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GI symptoms during menopause deserve attention
This transcript has been edited for clarity.
Welcome back to another GI Common Concerns.
Today, I want to highlight some information about menopause.
Approximately 1.5 million women in the United States per year enter into menopause. Hysterectomy is also one of the most common surgeries for women worldwide, with an estimated 20%-40% undergoing this procedure by the age of 60.
Therefore, whether it’s because of biologic onset with age or surgical induction, menopause is a very common condition, and it’s important that we understand its symptoms and the latest information around it.
Impact on GI motility
One of the clearest functional symptoms to be aware of with menopause relates to alterations in hormonal balance. This has an impact on gastrointestinal (GI) motility by increasing abdominal muscle stimulation related to different patterns of secretion and can result in a number of symptomatic changes.
One such change that can occur is food intolerance. It is believed that menopause-associated food intolerance has multiple possible causes and may be related more to alterations to the microbiome, which can be contributed to by diet, activity, sleep cycle, and other factors.
When food intolerances are triggered in the perimenopausal or menopausal patient, it may lead you to recommend the well-established FODMAP diet, which is known to reduce symptoms. But the answer for every patient is not simply placing them on a FODMAP diet and telling them they have irritable bowel syndrome.
Other approaches can be considered for addressing food intolerance in these patients. The data are quite strong that adjunctive use of a dietitian is tremendously helpful in this particular population.
When it comes to menopausal patients, however, we need to consider other changes in their activity or adverse contributors to their mental health, such as stress or anxiety. These all contribute to more of a multifactorial composite in this population, for which irritable bowel syndrome serves as a similar example.
This means that we may need to expand our horizons rather than to focus on solely on antispasmodic or diet-related interventions.
Instead, we can start to consider more of a multidimensional treatment approach consisting of education, relaxation, cognitive-behavioral therapy, and physical activity. Certainly, there are now behavioral interventions using Internet-based digital formats to increase the acceptability and sustainability among patients.
Choosing such a multidisciplinary approach can be quite helpful.
The metabolic consequences of altering hormonal balance
Recent data from a rat model study investigated the metabolic impact of changing hormonal balance.
Investigators looked at ovariectomized rats and found that there was a biologic change in the diversity of the general GI biome. There were also noteworthy associations with weight fluctuations and dramatic changes in the spatial memory and cognitive performance characteristics of these rats, which was subsequently improved by supplemental estrogen.
This indicates that we may be able to remediate these effects with the similar use of supplemental hormone replacement treatments.
Another recent study looked at nonalcoholic fatty liver disease, which is very common in the general population and has a > 20% worldwide prevalence in postmenopausal women. Albeit small in numbers, this was a very interesting study.
Investigators looked at the delivery method for menopausal hormone therapy, which was transdermal for 75 patients and oral for 293 patients. Then, they looked at ultrasound definition of nonalcoholic fatty liver disease after 1 year as the endpoint. They found an approximate 7% reduction in the patients who received the transdermal administration compared with a 4% increase in the patients who received it orally.
Again, we have to remember this is a relatively small study, but the results indicate that the route of estrogen administration may be an important consideration in nonalcoholic fatty liver disease.
Sleep disturbances: fragmentation, duration, and quality
Sleep is something that’s near and dear to my heart and is the focus of a lot of our research.
Sleep disturbances are really part and parcel of menopause and are observed with hormonal imbalances and temperature intolerances. Disturbances such as sleep fragmentation, shorter sleep duration, and poorer sleep quality have a dramatic effect not only on the biome but also on sensory thresholds.
Therefore, as we start to look at mitigating strategies here, we need to focus on sleep and ask the right questions.
In my own practice, I try not to just ask, “How did you sleep last night?” That’s because sleep can be somewhat amnestic. You may have a cognitive awakening or a noncognitive awakening but still have experienced fragmentation.
As a result, my focus is on next-day function. I ask my patients, “When you get up in the morning, are you refreshed? Do you have the ability to perform daytime activities? Do you experience early fatigue or cognitive changes that occur?”
These questions can provide good insights into the sleep efficiency of the previous night.
The effect of the microbiome on osteoporosis
One final topic I found very interesting pertains to the effects of menopause on osteoporosis.
We certainly know that postmenopausal women have a very high prevalence of osteopenia, and that osteoporosis is a progression of that, as well as that increased bone-related disease affects fractures and related morbidity and mortality.
However, there’s accumulating evidence on the osteoporotic effects of biomarker changes in menopause, which shows that the biome regulates the pathophysiologic process of at least a large degree of osteoporosis.
This starts to make sense when you look at the pro-inflammatory factors that increase with changes in biome diversity, in particular tumor necrosis factor alpha (which is something we also see in inflammatory bowel disease), interleukin-1, and increased activated osteoclasts.
Therefore, when it comes to decreasing bone loss among patients who are perimenopausal or postmenopausal, we don’t yet have a clear answer. Hormone therapy, diet, activity, vitamin D supplementation, and other things may positively change the biome. They are worthy topics for patients to bring up with their ob.gyns. or primary care doctors.
Although it may be a little bit outside the scope of gastroenterology, in my opinion there are a number of new findings relating to menopause that we as a field need to be more proactive in addressing.
Ask the right questions when these people come in to you, irrespective of why they’re there. Start to ask about the quality of their sleep. What are their other functional symptoms? What are their other potential osteoporosis-related risks?
We must do a better job about individualizing care. Rather than treating patients as disease states, we must start to do specific patient-focused care.
I hope this gives you some provocative thoughts when you have your next session with a patient in the perimenopausal or menopausal state. There are lots of things that we continue to learn.
Dr. Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Va., and a past president of the American College of Gastroenterology. He serves as an adviser to ISOThrive and Johnson & Johnson.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
Welcome back to another GI Common Concerns.
Today, I want to highlight some information about menopause.
Approximately 1.5 million women in the United States per year enter into menopause. Hysterectomy is also one of the most common surgeries for women worldwide, with an estimated 20%-40% undergoing this procedure by the age of 60.
Therefore, whether it’s because of biologic onset with age or surgical induction, menopause is a very common condition, and it’s important that we understand its symptoms and the latest information around it.
Impact on GI motility
One of the clearest functional symptoms to be aware of with menopause relates to alterations in hormonal balance. This has an impact on gastrointestinal (GI) motility by increasing abdominal muscle stimulation related to different patterns of secretion and can result in a number of symptomatic changes.
One such change that can occur is food intolerance. It is believed that menopause-associated food intolerance has multiple possible causes and may be related more to alterations to the microbiome, which can be contributed to by diet, activity, sleep cycle, and other factors.
When food intolerances are triggered in the perimenopausal or menopausal patient, it may lead you to recommend the well-established FODMAP diet, which is known to reduce symptoms. But the answer for every patient is not simply placing them on a FODMAP diet and telling them they have irritable bowel syndrome.
Other approaches can be considered for addressing food intolerance in these patients. The data are quite strong that adjunctive use of a dietitian is tremendously helpful in this particular population.
When it comes to menopausal patients, however, we need to consider other changes in their activity or adverse contributors to their mental health, such as stress or anxiety. These all contribute to more of a multifactorial composite in this population, for which irritable bowel syndrome serves as a similar example.
This means that we may need to expand our horizons rather than to focus on solely on antispasmodic or diet-related interventions.
Instead, we can start to consider more of a multidimensional treatment approach consisting of education, relaxation, cognitive-behavioral therapy, and physical activity. Certainly, there are now behavioral interventions using Internet-based digital formats to increase the acceptability and sustainability among patients.
Choosing such a multidisciplinary approach can be quite helpful.
The metabolic consequences of altering hormonal balance
Recent data from a rat model study investigated the metabolic impact of changing hormonal balance.
Investigators looked at ovariectomized rats and found that there was a biologic change in the diversity of the general GI biome. There were also noteworthy associations with weight fluctuations and dramatic changes in the spatial memory and cognitive performance characteristics of these rats, which was subsequently improved by supplemental estrogen.
This indicates that we may be able to remediate these effects with the similar use of supplemental hormone replacement treatments.
Another recent study looked at nonalcoholic fatty liver disease, which is very common in the general population and has a > 20% worldwide prevalence in postmenopausal women. Albeit small in numbers, this was a very interesting study.
Investigators looked at the delivery method for menopausal hormone therapy, which was transdermal for 75 patients and oral for 293 patients. Then, they looked at ultrasound definition of nonalcoholic fatty liver disease after 1 year as the endpoint. They found an approximate 7% reduction in the patients who received the transdermal administration compared with a 4% increase in the patients who received it orally.
Again, we have to remember this is a relatively small study, but the results indicate that the route of estrogen administration may be an important consideration in nonalcoholic fatty liver disease.
Sleep disturbances: fragmentation, duration, and quality
Sleep is something that’s near and dear to my heart and is the focus of a lot of our research.
Sleep disturbances are really part and parcel of menopause and are observed with hormonal imbalances and temperature intolerances. Disturbances such as sleep fragmentation, shorter sleep duration, and poorer sleep quality have a dramatic effect not only on the biome but also on sensory thresholds.
Therefore, as we start to look at mitigating strategies here, we need to focus on sleep and ask the right questions.
In my own practice, I try not to just ask, “How did you sleep last night?” That’s because sleep can be somewhat amnestic. You may have a cognitive awakening or a noncognitive awakening but still have experienced fragmentation.
As a result, my focus is on next-day function. I ask my patients, “When you get up in the morning, are you refreshed? Do you have the ability to perform daytime activities? Do you experience early fatigue or cognitive changes that occur?”
These questions can provide good insights into the sleep efficiency of the previous night.
The effect of the microbiome on osteoporosis
One final topic I found very interesting pertains to the effects of menopause on osteoporosis.
We certainly know that postmenopausal women have a very high prevalence of osteopenia, and that osteoporosis is a progression of that, as well as that increased bone-related disease affects fractures and related morbidity and mortality.
However, there’s accumulating evidence on the osteoporotic effects of biomarker changes in menopause, which shows that the biome regulates the pathophysiologic process of at least a large degree of osteoporosis.
This starts to make sense when you look at the pro-inflammatory factors that increase with changes in biome diversity, in particular tumor necrosis factor alpha (which is something we also see in inflammatory bowel disease), interleukin-1, and increased activated osteoclasts.
Therefore, when it comes to decreasing bone loss among patients who are perimenopausal or postmenopausal, we don’t yet have a clear answer. Hormone therapy, diet, activity, vitamin D supplementation, and other things may positively change the biome. They are worthy topics for patients to bring up with their ob.gyns. or primary care doctors.
Although it may be a little bit outside the scope of gastroenterology, in my opinion there are a number of new findings relating to menopause that we as a field need to be more proactive in addressing.
Ask the right questions when these people come in to you, irrespective of why they’re there. Start to ask about the quality of their sleep. What are their other functional symptoms? What are their other potential osteoporosis-related risks?
We must do a better job about individualizing care. Rather than treating patients as disease states, we must start to do specific patient-focused care.
I hope this gives you some provocative thoughts when you have your next session with a patient in the perimenopausal or menopausal state. There are lots of things that we continue to learn.
Dr. Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Va., and a past president of the American College of Gastroenterology. He serves as an adviser to ISOThrive and Johnson & Johnson.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
Welcome back to another GI Common Concerns.
Today, I want to highlight some information about menopause.
Approximately 1.5 million women in the United States per year enter into menopause. Hysterectomy is also one of the most common surgeries for women worldwide, with an estimated 20%-40% undergoing this procedure by the age of 60.
Therefore, whether it’s because of biologic onset with age or surgical induction, menopause is a very common condition, and it’s important that we understand its symptoms and the latest information around it.
Impact on GI motility
One of the clearest functional symptoms to be aware of with menopause relates to alterations in hormonal balance. This has an impact on gastrointestinal (GI) motility by increasing abdominal muscle stimulation related to different patterns of secretion and can result in a number of symptomatic changes.
One such change that can occur is food intolerance. It is believed that menopause-associated food intolerance has multiple possible causes and may be related more to alterations to the microbiome, which can be contributed to by diet, activity, sleep cycle, and other factors.
When food intolerances are triggered in the perimenopausal or menopausal patient, it may lead you to recommend the well-established FODMAP diet, which is known to reduce symptoms. But the answer for every patient is not simply placing them on a FODMAP diet and telling them they have irritable bowel syndrome.
Other approaches can be considered for addressing food intolerance in these patients. The data are quite strong that adjunctive use of a dietitian is tremendously helpful in this particular population.
When it comes to menopausal patients, however, we need to consider other changes in their activity or adverse contributors to their mental health, such as stress or anxiety. These all contribute to more of a multifactorial composite in this population, for which irritable bowel syndrome serves as a similar example.
This means that we may need to expand our horizons rather than to focus on solely on antispasmodic or diet-related interventions.
Instead, we can start to consider more of a multidimensional treatment approach consisting of education, relaxation, cognitive-behavioral therapy, and physical activity. Certainly, there are now behavioral interventions using Internet-based digital formats to increase the acceptability and sustainability among patients.
Choosing such a multidisciplinary approach can be quite helpful.
The metabolic consequences of altering hormonal balance
Recent data from a rat model study investigated the metabolic impact of changing hormonal balance.
Investigators looked at ovariectomized rats and found that there was a biologic change in the diversity of the general GI biome. There were also noteworthy associations with weight fluctuations and dramatic changes in the spatial memory and cognitive performance characteristics of these rats, which was subsequently improved by supplemental estrogen.
This indicates that we may be able to remediate these effects with the similar use of supplemental hormone replacement treatments.
Another recent study looked at nonalcoholic fatty liver disease, which is very common in the general population and has a > 20% worldwide prevalence in postmenopausal women. Albeit small in numbers, this was a very interesting study.
Investigators looked at the delivery method for menopausal hormone therapy, which was transdermal for 75 patients and oral for 293 patients. Then, they looked at ultrasound definition of nonalcoholic fatty liver disease after 1 year as the endpoint. They found an approximate 7% reduction in the patients who received the transdermal administration compared with a 4% increase in the patients who received it orally.
Again, we have to remember this is a relatively small study, but the results indicate that the route of estrogen administration may be an important consideration in nonalcoholic fatty liver disease.
Sleep disturbances: fragmentation, duration, and quality
Sleep is something that’s near and dear to my heart and is the focus of a lot of our research.
Sleep disturbances are really part and parcel of menopause and are observed with hormonal imbalances and temperature intolerances. Disturbances such as sleep fragmentation, shorter sleep duration, and poorer sleep quality have a dramatic effect not only on the biome but also on sensory thresholds.
Therefore, as we start to look at mitigating strategies here, we need to focus on sleep and ask the right questions.
In my own practice, I try not to just ask, “How did you sleep last night?” That’s because sleep can be somewhat amnestic. You may have a cognitive awakening or a noncognitive awakening but still have experienced fragmentation.
As a result, my focus is on next-day function. I ask my patients, “When you get up in the morning, are you refreshed? Do you have the ability to perform daytime activities? Do you experience early fatigue or cognitive changes that occur?”
These questions can provide good insights into the sleep efficiency of the previous night.
The effect of the microbiome on osteoporosis
One final topic I found very interesting pertains to the effects of menopause on osteoporosis.
We certainly know that postmenopausal women have a very high prevalence of osteopenia, and that osteoporosis is a progression of that, as well as that increased bone-related disease affects fractures and related morbidity and mortality.
However, there’s accumulating evidence on the osteoporotic effects of biomarker changes in menopause, which shows that the biome regulates the pathophysiologic process of at least a large degree of osteoporosis.
This starts to make sense when you look at the pro-inflammatory factors that increase with changes in biome diversity, in particular tumor necrosis factor alpha (which is something we also see in inflammatory bowel disease), interleukin-1, and increased activated osteoclasts.
Therefore, when it comes to decreasing bone loss among patients who are perimenopausal or postmenopausal, we don’t yet have a clear answer. Hormone therapy, diet, activity, vitamin D supplementation, and other things may positively change the biome. They are worthy topics for patients to bring up with their ob.gyns. or primary care doctors.
Although it may be a little bit outside the scope of gastroenterology, in my opinion there are a number of new findings relating to menopause that we as a field need to be more proactive in addressing.
Ask the right questions when these people come in to you, irrespective of why they’re there. Start to ask about the quality of their sleep. What are their other functional symptoms? What are their other potential osteoporosis-related risks?
We must do a better job about individualizing care. Rather than treating patients as disease states, we must start to do specific patient-focused care.
I hope this gives you some provocative thoughts when you have your next session with a patient in the perimenopausal or menopausal state. There are lots of things that we continue to learn.
Dr. Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Va., and a past president of the American College of Gastroenterology. He serves as an adviser to ISOThrive and Johnson & Johnson.
A version of this article first appeared on Medscape.com.
Postmenopausal testosterone for low libido only, doctors say
Your patients may see ads claiming that testosterone replacement therapy (TRT) offers postmenopausal women health benefits beyond restored sex drive: that TRT can improve their mood, energy, and thinking and give them stronger bones and bigger muscles.
How accurate are these claims? According to six experts who talked with this news organization, not very.
“Right now in this country and around the world, testosterone’s only use in postmenopausal women is for libido,” said Adrian Sandra Dobs, MD, MHS, professor of medicine and director of the Johns Hopkins Clinical Research Network at Johns Hopkins Medicine, Baltimore.
“Treating postmenopausal women with testosterone is a rarity. Some physicians and some wellness centers make their money out of prescribing estrogen and testosterone to women in patches, gels, creams, capsules, pellets, and other forms. she added by phone.
“One has to be very careful about using testosterone in women,” Dr. Dobs cautioned. “There’s a lot of hype out there.”
Low testosterone in women has not been well studied, and no testosterone treatments for this condition have been approved by the U.S. Food and Drug Administration. Providers need to adjust male treatment data to their female patients, who require significantly lower doses than males. Contraindications and long-term side effects are poorly understood, said Mary Rosser, MD, PhD, assistant professor of women’s health and director of integrated women’s health at Columbia University Irving Medical Center, New York.
“Despite this preponderance of scientific evidence and recommendations, the myths about testosterone die hard, including that it improves women’s muscle function, endurance, and well-being,” Dr. Rosser said.
“Websites that use compounded products or pellets are not FDA-regulated; therefore, they have no responsibility to prove their claims. They can entice women into using this stuff with all kinds of promises about ‘hormone balancing’ and other meaningless terms. The Endocrine Society statement reviewed the clinical studies on testosterone for various indications surrounding physical endurance, well-being, and mental health – and the studies do not support its use,” Dr. Rosser added.
According to the Australasian Menopause Society, women’s blood testosterone levels tend to peak in their 20s, slowly decline to around 25% of peak levels at menopause, then rise again in later years.
Susan Davis, PhD, and her colleagues at Monash University, Melbourne, found in a study that TRT in postmenopausal women may improve sexual well-being and that side effects include acne and increased hair growth. But they found no benefits for cognition, bone mineral density, body composition, muscle strength, or psychological well-being, and they note that more data are needed on long-term safety.
Postmenopausal testosterone recommended for libido only
“Hypoactive sexual desire disorder (HSDD) is really the only indication for postmenopausal testosterone use,” Nanette F. Santoro, MD, professor and chair of obstetrics and gynecology at the University of Colorado School of Medicine, Aurora, noted by email. “In clinical studies using androgen gel containing testosterone, testosterone treatment has resulted in a mean of one more satisfying sexual encounter per month. Consensus statements issued by the Endocrine Society, The International Menopause Society, and the North American Menopause Society have come to similar conclusions: The only indication for androgen therapy for women is HSDD,” added Santoro, an author of the Endocrine Society statement.
“Sexual health and the sense of well-being are very much related,” Sandra Ann Carson, MD, professor of obstetrics and gynecology at Yale Medicine, New Haven, Conn., said by phone. “So we give testosterone to increase sexual desire. Testosterone is not a treatment for decreased sense of well-being alone. Women who lose their sense of well-being due to depression or other factors need to have a mental health evaluation, not testosterone.”
“Because no female product is presently approved by a national regulatory body, male formulations can be judiciously used in female doses and blood testosterone concentrations must be monitored regularly,” Dr. Rosser said. “The recommendation is for considering use of compounded testosterone for hypoactive sexual desire only; it is against use for overall health and wellness.”
“The real mischief occurs when women are exposed to doses that are supraphysiologic,” Dr. Rosser cautioned. “At high doses that approach and sometimes exceed men’s levels of testosterone, women can have deepening of the voice, adverse changes in cholesterol, and even breast atrophy. This can occur with bioidentical compounded testosterone and with testosterone pellets. The National Academies of Science, Engineering, and Medicine recommend unequivocally that such preparations not be used.”
