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New Research Consortium on Quest to Improve Male Infertility Treatment
A study by researchers at two academic medical centers determined which infertile men may benefit from treatment with anastrozole. They found that those with azoospermia (no sperm in their ejaculate) rarely respond to the drug while those with baseline nonazoospermia, lower levels of luteinizing hormone and follicle-stimulating hormone, and higher levels of testosterone are more likely to obtain improvement in semen parameters.
The retrospective cohort study of 90 infertile men, published in the October 2023 issue of Fertility and Sterility, was conducted by researchers at Cleveland Clinic and the University of California Los Angeles. It is the first project of Male Organ Biology Yielding United Science (MOBYUS), a new, multi-institutional research consortium seeking to better understand male infertility and expand treatment options.
Launched last year, MOBYUS now includes investigators from 14 large US-based academic medical centers. They select research topics and search their patient population for eligible participants and share resulting deidentified data for analysis and publication.
Members of the consortium conducted another study which found that combination therapy with clomiphene citrate and anastrozole was associated with modest benefits on semen parameters, including volume, concentration, and motility after treatment, compared with anastrozole monotherapy. That retrospective cohort analysis of 21 men was published online in Translational Andrology and Urology in February.
“We know that if we treat the right men with these medications, about 40% will improve their fertility, but only if we choose the right population. These studies identified those groups,” Scott Lundy, MD, PhD, section head of male infertility at Cleveland Clinic’s Glickman Urological and Kidney Institute in Cleveland, and director of the clinic’s andrology lab, told Medscape Medical News.
Dr. Lundy, a coauthor of both papers, conceived MOBYUS to overcome constraints in research into male infertility. Many studies in the field are limited by small numbers of patients and retrospective designs, he said. “I sought to develop a collaborative network of reproductive urologists and hospitals like ours, so that we can combine our data and generate large series of data, even for rare patient groups, so that we can improve their patient outcomes,” he said.
“Our treatments are in the stone age in many ways. We are far behind other types of treatment for other conditions, including female infertility,” Dr. Lundy added. “And so, our goal is to identify new and data-driven ways to help these men become fathers, whether those are medications or surgeries or combinations of treatments.”
Moving the Field Forward
The name of the consortium is a cheeky play on Moby Dick, the most famous sperm whale. MOBYUS investigators conveyed the challenges that patients, doctors, and researchers experience in an article published last December in the Journal of Urology.
They noted that 1 in 6 couples will have difficulty conceiving a child, with male-factor infertility contributing to at least half of such cases. The lead author, Catherine Nam, MD, a principal investigator for MOBYUS at the University of Michigan, in Ann Arbor, said the paper is unusual for a medical journal, as it provides personal accounts of the psychological and emotional aspects of infertility as well as factors that have led to a global decline in sperm counts among men and the financial costs of treatment.
Dr. Nam said infertility is a sensitive topic for couples and families to talk about and there is less conversation about male infertility than female infertility. “I think the only way that we can be able to make headway, both in terms of protocol and policy outcomes, is to really start to raise awareness,” said Dr. Nam, who is doing a fellowship in clinical andrology at Northwestern University, in Chicago.
Dr. Nam said the collaborative environment of MOBYUS has enabled her to learn about different practice patterns across different institutions. “For someone like me just starting off my professional career in male infertility, an opportunity like this is incredibly exciting and makes me very hopeful about the kinds of collaboration and scientific discovery that we’re able to do together as a group,” she said.
Robert E. Brannigan, MD, vice chair of clinical urology at Northwestern University Feinberg School of Medicine, Chicago, said the consortium is drawing on the strength of many individual centers and allowing them to study critical issues in the field. The group’s outstanding clinicians and scientists “are looking to move the field forward, and I applaud them and I’m eager to watch things unfold,” said Dr. Brannigan, who is not a member of the group.
Dr. Brannigan noted that for a large percentage of patients, clinicians cannot identify the root cause of their impaired reproductive potential. Some people may have a recognizable decline in semen parameters over time without clear lifestyle issues or clear hormonal imbalances or anatomical problems.
“And the question is, what’s causing that? Is there some as yet unrecognized environmental exposure? Is there some underlying genetic issue that’s predisposing to decline in semen parameters over time? We see this, and we don’t have answers,” Dr. Brannigan said.
“This is where I think the potential power of a large group like MOBYUS comes into play,” he added. “When you’ve got large datasets and very granular information about your patients, sometimes that can provide the opportunity for insights that can then answer the question, ‘What is the root cause of my patient’s challenges?’ ”
Dr. Brannigan was part of a previous group, the Andrology Research Consortium, which collected data on patient history and treatment through a standardized questionnaire. The consortium was founded in 2013 by the Society for the Study of Male Reproduction, a specialty section of the American Urological Association, to obtain data on the demographics, clinical characteristics, and fertility histories and therapies of men referred for a male infertility investigation at clinics across North America.
