analyses evaluated the impact of age, race, and type of hormone-modulating therapy on Alzheimer’s disease/dementia risk.

TAKEAWAY:

• Among the 18,808 women included in the analysis, 66% received hormone-modulating therapy and 34% did not. During the mean follow-up of 12 years, 24% of hormone-modulating therapy users and 28% of nonusers developed Alzheimer’s disease/dementia.
• Overall, hormone-modulating therapy use (vs nonuse) was associated with a significant 7% lower risk for Alzheimer’s disease/dementia (hazard ratio [HR], 0.93; P = .005), with notable age and racial differences.
• Hormone-modulating therapy use was associated with a 24% lower risk for Alzheimer’s disease/dementia in Black women aged 65-74 years (HR, 0.76), but that protective effect decreased to 19% in Black women aged 75 years or older (HR, 0.81). White women aged 65-74 years who received hormone-modulating therapy (vs those who did not) had an 11% lower risk for Alzheimer’s disease/dementia (HR, 0.89), but the association disappeared among those aged 75 years or older (HR, 0.96; 95% CI, 0.90-1.02). Other races demonstrated no significant association between hormone-modulating therapy use and Alzheimer’s disease/dementia.
• Overall, the use of an aromatase inhibitor or a selective estrogen receptor modulator was associated with a significantly lower risk for Alzheimer’s disease/dementia (HR, 0.93 and HR, 0.89, respectively).

IN PRACTICE:

Overall, the retrospective study found that “hormone therapy was associated with protection against [Alzheimer’s/dementia] in women aged 65 years or older with newly diagnosed breast cancer,” with the decrease in risk relatively greater for Black women and women younger than 75 years, the authors concluded.

“The results highlight the critical need for personalized breast cancer treatment plans that are tailored to the individual characteristics of each patient, particularly given the significantly higher likelihood (two to three times more) of Black women developing [Alzheimer’s/dementia], compared with their White counterparts,” the researchers added.
 

SOURCE:

The study, with first author Chao Cai, PhD, Department of Clinical Pharmacy and Outcomes Sciences, University of South Carolina, Columbia, was published online on July 16 in JAMA Network Open.

LIMITATIONS:

The study included only women aged 65 years or older, limiting generalizability to younger women. The dataset lacked genetic information and laboratory data related to dementia. The duration of hormone-modulating therapy use beyond 3 years and specific formulations were not assessed. Potential confounders such as variations in chemotherapy, radiation, and surgery were not fully addressed.

DISCLOSURES:

Support for the study was provided by the National Institutes of Health; Carolina Center on Alzheimer’s Disease and Minority Research pilot project; and the Dean’s Faculty Advancement Fund, University of Pittsburgh, Pennsylvania. The authors reported no relevant disclosures.

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

TOPLINE:

Hormone-modulating therapy for breast cancer may protect older women from Alzheimer’s disease and related dementias, although the protective effect varies by age and race, with the greatest benefit seen in younger Black women.

METHODOLOGY:

• Hormone-modulating therapy is widely used to treat hormone receptor–positive breast cancer, but the cognitive effects of the treatment, including a potential link to dementia, remain unclear.
• To investigate, researchers used the SEER-Medicare linked database to identify women aged 65 years or older with breast cancer who did and did not receive hormone-modulating therapy within 3 years following their diagnosis.
• The researchers excluded women with preexisting Alzheimer’s disease/dementia diagnoses or those who had received hormone-modulating therapy before their breast cancer diagnosis.
• Analyses were adjusted for demographic, sociocultural, and clinical variables, and subgroup analyses evaluated the impact of age, race, and type of hormone-modulating therapy on Alzheimer’s disease/dementia risk.

TAKEAWAY:

• Among the 18,808 women included in the analysis, 66% received hormone-modulating therapy and 34% did not. During the mean follow-up of 12 years, 24% of hormone-modulating therapy users and 28% of nonusers developed Alzheimer’s disease/dementia.
• Overall, hormone-modulating therapy use (vs nonuse) was associated with a significant 7% lower risk for Alzheimer’s disease/dementia (hazard ratio [HR], 0.93; P = .005), with notable age and racial differences.
• Hormone-modulating therapy use was associated with a 24% lower risk for Alzheimer’s disease/dementia in Black women aged 65-74 years (HR, 0.76), but that protective effect decreased to 19% in Black women aged 75 years or older (HR, 0.81). White women aged 65-74 years who received hormone-modulating therapy (vs those who did not) had an 11% lower risk for Alzheimer’s disease/dementia (HR, 0.89), but the association disappeared among those aged 75 years or older (HR, 0.96; 95% CI, 0.90-1.02). Other races demonstrated no significant association between hormone-modulating therapy use and Alzheimer’s disease/dementia.
• Overall, the use of an aromatase inhibitor or a selective estrogen receptor modulator was associated with a significantly lower risk for Alzheimer’s disease/dementia (HR, 0.93 and HR, 0.89, respectively).

IN PRACTICE:

Overall, the retrospective study found that “hormone therapy was associated with protection against [Alzheimer’s/dementia] in women aged 65 years or older with newly diagnosed breast cancer,” with the decrease in risk relatively greater for Black women and women younger than 75 years, the authors concluded.

“The results highlight the critical need for personalized breast cancer treatment plans that are tailored to the individual characteristics of each patient, particularly given the significantly higher likelihood (two to three times more) of Black women developing [Alzheimer’s/dementia], compared with their White counterparts,” the researchers added.
 

SOURCE:

The study, with first author Chao Cai, PhD, Department of Clinical Pharmacy and Outcomes Sciences, University of South Carolina, Columbia, was published online on July 16 in JAMA Network Open.

LIMITATIONS:

The study included only women aged 65 years or older, limiting generalizability to younger women. The dataset lacked genetic information and laboratory data related to dementia. The duration of hormone-modulating therapy use beyond 3 years and specific formulations were not assessed. Potential confounders such as variations in chemotherapy, radiation, and surgery were not fully addressed.

DISCLOSURES:

Support for the study was provided by the National Institutes of Health; Carolina Center on Alzheimer’s Disease and Minority Research pilot project; and the Dean’s Faculty Advancement Fund, University of Pittsburgh, Pennsylvania. The authors reported no relevant disclosures.

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

TOPLINE:

Hormone-modulating therapy for breast cancer may protect older women from Alzheimer’s disease and related dementias, although the protective effect varies by age and race, with the greatest benefit seen in younger Black women.

METHODOLOGY:

• Hormone-modulating therapy is widely used to treat hormone receptor–positive breast cancer, but the cognitive effects of the treatment, including a potential link to dementia, remain unclear.
• To investigate, researchers used the SEER-Medicare linked database to identify women aged 65 years or older with breast cancer who did and did not receive hormone-modulating therapy within 3 years following their diagnosis.
• The researchers excluded women with preexisting Alzheimer’s disease/dementia diagnoses or those who had received hormone-modulating therapy before their breast cancer diagnosis.
• Analyses were adjusted for demographic, sociocultural, and clinical variables, and subgroup analyses evaluated the impact of age, race, and type of hormone-modulating therapy on Alzheimer’s disease/dementia risk.

TAKEAWAY:

• Among the 18,808 women included in the analysis, 66% received hormone-modulating therapy and 34% did not. During the mean follow-up of 12 years, 24% of hormone-modulating therapy users and 28% of nonusers developed Alzheimer’s disease/dementia.
• Overall, hormone-modulating therapy use (vs nonuse) was associated with a significant 7% lower risk for Alzheimer’s disease/dementia (hazard ratio [HR], 0.93; P = .005), with notable age and racial differences.
• Hormone-modulating therapy use was associated with a 24% lower risk for Alzheimer’s disease/dementia in Black women aged 65-74 years (HR, 0.76), but that protective effect decreased to 19% in Black women aged 75 years or older (HR, 0.81). White women aged 65-74 years who received hormone-modulating therapy (vs those who did not) had an 11% lower risk for Alzheimer’s disease/dementia (HR, 0.89), but the association disappeared among those aged 75 years or older (HR, 0.96; 95% CI, 0.90-1.02). Other races demonstrated no significant association between hormone-modulating therapy use and Alzheimer’s disease/dementia.
• Overall, the use of an aromatase inhibitor or a selective estrogen receptor modulator was associated with a significantly lower risk for Alzheimer’s disease/dementia (HR, 0.93 and HR, 0.89, respectively).

IN PRACTICE:

Overall, the retrospective study found that “hormone therapy was associated with protection against [Alzheimer’s/dementia] in women aged 65 years or older with newly diagnosed breast cancer,” with the decrease in risk relatively greater for Black women and women younger than 75 years, the authors concluded.

“The results highlight the critical need for personalized breast cancer treatment plans that are tailored to the individual characteristics of each patient, particularly given the significantly higher likelihood (two to three times more) of Black women developing [Alzheimer’s/dementia], compared with their White counterparts,” the researchers added.
 

SOURCE:

The study, with first author Chao Cai, PhD, Department of Clinical Pharmacy and Outcomes Sciences, University of South Carolina, Columbia, was published online on July 16 in JAMA Network Open.

LIMITATIONS:

The study included only women aged 65 years or older, limiting generalizability to younger women. The dataset lacked genetic information and laboratory data related to dementia. The duration of hormone-modulating therapy use beyond 3 years and specific formulations were not assessed. Potential confounders such as variations in chemotherapy, radiation, and surgery were not fully addressed.

DISCLOSURES:

Support for the study was provided by the National Institutes of Health; Carolina Center on Alzheimer’s Disease and Minority Research pilot project; and the Dean’s Faculty Advancement Fund, University of Pittsburgh, Pennsylvania. The authors reported no relevant disclosures.

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

TOPLINE:

Women who received false-positive mammography results were less likely to return for future screenings.

METHODOLOGY:

• Researchers analyzed more than three million screening mammograms from more than one million women aged between 40 and 73 years at nearly 200 facilities in the Breast Cancer Surveillance Consortium between 2005 and 2017.
• Mammography results were classified as true negative or false positive; women who received false-positive results were either asked to come back for additional imaging, a short interval follow-up or biopsy recommendations.
• The primary outcome was the probability of returning for routine screening within 9-30 months after a false-positive or true-negative result, adjusted for race, ethnicity, age, and time since the last mammogram.
• Women with two screening mammograms within 5 years were also analyzed to evaluate the probability of returning for a third screening based on combinations of true-negative and false-positive results.

TAKEAWAY:

• Nearly 10.0% (95% CI, 9.1%-10.5%) of women who received screening mammograms got a false-positive result, 5.8% (95% CI, 5.5%-6.2%) of whom needed immediate additional imaging, 2.7% (95% CI, 2.3%-3.2%) needed short-interval follow-up, and 1.3% (95% CI, 1.1%-1.4%) were recommended for a biopsy.
• Women were more likely to return for screening after a true-negative result (76.9%) than after a false positive to obtain more data through additional imaging (72.4%), short-interval follow-ups (54.7%), or biopsy (61.0%).
• Asian and Hispanic/Latinx women who received a false-positive result were much less likely to return for a screening than women of the same groups who received a true-negative result, with recommendations for short interval follow-up (decrease of 20-25 percentage points) or biopsy (decrease of 13-14 percentage points).
• For women who had two screening mammograms within 5 years, receiving a false-positive result on the second was linked to a lower likelihood of returning for a third screening, regardless of results for the first.