Not all postmenopausal women should take TRT, said Meredith McClure, MD, assistant professor in the department of obstetrics and gynecology of UT Southwestern Medical School, Dallas, because it has only been shown in trials to help with HSDD.
She advised clinicians to avoid prescribing testosterone to patients who “can’t take estrogen, including if [they] have hormone-sensitive cancer, blood clot risk, liver disease, heart attack, stroke, or undiagnosed genital bleeding.”
TRT for non-libido issues may sometimes be appropriate
“Perhaps women with hip fracture or cancer cachexia could benefit from testosterone to build muscle mass,” said Dr. Dobbs, who is involved in an ongoing study of testosterone treatment in women with hip fracture. “But as yet, we have no proof that testosterone helps.”
In rare cases, Stanley G. Korenman, MD, a reproductive endocrinologist and associate dean for ethics at UCLA Health, treats postmenopausal patients with TRT for reasons other than low libido. “I have a very specialized practice in reproductive endocrinology and internal medicine and am one of very few people in the country who do this kind of management,” he said in an interview. “If my postmenopausal patients have low testosterone and lack energy, I’m willing to give them low doses. If they feel more energetic, we continue, but if they don’t, we stop. I don’t think there’s any risk whatsoever at the low level I prescribe.
“I prescribe standard gel that comes in a squirt bottle, and I suggest they take half a squirt every other day – about one-eighth of a male dose – on the sole of the foot, where hair does not grow.
“I would not prescribe testosterone for bone health. We have bisphosphonates and other much better treatments for that. And I would not prescribe it to someone who is seriously emotionally disturbed or seriously depressed. This is not a treatment for depression.”
“Postmenopausal testosterone is not ‘the latest greatest thing,’ but being very low risk, it’s worth trying once in a while, in the appropriate patient, at the right dose,” Dr. Korenman advised. He cautioned people to “avoid the longevity salespeople who sell all sorts of things in all sorts of doses to try to keep us alive forever.”
All contributors report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Your patients may see ads claiming that testosterone replacement therapy (TRT) offers postmenopausal women health benefits beyond restored sex drive: that TRT can improve their mood, energy, and thinking and give them stronger bones and bigger muscles.
How accurate are these claims? According to six experts who talked with this news organization, not very.
“Right now in this country and around the world, testosterone’s only use in postmenopausal women is for libido,” said Adrian Sandra Dobs, MD, MHS, professor of medicine and director of the Johns Hopkins Clinical Research Network at Johns Hopkins Medicine, Baltimore.
“Treating postmenopausal women with testosterone is a rarity. Some physicians and some wellness centers make their money out of prescribing estrogen and testosterone to women in patches, gels, creams, capsules, pellets, and other forms. she added by phone.
“One has to be very careful about using testosterone in women,” Dr. Dobs cautioned. “There’s a lot of hype out there.”
Low testosterone in women has not been well studied, and no testosterone treatments for this condition have been approved by the U.S. Food and Drug Administration. Providers need to adjust male treatment data to their female patients, who require significantly lower doses than males. Contraindications and long-term side effects are poorly understood, said Mary Rosser, MD, PhD, assistant professor of women’s health and director of integrated women’s health at Columbia University Irving Medical Center, New York.
“Despite this preponderance of scientific evidence and recommendations, the myths about testosterone die hard, including that it improves women’s muscle function, endurance, and well-being,” Dr. Rosser said.
“Websites that use compounded products or pellets are not FDA-regulated; therefore, they have no responsibility to prove their claims. They can entice women into using this stuff with all kinds of promises about ‘hormone balancing’ and other meaningless terms. The Endocrine Society statement reviewed the clinical studies on testosterone for various indications surrounding physical endurance, well-being, and mental health – and the studies do not support its use,” Dr. Rosser added.
According to the Australasian Menopause Society, women’s blood testosterone levels tend to peak in their 20s, slowly decline to around 25% of peak levels at menopause, then rise again in later years.
Susan Davis, PhD, and her colleagues at Monash University, Melbourne, found in a study that TRT in postmenopausal women may improve sexual well-being and that side effects include acne and increased hair growth. But they found no benefits for cognition, bone mineral density, body composition, muscle strength, or psychological well-being, and they note that more data are needed on long-term safety.
Postmenopausal testosterone recommended for libido only
“Hypoactive sexual desire disorder (HSDD) is really the only indication for postmenopausal testosterone use,” Nanette F. Santoro, MD, professor and chair of obstetrics and gynecology at the University of Colorado School of Medicine, Aurora, noted by email. “In clinical studies using androgen gel containing testosterone, testosterone treatment has resulted in a mean of one more satisfying sexual encounter per month. Consensus statements issued by the Endocrine Society, The International Menopause Society, and the North American Menopause Society have come to similar conclusions: The only indication for androgen therapy for women is HSDD,” added Santoro, an author of the Endocrine Society statement.
“Sexual health and the sense of well-being are very much related,” Sandra Ann Carson, MD, professor of obstetrics and gynecology at Yale Medicine, New Haven, Conn., said by phone. “So we give testosterone to increase sexual desire. Testosterone is not a treatment for decreased sense of well-being alone. Women who lose their sense of well-being due to depression or other factors need to have a mental health evaluation, not testosterone.”
“Because no female product is presently approved by a national regulatory body, male formulations can be judiciously used in female doses and blood testosterone concentrations must be monitored regularly,” Dr. Rosser said. “The recommendation is for considering use of compounded testosterone for hypoactive sexual desire only; it is against use for overall health and wellness.”
“The real mischief occurs when women are exposed to doses that are supraphysiologic,” Dr. Rosser cautioned. “At high doses that approach and sometimes exceed men’s levels of testosterone, women can have deepening of the voice, adverse changes in cholesterol, and even breast atrophy. This can occur with bioidentical compounded testosterone and with testosterone pellets. The National Academies of Science, Engineering, and Medicine recommend unequivocally that such preparations not be used.”
Not all postmenopausal women should take TRT, said Meredith McClure, MD, assistant professor in the department of obstetrics and gynecology of UT Southwestern Medical School, Dallas, because it has only been shown in trials to help with HSDD.
She advised clinicians to avoid prescribing testosterone to patients who “can’t take estrogen, including if [they] have hormone-sensitive cancer, blood clot risk, liver disease, heart attack, stroke, or undiagnosed genital bleeding.”
TRT for non-libido issues may sometimes be appropriate
“Perhaps women with hip fracture or cancer cachexia could benefit from testosterone to build muscle mass,” said Dr. Dobbs, who is involved in an ongoing study of testosterone treatment in women with hip fracture. “But as yet, we have no proof that testosterone helps.”
In rare cases, Stanley G. Korenman, MD, a reproductive endocrinologist and associate dean for ethics at UCLA Health, treats postmenopausal patients with TRT for reasons other than low libido. “I have a very specialized practice in reproductive endocrinology and internal medicine and am one of very few people in the country who do this kind of management,” he said in an interview. “If my postmenopausal patients have low testosterone and lack energy, I’m willing to give them low doses. If they feel more energetic, we continue, but if they don’t, we stop. I don’t think there’s any risk whatsoever at the low level I prescribe.
“I prescribe standard gel that comes in a squirt bottle, and I suggest they take half a squirt every other day – about one-eighth of a male dose – on the sole of the foot, where hair does not grow.
“I would not prescribe testosterone for bone health. We have bisphosphonates and other much better treatments for that. And I would not prescribe it to someone who is seriously emotionally disturbed or seriously depressed. This is not a treatment for depression.”
“Postmenopausal testosterone is not ‘the latest greatest thing,’ but being very low risk, it’s worth trying once in a while, in the appropriate patient, at the right dose,” Dr. Korenman advised. He cautioned people to “avoid the longevity salespeople who sell all sorts of things in all sorts of doses to try to keep us alive forever.”
All contributors report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Your patients may see ads claiming that testosterone replacement therapy (TRT) offers postmenopausal women health benefits beyond restored sex drive: that TRT can improve their mood, energy, and thinking and give them stronger bones and bigger muscles.
How accurate are these claims? According to six experts who talked with this news organization, not very.
“Right now in this country and around the world, testosterone’s only use in postmenopausal women is for libido,” said Adrian Sandra Dobs, MD, MHS, professor of medicine and director of the Johns Hopkins Clinical Research Network at Johns Hopkins Medicine, Baltimore.
“Treating postmenopausal women with testosterone is a rarity. Some physicians and some wellness centers make their money out of prescribing estrogen and testosterone to women in patches, gels, creams, capsules, pellets, and other forms. she added by phone.
“One has to be very careful about using testosterone in women,” Dr. Dobs cautioned. “There’s a lot of hype out there.”
Low testosterone in women has not been well studied, and no testosterone treatments for this condition have been approved by the U.S. Food and Drug Administration. Providers need to adjust male treatment data to their female patients, who require significantly lower doses than males. Contraindications and long-term side effects are poorly understood, said Mary Rosser, MD, PhD, assistant professor of women’s health and director of integrated women’s health at Columbia University Irving Medical Center, New York.
“Despite this preponderance of scientific evidence and recommendations, the myths about testosterone die hard, including that it improves women’s muscle function, endurance, and well-being,” Dr. Rosser said.
“Websites that use compounded products or pellets are not FDA-regulated; therefore, they have no responsibility to prove their claims. They can entice women into using this stuff with all kinds of promises about ‘hormone balancing’ and other meaningless terms. The Endocrine Society statement reviewed the clinical studies on testosterone for various indications surrounding physical endurance, well-being, and mental health – and the studies do not support its use,” Dr. Rosser added.
According to the Australasian Menopause Society, women’s blood testosterone levels tend to peak in their 20s, slowly decline to around 25% of peak levels at menopause, then rise again in later years.
Susan Davis, PhD, and her colleagues at Monash University, Melbourne, found in a study that TRT in postmenopausal women may improve sexual well-being and that side effects include acne and increased hair growth. But they found no benefits for cognition, bone mineral density, body composition, muscle strength, or psychological well-being, and they note that more data are needed on long-term safety.
Postmenopausal testosterone recommended for libido only
“Hypoactive sexual desire disorder (HSDD) is really the only indication for postmenopausal testosterone use,” Nanette F. Santoro, MD, professor and chair of obstetrics and gynecology at the University of Colorado School of Medicine, Aurora, noted by email. “In clinical studies using androgen gel containing testosterone, testosterone treatment has resulted in a mean of one more satisfying sexual encounter per month. Consensus statements issued by the Endocrine Society, The International Menopause Society, and the North American Menopause Society have come to similar conclusions: The only indication for androgen therapy for women is HSDD,” added Santoro, an author of the Endocrine Society statement.
“Sexual health and the sense of well-being are very much related,” Sandra Ann Carson, MD, professor of obstetrics and gynecology at Yale Medicine, New Haven, Conn., said by phone. “So we give testosterone to increase sexual desire. Testosterone is not a treatment for decreased sense of well-being alone. Women who lose their sense of well-being due to depression or other factors need to have a mental health evaluation, not testosterone.”
“Because no female product is presently approved by a national regulatory body, male formulations can be judiciously used in female doses and blood testosterone concentrations must be monitored regularly,” Dr. Rosser said. “The recommendation is for considering use of compounded testosterone for hypoactive sexual desire only; it is against use for overall health and wellness.”
“The real mischief occurs when women are exposed to doses that are supraphysiologic,” Dr. Rosser cautioned. “At high doses that approach and sometimes exceed men’s levels of testosterone, women can have deepening of the voice, adverse changes in cholesterol, and even breast atrophy. This can occur with bioidentical compounded testosterone and with testosterone pellets. The National Academies of Science, Engineering, and Medicine recommend unequivocally that such preparations not be used.”
Not all postmenopausal women should take TRT, said Meredith McClure, MD, assistant professor in the department of obstetrics and gynecology of UT Southwestern Medical School, Dallas, because it has only been shown in trials to help with HSDD.
She advised clinicians to avoid prescribing testosterone to patients who “can’t take estrogen, including if [they] have hormone-sensitive cancer, blood clot risk, liver disease, heart attack, stroke, or undiagnosed genital bleeding.”
TRT for non-libido issues may sometimes be appropriate
“Perhaps women with hip fracture or cancer cachexia could benefit from testosterone to build muscle mass,” said Dr. Dobbs, who is involved in an ongoing study of testosterone treatment in women with hip fracture. “But as yet, we have no proof that testosterone helps.”
In rare cases, Stanley G. Korenman, MD, a reproductive endocrinologist and associate dean for ethics at UCLA Health, treats postmenopausal patients with TRT for reasons other than low libido. “I have a very specialized practice in reproductive endocrinology and internal medicine and am one of very few people in the country who do this kind of management,” he said in an interview. “If my postmenopausal patients have low testosterone and lack energy, I’m willing to give them low doses. If they feel more energetic, we continue, but if they don’t, we stop. I don’t think there’s any risk whatsoever at the low level I prescribe.
“I prescribe standard gel that comes in a squirt bottle, and I suggest they take half a squirt every other day – about one-eighth of a male dose – on the sole of the foot, where hair does not grow.
“I would not prescribe testosterone for bone health. We have bisphosphonates and other much better treatments for that. And I would not prescribe it to someone who is seriously emotionally disturbed or seriously depressed. This is not a treatment for depression.”
“Postmenopausal testosterone is not ‘the latest greatest thing,’ but being very low risk, it’s worth trying once in a while, in the appropriate patient, at the right dose,” Dr. Korenman advised. He cautioned people to “avoid the longevity salespeople who sell all sorts of things in all sorts of doses to try to keep us alive forever.”
All contributors report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Postmenopausal stress linked to mood, cognitive symptoms
PHILADELPHIA – , according to research presented at the annual meeting of the Menopause Society (formerly the North American Menopause Society).
“This work suggests that markers of hypothalamic-pituitary-axis activation that capture total cortisol secretion over multiple months, [such as] hair cortisol, strongly correlate with cognitive performance on attention and working memory tasks, whereas measures of more acute cortisol, [such as] salivary cortisol, may be more strongly associated with depression symptom severity and verbal learning,” Christina Metcalf, PhD, an assistant professor of psychiatry in the Colorado Center for Women’s Behavioral Health and Wellness at the University of Colorado at Denver, Aurora, told attendees. “Given the associations with chronic stress, there’s a lot of potential here to increase our knowledge about how women are doing and managing stress and life stressors during this life transition,” she said.
The study involved collecting hair and saliva samples from 43 healthy women in late perimenopause or early postmenopause with an average age of 51. The participants were predominantly white and college educated. The hair sample was taken within 2 cm of the scalp, and the saliva samples were collected the day after the hair sample collection, at the start and end of a 30-minute rest period that took place between 2:00 and 3:00 p.m. local time.
All the participants had an intact uterus and at least one ovary. None of the participants were current smokers or had recent alcohol or drug dependence, and none had used hormones within the previous 6 months. The study also excluded women who were pregnant or breastfeeding, who had bleached hair or no hair, who were taking steroids, beta blockers or opioid medication, and who had recently taken NSAIDS.
Measuring hair cortisol more feasible
The study was conducted remotely, with participants using video conferencing to communicate with the study personnel and then completing study procedures at home, including 2 days of cognitive testing with the California Verbal Learning Test – Third Edition and the n-back and continuous performance tasks. The participants also completed the Center for Epidemiologic Studies Depression Scale (CES-D).
Participants with higher levels of hair cortisol and salivary cortisol also had more severe depression symptoms (P < .001). Hair cortisol was also significantly associated with attention and working memory: Women with higher levels had fewer correct answers on the 0-back and 1-back trials (P < .01) and made more mistakes on the 2-back trial (P < .001). They also scored with less specificity on the continuous performance tasks (P = .022).
Although no association existed between hair cortisol levels and verbal learning or verbal memory (P > .05), participants with higher hair cortisol did score worse on the immediate recall trials (P = .034). Salivary cortisol levels, on the other hand, showed no association with memory recall trials, attention or working memory (P > .05).
Measuring cortisol from hair samples is more feasible than using saliva samples and may offer valuable insights regarding hypothalamic-pituitary-axis activity “to consider alongside the cognitive and mental health of late peri-/early postmenopausal women,” Dr. Metcalf told attendees. The next step is to find out whether the hypothalamic-pituitary-axis axis is a modifiable biomarker that can be used to improve executive function.
The study was limited by its small population, its cross-sectional design, and the lack of covariates in the current analyses.
Monitor symptoms in midlife
Hadine Joffe, MD, MSc, a professor of psychiatry and executive director of the Mary Horrigan Connors Center for Women’s Health and Gender Biology at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, said the study findings were not surprising given how common the complaints of stress and depressive symptoms are.
“Mood changes are linked with acute, immediate cortisol levels at the same point in time, and cognitive symptoms were linked to more chronically elevated cortisol levels,” Dr. Joffe said in an interview. “Women and their providers should monitor for these challenging brain symptoms in midlife as they affect performance and quality of life and are linked with changes in the HPA axis as stress biomarkers.”
Because the study is small and has a cross-sectional design, it’s not possible to determine the direction of the associations or to make any inferences about causation, Dr. Joffe said.
“We cannot make the conclusion that stress is adversely affecting mood and cognitive performance given the design limitations. It is possible that mood and cognitive issues contributed to these stress markers,” Dr. Joffe said.“However, it is known that the experience of stress is linked with vulnerability to mood and cognitive symptoms, and also that mood and cognitive symptoms induce significant stress.”
The research was funded by the Menopause Society, Colorado University, the Ludeman Family Center for Women’s Health Research, the National Institute of Mental Health, and the National Institute of Aging. Dr. Metcalf had no disclosures. Dr. Joffe has received grant support from Merck, Pfizer and Sage, and has been a consultant or advisor for Bayer, Merck and Hello Therapeutics.
PHILADELPHIA – , according to research presented at the annual meeting of the Menopause Society (formerly the North American Menopause Society).
“This work suggests that markers of hypothalamic-pituitary-axis activation that capture total cortisol secretion over multiple months, [such as] hair cortisol, strongly correlate with cognitive performance on attention and working memory tasks, whereas measures of more acute cortisol, [such as] salivary cortisol, may be more strongly associated with depression symptom severity and verbal learning,” Christina Metcalf, PhD, an assistant professor of psychiatry in the Colorado Center for Women’s Behavioral Health and Wellness at the University of Colorado at Denver, Aurora, told attendees. “Given the associations with chronic stress, there’s a lot of potential here to increase our knowledge about how women are doing and managing stress and life stressors during this life transition,” she said.
The study involved collecting hair and saliva samples from 43 healthy women in late perimenopause or early postmenopause with an average age of 51. The participants were predominantly white and college educated. The hair sample was taken within 2 cm of the scalp, and the saliva samples were collected the day after the hair sample collection, at the start and end of a 30-minute rest period that took place between 2:00 and 3:00 p.m. local time.
All the participants had an intact uterus and at least one ovary. None of the participants were current smokers or had recent alcohol or drug dependence, and none had used hormones within the previous 6 months. The study also excluded women who were pregnant or breastfeeding, who had bleached hair or no hair, who were taking steroids, beta blockers or opioid medication, and who had recently taken NSAIDS.
Measuring hair cortisol more feasible
The study was conducted remotely, with participants using video conferencing to communicate with the study personnel and then completing study procedures at home, including 2 days of cognitive testing with the California Verbal Learning Test – Third Edition and the n-back and continuous performance tasks. The participants also completed the Center for Epidemiologic Studies Depression Scale (CES-D).
Participants with higher levels of hair cortisol and salivary cortisol also had more severe depression symptoms (P < .001). Hair cortisol was also significantly associated with attention and working memory: Women with higher levels had fewer correct answers on the 0-back and 1-back trials (P < .01) and made more mistakes on the 2-back trial (P < .001). They also scored with less specificity on the continuous performance tasks (P = .022).
Although no association existed between hair cortisol levels and verbal learning or verbal memory (P > .05), participants with higher hair cortisol did score worse on the immediate recall trials (P = .034). Salivary cortisol levels, on the other hand, showed no association with memory recall trials, attention or working memory (P > .05).
Measuring cortisol from hair samples is more feasible than using saliva samples and may offer valuable insights regarding hypothalamic-pituitary-axis activity “to consider alongside the cognitive and mental health of late peri-/early postmenopausal women,” Dr. Metcalf told attendees. The next step is to find out whether the hypothalamic-pituitary-axis axis is a modifiable biomarker that can be used to improve executive function.
The study was limited by its small population, its cross-sectional design, and the lack of covariates in the current analyses.