Clinicians analyzed data from the questionnaires, which a team in Toronto collected and stored, in a series of studies, including a comparison of fertility characteristics between men in the United States and Canada. Dr. Brannigan said MOBYUS is poised to produce a large dataset that can address retrospective questions and potentially prospectively collect data to answer prospective questions.
Clinical Implications
Dr. Lundy said between 100 and 200 practicing reproductive urologists across the country regularly communicate with each other. He first raised the idea of creating a consortium with friends and colleagues and then discussed it at scientific meetings. The network steadily gained traction and is continuing to add institutions. “There’s a great deal of excitement in our community about this,” Dr. Lundy said.
MOBYUS, which is IRB approved, has a database with data from more than 4000 patients. The consortium has not received any industry funding but plans to pursue grant applications in the future.
The MOBYUS website includes a list of its member institutions and leading investigators and its three proof-of-principle manuscripts published to date. The team identifies new research projects at monthly virtual meetings.
Dr. Lundy said MOBYUS’ main goal is to identify a treatment that will change the avenue available for a couple to get pregnant. For example, he said, if a man has zero sperm in his semen, he often requires surgery to find and remove sperm from the testicle. If medications can produce low sperm counts, sperm found in the ejaculate can be frozen and surgery can be avoided.
Dr. Lundy said MOBYUS’ two publications on medical therapies have changed clinical practice, as he and many others have begun to provide the treatments on more carefully selected patients with good outcomes.
Dr. Nam said patients want to know what they can expect from therapies and these research findings will have “a lot of clinical implications” in counseling them.
The MOBYUS team will be describing the consortium and its goals in an abstract presentation at the American Society for Reproductive Medicine Scientific Congress & Expo, to be held October 19-23 in Denver, Colorado, and in an oral presentation at the Sexual Medicine Society of North America’s annual fall scientific meeting, to be held October 17-20 in Scottsdale, Arizona.
The sources in this story reported no relevant financial conflicts of interest.
A version of this article first appeared on Medscape.com.
A study by researchers at two academic medical centers determined which infertile men may benefit from treatment with anastrozole. They found that those with azoospermia (no sperm in their ejaculate) rarely respond to the drug while those with baseline nonazoospermia, lower levels of luteinizing hormone and follicle-stimulating hormone, and higher levels of testosterone are more likely to obtain improvement in semen parameters.
The retrospective cohort study of 90 infertile men, published in the October 2023 issue of Fertility and Sterility, was conducted by researchers at Cleveland Clinic and the University of California Los Angeles. It is the first project of Male Organ Biology Yielding United Science (MOBYUS), a new, multi-institutional research consortium seeking to better understand male infertility and expand treatment options.
Launched last year, MOBYUS now includes investigators from 14 large US-based academic medical centers. They select research topics and search their patient population for eligible participants and share resulting deidentified data for analysis and publication.
Members of the consortium conducted another study which found that combination therapy with clomiphene citrate and anastrozole was associated with modest benefits on semen parameters, including volume, concentration, and motility after treatment, compared with anastrozole monotherapy. That retrospective cohort analysis of 21 men was published online in Translational Andrology and Urology in February.
“We know that if we treat the right men with these medications, about 40% will improve their fertility, but only if we choose the right population. These studies identified those groups,” Scott Lundy, MD, PhD, section head of male infertility at Cleveland Clinic’s Glickman Urological and Kidney Institute in Cleveland, and director of the clinic’s andrology lab, told Medscape Medical News.
Dr. Lundy, a coauthor of both papers, conceived MOBYUS to overcome constraints in research into male infertility. Many studies in the field are limited by small numbers of patients and retrospective designs, he said. “I sought to develop a collaborative network of reproductive urologists and hospitals like ours, so that we can combine our data and generate large series of data, even for rare patient groups, so that we can improve their patient outcomes,” he said.
“Our treatments are in the stone age in many ways. We are far behind other types of treatment for other conditions, including female infertility,” Dr. Lundy added. “And so, our goal is to identify new and data-driven ways to help these men become fathers, whether those are medications or surgeries or combinations of treatments.”
Moving the Field Forward
The name of the consortium is a cheeky play on Moby Dick, the most famous sperm whale. MOBYUS investigators conveyed the challenges that patients, doctors, and researchers experience in an article published last December in the Journal of Urology.
They noted that 1 in 6 couples will have difficulty conceiving a child, with male-factor infertility contributing to at least half of such cases. The lead author, Catherine Nam, MD, a principal investigator for MOBYUS at the University of Michigan, in Ann Arbor, said the paper is unusual for a medical journal, as it provides personal accounts of the psychological and emotional aspects of infertility as well as factors that have led to a global decline in sperm counts among men and the financial costs of treatment.