IN PRACTICE:

“Physicians should educate their patients about the importance of continued screening after false-positive results, especially given the associated increased future risk for breast cancer,” study authors wrote.

SOURCE:

The study was led by Diana L. Miglioretti, PhD, of the Department of Public Health Sciences at the University of California, Davis, and published online on September 3 in Annals of Internal Medicine.

LIMITATIONS:

Women could receive care at facilities outside of the trial, which may have affected the accuracy of return rates. The study did not track a complete history of false-positive results. The study did not have information about how often physicians recommend screenings and did not account for other health conditions.

DISCLOSURES:

One coauthor reported receiving grants from the National Institutes of Health and the American Cancer Society, as well as consulting fees from the University of Florida, Gainesville.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

Women who received false-positive mammography results were less likely to return for future screenings.

METHODOLOGY:

• Researchers analyzed more than three million screening mammograms from more than one million women aged between 40 and 73 years at nearly 200 facilities in the Breast Cancer Surveillance Consortium between 2005 and 2017.
• Mammography results were classified as true negative or false positive; women who received false-positive results were either asked to come back for additional imaging, a short interval follow-up or biopsy recommendations.
• The primary outcome was the probability of returning for routine screening within 9-30 months after a false-positive or true-negative result, adjusted for race, ethnicity, age, and time since the last mammogram.
• Women with two screening mammograms within 5 years were also analyzed to evaluate the probability of returning for a third screening based on combinations of true-negative and false-positive results.

TAKEAWAY:

• Nearly 10.0% (95% CI, 9.1%-10.5%) of women who received screening mammograms got a false-positive result, 5.8% (95% CI, 5.5%-6.2%) of whom needed immediate additional imaging, 2.7% (95% CI, 2.3%-3.2%) needed short-interval follow-up, and 1.3% (95% CI, 1.1%-1.4%) were recommended for a biopsy.
• Women were more likely to return for screening after a true-negative result (76.9%) than after a false positive to obtain more data through additional imaging (72.4%), short-interval follow-ups (54.7%), or biopsy (61.0%).
• Asian and Hispanic/Latinx women who received a false-positive result were much less likely to return for a screening than women of the same groups who received a true-negative result, with recommendations for short interval follow-up (decrease of 20-25 percentage points) or biopsy (decrease of 13-14 percentage points).
• For women who had two screening mammograms within 5 years, receiving a false-positive result on the second was linked to a lower likelihood of returning for a third screening, regardless of results for the first.

IN PRACTICE:

“Physicians should educate their patients about the importance of continued screening after false-positive results, especially given the associated increased future risk for breast cancer,” study authors wrote.

SOURCE:

The study was led by Diana L. Miglioretti, PhD, of the Department of Public Health Sciences at the University of California, Davis, and published online on September 3 in Annals of Internal Medicine.

LIMITATIONS:

Women could receive care at facilities outside of the trial, which may have affected the accuracy of return rates. The study did not track a complete history of false-positive results. The study did not have information about how often physicians recommend screenings and did not account for other health conditions.

DISCLOSURES:

One coauthor reported receiving grants from the National Institutes of Health and the American Cancer Society, as well as consulting fees from the University of Florida, Gainesville.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

Women who received false-positive mammography results were less likely to return for future screenings.

METHODOLOGY:

• Researchers analyzed more than three million screening mammograms from more than one million women aged between 40 and 73 years at nearly 200 facilities in the Breast Cancer Surveillance Consortium between 2005 and 2017.
• Mammography results were classified as true negative or false positive; women who received false-positive results were either asked to come back for additional imaging, a short interval follow-up or biopsy recommendations.
• The primary outcome was the probability of returning for routine screening within 9-30 months after a false-positive or true-negative result, adjusted for race, ethnicity, age, and time since the last mammogram.
• Women with two screening mammograms within 5 years were also analyzed to evaluate the probability of returning for a third screening based on combinations of true-negative and false-positive results.

TAKEAWAY:

• Nearly 10.0% (95% CI, 9.1%-10.5%) of women who received screening mammograms got a false-positive result, 5.8% (95% CI, 5.5%-6.2%) of whom needed immediate additional imaging, 2.7% (95% CI, 2.3%-3.2%) needed short-interval follow-up, and 1.3% (95% CI, 1.1%-1.4%) were recommended for a biopsy.
• Women were more likely to return for screening after a true-negative result (76.9%) than after a false positive to obtain more data through additional imaging (72.4%), short-interval follow-ups (54.7%), or biopsy (61.0%).
• Asian and Hispanic/Latinx women who received a false-positive result were much less likely to return for a screening than women of the same groups who received a true-negative result, with recommendations for short interval follow-up (decrease of 20-25 percentage points) or biopsy (decrease of 13-14 percentage points).
• For women who had two screening mammograms within 5 years, receiving a false-positive result on the second was linked to a lower likelihood of returning for a third screening, regardless of results for the first.

IN PRACTICE:

“Physicians should educate their patients about the importance of continued screening after false-positive results, especially given the associated increased future risk for breast cancer,” study authors wrote.

SOURCE:

The study was led by Diana L. Miglioretti, PhD, of the Department of Public Health Sciences at the University of California, Davis, and published online on September 3 in Annals of Internal Medicine.

LIMITATIONS:

Women could receive care at facilities outside of the trial, which may have affected the accuracy of return rates. The study did not track a complete history of false-positive results. The study did not have information about how often physicians recommend screenings and did not account for other health conditions.

DISCLOSURES:

One coauthor reported receiving grants from the National Institutes of Health and the American Cancer Society, as well as consulting fees from the University of Florida, Gainesville.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

Clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) are associated with an increased risk for breast cancer, and CHIP is associated with increased mortality in patients with colon cancer, according to the authors of new research.

These findings, drawn from almost 11,000 patients in the Women’s Health Initiative (WHI) study, add further evidence that CHIP and mCA drive solid tumor risk, alongside known associations with hematologic malignancies, reported lead author Pinkal Desai, MD, associate professor of medicine and clinical director of molecular aging at Englander Institute for Precision Medicine, Weill Cornell Medical College, New York City, and colleagues.
 

How This Study Differs From Others of Breast Cancer Risk Factors

“The independent effect of CHIP and mCA on risk and mortality from solid tumors has not been elucidated due to lack of detailed data on mortality outcomes and risk factors,” the investigators wrote in Cancer, although some previous studies have suggested a link.

In particular, the investigators highlighted a 2022 UK Biobank study, which reported an association between CHIP and lung cancer and a borderline association with breast cancer that did not quite reach statistical significance.

But the UK Biobank study was confined to a UK population, Dr. Desai noted in an interview, and the data were less detailed than those in the present investigation.

“In terms of risk, the part that was lacking in previous studies was a comprehensive assessment of risk factors that increase risk for all these cancers,” Dr. Desai said. “For example, for breast cancer, we had very detailed data on [participants’] Gail risk score, which is known to impact breast cancer risk. We also had mammogram data and colonoscopy data.”

In an accompanying editorial, Koichi Takahashi, MD, PhD , and Nehali Shah, BS, of The University of Texas MD Anderson Cancer Center, Houston, Texas, pointed out the same UK Biobank findings, then noted that CHIP has also been linked with worse overall survival in unselected cancer patients. Still, they wrote, “the impact of CH on cancer risk and mortality remains controversial due to conflicting data and context‐dependent effects,” necessitating studies like this one by Dr. Desai and colleagues.
 

How Was the Relationship Between CHIP, MCA, and Solid Tumor Risk Assessed?

To explore possible associations between CHIP, mCA, and solid tumors, the investigators analyzed whole genome sequencing data from 10,866 women in the WHI, a multi-study program that began in 1992 and involved 161,808 women in both observational and clinical trial cohorts.

In 2002, the first big data release from the WHI suggested that hormone replacement therapy (HRT) increased breast cancer risk, leading to widespread reduction in HRT use.

More recent reports continue to shape our understanding of these risks, suggesting differences across cancer types. For breast cancer, the WHI data suggested that HRT-associated risk was largely driven by formulations involving progesterone and estrogen, whereas estrogen-only formulations, now more common, are generally considered to present an acceptable risk profile for suitable patients.

The new study accounted for this potential HRT-associated risk, including by adjusting for patients who received HRT, type of HRT received, and duration of HRT received. According to Desai, this approach is commonly used when analyzing data from the WHI, nullifying concerns about the potentially deleterious effects of the hormones used in the study.

“Our question was not ‘does HRT cause cancer?’ ” Dr. Desai said in an interview. “But HRT can be linked to breast cancer risk and has a potential to be a confounder, and hence the above methodology.

“So I can say that the confounding/effect modification that HRT would have contributed to in the relationship between exposure (CH and mCA) and outcome (cancer) is well adjusted for as described above. This is standard in WHI analyses,” she continued.

“Every Women’s Health Initiative analysis that comes out — not just for our study — uses a standard method ... where you account for hormonal therapy,” Dr. Desai added, again noting that many other potential risk factors were considered, enabling a “detailed, robust” analysis.

Dr. Takahashi and Ms. Shah agreed. “A notable strength of this study is its adjustment for many confounding factors,” they wrote. “The cohort’s well‐annotated data on other known cancer risk factors allowed for a robust assessment of CH’s independent risk.”
 

How Do Findings Compare With Those of the UK Biobank Study?

CHIP was associated with a 30% increased risk for breast cancer (hazard ratio [HR], 1.30; 95% CI, 1.03-1.64; P = .02), strengthening the borderline association reported by the UK Biobank study.

In contrast with the UK Biobank study, CHIP was not associated with lung cancer risk, although this may have been caused by fewer cases of lung cancer and a lack of male patients, Dr. Desai suggested.

“The discrepancy between the studies lies in the risk of lung cancer, although the point estimate in the current study suggested a positive association,” wrote Dr. Takahashi and Ms. Shah.

As in the UK Biobank study, CHIP was not associated with increased risk of developing colorectal cancer.

Mortality analysis, however, which was not conducted in the UK Biobank study, offered a new insight: Patients with existing colorectal cancer and CHIP had a significantly higher mortality risk than those without CHIP. Before stage adjustment, risk for mortality among those with colorectal cancer and CHIP was fourfold higher than those without CHIP (HR, 3.99; 95% CI, 2.41-6.62; P < .001). After stage adjustment, CHIP was still associated with a twofold higher mortality risk (HR, 2.50; 95% CI, 1.32-4.72; P = .004).

The investigators’ first mCA analyses, which employed a cell fraction cutoff greater than 3%, were unfruitful. But raising the cell fraction threshold to 5% in an exploratory analysis showed that autosomal mCA was associated with a 39% increased risk for breast cancer (HR, 1.39; 95% CI, 1.06-1.83; P = .01). No such associations were found between mCA and colorectal or lung cancer, regardless of cell fraction threshold.

The original 3% cell fraction threshold was selected on the basis of previous studies reporting a link between mCA and hematologic malignancies at this cutoff, Dr. Desai said.

She and her colleagues said a higher 5% cutoff might be needed, as they suspected that the link between mCA and solid tumors may not be causal, requiring a higher mutation rate.
 

Why Do Results Differ Between These Types of Studies?

Dr. Takahashi and Ms. Shah suggested that one possible limitation of the new study, and an obstacle to comparing results with the UK Biobank study and others like it, goes beyond population heterogeneity; incongruent findings could also be explained by differences in whole genome sequencing (WGS) technique.