Monitor symptoms in midlife
Hadine Joffe, MD, MSc, a professor of psychiatry and executive director of the Mary Horrigan Connors Center for Women’s Health and Gender Biology at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, said the study findings were not surprising given how common the complaints of stress and depressive symptoms are.
“Mood changes are linked with acute, immediate cortisol levels at the same point in time, and cognitive symptoms were linked to more chronically elevated cortisol levels,” Dr. Joffe said in an interview. “Women and their providers should monitor for these challenging brain symptoms in midlife as they affect performance and quality of life and are linked with changes in the HPA axis as stress biomarkers.”
Because the study is small and has a cross-sectional design, it’s not possible to determine the direction of the associations or to make any inferences about causation, Dr. Joffe said.
“We cannot make the conclusion that stress is adversely affecting mood and cognitive performance given the design limitations. It is possible that mood and cognitive issues contributed to these stress markers,” Dr. Joffe said.“However, it is known that the experience of stress is linked with vulnerability to mood and cognitive symptoms, and also that mood and cognitive symptoms induce significant stress.”
The research was funded by the Menopause Society, Colorado University, the Ludeman Family Center for Women’s Health Research, the National Institute of Mental Health, and the National Institute of Aging. Dr. Metcalf had no disclosures. Dr. Joffe has received grant support from Merck, Pfizer and Sage, and has been a consultant or advisor for Bayer, Merck and Hello Therapeutics.
PHILADELPHIA – , according to research presented at the annual meeting of the Menopause Society (formerly the North American Menopause Society).
“This work suggests that markers of hypothalamic-pituitary-axis activation that capture total cortisol secretion over multiple months, [such as] hair cortisol, strongly correlate with cognitive performance on attention and working memory tasks, whereas measures of more acute cortisol, [such as] salivary cortisol, may be more strongly associated with depression symptom severity and verbal learning,” Christina Metcalf, PhD, an assistant professor of psychiatry in the Colorado Center for Women’s Behavioral Health and Wellness at the University of Colorado at Denver, Aurora, told attendees. “Given the associations with chronic stress, there’s a lot of potential here to increase our knowledge about how women are doing and managing stress and life stressors during this life transition,” she said.
The study involved collecting hair and saliva samples from 43 healthy women in late perimenopause or early postmenopause with an average age of 51. The participants were predominantly white and college educated. The hair sample was taken within 2 cm of the scalp, and the saliva samples were collected the day after the hair sample collection, at the start and end of a 30-minute rest period that took place between 2:00 and 3:00 p.m. local time.
All the participants had an intact uterus and at least one ovary. None of the participants were current smokers or had recent alcohol or drug dependence, and none had used hormones within the previous 6 months. The study also excluded women who were pregnant or breastfeeding, who had bleached hair or no hair, who were taking steroids, beta blockers or opioid medication, and who had recently taken NSAIDS.
Measuring hair cortisol more feasible
The study was conducted remotely, with participants using video conferencing to communicate with the study personnel and then completing study procedures at home, including 2 days of cognitive testing with the California Verbal Learning Test – Third Edition and the n-back and continuous performance tasks. The participants also completed the Center for Epidemiologic Studies Depression Scale (CES-D).
Participants with higher levels of hair cortisol and salivary cortisol also had more severe depression symptoms (P < .001). Hair cortisol was also significantly associated with attention and working memory: Women with higher levels had fewer correct answers on the 0-back and 1-back trials (P < .01) and made more mistakes on the 2-back trial (P < .001). They also scored with less specificity on the continuous performance tasks (P = .022).
Although no association existed between hair cortisol levels and verbal learning or verbal memory (P > .05), participants with higher hair cortisol did score worse on the immediate recall trials (P = .034). Salivary cortisol levels, on the other hand, showed no association with memory recall trials, attention or working memory (P > .05).
Measuring cortisol from hair samples is more feasible than using saliva samples and may offer valuable insights regarding hypothalamic-pituitary-axis activity “to consider alongside the cognitive and mental health of late peri-/early postmenopausal women,” Dr. Metcalf told attendees. The next step is to find out whether the hypothalamic-pituitary-axis axis is a modifiable biomarker that can be used to improve executive function.
The study was limited by its small population, its cross-sectional design, and the lack of covariates in the current analyses.
Monitor symptoms in midlife
Hadine Joffe, MD, MSc, a professor of psychiatry and executive director of the Mary Horrigan Connors Center for Women’s Health and Gender Biology at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, said the study findings were not surprising given how common the complaints of stress and depressive symptoms are.
“Mood changes are linked with acute, immediate cortisol levels at the same point in time, and cognitive symptoms were linked to more chronically elevated cortisol levels,” Dr. Joffe said in an interview. “Women and their providers should monitor for these challenging brain symptoms in midlife as they affect performance and quality of life and are linked with changes in the HPA axis as stress biomarkers.”
Because the study is small and has a cross-sectional design, it’s not possible to determine the direction of the associations or to make any inferences about causation, Dr. Joffe said.
“We cannot make the conclusion that stress is adversely affecting mood and cognitive performance given the design limitations. It is possible that mood and cognitive issues contributed to these stress markers,” Dr. Joffe said.“However, it is known that the experience of stress is linked with vulnerability to mood and cognitive symptoms, and also that mood and cognitive symptoms induce significant stress.”
The research was funded by the Menopause Society, Colorado University, the Ludeman Family Center for Women’s Health Research, the National Institute of Mental Health, and the National Institute of Aging. Dr. Metcalf had no disclosures. Dr. Joffe has received grant support from Merck, Pfizer and Sage, and has been a consultant or advisor for Bayer, Merck and Hello Therapeutics.
AT NAMS 2023
Three-quarters of menopausal women report unexpected symptoms
GLASGOW – Three-quarters of women going through perimenopause and menopause experience unexpected distressing, debilitating, and embarrassing symptoms but often fail to receive appropriate treatment, a large U.K.-based survey found.
“For too long, many people have thought of menopause as just hot flashes and vaginal dryness. But we know hormones work all over our body, so there are many symptoms beyond that,” said Daniel Reisel, MBBS, PhD, a gynecologist at University College London, who presented the survey findings at the 2023 annual meeting of the Royal College of General Practitioners.
Primary care physicians in the United Kingdom have seen an increase in cases of women presenting with symptoms associated with menopause at a time when the country’s Parliament is debating whether all women should have a menopause check-up in their early 40s, he said.
Still, only around 14% of menopausal women in the United Kingdom are prescribed hormone replacement therapy (HRT), despite national and international guidelines clearly stating the benefits of the treatment generally outweigh the risks.
Louise Newson, MBChB, who runs the U.K.’s largest menopause clinic, said many women with symptoms of menopause feel the medical system “gaslights” them – dismissing their concerns as trivial or even fabricated.
In her clinic, she typically sees many women with poor sleep, as well as muscle and joint pains. “Yet [when they visit their GPs], they are incorrectly told that it can’t be hormones because they’re still having periods,” she said.
Prescribed antidepressants often precede HRT
The new study sought to learn what women knew and experienced with respect to menopause symptoms and what they thought was important.
Of the 5,744 women who responded to the survey, 79.4% were aged 40-60 years and 84.6% were White. “The survey respondents were not different from the distribution of ethnicities we see in NHS menopause care,” said Dr. Reisel, adding that “the barriers are greater for women in poorer areas and for those who are non-White.”
A total of 30.4% had two to five hospital consultations before the health care professional considered that symptoms were related to changing hormone levels; 38.5% were offered antidepressants before HRT. Nearly all (94.6%) said they had experienced negative mood changes and emotions since becoming perimenopausal or menopausal; of these, 19.1% were formally diagnosed with depression or a mood disorder.
“This all just highlights the frustrations I feel around menopause care,” Dr. Newson said. “Women are often not given the tools to properly understand what’s going on and then they don’t ask for the right treatment, and many are given antidepressants. It’s still medicalizing the menopause but in a different way.”
Education gap
The researchers also asked women if they had experienced any surprising or unexpected symptoms since becoming perimenopausal or menopausal. To this question, 74.2% said they had. Joint pain was the most common unexpected issue (34%), followed by dry eyes (26%), heart palpitations (25%), and hair issues such as dryness, thinning, and loss (20%).
Dr. Reisel said words used to describe these symptoms in free text responses included “distressing,” “debilitating,” “depressing,” and “embarrassing.”
“When an early-50s woman comes to the GP with dry eyes, joint pain, or recurrent urinary tract infections, for example, before prescribing ibuprofen, or antibiotics, GPs should consider replacing a woman’s hormones and then see what is left in terms of symptoms,” he said.
Cognitive problems and negative mood changes also are common and often overlooked, Dr. Reisel noted. “We often see striking improvements in mood and cognition in women who are prescribed testosterone for low libido, yet symptoms in these areas are not currently an indication to start treatment,” he said. “Data from Newson Health show that 18% have suicidal thoughts in the past 2 weeks, and not many people think about this.”
Much of this lack of understanding around unexpected symptoms relates to a lack of awareness and education. “It goes back to primary and secondary school, and more broadly, these issues are not often talked about in society,” he said.
Dr. Reisel also noted that language and cultural barriers often stand in the way. “Many cultures don’t discuss menopause and hormone health in general at all. For example, in Bengali, spoken by 300 million people, there is no word in for menopause. So many women are gaslighted when they try and describe their symptoms, or they’re simply just unaware.”
Dr. Reisel and Dr. Newson reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
GLASGOW – Three-quarters of women going through perimenopause and menopause experience unexpected distressing, debilitating, and embarrassing symptoms but often fail to receive appropriate treatment, a large U.K.-based survey found.
“For too long, many people have thought of menopause as just hot flashes and vaginal dryness. But we know hormones work all over our body, so there are many symptoms beyond that,” said Daniel Reisel, MBBS, PhD, a gynecologist at University College London, who presented the survey findings at the 2023 annual meeting of the Royal College of General Practitioners.
Primary care physicians in the United Kingdom have seen an increase in cases of women presenting with symptoms associated with menopause at a time when the country’s Parliament is debating whether all women should have a menopause check-up in their early 40s, he said.
Still, only around 14% of menopausal women in the United Kingdom are prescribed hormone replacement therapy (HRT), despite national and international guidelines clearly stating the benefits of the treatment generally outweigh the risks.
Louise Newson, MBChB, who runs the U.K.’s largest menopause clinic, said many women with symptoms of menopause feel the medical system “gaslights” them – dismissing their concerns as trivial or even fabricated.
In her clinic, she typically sees many women with poor sleep, as well as muscle and joint pains. “Yet [when they visit their GPs], they are incorrectly told that it can’t be hormones because they’re still having periods,” she said.
Prescribed antidepressants often precede HRT
The new study sought to learn what women knew and experienced with respect to menopause symptoms and what they thought was important.
Of the 5,744 women who responded to the survey, 79.4% were aged 40-60 years and 84.6% were White. “The survey respondents were not different from the distribution of ethnicities we see in NHS menopause care,” said Dr. Reisel, adding that “the barriers are greater for women in poorer areas and for those who are non-White.”
A total of 30.4% had two to five hospital consultations before the health care professional considered that symptoms were related to changing hormone levels; 38.5% were offered antidepressants before HRT. Nearly all (94.6%) said they had experienced negative mood changes and emotions since becoming perimenopausal or menopausal; of these, 19.1% were formally diagnosed with depression or a mood disorder.
“This all just highlights the frustrations I feel around menopause care,” Dr. Newson said. “Women are often not given the tools to properly understand what’s going on and then they don’t ask for the right treatment, and many are given antidepressants. It’s still medicalizing the menopause but in a different way.”
Education gap
The researchers also asked women if they had experienced any surprising or unexpected symptoms since becoming perimenopausal or menopausal. To this question, 74.2% said they had. Joint pain was the most common unexpected issue (34%), followed by dry eyes (26%), heart palpitations (25%), and hair issues such as dryness, thinning, and loss (20%).
Dr. Reisel said words used to describe these symptoms in free text responses included “distressing,” “debilitating,” “depressing,” and “embarrassing.”
“When an early-50s woman comes to the GP with dry eyes, joint pain, or recurrent urinary tract infections, for example, before prescribing ibuprofen, or antibiotics, GPs should consider replacing a woman’s hormones and then see what is left in terms of symptoms,” he said.
Cognitive problems and negative mood changes also are common and often overlooked, Dr. Reisel noted. “We often see striking improvements in mood and cognition in women who are prescribed testosterone for low libido, yet symptoms in these areas are not currently an indication to start treatment,” he said. “Data from Newson Health show that 18% have suicidal thoughts in the past 2 weeks, and not many people think about this.”
Much of this lack of understanding around unexpected symptoms relates to a lack of awareness and education. “It goes back to primary and secondary school, and more broadly, these issues are not often talked about in society,” he said.
Dr. Reisel also noted that language and cultural barriers often stand in the way. “Many cultures don’t discuss menopause and hormone health in general at all. For example, in Bengali, spoken by 300 million people, there is no word in for menopause. So many women are gaslighted when they try and describe their symptoms, or they’re simply just unaware.”
Dr. Reisel and Dr. Newson reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
GLASGOW – Three-quarters of women going through perimenopause and menopause experience unexpected distressing, debilitating, and embarrassing symptoms but often fail to receive appropriate treatment, a large U.K.-based survey found.
“For too long, many people have thought of menopause as just hot flashes and vaginal dryness. But we know hormones work all over our body, so there are many symptoms beyond that,” said Daniel Reisel, MBBS, PhD, a gynecologist at University College London, who presented the survey findings at the 2023 annual meeting of the Royal College of General Practitioners.
Primary care physicians in the United Kingdom have seen an increase in cases of women presenting with symptoms associated with menopause at a time when the country’s Parliament is debating whether all women should have a menopause check-up in their early 40s, he said.
Still, only around 14% of menopausal women in the United Kingdom are prescribed hormone replacement therapy (HRT), despite national and international guidelines clearly stating the benefits of the treatment generally outweigh the risks.
Louise Newson, MBChB, who runs the U.K.’s largest menopause clinic, said many women with symptoms of menopause feel the medical system “gaslights” them – dismissing their concerns as trivial or even fabricated.
In her clinic, she typically sees many women with poor sleep, as well as muscle and joint pains. “Yet [when they visit their GPs], they are incorrectly told that it can’t be hormones because they’re still having periods,” she said.
Prescribed antidepressants often precede HRT
The new study sought to learn what women knew and experienced with respect to menopause symptoms and what they thought was important.
Of the 5,744 women who responded to the survey, 79.4% were aged 40-60 years and 84.6% were White. “The survey respondents were not different from the distribution of ethnicities we see in NHS menopause care,” said Dr. Reisel, adding that “the barriers are greater for women in poorer areas and for those who are non-White.”
A total of 30.4% had two to five hospital consultations before the health care professional considered that symptoms were related to changing hormone levels; 38.5% were offered antidepressants before HRT. Nearly all (94.6%) said they had experienced negative mood changes and emotions since becoming perimenopausal or menopausal; of these, 19.1% were formally diagnosed with depression or a mood disorder.
“This all just highlights the frustrations I feel around menopause care,” Dr. Newson said. “Women are often not given the tools to properly understand what’s going on and then they don’t ask for the right treatment, and many are given antidepressants. It’s still medicalizing the menopause but in a different way.”
Education gap
The researchers also asked women if they had experienced any surprising or unexpected symptoms since becoming perimenopausal or menopausal. To this question, 74.2% said they had. Joint pain was the most common unexpected issue (34%), followed by dry eyes (26%), heart palpitations (25%), and hair issues such as dryness, thinning, and loss (20%).
Dr. Reisel said words used to describe these symptoms in free text responses included “distressing,” “debilitating,” “depressing,” and “embarrassing.”
“When an early-50s woman comes to the GP with dry eyes, joint pain, or recurrent urinary tract infections, for example, before prescribing ibuprofen, or antibiotics, GPs should consider replacing a woman’s hormones and then see what is left in terms of symptoms,” he said.
Cognitive problems and negative mood changes also are common and often overlooked, Dr. Reisel noted. “We often see striking improvements in mood and cognition in women who are prescribed testosterone for low libido, yet symptoms in these areas are not currently an indication to start treatment,” he said. “Data from Newson Health show that 18% have suicidal thoughts in the past 2 weeks, and not many people think about this.”
Much of this lack of understanding around unexpected symptoms relates to a lack of awareness and education. “It goes back to primary and secondary school, and more broadly, these issues are not often talked about in society,” he said.
Dr. Reisel also noted that language and cultural barriers often stand in the way. “Many cultures don’t discuss menopause and hormone health in general at all. For example, in Bengali, spoken by 300 million people, there is no word in for menopause. So many women are gaslighted when they try and describe their symptoms, or they’re simply just unaware.”
Dr. Reisel and Dr. Newson reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Metabolic effects of estetrol are promising in postmenopausal women
PHILADELPHIA – presented at the annual meeting of the Menopause Society (formerly The North American Menopause Society).
Participants taking estetrol experienced a decrease in hemoglobin A1c, fasting plasma glucose, total cholesterol, LDL and lipoprotein as well as an increase in HDL cholesterol, according to the findings presented by Wolf Utian, MD, PhD, DSC, a professor emeritus of reproductive biology at Case Western Reserve University, Cleveland, and medical director emeritus of the Menopause Society.
A separate poster at the conference from the same trial also reported significant improvements from estetrol in quality of life, including that related to vasomotor symptoms, and several psychosocial and sexual functioning areas.
E4 is already available as combination oral contraception and is now being considered for treating vasomotor symptoms, explained Chrisandra Shufelt, MD, professor and chair of general internal of medicine and associate director of the Women’s Health Research Center at Mayo Clinic Florida, who was not involved in the study.
Background on estetrol
E4 is a human fetal liver estrogen produced during pregnancy that’s synthesized from plants for pharmaceutical use, including as the oral contraceptive drospirenone, Dr. Utian told attendees. It’s classified as a native estrogen with selective tissue activity (NEST), he said.
“E4 is a completely different native estrogen with oral administration mimicking the benefits of transdermals and hence safe and effective,” Dr. Utian said in an interview. “It would be a significant new addition to the pharmaceutical armamentarium.”
Two phase 3 trials presented by Dr. Utian at the same conference last year found estetrol reduced the frequency and severity of moderate to severe vasomotor symptoms, and a previous phase 2 trial finding vasomotor and genitourinary symptom benefits suggested it had potential benefits for lipids, carbohydrate metabolism, and bone turnover.
“In summary, E4 at a daily dose of 15 mg exhibited estrogenic effects in the vagina, leading to improved vaginal health and reduced signs of atrophy, emerging as a promising treatment option not only for vasomotor symptoms but also for other significant menopausal symptoms,” Dr. Utian said. “E4 could offer comprehensive relief for women experiencing a range of menopause-related discomforts.”
Dr. Utian also referenced a 2017 trial in which estetrol positively impacted lipid profiles, “lowering low-density lipoprotein cholesterol, increasing high-density lipoprotein cholesterol, and showing minimal influence on triglycerides,” he said. “Importantly, estetrol was associated with a significant decrease in osteocalcin levels in the higher dose groups, suggesting a potential preventive effect on bone loss,” he added. A recent review of the overall evidence on estetrol suggests its use is “promising,” Dr. Utian noted.
Current trial
His current randomized controlled phase 3 trial included postmenopausal women ages 40-65 from 151 sites in 14 countries in Europe, Latin America, and North America, and Russia. Among the 640 participants in the trial, 213 women randomly received 15 mg of estetrol, 213 women received 20 mg of estetrol, and 214 women received a placebo every day for 3 months. All women without hysterectomies also received 200 mg of progesterone once daily for two weeks after completing the estetrol treatment to protect the endometrium.
Researchers took blood samples from the participants at baseline and week 12 to assess total cholesterol, LDL, HDL, the total cholesterol/HDL ratio, triglycerides, lipoprotein A, fasting plasma glucose, insulin, and A1c.
Compared with women in the placebo group, women in both the 15 mg and 20 mg groups saw a statistically significant decrease in lipoprotein A and in the ratio of total cholesterol to HDL, and a statistically significant increase in HDL. Only the women in the 15 mg group saw a statistically significant decrease in LDL and increase in triglycerides; an increase in triglycerides in the 20 mg group did not reach statistical significance.
Statistically significant decreases in fasting plasma glucose and A1c also occurred in both treatment groups, but a decrease in insulin levels and in the homeostasis model-assessment-estimated insulin resistance (HOMA-IR) seen in both treatment arms did not reach significance.