Dr. Nam said infertility is a sensitive topic for couples and families to talk about and there is less conversation about male infertility than female infertility. “I think the only way that we can be able to make headway, both in terms of protocol and policy outcomes, is to really start to raise awareness,” said Dr. Nam, who is doing a fellowship in clinical andrology at Northwestern University, in Chicago.
Dr. Nam said the collaborative environment of MOBYUS has enabled her to learn about different practice patterns across different institutions. “For someone like me just starting off my professional career in male infertility, an opportunity like this is incredibly exciting and makes me very hopeful about the kinds of collaboration and scientific discovery that we’re able to do together as a group,” she said.
Robert E. Brannigan, MD, vice chair of clinical urology at Northwestern University Feinberg School of Medicine, Chicago, said the consortium is drawing on the strength of many individual centers and allowing them to study critical issues in the field. The group’s outstanding clinicians and scientists “are looking to move the field forward, and I applaud them and I’m eager to watch things unfold,” said Dr. Brannigan, who is not a member of the group.
Dr. Brannigan noted that for a large percentage of patients, clinicians cannot identify the root cause of their impaired reproductive potential. Some people may have a recognizable decline in semen parameters over time without clear lifestyle issues or clear hormonal imbalances or anatomical problems.
“And the question is, what’s causing that? Is there some as yet unrecognized environmental exposure? Is there some underlying genetic issue that’s predisposing to decline in semen parameters over time? We see this, and we don’t have answers,” Dr. Brannigan said.
“This is where I think the potential power of a large group like MOBYUS comes into play,” he added. “When you’ve got large datasets and very granular information about your patients, sometimes that can provide the opportunity for insights that can then answer the question, ‘What is the root cause of my patient’s challenges?’ ”
Dr. Brannigan was part of a previous group, the Andrology Research Consortium, which collected data on patient history and treatment through a standardized questionnaire. The consortium was founded in 2013 by the Society for the Study of Male Reproduction, a specialty section of the American Urological Association, to obtain data on the demographics, clinical characteristics, and fertility histories and therapies of men referred for a male infertility investigation at clinics across North America.
Clinicians analyzed data from the questionnaires, which a team in Toronto collected and stored, in a series of studies, including a comparison of fertility characteristics between men in the United States and Canada. Dr. Brannigan said MOBYUS is poised to produce a large dataset that can address retrospective questions and potentially prospectively collect data to answer prospective questions.
Clinical Implications
Dr. Lundy said between 100 and 200 practicing reproductive urologists across the country regularly communicate with each other. He first raised the idea of creating a consortium with friends and colleagues and then discussed it at scientific meetings. The network steadily gained traction and is continuing to add institutions. “There’s a great deal of excitement in our community about this,” Dr. Lundy said.
MOBYUS, which is IRB approved, has a database with data from more than 4000 patients. The consortium has not received any industry funding but plans to pursue grant applications in the future.
The MOBYUS website includes a list of its member institutions and leading investigators and its three proof-of-principle manuscripts published to date. The team identifies new research projects at monthly virtual meetings.
Dr. Lundy said MOBYUS’ main goal is to identify a treatment that will change the avenue available for a couple to get pregnant. For example, he said, if a man has zero sperm in his semen, he often requires surgery to find and remove sperm from the testicle. If medications can produce low sperm counts, sperm found in the ejaculate can be frozen and surgery can be avoided.
Dr. Lundy said MOBYUS’ two publications on medical therapies have changed clinical practice, as he and many others have begun to provide the treatments on more carefully selected patients with good outcomes.
Dr. Nam said patients want to know what they can expect from therapies and these research findings will have “a lot of clinical implications” in counseling them.
The MOBYUS team will be describing the consortium and its goals in an abstract presentation at the American Society for Reproductive Medicine Scientific Congress & Expo, to be held October 19-23 in Denver, Colorado, and in an oral presentation at the Sexual Medicine Society of North America’s annual fall scientific meeting, to be held October 17-20 in Scottsdale, Arizona.
The sources in this story reported no relevant financial conflicts of interest.
A version of this article first appeared on Medscape.com.
A study by researchers at two academic medical centers determined which infertile men may benefit from treatment with anastrozole. They found that those with azoospermia (no sperm in their ejaculate) rarely respond to the drug while those with baseline nonazoospermia, lower levels of luteinizing hormone and follicle-stimulating hormone, and higher levels of testosterone are more likely to obtain improvement in semen parameters.
The retrospective cohort study of 90 infertile men, published in the October 2023 issue of Fertility and Sterility, was conducted by researchers at Cleveland Clinic and the University of California Los Angeles. It is the first project of Male Organ Biology Yielding United Science (MOBYUS), a new, multi-institutional research consortium seeking to better understand male infertility and expand treatment options.