“Although WGS allows sensitive detection of mCA through broad genomic coverage, it is less effective at detecting CHIP with low variant allele frequency (VAF) due to its relatively shallow depth (30x),” they wrote. “Consequently, the prevalence of mCA (18.8%) was much higher than that of CHIP (8.3%) in this cohort, contrasting with other studies using deeper sequencing.” As a result, the present study may have underestimated CHIP prevalence because of shallow sequencing depth.

“This inconsistency is a common challenge in CH population studies due to the lack of standardized methodologies and the frequent reliance on preexisting data not originally intended for CH detection,” Dr. Takahashi and Ms. Shah said.

Even so, despite the “heavily context-dependent” nature of these reported risks, the body of evidence to date now offers a convincing biological rationale linking CH with cancer development and outcomes, they added.
 

How Do the CHIP- and mCA-associated Risks Differ Between Solid Tumors and Blood Cancers?

“[These solid tumor risks are] not causal in the way CHIP mutations are causal for blood cancers,” Dr. Desai said. “Here we are talking about solid tumor risk, and it’s kind of scattered. It’s not just breast cancer ... there’s also increased colon cancer mortality. So I feel these mutations are doing something different ... they are sort of an added factor.”

Specific mechanisms remain unclear, Dr. Desai said, although she speculated about possible impacts on the inflammatory state or alterations to the tumor microenvironment.

“These are blood cells, right?” Dr. Desai asked. “They’re everywhere, and they’re changing something inherently in these tumors.”
 

Future research and therapeutic development

Siddhartha Jaiswal, MD, PhD, assistant professor in the Department of Pathology at Stanford University in California, whose lab focuses on clonal hematopoiesis, said the causality question is central to future research.

“The key question is, are these mutations acting because they alter the function of blood cells in some way to promote cancer risk, or is it reflective of some sort of shared etiology that’s not causal?” Dr. Jaiswal said in an interview.

Available data support both possibilities.

On one side, “reasonable evidence” supports the noncausal view, Dr. Jaiswal noted, because telomere length is one of the most common genetic risk factors for clonal hematopoiesis and also for solid tumors, suggesting a shared genetic factor. On the other hand, CHIP and mCA could be directly protumorigenic via conferred disturbances of immune cell function.

When asked if both causal and noncausal factors could be at play, Dr. Jaiswal said, “yeah, absolutely.”

The presence of a causal association could be promising from a therapeutic standpoint.

“If it turns out that this association is driven by a direct causal effect of the mutations, perhaps related to immune cell function or dysfunction, then targeting that dysfunction could be a therapeutic path to improve outcomes in people, and there’s a lot of interest in this,” Dr. Jaiswal said. He went on to explain how a trial exploring this approach via interleukin-8 inhibition in lung cancer fell short.

Yet earlier intervention may still hold promise, according to experts.

“[This study] provokes the hypothesis that CH‐targeted interventions could potentially reduce cancer risk in the future,” Dr. Takahashi and Ms. Shah said in their editorial.

The WHI program is funded by the National Heart, Lung, and Blood Institute; National Institutes of Health; and the Department of Health & Human Services. The investigators disclosed relationships with Eli Lilly, AbbVie, Celgene, and others. Dr. Jaiswal reported stock equity in a company that has an interest in clonal hematopoiesis.

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

Clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) are associated with an increased risk for breast cancer, and CHIP is associated with increased mortality in patients with colon cancer, according to the authors of new research.

These findings, drawn from almost 11,000 patients in the Women’s Health Initiative (WHI) study, add further evidence that CHIP and mCA drive solid tumor risk, alongside known associations with hematologic malignancies, reported lead author Pinkal Desai, MD, associate professor of medicine and clinical director of molecular aging at Englander Institute for Precision Medicine, Weill Cornell Medical College, New York City, and colleagues.
 

How This Study Differs From Others of Breast Cancer Risk Factors

“The independent effect of CHIP and mCA on risk and mortality from solid tumors has not been elucidated due to lack of detailed data on mortality outcomes and risk factors,” the investigators wrote in Cancer, although some previous studies have suggested a link.

In particular, the investigators highlighted a 2022 UK Biobank study, which reported an association between CHIP and lung cancer and a borderline association with breast cancer that did not quite reach statistical significance.

But the UK Biobank study was confined to a UK population, Dr. Desai noted in an interview, and the data were less detailed than those in the present investigation.

“In terms of risk, the part that was lacking in previous studies was a comprehensive assessment of risk factors that increase risk for all these cancers,” Dr. Desai said. “For example, for breast cancer, we had very detailed data on [participants’] Gail risk score, which is known to impact breast cancer risk. We also had mammogram data and colonoscopy data.”

In an accompanying editorial, Koichi Takahashi, MD, PhD , and Nehali Shah, BS, of The University of Texas MD Anderson Cancer Center, Houston, Texas, pointed out the same UK Biobank findings, then noted that CHIP has also been linked with worse overall survival in unselected cancer patients. Still, they wrote, “the impact of CH on cancer risk and mortality remains controversial due to conflicting data and context‐dependent effects,” necessitating studies like this one by Dr. Desai and colleagues.
 

How Was the Relationship Between CHIP, MCA, and Solid Tumor Risk Assessed?

To explore possible associations between CHIP, mCA, and solid tumors, the investigators analyzed whole genome sequencing data from 10,866 women in the WHI, a multi-study program that began in 1992 and involved 161,808 women in both observational and clinical trial cohorts.

In 2002, the first big data release from the WHI suggested that hormone replacement therapy (HRT) increased breast cancer risk, leading to widespread reduction in HRT use.

More recent reports continue to shape our understanding of these risks, suggesting differences across cancer types. For breast cancer, the WHI data suggested that HRT-associated risk was largely driven by formulations involving progesterone and estrogen, whereas estrogen-only formulations, now more common, are generally considered to present an acceptable risk profile for suitable patients.

The new study accounted for this potential HRT-associated risk, including by adjusting for patients who received HRT, type of HRT received, and duration of HRT received. According to Desai, this approach is commonly used when analyzing data from the WHI, nullifying concerns about the potentially deleterious effects of the hormones used in the study.

“Our question was not ‘does HRT cause cancer?’ ” Dr. Desai said in an interview. “But HRT can be linked to breast cancer risk and has a potential to be a confounder, and hence the above methodology.

“So I can say that the confounding/effect modification that HRT would have contributed to in the relationship between exposure (CH and mCA) and outcome (cancer) is well adjusted for as described above. This is standard in WHI analyses,” she continued.

“Every Women’s Health Initiative analysis that comes out — not just for our study — uses a standard method ... where you account for hormonal therapy,” Dr. Desai added, again noting that many other potential risk factors were considered, enabling a “detailed, robust” analysis.

Dr. Takahashi and Ms. Shah agreed. “A notable strength of this study is its adjustment for many confounding factors,” they wrote. “The cohort’s well‐annotated data on other known cancer risk factors allowed for a robust assessment of CH’s independent risk.”
 

How Do Findings Compare With Those of the UK Biobank Study?

CHIP was associated with a 30% increased risk for breast cancer (hazard ratio [HR], 1.30; 95% CI, 1.03-1.64; P = .02), strengthening the borderline association reported by the UK Biobank study.

In contrast with the UK Biobank study, CHIP was not associated with lung cancer risk, although this may have been caused by fewer cases of lung cancer and a lack of male patients, Dr. Desai suggested.

“The discrepancy between the studies lies in the risk of lung cancer, although the point estimate in the current study suggested a positive association,” wrote Dr. Takahashi and Ms. Shah.

As in the UK Biobank study, CHIP was not associated with increased risk of developing colorectal cancer.

Mortality analysis, however, which was not conducted in the UK Biobank study, offered a new insight: Patients with existing colorectal cancer and CHIP had a significantly higher mortality risk than those without CHIP. Before stage adjustment, risk for mortality among those with colorectal cancer and CHIP was fourfold higher than those without CHIP (HR, 3.99; 95% CI, 2.41-6.62; P < .001). After stage adjustment, CHIP was still associated with a twofold higher mortality risk (HR, 2.50; 95% CI, 1.32-4.72; P = .004).

The investigators’ first mCA analyses, which employed a cell fraction cutoff greater than 3%, were unfruitful. But raising the cell fraction threshold to 5% in an exploratory analysis showed that autosomal mCA was associated with a 39% increased risk for breast cancer (HR, 1.39; 95% CI, 1.06-1.83; P = .01). No such associations were found between mCA and colorectal or lung cancer, regardless of cell fraction threshold.

The original 3% cell fraction threshold was selected on the basis of previous studies reporting a link between mCA and hematologic malignancies at this cutoff, Dr. Desai said.

She and her colleagues said a higher 5% cutoff might be needed, as they suspected that the link between mCA and solid tumors may not be causal, requiring a higher mutation rate.
 

Why Do Results Differ Between These Types of Studies?

Dr. Takahashi and Ms. Shah suggested that one possible limitation of the new study, and an obstacle to comparing results with the UK Biobank study and others like it, goes beyond population heterogeneity; incongruent findings could also be explained by differences in whole genome sequencing (WGS) technique.

“Although WGS allows sensitive detection of mCA through broad genomic coverage, it is less effective at detecting CHIP with low variant allele frequency (VAF) due to its relatively shallow depth (30x),” they wrote. “Consequently, the prevalence of mCA (18.8%) was much higher than that of CHIP (8.3%) in this cohort, contrasting with other studies using deeper sequencing.” As a result, the present study may have underestimated CHIP prevalence because of shallow sequencing depth.

“This inconsistency is a common challenge in CH population studies due to the lack of standardized methodologies and the frequent reliance on preexisting data not originally intended for CH detection,” Dr. Takahashi and Ms. Shah said.

Even so, despite the “heavily context-dependent” nature of these reported risks, the body of evidence to date now offers a convincing biological rationale linking CH with cancer development and outcomes, they added.
 

How Do the CHIP- and mCA-associated Risks Differ Between Solid Tumors and Blood Cancers?

“[These solid tumor risks are] not causal in the way CHIP mutations are causal for blood cancers,” Dr. Desai said. “Here we are talking about solid tumor risk, and it’s kind of scattered. It’s not just breast cancer ... there’s also increased colon cancer mortality. So I feel these mutations are doing something different ... they are sort of an added factor.”

Specific mechanisms remain unclear, Dr. Desai said, although she speculated about possible impacts on the inflammatory state or alterations to the tumor microenvironment.

“These are blood cells, right?” Dr. Desai asked. “They’re everywhere, and they’re changing something inherently in these tumors.”
 

Future research and therapeutic development

Siddhartha Jaiswal, MD, PhD, assistant professor in the Department of Pathology at Stanford University in California, whose lab focuses on clonal hematopoiesis, said the causality question is central to future research.

“The key question is, are these mutations acting because they alter the function of blood cells in some way to promote cancer risk, or is it reflective of some sort of shared etiology that’s not causal?” Dr. Jaiswal said in an interview.

Available data support both possibilities.

On one side, “reasonable evidence” supports the noncausal view, Dr. Jaiswal noted, because telomere length is one of the most common genetic risk factors for clonal hematopoiesis and also for solid tumors, suggesting a shared genetic factor. On the other hand, CHIP and mCA could be directly protumorigenic via conferred disturbances of immune cell function.