“While the mean changes after 12 weeks from baseline overall were small changes to the cholesterol and blood sugar profiles, they are clinically meaningful because it suggests that E4 does not have any adverse effects to these measures,” Dr. Shufelt said in an interview. “An advantage is that this gives us another hormone option for vasomotor symptoms since it is a native estrogen with selective tissue.”
It’s too early, however, to determine whether estetrol offers benefits in terms of its safety profile, compared with currently available therapies, Dr. Shufelt said.
”These findings of E4 are similar to how oral estradiol changes lipids, which finds an increase in high-density lipoprotein cholesterol, and decreases plasma concentrations of total and low-density lipoprotein cholesterol. an increase in HDL-C and triglycerides and decrease in LDL-C,” she said.
Poster findings also promising
For the findings reported in the poster, researchers assessed quality of life and the clinical meaningfulness of vasomotor symptoms’ reduction at baseline and 12 weeks using the Menopause-Specific Quality of Life (MENQOL) questionnaire and the Clinical Global Impression questionnaire, respectively. They also assessed women’s self-reported genitourinary symptoms, including vaginal dryness, pain during urination, vaginal pain and bleeding related to sex, and vaginal or vulvar irritation or itching. Most of these findings primarily confirmed previous positive effects from E4 in other trials.
Women in both the 15 mg and 20 mg estetrol groups reported a statistically significant improvement at 12 weeks, compared with placebo, in their total MENQOL score and in the vasomotor, psychosocial, and sexual functioning domain scores (P < .05). Those in the 20 mg group also had a statistically significant improvement in their physical domain score (P < .05).
Although numerical improvements in genitourinary symptoms occurred at 12 weeks across all three groups, the only statistically significant difference from baseline occurred in patients taking 15 mg of estetrol, who experienced a decrease in vaginal dryness and vaginal pain during sex (P = .0142 and P = .003, respectively).
The Clinical Global Impression questionnaire asked women at 4 and 12 weeks to rate on a seven-item Likert scale their response to this question: “Rate the total improvement, whether or not in your judgment it is due entirely to drug treatment. Compared to your condition at admission to the study, how much has it changed?” Responses of “very much improved” and “much improved” counted as a clinically meaningful difference.
Compared with 27.9% of patients in the placebo group, 52.9% of patients in the 15 mg group and 59.8% of patients in the 20 mg group rated the weekly frequency of moderate to severe vasomotor symptoms as “much improved” or “very much improved” at 4 weeks (P < .0001). At 12 weeks, those numbers rose to 47% in the placebo group, 73.3% in the 15 mg group and 77.8% in the 20 mg group (P < .0001).
The trial’s primary limitation at this point is having only a 12-week follow-up, Dr. Shufelt said, though a few other questions remain.
“Because the two phase 3 RCTs included hysterectomized and nonhysterectomized women, it was unclear how many women in the study had E4 alone versus E4 with progesterone, as that might play a role in both cholesterol and carbohydrate metabolism,” Dr. Shufelt said. “While baseline data was not presented, it would also be important to know baseline values for the women and confirm that none were on lipid-lowering medications.”
The research was funded by Estetra SRL, an affiliate of Mithra Pharmaceuticals. Dr. Utian is a member of the Mithra and Elektra Scientific Advisory Boards. Dr. Shufelt has no disclosures.
PHILADELPHIA – presented at the annual meeting of the Menopause Society (formerly The North American Menopause Society).
Participants taking estetrol experienced a decrease in hemoglobin A1c, fasting plasma glucose, total cholesterol, LDL and lipoprotein as well as an increase in HDL cholesterol, according to the findings presented by Wolf Utian, MD, PhD, DSC, a professor emeritus of reproductive biology at Case Western Reserve University, Cleveland, and medical director emeritus of the Menopause Society.
A separate poster at the conference from the same trial also reported significant improvements from estetrol in quality of life, including that related to vasomotor symptoms, and several psychosocial and sexual functioning areas.
E4 is already available as combination oral contraception and is now being considered for treating vasomotor symptoms, explained Chrisandra Shufelt, MD, professor and chair of general internal of medicine and associate director of the Women’s Health Research Center at Mayo Clinic Florida, who was not involved in the study.
Background on estetrol
E4 is a human fetal liver estrogen produced during pregnancy that’s synthesized from plants for pharmaceutical use, including as the oral contraceptive drospirenone, Dr. Utian told attendees. It’s classified as a native estrogen with selective tissue activity (NEST), he said.
“E4 is a completely different native estrogen with oral administration mimicking the benefits of transdermals and hence safe and effective,” Dr. Utian said in an interview. “It would be a significant new addition to the pharmaceutical armamentarium.”
Two phase 3 trials presented by Dr. Utian at the same conference last year found estetrol reduced the frequency and severity of moderate to severe vasomotor symptoms, and a previous phase 2 trial finding vasomotor and genitourinary symptom benefits suggested it had potential benefits for lipids, carbohydrate metabolism, and bone turnover.
“In summary, E4 at a daily dose of 15 mg exhibited estrogenic effects in the vagina, leading to improved vaginal health and reduced signs of atrophy, emerging as a promising treatment option not only for vasomotor symptoms but also for other significant menopausal symptoms,” Dr. Utian said. “E4 could offer comprehensive relief for women experiencing a range of menopause-related discomforts.”
Dr. Utian also referenced a 2017 trial in which estetrol positively impacted lipid profiles, “lowering low-density lipoprotein cholesterol, increasing high-density lipoprotein cholesterol, and showing minimal influence on triglycerides,” he said. “Importantly, estetrol was associated with a significant decrease in osteocalcin levels in the higher dose groups, suggesting a potential preventive effect on bone loss,” he added. A recent review of the overall evidence on estetrol suggests its use is “promising,” Dr. Utian noted.
Current trial
His current randomized controlled phase 3 trial included postmenopausal women ages 40-65 from 151 sites in 14 countries in Europe, Latin America, and North America, and Russia. Among the 640 participants in the trial, 213 women randomly received 15 mg of estetrol, 213 women received 20 mg of estetrol, and 214 women received a placebo every day for 3 months. All women without hysterectomies also received 200 mg of progesterone once daily for two weeks after completing the estetrol treatment to protect the endometrium.
Researchers took blood samples from the participants at baseline and week 12 to assess total cholesterol, LDL, HDL, the total cholesterol/HDL ratio, triglycerides, lipoprotein A, fasting plasma glucose, insulin, and A1c.
Compared with women in the placebo group, women in both the 15 mg and 20 mg groups saw a statistically significant decrease in lipoprotein A and in the ratio of total cholesterol to HDL, and a statistically significant increase in HDL. Only the women in the 15 mg group saw a statistically significant decrease in LDL and increase in triglycerides; an increase in triglycerides in the 20 mg group did not reach statistical significance.
Statistically significant decreases in fasting plasma glucose and A1c also occurred in both treatment groups, but a decrease in insulin levels and in the homeostasis model-assessment-estimated insulin resistance (HOMA-IR) seen in both treatment arms did not reach significance.
“While the mean changes after 12 weeks from baseline overall were small changes to the cholesterol and blood sugar profiles, they are clinically meaningful because it suggests that E4 does not have any adverse effects to these measures,” Dr. Shufelt said in an interview. “An advantage is that this gives us another hormone option for vasomotor symptoms since it is a native estrogen with selective tissue.”
It’s too early, however, to determine whether estetrol offers benefits in terms of its safety profile, compared with currently available therapies, Dr. Shufelt said.
”These findings of E4 are similar to how oral estradiol changes lipids, which finds an increase in high-density lipoprotein cholesterol, and decreases plasma concentrations of total and low-density lipoprotein cholesterol. an increase in HDL-C and triglycerides and decrease in LDL-C,” she said.
Poster findings also promising
For the findings reported in the poster, researchers assessed quality of life and the clinical meaningfulness of vasomotor symptoms’ reduction at baseline and 12 weeks using the Menopause-Specific Quality of Life (MENQOL) questionnaire and the Clinical Global Impression questionnaire, respectively. They also assessed women’s self-reported genitourinary symptoms, including vaginal dryness, pain during urination, vaginal pain and bleeding related to sex, and vaginal or vulvar irritation or itching. Most of these findings primarily confirmed previous positive effects from E4 in other trials.
Women in both the 15 mg and 20 mg estetrol groups reported a statistically significant improvement at 12 weeks, compared with placebo, in their total MENQOL score and in the vasomotor, psychosocial, and sexual functioning domain scores (P < .05). Those in the 20 mg group also had a statistically significant improvement in their physical domain score (P < .05).
Although numerical improvements in genitourinary symptoms occurred at 12 weeks across all three groups, the only statistically significant difference from baseline occurred in patients taking 15 mg of estetrol, who experienced a decrease in vaginal dryness and vaginal pain during sex (P = .0142 and P = .003, respectively).
The Clinical Global Impression questionnaire asked women at 4 and 12 weeks to rate on a seven-item Likert scale their response to this question: “Rate the total improvement, whether or not in your judgment it is due entirely to drug treatment. Compared to your condition at admission to the study, how much has it changed?” Responses of “very much improved” and “much improved” counted as a clinically meaningful difference.
Compared with 27.9% of patients in the placebo group, 52.9% of patients in the 15 mg group and 59.8% of patients in the 20 mg group rated the weekly frequency of moderate to severe vasomotor symptoms as “much improved” or “very much improved” at 4 weeks (P < .0001). At 12 weeks, those numbers rose to 47% in the placebo group, 73.3% in the 15 mg group and 77.8% in the 20 mg group (P < .0001).
The trial’s primary limitation at this point is having only a 12-week follow-up, Dr. Shufelt said, though a few other questions remain.
“Because the two phase 3 RCTs included hysterectomized and nonhysterectomized women, it was unclear how many women in the study had E4 alone versus E4 with progesterone, as that might play a role in both cholesterol and carbohydrate metabolism,” Dr. Shufelt said. “While baseline data was not presented, it would also be important to know baseline values for the women and confirm that none were on lipid-lowering medications.”
The research was funded by Estetra SRL, an affiliate of Mithra Pharmaceuticals. Dr. Utian is a member of the Mithra and Elektra Scientific Advisory Boards. Dr. Shufelt has no disclosures.
PHILADELPHIA – presented at the annual meeting of the Menopause Society (formerly The North American Menopause Society).
Participants taking estetrol experienced a decrease in hemoglobin A1c, fasting plasma glucose, total cholesterol, LDL and lipoprotein as well as an increase in HDL cholesterol, according to the findings presented by Wolf Utian, MD, PhD, DSC, a professor emeritus of reproductive biology at Case Western Reserve University, Cleveland, and medical director emeritus of the Menopause Society.
A separate poster at the conference from the same trial also reported significant improvements from estetrol in quality of life, including that related to vasomotor symptoms, and several psychosocial and sexual functioning areas.
E4 is already available as combination oral contraception and is now being considered for treating vasomotor symptoms, explained Chrisandra Shufelt, MD, professor and chair of general internal of medicine and associate director of the Women’s Health Research Center at Mayo Clinic Florida, who was not involved in the study.
Background on estetrol
E4 is a human fetal liver estrogen produced during pregnancy that’s synthesized from plants for pharmaceutical use, including as the oral contraceptive drospirenone, Dr. Utian told attendees. It’s classified as a native estrogen with selective tissue activity (NEST), he said.
“E4 is a completely different native estrogen with oral administration mimicking the benefits of transdermals and hence safe and effective,” Dr. Utian said in an interview. “It would be a significant new addition to the pharmaceutical armamentarium.”
Two phase 3 trials presented by Dr. Utian at the same conference last year found estetrol reduced the frequency and severity of moderate to severe vasomotor symptoms, and a previous phase 2 trial finding vasomotor and genitourinary symptom benefits suggested it had potential benefits for lipids, carbohydrate metabolism, and bone turnover.
“In summary, E4 at a daily dose of 15 mg exhibited estrogenic effects in the vagina, leading to improved vaginal health and reduced signs of atrophy, emerging as a promising treatment option not only for vasomotor symptoms but also for other significant menopausal symptoms,” Dr. Utian said. “E4 could offer comprehensive relief for women experiencing a range of menopause-related discomforts.”
Dr. Utian also referenced a 2017 trial in which estetrol positively impacted lipid profiles, “lowering low-density lipoprotein cholesterol, increasing high-density lipoprotein cholesterol, and showing minimal influence on triglycerides,” he said. “Importantly, estetrol was associated with a significant decrease in osteocalcin levels in the higher dose groups, suggesting a potential preventive effect on bone loss,” he added. A recent review of the overall evidence on estetrol suggests its use is “promising,” Dr. Utian noted.
Current trial
His current randomized controlled phase 3 trial included postmenopausal women ages 40-65 from 151 sites in 14 countries in Europe, Latin America, and North America, and Russia. Among the 640 participants in the trial, 213 women randomly received 15 mg of estetrol, 213 women received 20 mg of estetrol, and 214 women received a placebo every day for 3 months. All women without hysterectomies also received 200 mg of progesterone once daily for two weeks after completing the estetrol treatment to protect the endometrium.
Researchers took blood samples from the participants at baseline and week 12 to assess total cholesterol, LDL, HDL, the total cholesterol/HDL ratio, triglycerides, lipoprotein A, fasting plasma glucose, insulin, and A1c.
Compared with women in the placebo group, women in both the 15 mg and 20 mg groups saw a statistically significant decrease in lipoprotein A and in the ratio of total cholesterol to HDL, and a statistically significant increase in HDL. Only the women in the 15 mg group saw a statistically significant decrease in LDL and increase in triglycerides; an increase in triglycerides in the 20 mg group did not reach statistical significance.
Statistically significant decreases in fasting plasma glucose and A1c also occurred in both treatment groups, but a decrease in insulin levels and in the homeostasis model-assessment-estimated insulin resistance (HOMA-IR) seen in both treatment arms did not reach significance.
“While the mean changes after 12 weeks from baseline overall were small changes to the cholesterol and blood sugar profiles, they are clinically meaningful because it suggests that E4 does not have any adverse effects to these measures,” Dr. Shufelt said in an interview. “An advantage is that this gives us another hormone option for vasomotor symptoms since it is a native estrogen with selective tissue.”
It’s too early, however, to determine whether estetrol offers benefits in terms of its safety profile, compared with currently available therapies, Dr. Shufelt said.
”These findings of E4 are similar to how oral estradiol changes lipids, which finds an increase in high-density lipoprotein cholesterol, and decreases plasma concentrations of total and low-density lipoprotein cholesterol. an increase in HDL-C and triglycerides and decrease in LDL-C,” she said.
Poster findings also promising
For the findings reported in the poster, researchers assessed quality of life and the clinical meaningfulness of vasomotor symptoms’ reduction at baseline and 12 weeks using the Menopause-Specific Quality of Life (MENQOL) questionnaire and the Clinical Global Impression questionnaire, respectively. They also assessed women’s self-reported genitourinary symptoms, including vaginal dryness, pain during urination, vaginal pain and bleeding related to sex, and vaginal or vulvar irritation or itching. Most of these findings primarily confirmed previous positive effects from E4 in other trials.
Women in both the 15 mg and 20 mg estetrol groups reported a statistically significant improvement at 12 weeks, compared with placebo, in their total MENQOL score and in the vasomotor, psychosocial, and sexual functioning domain scores (P < .05). Those in the 20 mg group also had a statistically significant improvement in their physical domain score (P < .05).
Although numerical improvements in genitourinary symptoms occurred at 12 weeks across all three groups, the only statistically significant difference from baseline occurred in patients taking 15 mg of estetrol, who experienced a decrease in vaginal dryness and vaginal pain during sex (P = .0142 and P = .003, respectively).
The Clinical Global Impression questionnaire asked women at 4 and 12 weeks to rate on a seven-item Likert scale their response to this question: “Rate the total improvement, whether or not in your judgment it is due entirely to drug treatment. Compared to your condition at admission to the study, how much has it changed?” Responses of “very much improved” and “much improved” counted as a clinically meaningful difference.
Compared with 27.9% of patients in the placebo group, 52.9% of patients in the 15 mg group and 59.8% of patients in the 20 mg group rated the weekly frequency of moderate to severe vasomotor symptoms as “much improved” or “very much improved” at 4 weeks (P < .0001). At 12 weeks, those numbers rose to 47% in the placebo group, 73.3% in the 15 mg group and 77.8% in the 20 mg group (P < .0001).
The trial’s primary limitation at this point is having only a 12-week follow-up, Dr. Shufelt said, though a few other questions remain.
“Because the two phase 3 RCTs included hysterectomized and nonhysterectomized women, it was unclear how many women in the study had E4 alone versus E4 with progesterone, as that might play a role in both cholesterol and carbohydrate metabolism,” Dr. Shufelt said. “While baseline data was not presented, it would also be important to know baseline values for the women and confirm that none were on lipid-lowering medications.”
The research was funded by Estetra SRL, an affiliate of Mithra Pharmaceuticals. Dr. Utian is a member of the Mithra and Elektra Scientific Advisory Boards. Dr. Shufelt has no disclosures.
AT NAMS 2023
Cannabis use growing among menopausal women
PHILADELPHIA – presented at the annual meeting of the Menopause Society (formerly The North American Menopause Society).
Though most women reported using cannabis for recreational reasons, 13% used it only for medical reasons, most often for chronic pain, anxiety, sleep, and stress.
“These findings highlight the importance of recognizing and discussing cannabis use in the health care setting, and the need for additional research to evaluate the potential harms and/or benefits of use in this vulnerable population,” Carolyn J. Gibson, PhD, MPH, a staff psychologist in women’s health at the San Francisco VA Health Care System and an assistant professor of psychiatry and behavioral sciences at the University of California, San Francisco, told attendees.
As cannabis has become more accessible, with its use legalized in 38 states and Washington, D.C., the proportion of U.S. adults using it has doubled over about a decade, from 6% in 2007 to 12% in 2019, Dr. Gibson said. Further, women aged 50 and older are among the fastest-growing groups of users of cannabis, and it’s being increasingly used – and marketed – for treating menopause-related and aging-related symptoms, including insomnia, anxiety, and chronic pain, she said.
“With these decisions to use cannabis, medically or for these other purposes, there’s this perception that it’s harmless,” Dr. Gibson said. Yet potential health risks associated with cannabis include the usual health effects associated with any kind of smoking as well as dependence in those who use it more frequently and/or develop a tolerance for it. She noted that average THC potency has increased over time, and acute risks for using cannabis with high levels of THC – at least 15% or at least 10 mg – can include anxiety/panic, confusion, disturbing/intrusive thoughts, psychosis, and effects on coordination and cognition. She also acknowledged, however, that most of the data available on risks come from studies of men and younger adults rather than older women.
Given the growing normalization of cannabis use, Dr. Gibson’s team sought to better understand prevalence of use as well as types of use and reasons for use in perimenopasual and postmenopausal women. They analyzed data from a cross-sectional survey of women and gender-diverse members, aged 45-64, of Ipsos KnowledgePanel, an online panel with more than 60,000 participating members in the United States.
All the respondents identified themselves as female at birth and had not used gender-affirming therapy or undergone gender-affirming surgery. The survey included questions on sociodemographics, menopause status, frequency of cannabis use, types of cannabis used, reasons for using cannabis, and use of cannabis in the previous 30 days. The 5,174 respondents were an average 55 years old and predominantly non-Hispanic white (63%), with 13% non-Hispanic Black and 16% Hispanic. Two-thirds of the women reported working full- or part-time (67%) and two-thirds were postmenopausal (68%), with 64% reporting experiencing menopause symptoms.
About two in five respondents (42%) had ever used cannabis in any form, most often smoking it (83%) or consuming edibles (51%). Among those who had ever used it, 30% reported having smoked it daily or nearly daily for at least a year at some point.
Ten percent of respondents had used cannabis in the past month, again primarily smoking (56%) or edibles (52%), though 39% said they used it in more than one form, including vaping, dabbing, or topical use. Nearly half (46%) of the respondents who smoked cannabis recently did not know the THC potency of what they consumed, and just over 20% of those consuming edibles didn’t know the THC potency of what they used. However, about a third of those taking edibles used cannabis with less than 10 mg of THC, and a little over a quarter used edibles with 10 mg of THC.
Within the 10% who had used cannabis in the past month, nearly a third (31%) of respondents – or around 3.1% of the total sample – reported smoking cannabis daily or almost daily, and 19% (or 1.9% of the overall sample) consumed cannabis edibles daily or almost daily.