When asked if both causal and noncausal factors could be at play, Dr. Jaiswal said, “yeah, absolutely.”

The presence of a causal association could be promising from a therapeutic standpoint.

“If it turns out that this association is driven by a direct causal effect of the mutations, perhaps related to immune cell function or dysfunction, then targeting that dysfunction could be a therapeutic path to improve outcomes in people, and there’s a lot of interest in this,” Dr. Jaiswal said. He went on to explain how a trial exploring this approach via interleukin-8 inhibition in lung cancer fell short.

Yet earlier intervention may still hold promise, according to experts.

“[This study] provokes the hypothesis that CH‐targeted interventions could potentially reduce cancer risk in the future,” Dr. Takahashi and Ms. Shah said in their editorial.

The WHI program is funded by the National Heart, Lung, and Blood Institute; National Institutes of Health; and the Department of Health & Human Services. The investigators disclosed relationships with Eli Lilly, AbbVie, Celgene, and others. Dr. Jaiswal reported stock equity in a company that has an interest in clonal hematopoiesis.

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

Clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) are associated with an increased risk for breast cancer, and CHIP is associated with increased mortality in patients with colon cancer, according to the authors of new research.

These findings, drawn from almost 11,000 patients in the Women’s Health Initiative (WHI) study, add further evidence that CHIP and mCA drive solid tumor risk, alongside known associations with hematologic malignancies, reported lead author Pinkal Desai, MD, associate professor of medicine and clinical director of molecular aging at Englander Institute for Precision Medicine, Weill Cornell Medical College, New York City, and colleagues.
 

How This Study Differs From Others of Breast Cancer Risk Factors

“The independent effect of CHIP and mCA on risk and mortality from solid tumors has not been elucidated due to lack of detailed data on mortality outcomes and risk factors,” the investigators wrote in Cancer, although some previous studies have suggested a link.

In particular, the investigators highlighted a 2022 UK Biobank study, which reported an association between CHIP and lung cancer and a borderline association with breast cancer that did not quite reach statistical significance.

But the UK Biobank study was confined to a UK population, Dr. Desai noted in an interview, and the data were less detailed than those in the present investigation.

“In terms of risk, the part that was lacking in previous studies was a comprehensive assessment of risk factors that increase risk for all these cancers,” Dr. Desai said. “For example, for breast cancer, we had very detailed data on [participants’] Gail risk score, which is known to impact breast cancer risk. We also had mammogram data and colonoscopy data.”

In an accompanying editorial, Koichi Takahashi, MD, PhD , and Nehali Shah, BS, of The University of Texas MD Anderson Cancer Center, Houston, Texas, pointed out the same UK Biobank findings, then noted that CHIP has also been linked with worse overall survival in unselected cancer patients. Still, they wrote, “the impact of CH on cancer risk and mortality remains controversial due to conflicting data and context‐dependent effects,” necessitating studies like this one by Dr. Desai and colleagues.
 

How Was the Relationship Between CHIP, MCA, and Solid Tumor Risk Assessed?

To explore possible associations between CHIP, mCA, and solid tumors, the investigators analyzed whole genome sequencing data from 10,866 women in the WHI, a multi-study program that began in 1992 and involved 161,808 women in both observational and clinical trial cohorts.

In 2002, the first big data release from the WHI suggested that hormone replacement therapy (HRT) increased breast cancer risk, leading to widespread reduction in HRT use.

More recent reports continue to shape our understanding of these risks, suggesting differences across cancer types. For breast cancer, the WHI data suggested that HRT-associated risk was largely driven by formulations involving progesterone and estrogen, whereas estrogen-only formulations, now more common, are generally considered to present an acceptable risk profile for suitable patients.

The new study accounted for this potential HRT-associated risk, including by adjusting for patients who received HRT, type of HRT received, and duration of HRT received. According to Desai, this approach is commonly used when analyzing data from the WHI, nullifying concerns about the potentially deleterious effects of the hormones used in the study.

“Our question was not ‘does HRT cause cancer?’ ” Dr. Desai said in an interview. “But HRT can be linked to breast cancer risk and has a potential to be a confounder, and hence the above methodology.

“So I can say that the confounding/effect modification that HRT would have contributed to in the relationship between exposure (CH and mCA) and outcome (cancer) is well adjusted for as described above. This is standard in WHI analyses,” she continued.

“Every Women’s Health Initiative analysis that comes out — not just for our study — uses a standard method ... where you account for hormonal therapy,” Dr. Desai added, again noting that many other potential risk factors were considered, enabling a “detailed, robust” analysis.

Dr. Takahashi and Ms. Shah agreed. “A notable strength of this study is its adjustment for many confounding factors,” they wrote. “The cohort’s well‐annotated data on other known cancer risk factors allowed for a robust assessment of CH’s independent risk.”
 

How Do Findings Compare With Those of the UK Biobank Study?

CHIP was associated with a 30% increased risk for breast cancer (hazard ratio [HR], 1.30; 95% CI, 1.03-1.64; P = .02), strengthening the borderline association reported by the UK Biobank study.

In contrast with the UK Biobank study, CHIP was not associated with lung cancer risk, although this may have been caused by fewer cases of lung cancer and a lack of male patients, Dr. Desai suggested.

“The discrepancy between the studies lies in the risk of lung cancer, although the point estimate in the current study suggested a positive association,” wrote Dr. Takahashi and Ms. Shah.

As in the UK Biobank study, CHIP was not associated with increased risk of developing colorectal cancer.

Mortality analysis, however, which was not conducted in the UK Biobank study, offered a new insight: Patients with existing colorectal cancer and CHIP had a significantly higher mortality risk than those without CHIP. Before stage adjustment, risk for mortality among those with colorectal cancer and CHIP was fourfold higher than those without CHIP (HR, 3.99; 95% CI, 2.41-6.62; P < .001). After stage adjustment, CHIP was still associated with a twofold higher mortality risk (HR, 2.50; 95% CI, 1.32-4.72; P = .004).

The investigators’ first mCA analyses, which employed a cell fraction cutoff greater than 3%, were unfruitful. But raising the cell fraction threshold to 5% in an exploratory analysis showed that autosomal mCA was associated with a 39% increased risk for breast cancer (HR, 1.39; 95% CI, 1.06-1.83; P = .01). No such associations were found between mCA and colorectal or lung cancer, regardless of cell fraction threshold.

The original 3% cell fraction threshold was selected on the basis of previous studies reporting a link between mCA and hematologic malignancies at this cutoff, Dr. Desai said.

She and her colleagues said a higher 5% cutoff might be needed, as they suspected that the link between mCA and solid tumors may not be causal, requiring a higher mutation rate.
 

Why Do Results Differ Between These Types of Studies?

Dr. Takahashi and Ms. Shah suggested that one possible limitation of the new study, and an obstacle to comparing results with the UK Biobank study and others like it, goes beyond population heterogeneity; incongruent findings could also be explained by differences in whole genome sequencing (WGS) technique.

“Although WGS allows sensitive detection of mCA through broad genomic coverage, it is less effective at detecting CHIP with low variant allele frequency (VAF) due to its relatively shallow depth (30x),” they wrote. “Consequently, the prevalence of mCA (18.8%) was much higher than that of CHIP (8.3%) in this cohort, contrasting with other studies using deeper sequencing.” As a result, the present study may have underestimated CHIP prevalence because of shallow sequencing depth.

“This inconsistency is a common challenge in CH population studies due to the lack of standardized methodologies and the frequent reliance on preexisting data not originally intended for CH detection,” Dr. Takahashi and Ms. Shah said.

Even so, despite the “heavily context-dependent” nature of these reported risks, the body of evidence to date now offers a convincing biological rationale linking CH with cancer development and outcomes, they added.
 

How Do the CHIP- and mCA-associated Risks Differ Between Solid Tumors and Blood Cancers?

“[These solid tumor risks are] not causal in the way CHIP mutations are causal for blood cancers,” Dr. Desai said. “Here we are talking about solid tumor risk, and it’s kind of scattered. It’s not just breast cancer ... there’s also increased colon cancer mortality. So I feel these mutations are doing something different ... they are sort of an added factor.”

Specific mechanisms remain unclear, Dr. Desai said, although she speculated about possible impacts on the inflammatory state or alterations to the tumor microenvironment.

“These are blood cells, right?” Dr. Desai asked. “They’re everywhere, and they’re changing something inherently in these tumors.”
 

Future research and therapeutic development

Siddhartha Jaiswal, MD, PhD, assistant professor in the Department of Pathology at Stanford University in California, whose lab focuses on clonal hematopoiesis, said the causality question is central to future research.

“The key question is, are these mutations acting because they alter the function of blood cells in some way to promote cancer risk, or is it reflective of some sort of shared etiology that’s not causal?” Dr. Jaiswal said in an interview.

Available data support both possibilities.

On one side, “reasonable evidence” supports the noncausal view, Dr. Jaiswal noted, because telomere length is one of the most common genetic risk factors for clonal hematopoiesis and also for solid tumors, suggesting a shared genetic factor. On the other hand, CHIP and mCA could be directly protumorigenic via conferred disturbances of immune cell function.

When asked if both causal and noncausal factors could be at play, Dr. Jaiswal said, “yeah, absolutely.”

The presence of a causal association could be promising from a therapeutic standpoint.

“If it turns out that this association is driven by a direct causal effect of the mutations, perhaps related to immune cell function or dysfunction, then targeting that dysfunction could be a therapeutic path to improve outcomes in people, and there’s a lot of interest in this,” Dr. Jaiswal said. He went on to explain how a trial exploring this approach via interleukin-8 inhibition in lung cancer fell short.

Yet earlier intervention may still hold promise, according to experts.

“[This study] provokes the hypothesis that CH‐targeted interventions could potentially reduce cancer risk in the future,” Dr. Takahashi and Ms. Shah said in their editorial.

The WHI program is funded by the National Heart, Lung, and Blood Institute; National Institutes of Health; and the Department of Health & Human Services. The investigators disclosed relationships with Eli Lilly, AbbVie, Celgene, and others. Dr. Jaiswal reported stock equity in a company that has an interest in clonal hematopoiesis.

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

One of California’s two programs for training nurse-midwives has stopped admitting students while it revamps its curriculum to offer only doctoral degrees, a move that’s drawn howls of protest from alumni, health policy experts, and faculty who accuse the University of California of putting profits above public health needs.

The University of California San Francisco’s (UCSF) renowned nursing school will graduate its final class of certified nurse-midwives in the spring of 2025. Then the university will cancel its 2-year master’s program in nurse-midwifery, along with other nursing disciplines, in favor of a 3-year doctor of nursing practice, or DNP, degree. The change will pause UCSF’s nearly 5 decades–long training of nurse-midwives until at least 2025 and will more than double the cost to students.

State Assembly member Mia Bonta, who chairs the health committee, said she was “disheartened” to learn that UCSF was eliminating its master’s nurse-midwifery program and feared the additional time and costs to get a doctorate would deter potential applicants. “Instead of adding hurdles, we need to be building and expanding a pipeline of culturally and racially concordant providers to support improved birth outcomes, especially for Black and Latina birthing people,” she said in an email.

The switch to doctoral education is part of a national movement to require all advanced-practice registered nurses, including nurse-midwives and nurse practitioners, to earn doctoral degrees, Kristen Bole, a UCSF spokesperson, said in response to written questions. The doctoral training will feature additional classes in leadership and quality improvement.