Most of the respondents who used cannabis said it was for recreational use (62%), but a quarter (25%) reported using it for both recreational and medical reasons, and 13% used it only for medical reasons. The most common reason women used cannabis was to treat chronic pain (28%), followed by nearly as many women reporting cannabis use for anxiety (24%), sleep (22%), and stress (22%). Six percent of women used cannabis specifically for menopause-related sleep and mood problems.
Given the growing use of cannabis in this population and the dearth of data on its effects in older women, Dr. Gibson highlighted the need for research examining the potential benefits and harms of cannabis for menopausal women.
Not risk-free
Susan D. Reed, MD, MPH, MSCP, a professor emeritus of ob.gyn. at the University of Washington, Seattle, and president of the Menopause Society, found the study well-executed and was not surprised by how many respondents had ever used cannabis.
“What did surprise me was that nearly a third reported daily use for at least 1 year and that 38% were medical marijuana users, not just recreational,” Dr. Reed said in an interview. The proportions of women using cannabis for menopausal symptoms or using it daily are concerning, she added.
“These individuals are at risk for dependence and health risks related to marijuana use,” Dr. Reed said. “Providers should always ask patients about OTC products, herbals, supplements, cannabis use, and alternative management of menopausal symptoms to better understand patient preferences for menopausal symptom therapies, so that treatment plans can be discussed with individual patient preferences in mind. We need to start with where the patient is coming from.”
Data presented throughout the conference has shown how people are “disillusioned with the care they are receiving for menopause,” Dr. Reed added. “It is so difficult to distinguish truth from myths based on information gained through social media, family, and friends, and that often is where most people are getting their information.”
Physicians often have not received adequate training on how to provide people with accurate information about menopause and managing menopausal symptoms, so she advises patients and physicians to visit reliable sites such as the Menopause Society, the Swan Study, and My Menoplan.
The research was funded by the Tobacco-Related Disease Research Program and the Veterans Administration. Dr. Gibson has provided unpaid consultation to Astellas Pharmaceuticals. Dr. Reed has received research support from Bayer and receives royalties from UpToDate.
PHILADELPHIA – presented at the annual meeting of the Menopause Society (formerly The North American Menopause Society).
Though most women reported using cannabis for recreational reasons, 13% used it only for medical reasons, most often for chronic pain, anxiety, sleep, and stress.
“These findings highlight the importance of recognizing and discussing cannabis use in the health care setting, and the need for additional research to evaluate the potential harms and/or benefits of use in this vulnerable population,” Carolyn J. Gibson, PhD, MPH, a staff psychologist in women’s health at the San Francisco VA Health Care System and an assistant professor of psychiatry and behavioral sciences at the University of California, San Francisco, told attendees.
As cannabis has become more accessible, with its use legalized in 38 states and Washington, D.C., the proportion of U.S. adults using it has doubled over about a decade, from 6% in 2007 to 12% in 2019, Dr. Gibson said. Further, women aged 50 and older are among the fastest-growing groups of users of cannabis, and it’s being increasingly used – and marketed – for treating menopause-related and aging-related symptoms, including insomnia, anxiety, and chronic pain, she said.
“With these decisions to use cannabis, medically or for these other purposes, there’s this perception that it’s harmless,” Dr. Gibson said. Yet potential health risks associated with cannabis include the usual health effects associated with any kind of smoking as well as dependence in those who use it more frequently and/or develop a tolerance for it. She noted that average THC potency has increased over time, and acute risks for using cannabis with high levels of THC – at least 15% or at least 10 mg – can include anxiety/panic, confusion, disturbing/intrusive thoughts, psychosis, and effects on coordination and cognition. She also acknowledged, however, that most of the data available on risks come from studies of men and younger adults rather than older women.
Given the growing normalization of cannabis use, Dr. Gibson’s team sought to better understand prevalence of use as well as types of use and reasons for use in perimenopasual and postmenopausal women. They analyzed data from a cross-sectional survey of women and gender-diverse members, aged 45-64, of Ipsos KnowledgePanel, an online panel with more than 60,000 participating members in the United States.
All the respondents identified themselves as female at birth and had not used gender-affirming therapy or undergone gender-affirming surgery. The survey included questions on sociodemographics, menopause status, frequency of cannabis use, types of cannabis used, reasons for using cannabis, and use of cannabis in the previous 30 days. The 5,174 respondents were an average 55 years old and predominantly non-Hispanic white (63%), with 13% non-Hispanic Black and 16% Hispanic. Two-thirds of the women reported working full- or part-time (67%) and two-thirds were postmenopausal (68%), with 64% reporting experiencing menopause symptoms.
About two in five respondents (42%) had ever used cannabis in any form, most often smoking it (83%) or consuming edibles (51%). Among those who had ever used it, 30% reported having smoked it daily or nearly daily for at least a year at some point.
Ten percent of respondents had used cannabis in the past month, again primarily smoking (56%) or edibles (52%), though 39% said they used it in more than one form, including vaping, dabbing, or topical use. Nearly half (46%) of the respondents who smoked cannabis recently did not know the THC potency of what they consumed, and just over 20% of those consuming edibles didn’t know the THC potency of what they used. However, about a third of those taking edibles used cannabis with less than 10 mg of THC, and a little over a quarter used edibles with 10 mg of THC.
Within the 10% who had used cannabis in the past month, nearly a third (31%) of respondents – or around 3.1% of the total sample – reported smoking cannabis daily or almost daily, and 19% (or 1.9% of the overall sample) consumed cannabis edibles daily or almost daily.
Most of the respondents who used cannabis said it was for recreational use (62%), but a quarter (25%) reported using it for both recreational and medical reasons, and 13% used it only for medical reasons. The most common reason women used cannabis was to treat chronic pain (28%), followed by nearly as many women reporting cannabis use for anxiety (24%), sleep (22%), and stress (22%). Six percent of women used cannabis specifically for menopause-related sleep and mood problems.
Given the growing use of cannabis in this population and the dearth of data on its effects in older women, Dr. Gibson highlighted the need for research examining the potential benefits and harms of cannabis for menopausal women.
Not risk-free
Susan D. Reed, MD, MPH, MSCP, a professor emeritus of ob.gyn. at the University of Washington, Seattle, and president of the Menopause Society, found the study well-executed and was not surprised by how many respondents had ever used cannabis.
“What did surprise me was that nearly a third reported daily use for at least 1 year and that 38% were medical marijuana users, not just recreational,” Dr. Reed said in an interview. The proportions of women using cannabis for menopausal symptoms or using it daily are concerning, she added.
“These individuals are at risk for dependence and health risks related to marijuana use,” Dr. Reed said. “Providers should always ask patients about OTC products, herbals, supplements, cannabis use, and alternative management of menopausal symptoms to better understand patient preferences for menopausal symptom therapies, so that treatment plans can be discussed with individual patient preferences in mind. We need to start with where the patient is coming from.”
Data presented throughout the conference has shown how people are “disillusioned with the care they are receiving for menopause,” Dr. Reed added. “It is so difficult to distinguish truth from myths based on information gained through social media, family, and friends, and that often is where most people are getting their information.”
Physicians often have not received adequate training on how to provide people with accurate information about menopause and managing menopausal symptoms, so she advises patients and physicians to visit reliable sites such as the Menopause Society, the Swan Study, and My Menoplan.
The research was funded by the Tobacco-Related Disease Research Program and the Veterans Administration. Dr. Gibson has provided unpaid consultation to Astellas Pharmaceuticals. Dr. Reed has received research support from Bayer and receives royalties from UpToDate.
PHILADELPHIA – presented at the annual meeting of the Menopause Society (formerly The North American Menopause Society).
Though most women reported using cannabis for recreational reasons, 13% used it only for medical reasons, most often for chronic pain, anxiety, sleep, and stress.
“These findings highlight the importance of recognizing and discussing cannabis use in the health care setting, and the need for additional research to evaluate the potential harms and/or benefits of use in this vulnerable population,” Carolyn J. Gibson, PhD, MPH, a staff psychologist in women’s health at the San Francisco VA Health Care System and an assistant professor of psychiatry and behavioral sciences at the University of California, San Francisco, told attendees.
As cannabis has become more accessible, with its use legalized in 38 states and Washington, D.C., the proportion of U.S. adults using it has doubled over about a decade, from 6% in 2007 to 12% in 2019, Dr. Gibson said. Further, women aged 50 and older are among the fastest-growing groups of users of cannabis, and it’s being increasingly used – and marketed – for treating menopause-related and aging-related symptoms, including insomnia, anxiety, and chronic pain, she said.
“With these decisions to use cannabis, medically or for these other purposes, there’s this perception that it’s harmless,” Dr. Gibson said. Yet potential health risks associated with cannabis include the usual health effects associated with any kind of smoking as well as dependence in those who use it more frequently and/or develop a tolerance for it. She noted that average THC potency has increased over time, and acute risks for using cannabis with high levels of THC – at least 15% or at least 10 mg – can include anxiety/panic, confusion, disturbing/intrusive thoughts, psychosis, and effects on coordination and cognition. She also acknowledged, however, that most of the data available on risks come from studies of men and younger adults rather than older women.
Given the growing normalization of cannabis use, Dr. Gibson’s team sought to better understand prevalence of use as well as types of use and reasons for use in perimenopasual and postmenopausal women. They analyzed data from a cross-sectional survey of women and gender-diverse members, aged 45-64, of Ipsos KnowledgePanel, an online panel with more than 60,000 participating members in the United States.
All the respondents identified themselves as female at birth and had not used gender-affirming therapy or undergone gender-affirming surgery. The survey included questions on sociodemographics, menopause status, frequency of cannabis use, types of cannabis used, reasons for using cannabis, and use of cannabis in the previous 30 days. The 5,174 respondents were an average 55 years old and predominantly non-Hispanic white (63%), with 13% non-Hispanic Black and 16% Hispanic. Two-thirds of the women reported working full- or part-time (67%) and two-thirds were postmenopausal (68%), with 64% reporting experiencing menopause symptoms.
About two in five respondents (42%) had ever used cannabis in any form, most often smoking it (83%) or consuming edibles (51%). Among those who had ever used it, 30% reported having smoked it daily or nearly daily for at least a year at some point.
Ten percent of respondents had used cannabis in the past month, again primarily smoking (56%) or edibles (52%), though 39% said they used it in more than one form, including vaping, dabbing, or topical use. Nearly half (46%) of the respondents who smoked cannabis recently did not know the THC potency of what they consumed, and just over 20% of those consuming edibles didn’t know the THC potency of what they used. However, about a third of those taking edibles used cannabis with less than 10 mg of THC, and a little over a quarter used edibles with 10 mg of THC.
Within the 10% who had used cannabis in the past month, nearly a third (31%) of respondents – or around 3.1% of the total sample – reported smoking cannabis daily or almost daily, and 19% (or 1.9% of the overall sample) consumed cannabis edibles daily or almost daily.
Most of the respondents who used cannabis said it was for recreational use (62%), but a quarter (25%) reported using it for both recreational and medical reasons, and 13% used it only for medical reasons. The most common reason women used cannabis was to treat chronic pain (28%), followed by nearly as many women reporting cannabis use for anxiety (24%), sleep (22%), and stress (22%). Six percent of women used cannabis specifically for menopause-related sleep and mood problems.
Given the growing use of cannabis in this population and the dearth of data on its effects in older women, Dr. Gibson highlighted the need for research examining the potential benefits and harms of cannabis for menopausal women.
Not risk-free
Susan D. Reed, MD, MPH, MSCP, a professor emeritus of ob.gyn. at the University of Washington, Seattle, and president of the Menopause Society, found the study well-executed and was not surprised by how many respondents had ever used cannabis.
“What did surprise me was that nearly a third reported daily use for at least 1 year and that 38% were medical marijuana users, not just recreational,” Dr. Reed said in an interview. The proportions of women using cannabis for menopausal symptoms or using it daily are concerning, she added.
“These individuals are at risk for dependence and health risks related to marijuana use,” Dr. Reed said. “Providers should always ask patients about OTC products, herbals, supplements, cannabis use, and alternative management of menopausal symptoms to better understand patient preferences for menopausal symptom therapies, so that treatment plans can be discussed with individual patient preferences in mind. We need to start with where the patient is coming from.”
Data presented throughout the conference has shown how people are “disillusioned with the care they are receiving for menopause,” Dr. Reed added. “It is so difficult to distinguish truth from myths based on information gained through social media, family, and friends, and that often is where most people are getting their information.”
Physicians often have not received adequate training on how to provide people with accurate information about menopause and managing menopausal symptoms, so she advises patients and physicians to visit reliable sites such as the Menopause Society, the Swan Study, and My Menoplan.
The research was funded by the Tobacco-Related Disease Research Program and the Veterans Administration. Dr. Gibson has provided unpaid consultation to Astellas Pharmaceuticals. Dr. Reed has received research support from Bayer and receives royalties from UpToDate.
AT NAMS 2023
‘Vaginal dryness’ can be fatal. No, really.
This transcript has been edited for clarity.
What do you mean, Dr. Rubin? How is vaginal dryness killing women? We minimize the term vaginal dryness. When women come to our offices and complain of a little vaginal dryness – or they don’t even come to our office to complain of it because the doctor can’t be bothered with a little vaginal dryness — what they don’t understand is that this “little vaginal dryness” is really something called genitourinary syndrome of menopause (GSM). They don’t know that because they’ve never heard of it, and you may have never heard of it either. In 2014, we changed the terms vaginal dryness and vulvovaginal atrophy or atrophic vaginitis to GSM to make it short and simple.
GSM – what does it mean? It’s not just a little vaginal dryness. It turns out that all of the genital and urinary symptoms from menopause just get worse over time. The bladder, the urethra, and the vagina have lots of hormone receptors, including estrogen and testosterone. When the body no longer makes those hormones, the system doesn’t work very well, and genital and urinary symptoms occur that just get worse over time without treatment. Unlike hot flashes, which tend to go away, GSM does not.
What are the symptoms of GSM? Some are sexual: a little vaginal dryness, pain with sex, and worsening orgasm. But there are also genital and urinary symptoms that get worse: itching, burning irritation, rawness, an awareness of their genitals that the patient has never had before. And as a urologist, we see frequency, urgency, and leakage.
The thing that kills women is recurrent urinary tract infections (UTIs). Did you know that UTIs account for 7 million visits and hospitalizations annually and 25% of all infections in older people? In fact, apparently one-third of the total Medicare expenditure is around UTIs. Not preventing UTIs is costing our health care system an enormous amount of money and resources.
Did you know we’ve had safe and effective treatment options for GSM since the 1970s? Vaginal hormones have existed since the 1970s, but we’re using them only for pain with sex and not for GSM. In fact, data show that by using vaginal hormones, we can prevent UTIs by more than 50%. We can save lives using safe, effective, local, low-dose vaginal hormone strategies. And they are safe and effective for all of our patients in pre- and post menopause.
There are five different treatment options: vaginal estrogen inserts, vaginal estrogen creams, vaginal dehydroepiandrosterone (DHEA), low-dose vaginal estrogen rings, and an oral pill option called ospemifene (Osphena). All are used to treat GSM and will only work if your patient actually uses them and continues to use them.
These treatments are safe. They are effective. They do not increase the level of systemic hormones in the bloodstream. I have many patients with breast cancer who use these products as well. The only patients you may want to talk to your oncology colleagues about is women on active aromatase inhibitors.
We have to understand that UTIs kill people and having GSM is debilitating, often requiring pain medication because it can hurt to sit or to wear pads and our patients’ quality of life is severely affected. So please consider learning how to treat GSM. It turns out you don’t have to do exams. You don’t have to do follow-up. You can give these therapies, and women can use them for life.
Now, if your patient has vaginal bleeding, of course they need to see their gynecologist. But this is something every primary care doctor can and should do. As a urologist, we prescribe a lot of tamsulosin (Flomax) for our male patients to help with urination. Vaginal estrogen or DHEA is basically like Flomax for women, but it prevents UTIs and actually works like sildenafil (Viagra) because it can help orgasm and reduce pain with sex.
You have access to affordable, safe, effective treatment options to treat GSM. So check them out and hopefully change the world.
Dr. Rubin is an assistant clinical professor in the department of urology at Georgetown University, Washington. She reported conflicts of interest with Sprout, Maternal Medical, Absorption Pharmaceuticals, GlaxoSmithKline, and Endo.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
What do you mean, Dr. Rubin? How is vaginal dryness killing women? We minimize the term vaginal dryness. When women come to our offices and complain of a little vaginal dryness – or they don’t even come to our office to complain of it because the doctor can’t be bothered with a little vaginal dryness — what they don’t understand is that this “little vaginal dryness” is really something called genitourinary syndrome of menopause (GSM). They don’t know that because they’ve never heard of it, and you may have never heard of it either. In 2014, we changed the terms vaginal dryness and vulvovaginal atrophy or atrophic vaginitis to GSM to make it short and simple.
GSM – what does it mean? It’s not just a little vaginal dryness. It turns out that all of the genital and urinary symptoms from menopause just get worse over time. The bladder, the urethra, and the vagina have lots of hormone receptors, including estrogen and testosterone. When the body no longer makes those hormones, the system doesn’t work very well, and genital and urinary symptoms occur that just get worse over time without treatment. Unlike hot flashes, which tend to go away, GSM does not.
What are the symptoms of GSM? Some are sexual: a little vaginal dryness, pain with sex, and worsening orgasm. But there are also genital and urinary symptoms that get worse: itching, burning irritation, rawness, an awareness of their genitals that the patient has never had before. And as a urologist, we see frequency, urgency, and leakage.
The thing that kills women is recurrent urinary tract infections (UTIs). Did you know that UTIs account for 7 million visits and hospitalizations annually and 25% of all infections in older people? In fact, apparently one-third of the total Medicare expenditure is around UTIs. Not preventing UTIs is costing our health care system an enormous amount of money and resources.
Did you know we’ve had safe and effective treatment options for GSM since the 1970s? Vaginal hormones have existed since the 1970s, but we’re using them only for pain with sex and not for GSM. In fact, data show that by using vaginal hormones, we can prevent UTIs by more than 50%. We can save lives using safe, effective, local, low-dose vaginal hormone strategies. And they are safe and effective for all of our patients in pre- and post menopause.
There are five different treatment options: vaginal estrogen inserts, vaginal estrogen creams, vaginal dehydroepiandrosterone (DHEA), low-dose vaginal estrogen rings, and an oral pill option called ospemifene (Osphena). All are used to treat GSM and will only work if your patient actually uses them and continues to use them.
These treatments are safe. They are effective. They do not increase the level of systemic hormones in the bloodstream. I have many patients with breast cancer who use these products as well. The only patients you may want to talk to your oncology colleagues about is women on active aromatase inhibitors.
We have to understand that UTIs kill people and having GSM is debilitating, often requiring pain medication because it can hurt to sit or to wear pads and our patients’ quality of life is severely affected. So please consider learning how to treat GSM. It turns out you don’t have to do exams. You don’t have to do follow-up. You can give these therapies, and women can use them for life.
Now, if your patient has vaginal bleeding, of course they need to see their gynecologist. But this is something every primary care doctor can and should do. As a urologist, we prescribe a lot of tamsulosin (Flomax) for our male patients to help with urination. Vaginal estrogen or DHEA is basically like Flomax for women, but it prevents UTIs and actually works like sildenafil (Viagra) because it can help orgasm and reduce pain with sex.
You have access to affordable, safe, effective treatment options to treat GSM. So check them out and hopefully change the world.
Dr. Rubin is an assistant clinical professor in the department of urology at Georgetown University, Washington. She reported conflicts of interest with Sprout, Maternal Medical, Absorption Pharmaceuticals, GlaxoSmithKline, and Endo.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
What do you mean, Dr. Rubin? How is vaginal dryness killing women? We minimize the term vaginal dryness. When women come to our offices and complain of a little vaginal dryness – or they don’t even come to our office to complain of it because the doctor can’t be bothered with a little vaginal dryness — what they don’t understand is that this “little vaginal dryness” is really something called genitourinary syndrome of menopause (GSM). They don’t know that because they’ve never heard of it, and you may have never heard of it either. In 2014, we changed the terms vaginal dryness and vulvovaginal atrophy or atrophic vaginitis to GSM to make it short and simple.
GSM – what does it mean? It’s not just a little vaginal dryness. It turns out that all of the genital and urinary symptoms from menopause just get worse over time. The bladder, the urethra, and the vagina have lots of hormone receptors, including estrogen and testosterone. When the body no longer makes those hormones, the system doesn’t work very well, and genital and urinary symptoms occur that just get worse over time without treatment. Unlike hot flashes, which tend to go away, GSM does not.