But the movement, which dates to 2004, has not caught on the way the American Association of Colleges of Nursing envisioned when it called for doctorate-level education to be required for entry-level advanced nursing practice by 2015. That deadline came and went. Now, an acute need for maternal health practitioners has some universities moving in the other direction.

This year, Rutgers University reinstated the nurse-midwifery master’s training it had eliminated in 2016. The University of Alabama at Birmingham also restarted its master’s in nurse-midwifery program in 2022 after a 25-year hiatus. In addition, George Washington University in Washington, DC, Loyola University in New Orleans, and the University of Nevada in Las Vagas added master’s training in nurse-midwifery.

UCSF estimates tuition and fees will cost $152,000 for a 3-year doctoral degree in midwifery, compared with $65,000 for a 2-year master’s. Studies show that 71% of nursing master’s students and 74% of nursing doctoral students rely on student loans, and nurses with doctorates earn negligibly or no more than nurses with master’s degrees.

Kim Q. Dau, who ran UCSF’s nurse-midwifery program for a decade, resigned in June because she was uncomfortable with the elimination of the master’s in favor of a doctoral requirement, she said, which is at odds with the state’s workforce needs and unnecessary for clinical practice.

“They’ll be equally prepared clinically but at more expense to the student and with a greater time investment,” she said.

Nurse-midwives are registered nurses with graduate degrees in nurse-midwifery. Licensed in all 50 states, they work mostly in hospitals and can perform abortions and prescribe medications, though they are also trained in managing labor pain with showers, massage, and other natural means. Certified midwives, by contrast, study midwifery at the graduate level outside of nursing schools and are licensed only in some states. Certified professional midwives attend births outside of hospitals.

The California Nurse-Midwives Association also criticized UCSF’s program change, which comes amid a national maternal mortality crisis, a serious shortage of obstetric providers, and a growing reliance on midwives. According to the 2022 “White House Blueprint for Addressing the Maternal Health Crisis” report, the United States has the highest maternal mortality rate of any developed nation and needs thousands more midwives and other women’s health providers to bridge the swelling gap.

Ginger Breedlove, founder and CEO of Grow Midwives, a national consulting firm, likened UCSF’s switch from master’s to doctoral training to “an earthquake.”

“Why are we delaying the entry of essential care providers by making them go to an additional year of school, which adds nothing to their clinical preparedness or safety to serve the community?” asked Ms. Breedlove, a past president of the American College of Nurse-Midwives. “Why they have chosen this during one of the worst workforce shortages combined with the worst maternal health crisis we have had in 50 years is beyond my imagination.”

A 2020 report published in Nursing Outlook failed to find that advanced-practice registered nurses with doctorates were more clinically proficient than those with master’s degrees. “Unfortunately, to date, the data are sparse,” it concluded.

The American College of Nurse-Midwives also denounced the doctoral requirement, as have trade associations for neonatal nurse practitioners and neonatal nurses, citing “the lack of scientific evidence that ... doctoral-level education is beneficial to patients, practitioners, or society.”

There is no evidence that doctoral-level nurse-midwives will provide better care, Ms. Breedlove said.

“This is profit over purpose,” she added.

Ms. Bole disputed Ms. Breedlove’s accusation of a profit motive. Asked for reasons for the change, she offered broad statements: “The decision to upgrade our program was made to ensure that our graduates are prepared for the challenges they will face in the evolving health care landscape.”

Like Ms. Breedlove, Liz Donnelly, vice chair of the health policy committee for the California Nurse-Midwives Association, worries that UCSF’s switch to a doctoral degree will exacerbate the twin crises of maternal mortality and a shrinking obstetrics workforce across California and the nation.

On average, 10-12 nurse-midwives graduated from the UCSF master’s program each year over the past decade, Ms. Bole said. California’s remaining master’s program in nurse-midwifery is at California State University in Fullerton, south of Los Angeles, and it graduated 8 nurse-midwives in 2023 and 11 in 2024.

More than half of rural counties in the United States lacked obstetric care in 2018, according to a Government Accountability Office report.

In some parts of California, expectant mothers must drive 2 hours for care, said Bethany Sasaki, who runs Midtown Nurse Midwives, a Sacramento birth center. It has had to stop accepting new clients because it cannot find midwives.

Ms. Donnelly predicted the closure of UCSF’s midwifery program will significantly reduce the number of nurse-midwives entering the workforce and will inhibit people with fewer resources from attending the program. “Specifically, I think it’s going to reduce folks of color, people from rural communities, people from poor communities,” she said.

UCSF’s change will also likely undercut efforts to train providers from diverse backgrounds.

Natasha, a 37-year-old Afro-Puerto Rican mother of two, has spent a decade preparing to train as a nurse-midwife so she could help women like herself through pregnancy and childbirth. She asked to be identified only by her first name out of fear of reducing her chances of graduate school admission.

The UCSF program’s pause, plus the added time and expense to get a doctoral degree, has muddied her career path.

“The master’s was just the perfect program,” said Natasha, who lives in the Bay Area and cannot travel to the other end of the state to attend California State University-Fullerton. “I’m frustrated, and I feel deflated. I now have to find another career path.”

This article was produced by KFF Health News, which publishes California Healthline, an editorially independent service of the California Health Care Foundation. KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

One of California’s two programs for training nurse-midwives has stopped admitting students while it revamps its curriculum to offer only doctoral degrees, a move that’s drawn howls of protest from alumni, health policy experts, and faculty who accuse the University of California of putting profits above public health needs.

The University of California San Francisco’s (UCSF) renowned nursing school will graduate its final class of certified nurse-midwives in the spring of 2025. Then the university will cancel its 2-year master’s program in nurse-midwifery, along with other nursing disciplines, in favor of a 3-year doctor of nursing practice, or DNP, degree. The change will pause UCSF’s nearly 5 decades–long training of nurse-midwives until at least 2025 and will more than double the cost to students.

State Assembly member Mia Bonta, who chairs the health committee, said she was “disheartened” to learn that UCSF was eliminating its master’s nurse-midwifery program and feared the additional time and costs to get a doctorate would deter potential applicants. “Instead of adding hurdles, we need to be building and expanding a pipeline of culturally and racially concordant providers to support improved birth outcomes, especially for Black and Latina birthing people,” she said in an email.

The switch to doctoral education is part of a national movement to require all advanced-practice registered nurses, including nurse-midwives and nurse practitioners, to earn doctoral degrees, Kristen Bole, a UCSF spokesperson, said in response to written questions. The doctoral training will feature additional classes in leadership and quality improvement.

But the movement, which dates to 2004, has not caught on the way the American Association of Colleges of Nursing envisioned when it called for doctorate-level education to be required for entry-level advanced nursing practice by 2015. That deadline came and went. Now, an acute need for maternal health practitioners has some universities moving in the other direction.

This year, Rutgers University reinstated the nurse-midwifery master’s training it had eliminated in 2016. The University of Alabama at Birmingham also restarted its master’s in nurse-midwifery program in 2022 after a 25-year hiatus. In addition, George Washington University in Washington, DC, Loyola University in New Orleans, and the University of Nevada in Las Vagas added master’s training in nurse-midwifery.

UCSF estimates tuition and fees will cost $152,000 for a 3-year doctoral degree in midwifery, compared with $65,000 for a 2-year master’s. Studies show that 71% of nursing master’s students and 74% of nursing doctoral students rely on student loans, and nurses with doctorates earn negligibly or no more than nurses with master’s degrees.

Kim Q. Dau, who ran UCSF’s nurse-midwifery program for a decade, resigned in June because she was uncomfortable with the elimination of the master’s in favor of a doctoral requirement, she said, which is at odds with the state’s workforce needs and unnecessary for clinical practice.

“They’ll be equally prepared clinically but at more expense to the student and with a greater time investment,” she said.

Nurse-midwives are registered nurses with graduate degrees in nurse-midwifery. Licensed in all 50 states, they work mostly in hospitals and can perform abortions and prescribe medications, though they are also trained in managing labor pain with showers, massage, and other natural means. Certified midwives, by contrast, study midwifery at the graduate level outside of nursing schools and are licensed only in some states. Certified professional midwives attend births outside of hospitals.

The California Nurse-Midwives Association also criticized UCSF’s program change, which comes amid a national maternal mortality crisis, a serious shortage of obstetric providers, and a growing reliance on midwives. According to the 2022 “White House Blueprint for Addressing the Maternal Health Crisis” report, the United States has the highest maternal mortality rate of any developed nation and needs thousands more midwives and other women’s health providers to bridge the swelling gap.

Ginger Breedlove, founder and CEO of Grow Midwives, a national consulting firm, likened UCSF’s switch from master’s to doctoral training to “an earthquake.”

“Why are we delaying the entry of essential care providers by making them go to an additional year of school, which adds nothing to their clinical preparedness or safety to serve the community?” asked Ms. Breedlove, a past president of the American College of Nurse-Midwives. “Why they have chosen this during one of the worst workforce shortages combined with the worst maternal health crisis we have had in 50 years is beyond my imagination.”

A 2020 report published in Nursing Outlook failed to find that advanced-practice registered nurses with doctorates were more clinically proficient than those with master’s degrees. “Unfortunately, to date, the data are sparse,” it concluded.

The American College of Nurse-Midwives also denounced the doctoral requirement, as have trade associations for neonatal nurse practitioners and neonatal nurses, citing “the lack of scientific evidence that ... doctoral-level education is beneficial to patients, practitioners, or society.”

There is no evidence that doctoral-level nurse-midwives will provide better care, Ms. Breedlove said.

“This is profit over purpose,” she added.

Ms. Bole disputed Ms. Breedlove’s accusation of a profit motive. Asked for reasons for the change, she offered broad statements: “The decision to upgrade our program was made to ensure that our graduates are prepared for the challenges they will face in the evolving health care landscape.”

Like Ms. Breedlove, Liz Donnelly, vice chair of the health policy committee for the California Nurse-Midwives Association, worries that UCSF’s switch to a doctoral degree will exacerbate the twin crises of maternal mortality and a shrinking obstetrics workforce across California and the nation.

On average, 10-12 nurse-midwives graduated from the UCSF master’s program each year over the past decade, Ms. Bole said. California’s remaining master’s program in nurse-midwifery is at California State University in Fullerton, south of Los Angeles, and it graduated 8 nurse-midwives in 2023 and 11 in 2024.

More than half of rural counties in the United States lacked obstetric care in 2018, according to a Government Accountability Office report.

In some parts of California, expectant mothers must drive 2 hours for care, said Bethany Sasaki, who runs Midtown Nurse Midwives, a Sacramento birth center. It has had to stop accepting new clients because it cannot find midwives.

Ms. Donnelly predicted the closure of UCSF’s midwifery program will significantly reduce the number of nurse-midwives entering the workforce and will inhibit people with fewer resources from attending the program. “Specifically, I think it’s going to reduce folks of color, people from rural communities, people from poor communities,” she said.

UCSF’s change will also likely undercut efforts to train providers from diverse backgrounds.

Natasha, a 37-year-old Afro-Puerto Rican mother of two, has spent a decade preparing to train as a nurse-midwife so she could help women like herself through pregnancy and childbirth. She asked to be identified only by her first name out of fear of reducing her chances of graduate school admission.

The UCSF program’s pause, plus the added time and expense to get a doctoral degree, has muddied her career path.