What are the symptoms of GSM? Some are sexual: a little vaginal dryness, pain with sex, and worsening orgasm. But there are also genital and urinary symptoms that get worse: itching, burning irritation, rawness, an awareness of their genitals that the patient has never had before. And as a urologist, we see frequency, urgency, and leakage.
The thing that kills women is recurrent urinary tract infections (UTIs). Did you know that UTIs account for 7 million visits and hospitalizations annually and 25% of all infections in older people? In fact, apparently one-third of the total Medicare expenditure is around UTIs. Not preventing UTIs is costing our health care system an enormous amount of money and resources.
Did you know we’ve had safe and effective treatment options for GSM since the 1970s? Vaginal hormones have existed since the 1970s, but we’re using them only for pain with sex and not for GSM. In fact, data show that by using vaginal hormones, we can prevent UTIs by more than 50%. We can save lives using safe, effective, local, low-dose vaginal hormone strategies. And they are safe and effective for all of our patients in pre- and post menopause.
There are five different treatment options: vaginal estrogen inserts, vaginal estrogen creams, vaginal dehydroepiandrosterone (DHEA), low-dose vaginal estrogen rings, and an oral pill option called ospemifene (Osphena). All are used to treat GSM and will only work if your patient actually uses them and continues to use them.
These treatments are safe. They are effective. They do not increase the level of systemic hormones in the bloodstream. I have many patients with breast cancer who use these products as well. The only patients you may want to talk to your oncology colleagues about is women on active aromatase inhibitors.
We have to understand that UTIs kill people and having GSM is debilitating, often requiring pain medication because it can hurt to sit or to wear pads and our patients’ quality of life is severely affected. So please consider learning how to treat GSM. It turns out you don’t have to do exams. You don’t have to do follow-up. You can give these therapies, and women can use them for life.
Now, if your patient has vaginal bleeding, of course they need to see their gynecologist. But this is something every primary care doctor can and should do. As a urologist, we prescribe a lot of tamsulosin (Flomax) for our male patients to help with urination. Vaginal estrogen or DHEA is basically like Flomax for women, but it prevents UTIs and actually works like sildenafil (Viagra) because it can help orgasm and reduce pain with sex.
You have access to affordable, safe, effective treatment options to treat GSM. So check them out and hopefully change the world.
Dr. Rubin is an assistant clinical professor in the department of urology at Georgetown University, Washington. She reported conflicts of interest with Sprout, Maternal Medical, Absorption Pharmaceuticals, GlaxoSmithKline, and Endo.
A version of this article first appeared on Medscape.com.
Nonhormonal medication treatment of VMS
VMS, also known as hot flashes, night sweats, or cold sweats, occur for the majority of perimenopausal and menopausal women.1 In one study, the mean duration of clinically significant VMS was 5 years, and one-third of participants continued to have bothersome hot flashes 10 or more years after the onset of menopause.2 VMS may contribute to disrupted sleep patterns and depressed mood.3
All obstetrician-gynecologists know that estradiol and other estrogens are highly effective in the treatment of bothersome VMS. A meta-analysis reported that the frequency of VMS was reduced by 60% to 80% with oral estradiol (1 mg/day), transdermal estradiol(0.05 mg/day), and conjugated estrogen (0.625 mg).4 Breast tenderness and irregular uterine bleeding are common side effects of estrogen treatment of VMS. Estrogen treatment is contraindicated in patients with estrogen-responsive cancers, coronary heart disease, myocardial infarction, stroke, venous thromboembolism, and some cases of inherited thrombophilia. For these patients, an important option is the nonhormonal treatment of VMS, and several nonhormonal medications have been demonstrated to be effective therapy (TABLE 1). In this editorial I will review the medication treatment of VMS with escitalopram, paroxetine, gabapentin, and fezolinetant.
Escitalopram and paroxetine
Escitalopram and paroxetine have been shown to reduce VMS more than placebo in multiple clinical trials.5-10 In addition, escitalopram and paroxetine, at the doses tested, may be more effective for the treatment of VMS than sertraline, citalopram, or fluoxetine.11 In one trial assessing the efficacy of escitalopram to treat VMS, 205 patients with VMS were randomly assigned to 8 weeks of treatment with placebo or escitalopram.5 The initial escitalopram dose was 10 mg daily. At week 4:
- if VMS frequency was reduced by ≥ 50%, the patient remained on the 10-mg dose
- if VMS frequency was reduced by < 50%, the escitalopram dose was increased to 20 mg daily.
Following 8 weeks of treatment, the frequency of VMS decreased for patients in the placebo and escitalopram groups by 33% and 47%, respectively. Similar results have been reported in other studies.6
Paroxetine at a dose of 7.5 mg/day administered at bedtime is approved by the US Food and Drug Administration (FDA) for the treatment of VMS. In a pivotal study, 1,112 patients with VMS were randomly assigned to receive a placebo or paroxetine 7.5 mg at bedtime.9 In the 12-week study the reported decrease in mean weekly frequency of VMS for patients in the placebo and paroxetine groups were -37 and -44, respectively.9 Paroxetine 7.5 mg also reduced awakenings per night attributed to VMS and increased nighttime sleep duration.10
Depressed mood is prevalent among perimenopausal and postmenopausal patients.12 Prescribing escitalopram or paroxetine for VMS also may improve mood. Venlafaxine and desvenlafaxine are effective for the treatment of VMS;13,14 however, I seldom prescribe these medications for VMS because in my experience they are associated with more bothersome side effects, including dry mouth, decreased appetite, nausea, and insomnia than escitalopram or low-dose paroxetine.
Gabapentin
Numerous randomized clinical trials have reported that gabapentin is superior to placebo for the treatment of VMS.15 In one trial, 420 patients with breast cancer and VMS were randomly assigned to 8 weeks of treatment with placebo, gabapentin 300 mg/day (G300), or gabapentin 900 mg/day (G900) in 3 divided doses.16 Following 8 weeks of treatment, reduction in hot-flash severity score among patients receiving placebo, G300, or G900 was 15%, 31%, and 46%, respectively. Fatigue and somnolence were reported more frequently among patients taking gabapentin 900 mg/day. In a small trial, 60 patients with VMS were randomized to receive placebo, conjugated estrogen (0.2625 mg/day),or gabapentin (target dose of 2,400 mg/day in 3 divided doses).17 Following 12 weeks of treatment, the patient-reported decrease in VMS for those taking placebo, estrogen, or gabapentin was 54%, 72%, and 71%, respectively.
High-dose gabapentin treatment was associated with side effects of headache and dizziness more often than placebo or estrogen. Although gabapentin is not a treatment for insomnia, in my practice if a menopausal patient has prominent and bothersome symptoms of sleep disturbance and mild VMS symptoms, I will consider a trial of low-dose gabapentin. Some experts recommend initiating gabapentin at a dose of 100 mgdaily before bedtime to assess the effectiveness of a low dose that seldom causes significant side effects.
Fezolinetant
In a study of genetic variation associated with VMS, investigators discovered that nucleic acid variation in the neurokinin 3 (NK3) receptor was strongly associated with the prevalence of VMS, suggesting that this receptor is in the causal pathway to menopausal VMS.18 Additional research demonstrated that the kisspeptin/neurokinin B/dynorphin (KNDy) neurons, which are involved in the control of hypothalamic thermoregulation, are stimulated by neurokinin B, acting through the NK3 receptor, and suppressed by estradiol. A reduction in hypothalamic estrogen results in unopposed neurokinin B activity, which stimulates KNDy neurons, destabilizing the hypothalamic thermoregulatory center, causing vasodilation, which is perceived as hot flashes and sweating followed by chills.19
Fezolinetant is a high-affinity NK3 receptor antagonist that blocks the activity of neurokinin B, stabilizing the hypothalamic thermoregulatory center, thereby suppressing hot flashes. It is approved by the FDA for the treatment of moderate to severe VMS due to menopause using a fixed dose of 45 mg daily.20 In one clinical trial, 500 menopausal patients with bothersome VMS were randomly assigned to 12 weeks of treatment with placebo, fezolinetant 30 mg/day, or fezolinetant 45 mg/day. Following 12 weeks of treatment, the reported frequency rates of VMS among patients in the placebo, F30, and F45 groups were reduced by 43%, 61%, and 64%, respectively.21 In addition, following 12 weeks of treatment, the severity of VMS rates among patients in the placebo, F30, and F45 groups were reduced by 20%, 26%, and 32%, respectively.
Fezolinetant improved the quality of sleep and was associated with an improvement in patient-reported quality of life. Following 12 weeks of treatment, sleep quality among patients in the placebo, F30, and F45 groups was reported to be “much or moderately better” in 34%, 45%, and 54% of the patients, respectively.21 Similar results were reported in a companion study.22
Fezolinetant is contraindicated for patients with liver cirrhosis or severe renal impairment (estimated glomerular filtration rate of < 30 mL/min/1.73 m2). Before initiating treatment, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin (total and direct). Fezolinetant should not be prescribed if any of these tests are greater than twice the upper limit of normal. These tests should be repeated at 3, 6, and 9 months, and if the patient reports symptoms or signs of liver injury (nausea, vomiting, jaundice). Fezolinetant is metabolized by CYP1A2 and should not be prescribed to patients taking strong CYP1A2 inhibitors. The most common side effects associated with fezolinetant treatment are abdominal pain (4.3%), diarrhea (3.9%), insomnia (3.9%), back pain (3.0%), and hepatic transaminase elevation (2.3%). Fezolinetant has not been thoroughly evaluated in patients older than age 65. Following an oral dose of the medication, the median maximum concentration is reached in 1.5 hours, and the half-life is estimated to be 10 hours.20 Of all the medications discussed in this editorial, fezolinetant is the most expensive.
Effective VMS treatment improves overall health
Estrogen therapy is the gold standard treatment of VMS. However, many menopausal patients with bothersome VMS prefer not to take estrogen, and some have a medical condition that is a contraindication to estrogen treatment. The nonhormonal medication options for the treatment of VMS include escitalopram, paroxetine, gabapentin, and fezolinetant. Patients value the ability to choose the treatment they prefer, among all available hormonal and nonhormonal medication options. For mid-life women, effectively treating bothersome VMS is only one of many interventions that improves health. Optimal health is best achieved with23:
- high-quality diet
- daily physical activity
- appropriate body mass index
- nicotine avoidance
- a healthy sleep schedule
- normal blood pressure, lipid, and glucose levels.
Women who have a high-quality diet; daily physical activity; an appropriate body mass index; and normal blood pressure, cholesterol, and glucose levels are estimated to live 9 disease-free years longer than other women.24 ●
- Gold EB, Colvin A, Avis N, et al. Longitudinal analysis of the association between vasomotor symptoms and race/ethnicity across the menopause transition: study of women’s health across the nation. Am J Pub Health. 2006;1226-1235.
- Freeman EW, Sammel MD, Sanders RJ. Risk of long-term hot flashes after natural menopause: evidence from the Penn Ovarian Aging Study cohort. Menopause. 2014;21:924-932.
- Hatcher KM, Smith RL, Chiang C, et al. Nocturnal hot flashes, but not serum hormone concentrations as a predictor of insomnia in menopausal women: results from the Midlife Women’s Health Study. J Women’s Health. 2023;32:94-101.
- Nelson HD. Commonly used types of postmenopausal estrogen for treatment of hot flashes: scientific review. JAMA. 2004;291:1610.
- Freeman EW, Guthrie KA, Caan B, et al. Efficacy of escitalopram for hot flashes in healthy menopausal women: a randomized controlled trial. JAMA. 2011;305:267-227.
- Carpenter JS, Guthrie KA, Larson JC, et al. Effect of escitalopram on hot flash interference: a randomized, controlled trial. Fertil Steril. 2012;97:1399-1404.e1.
- Slaton RM, Champion MN, Palmore KB. A review of paroxetine for the treatment of vasomotor symptoms. J Pharm Pract. 2015;28:266-274.
- Stearns V, Slack R, Greep N, et al. Paroxetine is an effective treatment for hot flashes: results from a prospective randomized clinical trial. J Clin Oncol. 2005;23:6919-6930.
- Simon JA, Portman DJ, Kaunitz AM, et al. Lowdose paroxetine 7.5 mg for menopausal vasomotor symptoms: two randomized controlled trials. Menopause. 2013;20:1027-1035.
- Pinkerton JV, Joffe H, Kazempour K, et al. Lowdose paroxetine (7.5 mg) improves sleep in women with vasomotor symptoms associated with menopause. Menopause. 2015;22:50-58.
- Shams T, Firwana B, Habib F, et al. SSRIs for hot flashes: a systematic review and metaanalysis of randomized trials. J Gen Intern Med. 2014;29:204-213.
- Freeman EW. Depression in the menopause transition: risks in the changing hormone milieu as observed in the general population. Womens Midlife Health. 2015;1:2.
- Loprinzi CL, Kugler JW, Sloan JA, et al. Venlafaxine in management of hot flashes in survivors of breast cancer: a randomised controlled trial. Lancet. 2000;356:2059-2063.
- Sun Z, Hao Y, Zhang M. Efficacy and safety of desvenlafaxine treatment for hot flashes associated with menopause: a meta-analysis of randomized controlled trials. Gynecol Obstet Invest. 2013;75:255-262.
- Toulis KA, Tzellos T, Kouvelas D, et al. Gabapentin for the treatment of hot flashes in women with natural or tamoxifen-induced menopause: a systematic review and meta-analysis. Clin Ther. 2009;31:221-235.
- Pandya KJ, Morrow GR, Roscoe JA, et al. Gabapentin for hot flashes in 420 women with breast cancer: a randomized double-blind placebocontrolled trial. Lancet. 2005;366:818-824.
- Reddy SY, Warner H, Guttuso T Jr, et al. Gabapentin, estrogen, and placebo for treating hot flushes: a randomized controlled trial. Obstet Gynecol. 2006;108:41-48.
- Crandall CJ, Manson JE, Hohensee C, et al. Association of genetic variation in the tachykinin receptor 3 locus with hot flashes and night sweats in the Women’s Health Initiative Study. Menopause. 2017;24:252.
- Rance NE, Dacks PA, Mittelman-Smith MA, et al. Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: a novel hypothesis on the mechanism of hot flushes. Front Neurendocrinol. 2013;34:211-227.
- Veozah (package insert). Astellas Pharma; Northbrook, Illinois. May 2023.
- Johnson KA, Martin N, Nappi RE, et al. Efficacy and safety of fezolinetant in moderate-to-severe vasomotor symptoms associated with menopause: a Phase 3 RCT. J Clin Endocrinol Metab. 2023;108:1981-1997.
- Lederman S, Ottery FD, Cano A, et al. Fezolinetant for treatment of moderate-to-severe vasomotor symptoms associated with menopause (SKYLIGHT 1): a phase 3 randomised controlled study. Lancet. 2023;401:1091-1102.
- Lloyd-Jones DM, Allen NB, Anderson CAM, et al. Life’s essential 8: updating and enhancing the American Heart Association’s construct of cardiovascular health: a presidential advisory from the American Heart Association. Circulation. 2022;146:e18-43.
- Wang X, Ma H, Li X, et al. Association of cardiovascular health with life expectancy free of cardiovascular disease, diabetes, cancer, and dementia in U.K. adults. JAMA Int Med. 2023;183:340-349.
Robert L. Barbieri, MD
Editor in Chief, OBG Management
Chair Emeritus, Department of Obstetrics and Gynecology
Brigham and Women’s Hospital
Kate Macy Ladd Distinguished Professor of Obstetrics,
Gynecology and Reproductive Biology
Harvard Medical School
Boston, Massachusetts
The author reports no financial relationships relevant to this article.
Robert L. Barbieri, MD
Editor in Chief, OBG Management
Chair Emeritus, Department of Obstetrics and Gynecology
Brigham and Women’s Hospital
Kate Macy Ladd Distinguished Professor of Obstetrics,
Gynecology and Reproductive Biology
Harvard Medical School
Boston, Massachusetts
The author reports no financial relationships relevant to this article.
Robert L. Barbieri, MD
Editor in Chief, OBG Management
Chair Emeritus, Department of Obstetrics and Gynecology
Brigham and Women’s Hospital
Kate Macy Ladd Distinguished Professor of Obstetrics,
Gynecology and Reproductive Biology
Harvard Medical School
Boston, Massachusetts
The author reports no financial relationships relevant to this article.
VMS, also known as hot flashes, night sweats, or cold sweats, occur for the majority of perimenopausal and menopausal women.1 In one study, the mean duration of clinically significant VMS was 5 years, and one-third of participants continued to have bothersome hot flashes 10 or more years after the onset of menopause.2 VMS may contribute to disrupted sleep patterns and depressed mood.3
All obstetrician-gynecologists know that estradiol and other estrogens are highly effective in the treatment of bothersome VMS. A meta-analysis reported that the frequency of VMS was reduced by 60% to 80% with oral estradiol (1 mg/day), transdermal estradiol(0.05 mg/day), and conjugated estrogen (0.625 mg).4 Breast tenderness and irregular uterine bleeding are common side effects of estrogen treatment of VMS. Estrogen treatment is contraindicated in patients with estrogen-responsive cancers, coronary heart disease, myocardial infarction, stroke, venous thromboembolism, and some cases of inherited thrombophilia. For these patients, an important option is the nonhormonal treatment of VMS, and several nonhormonal medications have been demonstrated to be effective therapy (TABLE 1). In this editorial I will review the medication treatment of VMS with escitalopram, paroxetine, gabapentin, and fezolinetant.
Escitalopram and paroxetine
Escitalopram and paroxetine have been shown to reduce VMS more than placebo in multiple clinical trials.5-10 In addition, escitalopram and paroxetine, at the doses tested, may be more effective for the treatment of VMS than sertraline, citalopram, or fluoxetine.11 In one trial assessing the efficacy of escitalopram to treat VMS, 205 patients with VMS were randomly assigned to 8 weeks of treatment with placebo or escitalopram.5 The initial escitalopram dose was 10 mg daily. At week 4:
- if VMS frequency was reduced by ≥ 50%, the patient remained on the 10-mg dose
- if VMS frequency was reduced by < 50%, the escitalopram dose was increased to 20 mg daily.
Following 8 weeks of treatment, the frequency of VMS decreased for patients in the placebo and escitalopram groups by 33% and 47%, respectively. Similar results have been reported in other studies.6
Paroxetine at a dose of 7.5 mg/day administered at bedtime is approved by the US Food and Drug Administration (FDA) for the treatment of VMS. In a pivotal study, 1,112 patients with VMS were randomly assigned to receive a placebo or paroxetine 7.5 mg at bedtime.9 In the 12-week study the reported decrease in mean weekly frequency of VMS for patients in the placebo and paroxetine groups were -37 and -44, respectively.9 Paroxetine 7.5 mg also reduced awakenings per night attributed to VMS and increased nighttime sleep duration.10
Depressed mood is prevalent among perimenopausal and postmenopausal patients.12 Prescribing escitalopram or paroxetine for VMS also may improve mood. Venlafaxine and desvenlafaxine are effective for the treatment of VMS;13,14 however, I seldom prescribe these medications for VMS because in my experience they are associated with more bothersome side effects, including dry mouth, decreased appetite, nausea, and insomnia than escitalopram or low-dose paroxetine.
Gabapentin
Numerous randomized clinical trials have reported that gabapentin is superior to placebo for the treatment of VMS.15 In one trial, 420 patients with breast cancer and VMS were randomly assigned to 8 weeks of treatment with placebo, gabapentin 300 mg/day (G300), or gabapentin 900 mg/day (G900) in 3 divided doses.16 Following 8 weeks of treatment, reduction in hot-flash severity score among patients receiving placebo, G300, or G900 was 15%, 31%, and 46%, respectively. Fatigue and somnolence were reported more frequently among patients taking gabapentin 900 mg/day. In a small trial, 60 patients with VMS were randomized to receive placebo, conjugated estrogen (0.2625 mg/day),or gabapentin (target dose of 2,400 mg/day in 3 divided doses).17 Following 12 weeks of treatment, the patient-reported decrease in VMS for those taking placebo, estrogen, or gabapentin was 54%, 72%, and 71%, respectively.
High-dose gabapentin treatment was associated with side effects of headache and dizziness more often than placebo or estrogen. Although gabapentin is not a treatment for insomnia, in my practice if a menopausal patient has prominent and bothersome symptoms of sleep disturbance and mild VMS symptoms, I will consider a trial of low-dose gabapentin. Some experts recommend initiating gabapentin at a dose of 100 mgdaily before bedtime to assess the effectiveness of a low dose that seldom causes significant side effects.