“The master’s was just the perfect program,” said Natasha, who lives in the Bay Area and cannot travel to the other end of the state to attend California State University-Fullerton. “I’m frustrated, and I feel deflated. I now have to find another career path.”

This article was produced by KFF Health News, which publishes California Healthline, an editorially independent service of the California Health Care Foundation. KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

One of California’s two programs for training nurse-midwives has stopped admitting students while it revamps its curriculum to offer only doctoral degrees, a move that’s drawn howls of protest from alumni, health policy experts, and faculty who accuse the University of California of putting profits above public health needs.

The University of California San Francisco’s (UCSF) renowned nursing school will graduate its final class of certified nurse-midwives in the spring of 2025. Then the university will cancel its 2-year master’s program in nurse-midwifery, along with other nursing disciplines, in favor of a 3-year doctor of nursing practice, or DNP, degree. The change will pause UCSF’s nearly 5 decades–long training of nurse-midwives until at least 2025 and will more than double the cost to students.

State Assembly member Mia Bonta, who chairs the health committee, said she was “disheartened” to learn that UCSF was eliminating its master’s nurse-midwifery program and feared the additional time and costs to get a doctorate would deter potential applicants. “Instead of adding hurdles, we need to be building and expanding a pipeline of culturally and racially concordant providers to support improved birth outcomes, especially for Black and Latina birthing people,” she said in an email.

The switch to doctoral education is part of a national movement to require all advanced-practice registered nurses, including nurse-midwives and nurse practitioners, to earn doctoral degrees, Kristen Bole, a UCSF spokesperson, said in response to written questions. The doctoral training will feature additional classes in leadership and quality improvement.

But the movement, which dates to 2004, has not caught on the way the American Association of Colleges of Nursing envisioned when it called for doctorate-level education to be required for entry-level advanced nursing practice by 2015. That deadline came and went. Now, an acute need for maternal health practitioners has some universities moving in the other direction.

This year, Rutgers University reinstated the nurse-midwifery master’s training it had eliminated in 2016. The University of Alabama at Birmingham also restarted its master’s in nurse-midwifery program in 2022 after a 25-year hiatus. In addition, George Washington University in Washington, DC, Loyola University in New Orleans, and the University of Nevada in Las Vagas added master’s training in nurse-midwifery.

UCSF estimates tuition and fees will cost $152,000 for a 3-year doctoral degree in midwifery, compared with $65,000 for a 2-year master’s. Studies show that 71% of nursing master’s students and 74% of nursing doctoral students rely on student loans, and nurses with doctorates earn negligibly or no more than nurses with master’s degrees.

Kim Q. Dau, who ran UCSF’s nurse-midwifery program for a decade, resigned in June because she was uncomfortable with the elimination of the master’s in favor of a doctoral requirement, she said, which is at odds with the state’s workforce needs and unnecessary for clinical practice.

“They’ll be equally prepared clinically but at more expense to the student and with a greater time investment,” she said.

Nurse-midwives are registered nurses with graduate degrees in nurse-midwifery. Licensed in all 50 states, they work mostly in hospitals and can perform abortions and prescribe medications, though they are also trained in managing labor pain with showers, massage, and other natural means. Certified midwives, by contrast, study midwifery at the graduate level outside of nursing schools and are licensed only in some states. Certified professional midwives attend births outside of hospitals.

The California Nurse-Midwives Association also criticized UCSF’s program change, which comes amid a national maternal mortality crisis, a serious shortage of obstetric providers, and a growing reliance on midwives. According to the 2022 “White House Blueprint for Addressing the Maternal Health Crisis” report, the United States has the highest maternal mortality rate of any developed nation and needs thousands more midwives and other women’s health providers to bridge the swelling gap.

Ginger Breedlove, founder and CEO of Grow Midwives, a national consulting firm, likened UCSF’s switch from master’s to doctoral training to “an earthquake.”

“Why are we delaying the entry of essential care providers by making them go to an additional year of school, which adds nothing to their clinical preparedness or safety to serve the community?” asked Ms. Breedlove, a past president of the American College of Nurse-Midwives. “Why they have chosen this during one of the worst workforce shortages combined with the worst maternal health crisis we have had in 50 years is beyond my imagination.”

A 2020 report published in Nursing Outlook failed to find that advanced-practice registered nurses with doctorates were more clinically proficient than those with master’s degrees. “Unfortunately, to date, the data are sparse,” it concluded.

The American College of Nurse-Midwives also denounced the doctoral requirement, as have trade associations for neonatal nurse practitioners and neonatal nurses, citing “the lack of scientific evidence that ... doctoral-level education is beneficial to patients, practitioners, or society.”

There is no evidence that doctoral-level nurse-midwives will provide better care, Ms. Breedlove said.

“This is profit over purpose,” she added.

Ms. Bole disputed Ms. Breedlove’s accusation of a profit motive. Asked for reasons for the change, she offered broad statements: “The decision to upgrade our program was made to ensure that our graduates are prepared for the challenges they will face in the evolving health care landscape.”

Like Ms. Breedlove, Liz Donnelly, vice chair of the health policy committee for the California Nurse-Midwives Association, worries that UCSF’s switch to a doctoral degree will exacerbate the twin crises of maternal mortality and a shrinking obstetrics workforce across California and the nation.

On average, 10-12 nurse-midwives graduated from the UCSF master’s program each year over the past decade, Ms. Bole said. California’s remaining master’s program in nurse-midwifery is at California State University in Fullerton, south of Los Angeles, and it graduated 8 nurse-midwives in 2023 and 11 in 2024.

More than half of rural counties in the United States lacked obstetric care in 2018, according to a Government Accountability Office report.

In some parts of California, expectant mothers must drive 2 hours for care, said Bethany Sasaki, who runs Midtown Nurse Midwives, a Sacramento birth center. It has had to stop accepting new clients because it cannot find midwives.

Ms. Donnelly predicted the closure of UCSF’s midwifery program will significantly reduce the number of nurse-midwives entering the workforce and will inhibit people with fewer resources from attending the program. “Specifically, I think it’s going to reduce folks of color, people from rural communities, people from poor communities,” she said.

UCSF’s change will also likely undercut efforts to train providers from diverse backgrounds.

Natasha, a 37-year-old Afro-Puerto Rican mother of two, has spent a decade preparing to train as a nurse-midwife so she could help women like herself through pregnancy and childbirth. She asked to be identified only by her first name out of fear of reducing her chances of graduate school admission.

The UCSF program’s pause, plus the added time and expense to get a doctoral degree, has muddied her career path.

“The master’s was just the perfect program,” said Natasha, who lives in the Bay Area and cannot travel to the other end of the state to attend California State University-Fullerton. “I’m frustrated, and I feel deflated. I now have to find another career path.”

This article was produced by KFF Health News, which publishes California Healthline, an editorially independent service of the California Health Care Foundation. KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

Listeriosis during pregnancy, when invasive, can be fatal for the fetus, with a rate of fetal loss or neonatal death of 29%, investigators reported in an article alerting clinicians to this condition.

The article was prompted when the Reproductive Infectious Diseases team at The University of British Columbia in Vancouver, British Columbia, Canada, “received many phone calls from concerned doctors and patients after the plant-based milk recall in early July,” Jeffrey Man Hay Wong, MD, told this news organization. “With such concerns, we updated our British Columbia guidelines for our patients but quickly realized that our recommendations would be useful across the country.”

The article was published online in the Canadian Medical Association Journal.


 

Five Key Points

Dr. Wong and colleagues provided the following five points and recommendations:

First, invasive listeriosis (bacteremia or meningitis) in pregnancy can have major fetal consequences, including fetal loss or neonatal death in 29% of cases. Affected patients can be asymptomatic or experience gastrointestinal symptoms, myalgias, fevers, acute respiratory distress syndrome, or sepsis.

Second, pregnant people should avoid foods at a high risk for Listeria monocytogenes contamination, including unpasteurized dairy products, luncheon meats, refrigerated meat spreads, and prepared salads. They also should stay aware of Health Canada recalls.

Third, it is not necessary to investigate or treat patients who may have ingested contaminated food but are asymptomatic. Listeriosis can present at 2-3 months after exposure because the incubation period can be as long as 70 days.

Fourth, for patients with mild gastroenteritis or flu-like symptoms who may have ingested contaminated food, obtaining blood cultures or starting a 2-week course of oral amoxicillin (500 mg, three times daily) could be considered.

Fifth, for patients with fever and possible exposure to L monocytogenes, blood cultures should be drawn immediately, and high-dose ampicillin should be initiated, along with electronic fetal heart rate monitoring.

“While choosing safer foods in pregnancy is recommended, it is most important to be aware of Health Canada food recalls and pay attention to symptoms if you’ve ingested these foods,” said Dr. Wong. “Working with the BC Centre for Disease Control, our teams are actively monitoring for cases of listeriosis in pregnancy here in British Columbia.

“Thankfully,” he said, “there haven’t been any confirmed cases in British Columbia related to the plant-based milk recall, though the bacteria’s incubation period can be up to 70 days in pregnancy.”
 

No Increase Suspected

Commenting on the article, Khady Diouf, MD, director of global obstetrics and gynecology at Brigham and Women’s Hospital in Boston, said, “It summarizes the main management, which is based mostly on expert opinion.”

US clinicians also should be reminded about listeriosis in pregnancy, she noted, pointing to “helpful guidance” from the American College of Obstetrics and Gynecology.

Although the United States similarly experienced a recent listeriosis outbreak resulting from contaminated deli meats, both Dr. Wong and Dr. Diouf said that these outbreaks do not seem to signal an increase in listeriosis cases overall.

“Food-borne listeriosis seems to come in waves,” said Dr. Wong. “At a public health level, we certainly have better surveillance programs for Listeria infections. In 2023, Health Canada updated its Policy on L monocytogenes in ready-to-eat foods, which emphasizes the good manufacturing practices recommended for food processing environments to identify outbreaks earlier.”

“I think we get these recalls yearly, and this has been the case for as long as I can remember,” Dr. Diouf agreed.

No funding was declared, and the authors declared no relevant financial relationships.

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

Listeriosis during pregnancy, when invasive, can be fatal for the fetus, with a rate of fetal loss or neonatal death of 29%, investigators reported in an article alerting clinicians to this condition.

The article was prompted when the Reproductive Infectious Diseases team at The University of British Columbia in Vancouver, British Columbia, Canada, “received many phone calls from concerned doctors and patients after the plant-based milk recall in early July,” Jeffrey Man Hay Wong, MD, told this news organization. “With such concerns, we updated our British Columbia guidelines for our patients but quickly realized that our recommendations would be useful across the country.”

The article was published online in the Canadian Medical Association Journal.


 

Five Key Points

Dr. Wong and colleagues provided the following five points and recommendations:

First, invasive listeriosis (bacteremia or meningitis) in pregnancy can have major fetal consequences, including fetal loss or neonatal death in 29% of cases. Affected patients can be asymptomatic or experience gastrointestinal symptoms, myalgias, fevers, acute respiratory distress syndrome, or sepsis.

Second, pregnant people should avoid foods at a high risk for Listeria monocytogenes contamination, including unpasteurized dairy products, luncheon meats, refrigerated meat spreads, and prepared salads. They also should stay aware of Health Canada recalls.

Third, it is not necessary to investigate or treat patients who may have ingested contaminated food but are asymptomatic. Listeriosis can present at 2-3 months after exposure because the incubation period can be as long as 70 days.