Fezolinetant
In a study of genetic variation associated with VMS, investigators discovered that nucleic acid variation in the neurokinin 3 (NK3) receptor was strongly associated with the prevalence of VMS, suggesting that this receptor is in the causal pathway to menopausal VMS.18 Additional research demonstrated that the kisspeptin/neurokinin B/dynorphin (KNDy) neurons, which are involved in the control of hypothalamic thermoregulation, are stimulated by neurokinin B, acting through the NK3 receptor, and suppressed by estradiol. A reduction in hypothalamic estrogen results in unopposed neurokinin B activity, which stimulates KNDy neurons, destabilizing the hypothalamic thermoregulatory center, causing vasodilation, which is perceived as hot flashes and sweating followed by chills.19
Fezolinetant is a high-affinity NK3 receptor antagonist that blocks the activity of neurokinin B, stabilizing the hypothalamic thermoregulatory center, thereby suppressing hot flashes. It is approved by the FDA for the treatment of moderate to severe VMS due to menopause using a fixed dose of 45 mg daily.20 In one clinical trial, 500 menopausal patients with bothersome VMS were randomly assigned to 12 weeks of treatment with placebo, fezolinetant 30 mg/day, or fezolinetant 45 mg/day. Following 12 weeks of treatment, the reported frequency rates of VMS among patients in the placebo, F30, and F45 groups were reduced by 43%, 61%, and 64%, respectively.21 In addition, following 12 weeks of treatment, the severity of VMS rates among patients in the placebo, F30, and F45 groups were reduced by 20%, 26%, and 32%, respectively.
Fezolinetant improved the quality of sleep and was associated with an improvement in patient-reported quality of life. Following 12 weeks of treatment, sleep quality among patients in the placebo, F30, and F45 groups was reported to be “much or moderately better” in 34%, 45%, and 54% of the patients, respectively.21 Similar results were reported in a companion study.22
Fezolinetant is contraindicated for patients with liver cirrhosis or severe renal impairment (estimated glomerular filtration rate of < 30 mL/min/1.73 m2). Before initiating treatment, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin (total and direct). Fezolinetant should not be prescribed if any of these tests are greater than twice the upper limit of normal. These tests should be repeated at 3, 6, and 9 months, and if the patient reports symptoms or signs of liver injury (nausea, vomiting, jaundice). Fezolinetant is metabolized by CYP1A2 and should not be prescribed to patients taking strong CYP1A2 inhibitors. The most common side effects associated with fezolinetant treatment are abdominal pain (4.3%), diarrhea (3.9%), insomnia (3.9%), back pain (3.0%), and hepatic transaminase elevation (2.3%). Fezolinetant has not been thoroughly evaluated in patients older than age 65. Following an oral dose of the medication, the median maximum concentration is reached in 1.5 hours, and the half-life is estimated to be 10 hours.20 Of all the medications discussed in this editorial, fezolinetant is the most expensive.
Effective VMS treatment improves overall health
Estrogen therapy is the gold standard treatment of VMS. However, many menopausal patients with bothersome VMS prefer not to take estrogen, and some have a medical condition that is a contraindication to estrogen treatment. The nonhormonal medication options for the treatment of VMS include escitalopram, paroxetine, gabapentin, and fezolinetant. Patients value the ability to choose the treatment they prefer, among all available hormonal and nonhormonal medication options. For mid-life women, effectively treating bothersome VMS is only one of many interventions that improves health. Optimal health is best achieved with23:
- high-quality diet
- daily physical activity
- appropriate body mass index
- nicotine avoidance
- a healthy sleep schedule
- normal blood pressure, lipid, and glucose levels.
Women who have a high-quality diet; daily physical activity; an appropriate body mass index; and normal blood pressure, cholesterol, and glucose levels are estimated to live 9 disease-free years longer than other women.24 ●
VMS, also known as hot flashes, night sweats, or cold sweats, occur for the majority of perimenopausal and menopausal women.1 In one study, the mean duration of clinically significant VMS was 5 years, and one-third of participants continued to have bothersome hot flashes 10 or more years after the onset of menopause.2 VMS may contribute to disrupted sleep patterns and depressed mood.3
All obstetrician-gynecologists know that estradiol and other estrogens are highly effective in the treatment of bothersome VMS. A meta-analysis reported that the frequency of VMS was reduced by 60% to 80% with oral estradiol (1 mg/day), transdermal estradiol(0.05 mg/day), and conjugated estrogen (0.625 mg).4 Breast tenderness and irregular uterine bleeding are common side effects of estrogen treatment of VMS. Estrogen treatment is contraindicated in patients with estrogen-responsive cancers, coronary heart disease, myocardial infarction, stroke, venous thromboembolism, and some cases of inherited thrombophilia. For these patients, an important option is the nonhormonal treatment of VMS, and several nonhormonal medications have been demonstrated to be effective therapy (TABLE 1). In this editorial I will review the medication treatment of VMS with escitalopram, paroxetine, gabapentin, and fezolinetant.
Escitalopram and paroxetine
Escitalopram and paroxetine have been shown to reduce VMS more than placebo in multiple clinical trials.5-10 In addition, escitalopram and paroxetine, at the doses tested, may be more effective for the treatment of VMS than sertraline, citalopram, or fluoxetine.11 In one trial assessing the efficacy of escitalopram to treat VMS, 205 patients with VMS were randomly assigned to 8 weeks of treatment with placebo or escitalopram.5 The initial escitalopram dose was 10 mg daily. At week 4:
- if VMS frequency was reduced by ≥ 50%, the patient remained on the 10-mg dose
- if VMS frequency was reduced by < 50%, the escitalopram dose was increased to 20 mg daily.
Following 8 weeks of treatment, the frequency of VMS decreased for patients in the placebo and escitalopram groups by 33% and 47%, respectively. Similar results have been reported in other studies.6
Paroxetine at a dose of 7.5 mg/day administered at bedtime is approved by the US Food and Drug Administration (FDA) for the treatment of VMS. In a pivotal study, 1,112 patients with VMS were randomly assigned to receive a placebo or paroxetine 7.5 mg at bedtime.9 In the 12-week study the reported decrease in mean weekly frequency of VMS for patients in the placebo and paroxetine groups were -37 and -44, respectively.9 Paroxetine 7.5 mg also reduced awakenings per night attributed to VMS and increased nighttime sleep duration.10
Depressed mood is prevalent among perimenopausal and postmenopausal patients.12 Prescribing escitalopram or paroxetine for VMS also may improve mood. Venlafaxine and desvenlafaxine are effective for the treatment of VMS;13,14 however, I seldom prescribe these medications for VMS because in my experience they are associated with more bothersome side effects, including dry mouth, decreased appetite, nausea, and insomnia than escitalopram or low-dose paroxetine.
Gabapentin
Numerous randomized clinical trials have reported that gabapentin is superior to placebo for the treatment of VMS.15 In one trial, 420 patients with breast cancer and VMS were randomly assigned to 8 weeks of treatment with placebo, gabapentin 300 mg/day (G300), or gabapentin 900 mg/day (G900) in 3 divided doses.16 Following 8 weeks of treatment, reduction in hot-flash severity score among patients receiving placebo, G300, or G900 was 15%, 31%, and 46%, respectively. Fatigue and somnolence were reported more frequently among patients taking gabapentin 900 mg/day. In a small trial, 60 patients with VMS were randomized to receive placebo, conjugated estrogen (0.2625 mg/day),or gabapentin (target dose of 2,400 mg/day in 3 divided doses).17 Following 12 weeks of treatment, the patient-reported decrease in VMS for those taking placebo, estrogen, or gabapentin was 54%, 72%, and 71%, respectively.
High-dose gabapentin treatment was associated with side effects of headache and dizziness more often than placebo or estrogen. Although gabapentin is not a treatment for insomnia, in my practice if a menopausal patient has prominent and bothersome symptoms of sleep disturbance and mild VMS symptoms, I will consider a trial of low-dose gabapentin. Some experts recommend initiating gabapentin at a dose of 100 mgdaily before bedtime to assess the effectiveness of a low dose that seldom causes significant side effects.
Fezolinetant
In a study of genetic variation associated with VMS, investigators discovered that nucleic acid variation in the neurokinin 3 (NK3) receptor was strongly associated with the prevalence of VMS, suggesting that this receptor is in the causal pathway to menopausal VMS.18 Additional research demonstrated that the kisspeptin/neurokinin B/dynorphin (KNDy) neurons, which are involved in the control of hypothalamic thermoregulation, are stimulated by neurokinin B, acting through the NK3 receptor, and suppressed by estradiol. A reduction in hypothalamic estrogen results in unopposed neurokinin B activity, which stimulates KNDy neurons, destabilizing the hypothalamic thermoregulatory center, causing vasodilation, which is perceived as hot flashes and sweating followed by chills.19
Fezolinetant is a high-affinity NK3 receptor antagonist that blocks the activity of neurokinin B, stabilizing the hypothalamic thermoregulatory center, thereby suppressing hot flashes. It is approved by the FDA for the treatment of moderate to severe VMS due to menopause using a fixed dose of 45 mg daily.20 In one clinical trial, 500 menopausal patients with bothersome VMS were randomly assigned to 12 weeks of treatment with placebo, fezolinetant 30 mg/day, or fezolinetant 45 mg/day. Following 12 weeks of treatment, the reported frequency rates of VMS among patients in the placebo, F30, and F45 groups were reduced by 43%, 61%, and 64%, respectively.21 In addition, following 12 weeks of treatment, the severity of VMS rates among patients in the placebo, F30, and F45 groups were reduced by 20%, 26%, and 32%, respectively.
Fezolinetant improved the quality of sleep and was associated with an improvement in patient-reported quality of life. Following 12 weeks of treatment, sleep quality among patients in the placebo, F30, and F45 groups was reported to be “much or moderately better” in 34%, 45%, and 54% of the patients, respectively.21 Similar results were reported in a companion study.22
Fezolinetant is contraindicated for patients with liver cirrhosis or severe renal impairment (estimated glomerular filtration rate of < 30 mL/min/1.73 m2). Before initiating treatment, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin (total and direct). Fezolinetant should not be prescribed if any of these tests are greater than twice the upper limit of normal. These tests should be repeated at 3, 6, and 9 months, and if the patient reports symptoms or signs of liver injury (nausea, vomiting, jaundice). Fezolinetant is metabolized by CYP1A2 and should not be prescribed to patients taking strong CYP1A2 inhibitors. The most common side effects associated with fezolinetant treatment are abdominal pain (4.3%), diarrhea (3.9%), insomnia (3.9%), back pain (3.0%), and hepatic transaminase elevation (2.3%). Fezolinetant has not been thoroughly evaluated in patients older than age 65. Following an oral dose of the medication, the median maximum concentration is reached in 1.5 hours, and the half-life is estimated to be 10 hours.20 Of all the medications discussed in this editorial, fezolinetant is the most expensive.
Effective VMS treatment improves overall health
Estrogen therapy is the gold standard treatment of VMS. However, many menopausal patients with bothersome VMS prefer not to take estrogen, and some have a medical condition that is a contraindication to estrogen treatment. The nonhormonal medication options for the treatment of VMS include escitalopram, paroxetine, gabapentin, and fezolinetant. Patients value the ability to choose the treatment they prefer, among all available hormonal and nonhormonal medication options. For mid-life women, effectively treating bothersome VMS is only one of many interventions that improves health. Optimal health is best achieved with23:
- high-quality diet
- daily physical activity
- appropriate body mass index
- nicotine avoidance
- a healthy sleep schedule
- normal blood pressure, lipid, and glucose levels.
Women who have a high-quality diet; daily physical activity; an appropriate body mass index; and normal blood pressure, cholesterol, and glucose levels are estimated to live 9 disease-free years longer than other women.24 ●
- Gold EB, Colvin A, Avis N, et al. Longitudinal analysis of the association between vasomotor symptoms and race/ethnicity across the menopause transition: study of women’s health across the nation. Am J Pub Health. 2006;1226-1235.
- Freeman EW, Sammel MD, Sanders RJ. Risk of long-term hot flashes after natural menopause: evidence from the Penn Ovarian Aging Study cohort. Menopause. 2014;21:924-932.
- Hatcher KM, Smith RL, Chiang C, et al. Nocturnal hot flashes, but not serum hormone concentrations as a predictor of insomnia in menopausal women: results from the Midlife Women’s Health Study. J Women’s Health. 2023;32:94-101.
- Nelson HD. Commonly used types of postmenopausal estrogen for treatment of hot flashes: scientific review. JAMA. 2004;291:1610.
- Freeman EW, Guthrie KA, Caan B, et al. Efficacy of escitalopram for hot flashes in healthy menopausal women: a randomized controlled trial. JAMA. 2011;305:267-227.
- Carpenter JS, Guthrie KA, Larson JC, et al. Effect of escitalopram on hot flash interference: a randomized, controlled trial. Fertil Steril. 2012;97:1399-1404.e1.
- Slaton RM, Champion MN, Palmore KB. A review of paroxetine for the treatment of vasomotor symptoms. J Pharm Pract. 2015;28:266-274.
- Stearns V, Slack R, Greep N, et al. Paroxetine is an effective treatment for hot flashes: results from a prospective randomized clinical trial. J Clin Oncol. 2005;23:6919-6930.
- Simon JA, Portman DJ, Kaunitz AM, et al. Lowdose paroxetine 7.5 mg for menopausal vasomotor symptoms: two randomized controlled trials. Menopause. 2013;20:1027-1035.
- Pinkerton JV, Joffe H, Kazempour K, et al. Lowdose paroxetine (7.5 mg) improves sleep in women with vasomotor symptoms associated with menopause. Menopause. 2015;22:50-58.
- Shams T, Firwana B, Habib F, et al. SSRIs for hot flashes: a systematic review and metaanalysis of randomized trials. J Gen Intern Med. 2014;29:204-213.
- Freeman EW. Depression in the menopause transition: risks in the changing hormone milieu as observed in the general population. Womens Midlife Health. 2015;1:2.
- Loprinzi CL, Kugler JW, Sloan JA, et al. Venlafaxine in management of hot flashes in survivors of breast cancer: a randomised controlled trial. Lancet. 2000;356:2059-2063.
- Sun Z, Hao Y, Zhang M. Efficacy and safety of desvenlafaxine treatment for hot flashes associated with menopause: a meta-analysis of randomized controlled trials. Gynecol Obstet Invest. 2013;75:255-262.
- Toulis KA, Tzellos T, Kouvelas D, et al. Gabapentin for the treatment of hot flashes in women with natural or tamoxifen-induced menopause: a systematic review and meta-analysis. Clin Ther. 2009;31:221-235.
- Pandya KJ, Morrow GR, Roscoe JA, et al. Gabapentin for hot flashes in 420 women with breast cancer: a randomized double-blind placebocontrolled trial. Lancet. 2005;366:818-824.
- Reddy SY, Warner H, Guttuso T Jr, et al. Gabapentin, estrogen, and placebo for treating hot flushes: a randomized controlled trial. Obstet Gynecol. 2006;108:41-48.
- Crandall CJ, Manson JE, Hohensee C, et al. Association of genetic variation in the tachykinin receptor 3 locus with hot flashes and night sweats in the Women’s Health Initiative Study. Menopause. 2017;24:252.
- Rance NE, Dacks PA, Mittelman-Smith MA, et al. Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: a novel hypothesis on the mechanism of hot flushes. Front Neurendocrinol. 2013;34:211-227.
- Veozah (package insert). Astellas Pharma; Northbrook, Illinois. May 2023.
- Johnson KA, Martin N, Nappi RE, et al. Efficacy and safety of fezolinetant in moderate-to-severe vasomotor symptoms associated with menopause: a Phase 3 RCT. J Clin Endocrinol Metab. 2023;108:1981-1997.
- Lederman S, Ottery FD, Cano A, et al. Fezolinetant for treatment of moderate-to-severe vasomotor symptoms associated with menopause (SKYLIGHT 1): a phase 3 randomised controlled study. Lancet. 2023;401:1091-1102.
- Lloyd-Jones DM, Allen NB, Anderson CAM, et al. Life’s essential 8: updating and enhancing the American Heart Association’s construct of cardiovascular health: a presidential advisory from the American Heart Association. Circulation. 2022;146:e18-43.
- Wang X, Ma H, Li X, et al. Association of cardiovascular health with life expectancy free of cardiovascular disease, diabetes, cancer, and dementia in U.K. adults. JAMA Int Med. 2023;183:340-349.
- Gold EB, Colvin A, Avis N, et al. Longitudinal analysis of the association between vasomotor symptoms and race/ethnicity across the menopause transition: study of women’s health across the nation. Am J Pub Health. 2006;1226-1235.
- Freeman EW, Sammel MD, Sanders RJ. Risk of long-term hot flashes after natural menopause: evidence from the Penn Ovarian Aging Study cohort. Menopause. 2014;21:924-932.
- Hatcher KM, Smith RL, Chiang C, et al. Nocturnal hot flashes, but not serum hormone concentrations as a predictor of insomnia in menopausal women: results from the Midlife Women’s Health Study. J Women’s Health. 2023;32:94-101.
- Nelson HD. Commonly used types of postmenopausal estrogen for treatment of hot flashes: scientific review. JAMA. 2004;291:1610.
- Freeman EW, Guthrie KA, Caan B, et al. Efficacy of escitalopram for hot flashes in healthy menopausal women: a randomized controlled trial. JAMA. 2011;305:267-227.
- Carpenter JS, Guthrie KA, Larson JC, et al. Effect of escitalopram on hot flash interference: a randomized, controlled trial. Fertil Steril. 2012;97:1399-1404.e1.
- Slaton RM, Champion MN, Palmore KB. A review of paroxetine for the treatment of vasomotor symptoms. J Pharm Pract. 2015;28:266-274.
- Stearns V, Slack R, Greep N, et al. Paroxetine is an effective treatment for hot flashes: results from a prospective randomized clinical trial. J Clin Oncol. 2005;23:6919-6930.
- Simon JA, Portman DJ, Kaunitz AM, et al. Lowdose paroxetine 7.5 mg for menopausal vasomotor symptoms: two randomized controlled trials. Menopause. 2013;20:1027-1035.
- Pinkerton JV, Joffe H, Kazempour K, et al. Lowdose paroxetine (7.5 mg) improves sleep in women with vasomotor symptoms associated with menopause. Menopause. 2015;22:50-58.
- Shams T, Firwana B, Habib F, et al. SSRIs for hot flashes: a systematic review and metaanalysis of randomized trials. J Gen Intern Med. 2014;29:204-213.
- Freeman EW. Depression in the menopause transition: risks in the changing hormone milieu as observed in the general population. Womens Midlife Health. 2015;1:2.
- Loprinzi CL, Kugler JW, Sloan JA, et al. Venlafaxine in management of hot flashes in survivors of breast cancer: a randomised controlled trial. Lancet. 2000;356:2059-2063.
- Sun Z, Hao Y, Zhang M. Efficacy and safety of desvenlafaxine treatment for hot flashes associated with menopause: a meta-analysis of randomized controlled trials. Gynecol Obstet Invest. 2013;75:255-262.
- Toulis KA, Tzellos T, Kouvelas D, et al. Gabapentin for the treatment of hot flashes in women with natural or tamoxifen-induced menopause: a systematic review and meta-analysis. Clin Ther. 2009;31:221-235.
- Pandya KJ, Morrow GR, Roscoe JA, et al. Gabapentin for hot flashes in 420 women with breast cancer: a randomized double-blind placebocontrolled trial. Lancet. 2005;366:818-824.
- Reddy SY, Warner H, Guttuso T Jr, et al. Gabapentin, estrogen, and placebo for treating hot flushes: a randomized controlled trial. Obstet Gynecol. 2006;108:41-48.
- Crandall CJ, Manson JE, Hohensee C, et al. Association of genetic variation in the tachykinin receptor 3 locus with hot flashes and night sweats in the Women’s Health Initiative Study. Menopause. 2017;24:252.
- Rance NE, Dacks PA, Mittelman-Smith MA, et al. Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: a novel hypothesis on the mechanism of hot flushes. Front Neurendocrinol. 2013;34:211-227.
- Veozah (package insert). Astellas Pharma; Northbrook, Illinois. May 2023.
- Johnson KA, Martin N, Nappi RE, et al. Efficacy and safety of fezolinetant in moderate-to-severe vasomotor symptoms associated with menopause: a Phase 3 RCT. J Clin Endocrinol Metab. 2023;108:1981-1997.