Fourth, for patients with mild gastroenteritis or flu-like symptoms who may have ingested contaminated food, obtaining blood cultures or starting a 2-week course of oral amoxicillin (500 mg, three times daily) could be considered.

Fifth, for patients with fever and possible exposure to L monocytogenes, blood cultures should be drawn immediately, and high-dose ampicillin should be initiated, along with electronic fetal heart rate monitoring.

“While choosing safer foods in pregnancy is recommended, it is most important to be aware of Health Canada food recalls and pay attention to symptoms if you’ve ingested these foods,” said Dr. Wong. “Working with the BC Centre for Disease Control, our teams are actively monitoring for cases of listeriosis in pregnancy here in British Columbia.

“Thankfully,” he said, “there haven’t been any confirmed cases in British Columbia related to the plant-based milk recall, though the bacteria’s incubation period can be up to 70 days in pregnancy.”
 

No Increase Suspected

Commenting on the article, Khady Diouf, MD, director of global obstetrics and gynecology at Brigham and Women’s Hospital in Boston, said, “It summarizes the main management, which is based mostly on expert opinion.”

US clinicians also should be reminded about listeriosis in pregnancy, she noted, pointing to “helpful guidance” from the American College of Obstetrics and Gynecology.

Although the United States similarly experienced a recent listeriosis outbreak resulting from contaminated deli meats, both Dr. Wong and Dr. Diouf said that these outbreaks do not seem to signal an increase in listeriosis cases overall.

“Food-borne listeriosis seems to come in waves,” said Dr. Wong. “At a public health level, we certainly have better surveillance programs for Listeria infections. In 2023, Health Canada updated its Policy on L monocytogenes in ready-to-eat foods, which emphasizes the good manufacturing practices recommended for food processing environments to identify outbreaks earlier.”

“I think we get these recalls yearly, and this has been the case for as long as I can remember,” Dr. Diouf agreed.

No funding was declared, and the authors declared no relevant financial relationships.

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

Listeriosis during pregnancy, when invasive, can be fatal for the fetus, with a rate of fetal loss or neonatal death of 29%, investigators reported in an article alerting clinicians to this condition.

The article was prompted when the Reproductive Infectious Diseases team at The University of British Columbia in Vancouver, British Columbia, Canada, “received many phone calls from concerned doctors and patients after the plant-based milk recall in early July,” Jeffrey Man Hay Wong, MD, told this news organization. “With such concerns, we updated our British Columbia guidelines for our patients but quickly realized that our recommendations would be useful across the country.”

The article was published online in the Canadian Medical Association Journal.


 

Five Key Points

Dr. Wong and colleagues provided the following five points and recommendations:

First, invasive listeriosis (bacteremia or meningitis) in pregnancy can have major fetal consequences, including fetal loss or neonatal death in 29% of cases. Affected patients can be asymptomatic or experience gastrointestinal symptoms, myalgias, fevers, acute respiratory distress syndrome, or sepsis.

Second, pregnant people should avoid foods at a high risk for Listeria monocytogenes contamination, including unpasteurized dairy products, luncheon meats, refrigerated meat spreads, and prepared salads. They also should stay aware of Health Canada recalls.

Third, it is not necessary to investigate or treat patients who may have ingested contaminated food but are asymptomatic. Listeriosis can present at 2-3 months after exposure because the incubation period can be as long as 70 days.

Fourth, for patients with mild gastroenteritis or flu-like symptoms who may have ingested contaminated food, obtaining blood cultures or starting a 2-week course of oral amoxicillin (500 mg, three times daily) could be considered.

Fifth, for patients with fever and possible exposure to L monocytogenes, blood cultures should be drawn immediately, and high-dose ampicillin should be initiated, along with electronic fetal heart rate monitoring.

“While choosing safer foods in pregnancy is recommended, it is most important to be aware of Health Canada food recalls and pay attention to symptoms if you’ve ingested these foods,” said Dr. Wong. “Working with the BC Centre for Disease Control, our teams are actively monitoring for cases of listeriosis in pregnancy here in British Columbia.

“Thankfully,” he said, “there haven’t been any confirmed cases in British Columbia related to the plant-based milk recall, though the bacteria’s incubation period can be up to 70 days in pregnancy.”
 

No Increase Suspected

Commenting on the article, Khady Diouf, MD, director of global obstetrics and gynecology at Brigham and Women’s Hospital in Boston, said, “It summarizes the main management, which is based mostly on expert opinion.”

US clinicians also should be reminded about listeriosis in pregnancy, she noted, pointing to “helpful guidance” from the American College of Obstetrics and Gynecology.

Although the United States similarly experienced a recent listeriosis outbreak resulting from contaminated deli meats, both Dr. Wong and Dr. Diouf said that these outbreaks do not seem to signal an increase in listeriosis cases overall.

“Food-borne listeriosis seems to come in waves,” said Dr. Wong. “At a public health level, we certainly have better surveillance programs for Listeria infections. In 2023, Health Canada updated its Policy on L monocytogenes in ready-to-eat foods, which emphasizes the good manufacturing practices recommended for food processing environments to identify outbreaks earlier.”

“I think we get these recalls yearly, and this has been the case for as long as I can remember,” Dr. Diouf agreed.

No funding was declared, and the authors declared no relevant financial relationships.

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

Prophylactic placement of balloon catheters or sheaths prior to planned cesarean delivery may reduce blood loss in women with placenta accreta spectrum disorder, according to a new systematic review of more than 5,000 individuals.

Placenta accreta spectrum disorder occurs when the endometrial-myometrial interface of the uterus is damaged, wrote Lisanne R. Bonsen, MD, of Leiden University Medical Center, the Netherlands, and colleagues. As a result, the placenta fails to detach at the time of birth and can result in life-threatening postpartum hemorrhage, the researchers said.

The greater the depth of placental invasiveness, the more severe the maternal outcomes, the researchers noted. Previous cesarean delivery is the primary risk factor for placenta accreta spectrum disorder, and the incidence has increased along with the increased rates of cesarean delivery on a global level, they explained.

More research is needed on intrapartum strategies to improve maternal outcomes, and prophylactic radiologic intervention to reduce perioperative blood loss has been explored, the researchers wrote. However, placenta accreta spectrum disorder remains relatively rare in most pregnancy settings, and data on the effect of prophylactic radiologic interventions to reduce bleeding in this high-risk population are limited they said.

In the review published in Obstetrics & Gynecology, the researchers analyzed data from 50 studies of prophylactic radiologic interventions (48 observational studies and 2 randomized, controlled trials) including 5,962 women.

The primary outcome was perioperative blood loss; secondary outcomes included the number of red blood cells transferred within 24 hours after delivery, maternal mortality, adverse events related to the interventions, and surgical complications.

Blood loss was significantly lower in the intervention groups compared with the control groups for patients who underwent distal balloon occlusion (30 studies), proximal balloon occlusion (14 studies), or uterine artery embolization (5 studies), with mean differences in blood loss of 406 mL, 1,041 mL, and 936 mL, respectively.

Results were similar with lower blood loss for intervention patients compared with controls in subgroup analyses of different types of placenta accreta spectrum disorder and those with placenta accreta spectrum disorder confirmed post partum.

Across the 35 studies that included data on blood transfusions, women who underwent any prophylactic radiologic intervention averaged fewer red blood cell units transferred than women who had no radiologic intervention, with a mean difference of 1.13, 1.90, and 1.86 units for distal prophylactic balloon occlusion, proximal prophylactic balloon occlusion, and prophylactic uterine artery embolization, respectively.

Data on adverse events related to the interventions were limited, but noted in approximately 2% of patients who underwent distal or proximal prophylactic balloon occlusion, and 45% of patients who underwent prophylactic uterine artery embolization. One maternal death was reported and attributed to diffuse intravascular coagulation. Three cardiac arrests occurred in control patients across different studies and all were successfully resuscitated.

Most of the studies did not report data on the researchers’ predefined secondary outcomes, including shock, transfer to a higher level of care, coagulopathy, organ dysfunction, and patient-reported outcomes.
 

What Works Best

“Our main analysis reveals differences in outcomes among the three interventions, with proximal balloon occlusion demonstrating the strongest effect,” the researchers wrote. “Our results show a blood loss reduction of 406 mL by distal prophylactic balloon occlusion. An explanation for the differences between the results of prophylactic balloon occlusion–distal and prophylactic balloon occlusion–proximal could be that implementing occlusion at a distal level may be less effective because of bleeding from the collateral circulation,” they said.

The findings were limited by several factors including the observational design of most of the studies, variation in measurements of blood loss among studies and in inclusion criteria, and insufficient adverse event data to draw conclusions about safety, the researchers noted. More research is needed to examine efficacy and safety of the interventions according to different sensitivities of placenta accreta spectrum disorder, they added.

Results Support Judicious Intervention

“Although previous studies showed mixed results, our meta-analysis demonstrated that prophylactic radiologic interventions, particularly balloon occlusion (both distal and proximal), were associated with reduced perioperative blood loss and less red blood cell unit transfusion; this was most pronounced in women with confirmed placenta percreta,” Bonsen said in an interview. However, the heterogeneity across the included studies prevents generalizations about the overall effects of the interventions across different severities of placenta accreta spectrum disorder, she said.*

Despite these limitations, the overview of the currently available evidence provides insights for clinical decision making, said Bonsen. “Our study highlights that, if we were to be certain of the diagnosis of placenta accreta spectrum disorder antepartum, prophylactic radiologic intervention could help reduce peripartum blood loss,” she said.

Risks vs Benefits

“Given the challenges in performing randomized surgical trials in a pregnant patient population with an uncommon disorder, this level of evidence provides important data to assist with clinical decision making in patients with placenta accreta spectrum disorder,” despite the limitations of the observational studies, wrote Jocelyn S. Chapman, MD, and Arianna M. Cassidy, MD, both affiliated with the Multidisciplinary Approach to Placenta Accreta Spectrum Disorder Service (MAPS) at the University of California, San Francisco, in an accompanying editorial.

Previous research has shown an increased risk of severe maternal morbidity among women with placenta accreta spectrum disorder and previous intervention strategies have involved protocols, surgical techniques, and management strategies, they wrote.

Uterine artery embolization after cesarean delivery also has been associated with reduced hemorrhage and no adverse events, but this procedure was not included in the studies reviewed and is best conducted in a delivery setup not available in many hospital systems, the editorialists noted.

The current study illustrates the value of prophylactic balloon occlusion and placement of vascular sheaths to reduce blood loss and blood transfusion, but the risk of thrombosis and lumbosacral pain must be considered, they said. These risks may be a reasonable trade-off to avoid severe blood loss and ICU care, and to preserve the uterus, Chapman and Cassidy added.

“However, we would urge continued critical appraisal of each placenta accreta spectrum disorder case with a multidisciplinary team to evaluate the available evidence-based strategies most likely to mitigate clinically relevant complications while minimizing the introduction of new ones,” the editorialists concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Chapman and Dr. Cassidy had no financial conflicts to disclose.

*This story was updated on August 28, 2024.

Prophylactic placement of balloon catheters or sheaths prior to planned cesarean delivery may reduce blood loss in women with placenta accreta spectrum disorder, according to a new systematic review of more than 5,000 individuals.