- Lederman S, Ottery FD, Cano A, et al. Fezolinetant for treatment of moderate-to-severe vasomotor symptoms associated with menopause (SKYLIGHT 1): a phase 3 randomised controlled study. Lancet. 2023;401:1091-1102.
- Lloyd-Jones DM, Allen NB, Anderson CAM, et al. Life’s essential 8: updating and enhancing the American Heart Association’s construct of cardiovascular health: a presidential advisory from the American Heart Association. Circulation. 2022;146:e18-43.
- Wang X, Ma H, Li X, et al. Association of cardiovascular health with life expectancy free of cardiovascular disease, diabetes, cancer, and dementia in U.K. adults. JAMA Int Med. 2023;183:340-349.
Hormone therapy less effective in menopausal women with obesity
PHILADELPHIA – , according to a small, retrospective study presented at the annual meeting of the Menopause Society (formerly the North American Menopause Society).
More than 40% of women over age 40 in the United States have obesity, presenter Anita Pershad, MD, an ob.gyn. medical resident at Eastern Virginia Medical School, Norfolk, told attendees. Yet most of the large-scale studies investigating perimenopausal and postmenopausal hormone therapy included participants without major medical comorbidities, so little data exist on how effectively HT works in women with these comorbidities, she said
“The main takeaway of our study is that obesity may worsen a woman’s menopausal symptoms and limit the amount of relief she gets from hormone therapy,” Dr. Pershad said in an interview. “It remains unclear if hormone therapy is less effective in women with obesity overall, or if the expected efficacy can be achieved with alternative design and administration routes. A potential mechanism of action for the observed decreased effect could be due to adipose tissue acting as a heat insulator, promoting the effects of vasomotor symptoms.”
Dr. Pershad and her colleagues conducted a retrospective review of the medical records of 119 patients who presented to a menopause clinic at a Midsouth urban academic medical center between July 2018 and December 2022. Obesity was defined as having a body mass index (BMI) of 30 kg/m2 or greater.
The patients with and without obesity were similar in terms of age, duration of menopause, use of hormone therapy, and therapy acceptance, but patients with obesity were more likely to identify themselves as Black (71% vs. 40%). Women with obesity were also significantly more likely than women without obesity to report vasomotor symptoms (74% vs. 45%, P = .002), genitourinary/vulvovaginal symptoms (60% vs. 21%, P < .001), mood disturbances (11% vs. 0%, P = .18), and decreased libido (29% vs. 11%, P = .017).
There were no significant differences in comorbidities between women with and without obesity, and among women who received systemic or localized HT, the same standard dosing was used for both groups.
Women with obesity were much less likely to see a satisfying reduction in their menopausal symptoms than women without obesity (odds ratio 0.07, 95% confidence interval, 0.01-0.64; P = .006), though the subgroups for each category of HT were small. Among the 20 women receiving systemic hormone therapy, only 1 of the 12 with obesity (8.3%) reported improvement in symptoms, compared with 7 of the 8 women without obesity (88%; P = .0004). Among 33 women using localized hormone therapy, 46% of the 24 women with obesity vs. 89% of the 9 women without obesity experienced symptom improvement (P = .026).
The proportions of women reporting relief from only lifestyle modifications or from nonhormonal medications, such as SSRIs/SNRIs, trazodone, and clonidine, were not statistically different. There were 33 women who relied only on lifestyle modifications, with 31% of the 16 women with obesity and 59% of the 17 women without obesity reporting improvement in their symptoms (P = .112). Similarly, among the 33 women using nonhormonal medications, 75% of the 20 women with obesity and 77% of the 13 women without obesity experienced relief (P = .9).
Women with obesity are undertreated
Dr. Pershad emphasized the need to improve care and counseling for diverse patients seeking treatment for menopausal symptoms.
“More research is needed to examine how women with medical comorbidities are uniquely impacted by menopause and respond to therapies,” Dr. Pershad said in an interview. “This can be achieved by actively including more diverse patient populations in women’s health studies, burdened by the social determinants of health and medical comorbidities such as obesity.”
Stephanie S. Faubion, MD, MBA, director for Mayo Clinic’s Center for Women’s Health, Rochester, Minn., and medical director for The Menopause Society, was not surprised by the findings, particularly given that women with obesity tend to have more hot flashes and night sweats as a result of their extra weight. However, dosage data was not adjusted for BMI in the study and data on hormone levels was unavailable, she said, so it’s difficult to determine from the data whether HT was less effective for women with obesity or whether they were underdosed.
“I think women with obesity are undertreated,” Dr. Faubion said in an interview. “My guess is people are afraid. Women with obesity also may have other comorbidities,” such as hypertension and diabetes, she said, and “the greater the number of cardiovascular risk factors, the higher risk hormone therapy is.” Providers may therefore be leery of prescribing HT or prescribing it at an appropriately high enough dose to treat menopausal symptoms.
Common practice is to start patients at the lowest dose and titrate up according to symptoms, but “if people are afraid of it, they’re going to start the lowest dose” and may not increase it, Dr. Faubion said. She noted that other nonhormonal options are available, though providers should be conscientious about selecting ones whose adverse events do not include weight gain.
Although the study focused on an understudied population within hormone therapy research, the study was limited by its small size, low overall use of hormone therapy, recall bias, and the researchers’ inability to control for other medications the participants may have been taking.
Dr. Pershad said she is continuing research to try to identify the mechanisms underlying the reduced efficacy in women with obesity.
The research did not use any external funding. Dr. Pershad had no industry disclosures, but her colleagues reported honoraria from or speaking for TherapeuticsMD, Astella Pharma, Scynexis, Pharmavite, and Pfizer. Dr. Faubion had no disclosures.
PHILADELPHIA – , according to a small, retrospective study presented at the annual meeting of the Menopause Society (formerly the North American Menopause Society).
More than 40% of women over age 40 in the United States have obesity, presenter Anita Pershad, MD, an ob.gyn. medical resident at Eastern Virginia Medical School, Norfolk, told attendees. Yet most of the large-scale studies investigating perimenopausal and postmenopausal hormone therapy included participants without major medical comorbidities, so little data exist on how effectively HT works in women with these comorbidities, she said
“The main takeaway of our study is that obesity may worsen a woman’s menopausal symptoms and limit the amount of relief she gets from hormone therapy,” Dr. Pershad said in an interview. “It remains unclear if hormone therapy is less effective in women with obesity overall, or if the expected efficacy can be achieved with alternative design and administration routes. A potential mechanism of action for the observed decreased effect could be due to adipose tissue acting as a heat insulator, promoting the effects of vasomotor symptoms.”
Dr. Pershad and her colleagues conducted a retrospective review of the medical records of 119 patients who presented to a menopause clinic at a Midsouth urban academic medical center between July 2018 and December 2022. Obesity was defined as having a body mass index (BMI) of 30 kg/m2 or greater.
The patients with and without obesity were similar in terms of age, duration of menopause, use of hormone therapy, and therapy acceptance, but patients with obesity were more likely to identify themselves as Black (71% vs. 40%). Women with obesity were also significantly more likely than women without obesity to report vasomotor symptoms (74% vs. 45%, P = .002), genitourinary/vulvovaginal symptoms (60% vs. 21%, P < .001), mood disturbances (11% vs. 0%, P = .18), and decreased libido (29% vs. 11%, P = .017).
There were no significant differences in comorbidities between women with and without obesity, and among women who received systemic or localized HT, the same standard dosing was used for both groups.
Women with obesity were much less likely to see a satisfying reduction in their menopausal symptoms than women without obesity (odds ratio 0.07, 95% confidence interval, 0.01-0.64; P = .006), though the subgroups for each category of HT were small. Among the 20 women receiving systemic hormone therapy, only 1 of the 12 with obesity (8.3%) reported improvement in symptoms, compared with 7 of the 8 women without obesity (88%; P = .0004). Among 33 women using localized hormone therapy, 46% of the 24 women with obesity vs. 89% of the 9 women without obesity experienced symptom improvement (P = .026).
The proportions of women reporting relief from only lifestyle modifications or from nonhormonal medications, such as SSRIs/SNRIs, trazodone, and clonidine, were not statistically different. There were 33 women who relied only on lifestyle modifications, with 31% of the 16 women with obesity and 59% of the 17 women without obesity reporting improvement in their symptoms (P = .112). Similarly, among the 33 women using nonhormonal medications, 75% of the 20 women with obesity and 77% of the 13 women without obesity experienced relief (P = .9).
Women with obesity are undertreated
Dr. Pershad emphasized the need to improve care and counseling for diverse patients seeking treatment for menopausal symptoms.
“More research is needed to examine how women with medical comorbidities are uniquely impacted by menopause and respond to therapies,” Dr. Pershad said in an interview. “This can be achieved by actively including more diverse patient populations in women’s health studies, burdened by the social determinants of health and medical comorbidities such as obesity.”
Stephanie S. Faubion, MD, MBA, director for Mayo Clinic’s Center for Women’s Health, Rochester, Minn., and medical director for The Menopause Society, was not surprised by the findings, particularly given that women with obesity tend to have more hot flashes and night sweats as a result of their extra weight. However, dosage data was not adjusted for BMI in the study and data on hormone levels was unavailable, she said, so it’s difficult to determine from the data whether HT was less effective for women with obesity or whether they were underdosed.
“I think women with obesity are undertreated,” Dr. Faubion said in an interview. “My guess is people are afraid. Women with obesity also may have other comorbidities,” such as hypertension and diabetes, she said, and “the greater the number of cardiovascular risk factors, the higher risk hormone therapy is.” Providers may therefore be leery of prescribing HT or prescribing it at an appropriately high enough dose to treat menopausal symptoms.
Common practice is to start patients at the lowest dose and titrate up according to symptoms, but “if people are afraid of it, they’re going to start the lowest dose” and may not increase it, Dr. Faubion said. She noted that other nonhormonal options are available, though providers should be conscientious about selecting ones whose adverse events do not include weight gain.
Although the study focused on an understudied population within hormone therapy research, the study was limited by its small size, low overall use of hormone therapy, recall bias, and the researchers’ inability to control for other medications the participants may have been taking.
Dr. Pershad said she is continuing research to try to identify the mechanisms underlying the reduced efficacy in women with obesity.
The research did not use any external funding. Dr. Pershad had no industry disclosures, but her colleagues reported honoraria from or speaking for TherapeuticsMD, Astella Pharma, Scynexis, Pharmavite, and Pfizer. Dr. Faubion had no disclosures.
PHILADELPHIA – , according to a small, retrospective study presented at the annual meeting of the Menopause Society (formerly the North American Menopause Society).
More than 40% of women over age 40 in the United States have obesity, presenter Anita Pershad, MD, an ob.gyn. medical resident at Eastern Virginia Medical School, Norfolk, told attendees. Yet most of the large-scale studies investigating perimenopausal and postmenopausal hormone therapy included participants without major medical comorbidities, so little data exist on how effectively HT works in women with these comorbidities, she said
“The main takeaway of our study is that obesity may worsen a woman’s menopausal symptoms and limit the amount of relief she gets from hormone therapy,” Dr. Pershad said in an interview. “It remains unclear if hormone therapy is less effective in women with obesity overall, or if the expected efficacy can be achieved with alternative design and administration routes. A potential mechanism of action for the observed decreased effect could be due to adipose tissue acting as a heat insulator, promoting the effects of vasomotor symptoms.”
Dr. Pershad and her colleagues conducted a retrospective review of the medical records of 119 patients who presented to a menopause clinic at a Midsouth urban academic medical center between July 2018 and December 2022. Obesity was defined as having a body mass index (BMI) of 30 kg/m2 or greater.
The patients with and without obesity were similar in terms of age, duration of menopause, use of hormone therapy, and therapy acceptance, but patients with obesity were more likely to identify themselves as Black (71% vs. 40%). Women with obesity were also significantly more likely than women without obesity to report vasomotor symptoms (74% vs. 45%, P = .002), genitourinary/vulvovaginal symptoms (60% vs. 21%, P < .001), mood disturbances (11% vs. 0%, P = .18), and decreased libido (29% vs. 11%, P = .017).
There were no significant differences in comorbidities between women with and without obesity, and among women who received systemic or localized HT, the same standard dosing was used for both groups.
Women with obesity were much less likely to see a satisfying reduction in their menopausal symptoms than women without obesity (odds ratio 0.07, 95% confidence interval, 0.01-0.64; P = .006), though the subgroups for each category of HT were small. Among the 20 women receiving systemic hormone therapy, only 1 of the 12 with obesity (8.3%) reported improvement in symptoms, compared with 7 of the 8 women without obesity (88%; P = .0004). Among 33 women using localized hormone therapy, 46% of the 24 women with obesity vs. 89% of the 9 women without obesity experienced symptom improvement (P = .026).
The proportions of women reporting relief from only lifestyle modifications or from nonhormonal medications, such as SSRIs/SNRIs, trazodone, and clonidine, were not statistically different. There were 33 women who relied only on lifestyle modifications, with 31% of the 16 women with obesity and 59% of the 17 women without obesity reporting improvement in their symptoms (P = .112). Similarly, among the 33 women using nonhormonal medications, 75% of the 20 women with obesity and 77% of the 13 women without obesity experienced relief (P = .9).
Women with obesity are undertreated
Dr. Pershad emphasized the need to improve care and counseling for diverse patients seeking treatment for menopausal symptoms.
“More research is needed to examine how women with medical comorbidities are uniquely impacted by menopause and respond to therapies,” Dr. Pershad said in an interview. “This can be achieved by actively including more diverse patient populations in women’s health studies, burdened by the social determinants of health and medical comorbidities such as obesity.”
Stephanie S. Faubion, MD, MBA, director for Mayo Clinic’s Center for Women’s Health, Rochester, Minn., and medical director for The Menopause Society, was not surprised by the findings, particularly given that women with obesity tend to have more hot flashes and night sweats as a result of their extra weight. However, dosage data was not adjusted for BMI in the study and data on hormone levels was unavailable, she said, so it’s difficult to determine from the data whether HT was less effective for women with obesity or whether they were underdosed.
“I think women with obesity are undertreated,” Dr. Faubion said in an interview. “My guess is people are afraid. Women with obesity also may have other comorbidities,” such as hypertension and diabetes, she said, and “the greater the number of cardiovascular risk factors, the higher risk hormone therapy is.” Providers may therefore be leery of prescribing HT or prescribing it at an appropriately high enough dose to treat menopausal symptoms.
Common practice is to start patients at the lowest dose and titrate up according to symptoms, but “if people are afraid of it, they’re going to start the lowest dose” and may not increase it, Dr. Faubion said. She noted that other nonhormonal options are available, though providers should be conscientious about selecting ones whose adverse events do not include weight gain.
Although the study focused on an understudied population within hormone therapy research, the study was limited by its small size, low overall use of hormone therapy, recall bias, and the researchers’ inability to control for other medications the participants may have been taking.
Dr. Pershad said she is continuing research to try to identify the mechanisms underlying the reduced efficacy in women with obesity.
The research did not use any external funding. Dr. Pershad had no industry disclosures, but her colleagues reported honoraria from or speaking for TherapeuticsMD, Astella Pharma, Scynexis, Pharmavite, and Pfizer. Dr. Faubion had no disclosures.
AT THE MENOPAUSE SOCIETY ANNUAL MEETING
False-positive Pap smear may indicate genitourinary syndrome
TOPLINE:
, according to a poster presented at The Menopause Society 2023 annual meeting.
METHODOLOGY:
- Starting in 2010, researchers in Florida and Antigua saw an increase in the number of perimenopausal women with no history of cervical abnormalities and low risk for sexually transmitted infections (STIs) presenting with abnormal Pap smears at their clinics.
- They studied 1,500 women aged 30-70 from several clinics. The women had low risk for STIs, a maximum of two sexual partners, and the presence of cervical dysplasia over a period of 12 years.
TAKEAWAY:
- Nearly all (96.7%) of the women who received local estrogen treatment had a normal Pap smear following therapy.
- A high number of patients who initially presented with cervical dysplasia underwent interventions such as colposcopies, biopsies, LEEP excisions, cryotherapy, cone biopsies, and hysterectomies because of cervical atrophy.
- The researchers concluded that local estrogen treatment could save patients money spent on treatments for cervical atrophy.
- Some women who underwent cone biopsies and hysterectomies and did not receive local estrogen still had vaginal dysplasia.
IN PRACTICE:
“In this study, we report an early sign of genitourinary syndrome of menopause: false positive cervical dysplasia caused by cervicovaginal atrophy resulting from decreased estrogen levels during perimenopause,” say the investigators. “We also demonstrate how the use of local estrogen therapy can prevent a significant number of interventions and procedures, resulting in significant cost savings. This is particularly relevant as the number of Pap smears conducted in this population represents 50%-60% of all Pap smears performed on women.”
SOURCE:
The data were presented at The Menopause Society 2023 annual meeting. The study was led by Alberto Dominguez-Bali, MD, from the Miami Center for Obstetrics, Gynecology and Human Sexuality.
LIMITATIONS:
The study authors report no limitations.
DISCLOSURES:
The authors report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
TOPLINE:
, according to a poster presented at The Menopause Society 2023 annual meeting.
METHODOLOGY:
- Starting in 2010, researchers in Florida and Antigua saw an increase in the number of perimenopausal women with no history of cervical abnormalities and low risk for sexually transmitted infections (STIs) presenting with abnormal Pap smears at their clinics.
- They studied 1,500 women aged 30-70 from several clinics. The women had low risk for STIs, a maximum of two sexual partners, and the presence of cervical dysplasia over a period of 12 years.
TAKEAWAY:
- Nearly all (96.7%) of the women who received local estrogen treatment had a normal Pap smear following therapy.
- A high number of patients who initially presented with cervical dysplasia underwent interventions such as colposcopies, biopsies, LEEP excisions, cryotherapy, cone biopsies, and hysterectomies because of cervical atrophy.
- The researchers concluded that local estrogen treatment could save patients money spent on treatments for cervical atrophy.
- Some women who underwent cone biopsies and hysterectomies and did not receive local estrogen still had vaginal dysplasia.
IN PRACTICE:
“In this study, we report an early sign of genitourinary syndrome of menopause: false positive cervical dysplasia caused by cervicovaginal atrophy resulting from decreased estrogen levels during perimenopause,” say the investigators. “We also demonstrate how the use of local estrogen therapy can prevent a significant number of interventions and procedures, resulting in significant cost savings. This is particularly relevant as the number of Pap smears conducted in this population represents 50%-60% of all Pap smears performed on women.”
SOURCE:
The data were presented at The Menopause Society 2023 annual meeting. The study was led by Alberto Dominguez-Bali, MD, from the Miami Center for Obstetrics, Gynecology and Human Sexuality.
LIMITATIONS:
The study authors report no limitations.
DISCLOSURES:
The authors report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
TOPLINE:
, according to a poster presented at The Menopause Society 2023 annual meeting.
METHODOLOGY:
- Starting in 2010, researchers in Florida and Antigua saw an increase in the number of perimenopausal women with no history of cervical abnormalities and low risk for sexually transmitted infections (STIs) presenting with abnormal Pap smears at their clinics.
- They studied 1,500 women aged 30-70 from several clinics. The women had low risk for STIs, a maximum of two sexual partners, and the presence of cervical dysplasia over a period of 12 years.
TAKEAWAY:
- Nearly all (96.7%) of the women who received local estrogen treatment had a normal Pap smear following therapy.
- A high number of patients who initially presented with cervical dysplasia underwent interventions such as colposcopies, biopsies, LEEP excisions, cryotherapy, cone biopsies, and hysterectomies because of cervical atrophy.
- The researchers concluded that local estrogen treatment could save patients money spent on treatments for cervical atrophy.
- Some women who underwent cone biopsies and hysterectomies and did not receive local estrogen still had vaginal dysplasia.
IN PRACTICE:
“In this study, we report an early sign of genitourinary syndrome of menopause: false positive cervical dysplasia caused by cervicovaginal atrophy resulting from decreased estrogen levels during perimenopause,” say the investigators. “We also demonstrate how the use of local estrogen therapy can prevent a significant number of interventions and procedures, resulting in significant cost savings. This is particularly relevant as the number of Pap smears conducted in this population represents 50%-60% of all Pap smears performed on women.”
SOURCE:
The data were presented at The Menopause Society 2023 annual meeting. The study was led by Alberto Dominguez-Bali, MD, from the Miami Center for Obstetrics, Gynecology and Human Sexuality.
LIMITATIONS:
The study authors report no limitations.
DISCLOSURES:
The authors report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE MENOPAUSE SOCIETY ANNUAL MEETING