Placenta accreta spectrum disorder occurs when the endometrial-myometrial interface of the uterus is damaged, wrote Lisanne R. Bonsen, MD, of Leiden University Medical Center, the Netherlands, and colleagues. As a result, the placenta fails to detach at the time of birth and can result in life-threatening postpartum hemorrhage, the researchers said.

The greater the depth of placental invasiveness, the more severe the maternal outcomes, the researchers noted. Previous cesarean delivery is the primary risk factor for placenta accreta spectrum disorder, and the incidence has increased along with the increased rates of cesarean delivery on a global level, they explained.

More research is needed on intrapartum strategies to improve maternal outcomes, and prophylactic radiologic intervention to reduce perioperative blood loss has been explored, the researchers wrote. However, placenta accreta spectrum disorder remains relatively rare in most pregnancy settings, and data on the effect of prophylactic radiologic interventions to reduce bleeding in this high-risk population are limited they said.

In the review published in Obstetrics & Gynecology, the researchers analyzed data from 50 studies of prophylactic radiologic interventions (48 observational studies and 2 randomized, controlled trials) including 5,962 women.

The primary outcome was perioperative blood loss; secondary outcomes included the number of red blood cells transferred within 24 hours after delivery, maternal mortality, adverse events related to the interventions, and surgical complications.

Blood loss was significantly lower in the intervention groups compared with the control groups for patients who underwent distal balloon occlusion (30 studies), proximal balloon occlusion (14 studies), or uterine artery embolization (5 studies), with mean differences in blood loss of 406 mL, 1,041 mL, and 936 mL, respectively.

Results were similar with lower blood loss for intervention patients compared with controls in subgroup analyses of different types of placenta accreta spectrum disorder and those with placenta accreta spectrum disorder confirmed post partum.

Across the 35 studies that included data on blood transfusions, women who underwent any prophylactic radiologic intervention averaged fewer red blood cell units transferred than women who had no radiologic intervention, with a mean difference of 1.13, 1.90, and 1.86 units for distal prophylactic balloon occlusion, proximal prophylactic balloon occlusion, and prophylactic uterine artery embolization, respectively.

Data on adverse events related to the interventions were limited, but noted in approximately 2% of patients who underwent distal or proximal prophylactic balloon occlusion, and 45% of patients who underwent prophylactic uterine artery embolization. One maternal death was reported and attributed to diffuse intravascular coagulation. Three cardiac arrests occurred in control patients across different studies and all were successfully resuscitated.

Most of the studies did not report data on the researchers’ predefined secondary outcomes, including shock, transfer to a higher level of care, coagulopathy, organ dysfunction, and patient-reported outcomes.
 

What Works Best

“Our main analysis reveals differences in outcomes among the three interventions, with proximal balloon occlusion demonstrating the strongest effect,” the researchers wrote. “Our results show a blood loss reduction of 406 mL by distal prophylactic balloon occlusion. An explanation for the differences between the results of prophylactic balloon occlusion–distal and prophylactic balloon occlusion–proximal could be that implementing occlusion at a distal level may be less effective because of bleeding from the collateral circulation,” they said.

The findings were limited by several factors including the observational design of most of the studies, variation in measurements of blood loss among studies and in inclusion criteria, and insufficient adverse event data to draw conclusions about safety, the researchers noted. More research is needed to examine efficacy and safety of the interventions according to different sensitivities of placenta accreta spectrum disorder, they added.

Results Support Judicious Intervention

“Although previous studies showed mixed results, our meta-analysis demonstrated that prophylactic radiologic interventions, particularly balloon occlusion (both distal and proximal), were associated with reduced perioperative blood loss and less red blood cell unit transfusion; this was most pronounced in women with confirmed placenta percreta,” Bonsen said in an interview. However, the heterogeneity across the included studies prevents generalizations about the overall effects of the interventions across different severities of placenta accreta spectrum disorder, she said.*

Despite these limitations, the overview of the currently available evidence provides insights for clinical decision making, said Bonsen. “Our study highlights that, if we were to be certain of the diagnosis of placenta accreta spectrum disorder antepartum, prophylactic radiologic intervention could help reduce peripartum blood loss,” she said.

Risks vs Benefits

“Given the challenges in performing randomized surgical trials in a pregnant patient population with an uncommon disorder, this level of evidence provides important data to assist with clinical decision making in patients with placenta accreta spectrum disorder,” despite the limitations of the observational studies, wrote Jocelyn S. Chapman, MD, and Arianna M. Cassidy, MD, both affiliated with the Multidisciplinary Approach to Placenta Accreta Spectrum Disorder Service (MAPS) at the University of California, San Francisco, in an accompanying editorial.

Previous research has shown an increased risk of severe maternal morbidity among women with placenta accreta spectrum disorder and previous intervention strategies have involved protocols, surgical techniques, and management strategies, they wrote.

Uterine artery embolization after cesarean delivery also has been associated with reduced hemorrhage and no adverse events, but this procedure was not included in the studies reviewed and is best conducted in a delivery setup not available in many hospital systems, the editorialists noted.

The current study illustrates the value of prophylactic balloon occlusion and placement of vascular sheaths to reduce blood loss and blood transfusion, but the risk of thrombosis and lumbosacral pain must be considered, they said. These risks may be a reasonable trade-off to avoid severe blood loss and ICU care, and to preserve the uterus, Chapman and Cassidy added.

“However, we would urge continued critical appraisal of each placenta accreta spectrum disorder case with a multidisciplinary team to evaluate the available evidence-based strategies most likely to mitigate clinically relevant complications while minimizing the introduction of new ones,” the editorialists concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Chapman and Dr. Cassidy had no financial conflicts to disclose.

*This story was updated on August 28, 2024.

Prophylactic placement of balloon catheters or sheaths prior to planned cesarean delivery may reduce blood loss in women with placenta accreta spectrum disorder, according to a new systematic review of more than 5,000 individuals.

Placenta accreta spectrum disorder occurs when the endometrial-myometrial interface of the uterus is damaged, wrote Lisanne R. Bonsen, MD, of Leiden University Medical Center, the Netherlands, and colleagues. As a result, the placenta fails to detach at the time of birth and can result in life-threatening postpartum hemorrhage, the researchers said.

The greater the depth of placental invasiveness, the more severe the maternal outcomes, the researchers noted. Previous cesarean delivery is the primary risk factor for placenta accreta spectrum disorder, and the incidence has increased along with the increased rates of cesarean delivery on a global level, they explained.

More research is needed on intrapartum strategies to improve maternal outcomes, and prophylactic radiologic intervention to reduce perioperative blood loss has been explored, the researchers wrote. However, placenta accreta spectrum disorder remains relatively rare in most pregnancy settings, and data on the effect of prophylactic radiologic interventions to reduce bleeding in this high-risk population are limited they said.

In the review published in Obstetrics & Gynecology, the researchers analyzed data from 50 studies of prophylactic radiologic interventions (48 observational studies and 2 randomized, controlled trials) including 5,962 women.

The primary outcome was perioperative blood loss; secondary outcomes included the number of red blood cells transferred within 24 hours after delivery, maternal mortality, adverse events related to the interventions, and surgical complications.

Blood loss was significantly lower in the intervention groups compared with the control groups for patients who underwent distal balloon occlusion (30 studies), proximal balloon occlusion (14 studies), or uterine artery embolization (5 studies), with mean differences in blood loss of 406 mL, 1,041 mL, and 936 mL, respectively.

Results were similar with lower blood loss for intervention patients compared with controls in subgroup analyses of different types of placenta accreta spectrum disorder and those with placenta accreta spectrum disorder confirmed post partum.

Across the 35 studies that included data on blood transfusions, women who underwent any prophylactic radiologic intervention averaged fewer red blood cell units transferred than women who had no radiologic intervention, with a mean difference of 1.13, 1.90, and 1.86 units for distal prophylactic balloon occlusion, proximal prophylactic balloon occlusion, and prophylactic uterine artery embolization, respectively.

Data on adverse events related to the interventions were limited, but noted in approximately 2% of patients who underwent distal or proximal prophylactic balloon occlusion, and 45% of patients who underwent prophylactic uterine artery embolization. One maternal death was reported and attributed to diffuse intravascular coagulation. Three cardiac arrests occurred in control patients across different studies and all were successfully resuscitated.

Most of the studies did not report data on the researchers’ predefined secondary outcomes, including shock, transfer to a higher level of care, coagulopathy, organ dysfunction, and patient-reported outcomes.
 

What Works Best

“Our main analysis reveals differences in outcomes among the three interventions, with proximal balloon occlusion demonstrating the strongest effect,” the researchers wrote. “Our results show a blood loss reduction of 406 mL by distal prophylactic balloon occlusion. An explanation for the differences between the results of prophylactic balloon occlusion–distal and prophylactic balloon occlusion–proximal could be that implementing occlusion at a distal level may be less effective because of bleeding from the collateral circulation,” they said.

The findings were limited by several factors including the observational design of most of the studies, variation in measurements of blood loss among studies and in inclusion criteria, and insufficient adverse event data to draw conclusions about safety, the researchers noted. More research is needed to examine efficacy and safety of the interventions according to different sensitivities of placenta accreta spectrum disorder, they added.

Results Support Judicious Intervention

“Although previous studies showed mixed results, our meta-analysis demonstrated that prophylactic radiologic interventions, particularly balloon occlusion (both distal and proximal), were associated with reduced perioperative blood loss and less red blood cell unit transfusion; this was most pronounced in women with confirmed placenta percreta,” Bonsen said in an interview. However, the heterogeneity across the included studies prevents generalizations about the overall effects of the interventions across different severities of placenta accreta spectrum disorder, she said.*

Despite these limitations, the overview of the currently available evidence provides insights for clinical decision making, said Bonsen. “Our study highlights that, if we were to be certain of the diagnosis of placenta accreta spectrum disorder antepartum, prophylactic radiologic intervention could help reduce peripartum blood loss,” she said.

Risks vs Benefits

“Given the challenges in performing randomized surgical trials in a pregnant patient population with an uncommon disorder, this level of evidence provides important data to assist with clinical decision making in patients with placenta accreta spectrum disorder,” despite the limitations of the observational studies, wrote Jocelyn S. Chapman, MD, and Arianna M. Cassidy, MD, both affiliated with the Multidisciplinary Approach to Placenta Accreta Spectrum Disorder Service (MAPS) at the University of California, San Francisco, in an accompanying editorial.

Previous research has shown an increased risk of severe maternal morbidity among women with placenta accreta spectrum disorder and previous intervention strategies have involved protocols, surgical techniques, and management strategies, they wrote.

Uterine artery embolization after cesarean delivery also has been associated with reduced hemorrhage and no adverse events, but this procedure was not included in the studies reviewed and is best conducted in a delivery setup not available in many hospital systems, the editorialists noted.

The current study illustrates the value of prophylactic balloon occlusion and placement of vascular sheaths to reduce blood loss and blood transfusion, but the risk of thrombosis and lumbosacral pain must be considered, they said. These risks may be a reasonable trade-off to avoid severe blood loss and ICU care, and to preserve the uterus, Chapman and Cassidy added.

“However, we would urge continued critical appraisal of each placenta accreta spectrum disorder case with a multidisciplinary team to evaluate the available evidence-based strategies most likely to mitigate clinically relevant complications while minimizing the introduction of new ones,” the editorialists concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Chapman and Dr. Cassidy had no financial conflicts to disclose.

*This story was updated on August 28, 2024.