Launched last year, MOBYUS now includes investigators from 14 large US-based academic medical centers. They select research topics and search their patient population for eligible participants and share resulting deidentified data for analysis and publication.
Members of the consortium conducted another study which found that combination therapy with clomiphene citrate and anastrozole was associated with modest benefits on semen parameters, including volume, concentration, and motility after treatment, compared with anastrozole monotherapy. That retrospective cohort analysis of 21 men was published online in Translational Andrology and Urology in February.
“We know that if we treat the right men with these medications, about 40% will improve their fertility, but only if we choose the right population. These studies identified those groups,” Scott Lundy, MD, PhD, section head of male infertility at Cleveland Clinic’s Glickman Urological and Kidney Institute in Cleveland, and director of the clinic’s andrology lab, told Medscape Medical News.
Dr. Lundy, a coauthor of both papers, conceived MOBYUS to overcome constraints in research into male infertility. Many studies in the field are limited by small numbers of patients and retrospective designs, he said. “I sought to develop a collaborative network of reproductive urologists and hospitals like ours, so that we can combine our data and generate large series of data, even for rare patient groups, so that we can improve their patient outcomes,” he said.
“Our treatments are in the stone age in many ways. We are far behind other types of treatment for other conditions, including female infertility,” Dr. Lundy added. “And so, our goal is to identify new and data-driven ways to help these men become fathers, whether those are medications or surgeries or combinations of treatments.”
Moving the Field Forward
The name of the consortium is a cheeky play on Moby Dick, the most famous sperm whale. MOBYUS investigators conveyed the challenges that patients, doctors, and researchers experience in an article published last December in the Journal of Urology.
They noted that 1 in 6 couples will have difficulty conceiving a child, with male-factor infertility contributing to at least half of such cases. The lead author, Catherine Nam, MD, a principal investigator for MOBYUS at the University of Michigan, in Ann Arbor, said the paper is unusual for a medical journal, as it provides personal accounts of the psychological and emotional aspects of infertility as well as factors that have led to a global decline in sperm counts among men and the financial costs of treatment.
Dr. Nam said infertility is a sensitive topic for couples and families to talk about and there is less conversation about male infertility than female infertility. “I think the only way that we can be able to make headway, both in terms of protocol and policy outcomes, is to really start to raise awareness,” said Dr. Nam, who is doing a fellowship in clinical andrology at Northwestern University, in Chicago.
Dr. Nam said the collaborative environment of MOBYUS has enabled her to learn about different practice patterns across different institutions. “For someone like me just starting off my professional career in male infertility, an opportunity like this is incredibly exciting and makes me very hopeful about the kinds of collaboration and scientific discovery that we’re able to do together as a group,” she said.
Robert E. Brannigan, MD, vice chair of clinical urology at Northwestern University Feinberg School of Medicine, Chicago, said the consortium is drawing on the strength of many individual centers and allowing them to study critical issues in the field. The group’s outstanding clinicians and scientists “are looking to move the field forward, and I applaud them and I’m eager to watch things unfold,” said Dr. Brannigan, who is not a member of the group.
Dr. Brannigan noted that for a large percentage of patients, clinicians cannot identify the root cause of their impaired reproductive potential. Some people may have a recognizable decline in semen parameters over time without clear lifestyle issues or clear hormonal imbalances or anatomical problems.
“And the question is, what’s causing that? Is there some as yet unrecognized environmental exposure? Is there some underlying genetic issue that’s predisposing to decline in semen parameters over time? We see this, and we don’t have answers,” Dr. Brannigan said.
“This is where I think the potential power of a large group like MOBYUS comes into play,” he added. “When you’ve got large datasets and very granular information about your patients, sometimes that can provide the opportunity for insights that can then answer the question, ‘What is the root cause of my patient’s challenges?’ ”
Dr. Brannigan was part of a previous group, the Andrology Research Consortium, which collected data on patient history and treatment through a standardized questionnaire. The consortium was founded in 2013 by the Society for the Study of Male Reproduction, a specialty section of the American Urological Association, to obtain data on the demographics, clinical characteristics, and fertility histories and therapies of men referred for a male infertility investigation at clinics across North America.
Clinicians analyzed data from the questionnaires, which a team in Toronto collected and stored, in a series of studies, including a comparison of fertility characteristics between men in the United States and Canada. Dr. Brannigan said MOBYUS is poised to produce a large dataset that can address retrospective questions and potentially prospectively collect data to answer prospective questions.
Clinical Implications
Dr. Lundy said between 100 and 200 practicing reproductive urologists across the country regularly communicate with each other. He first raised the idea of creating a consortium with friends and colleagues and then discussed it at scientific meetings. The network steadily gained traction and is continuing to add institutions. “There’s a great deal of excitement in our community about this,” Dr. Lundy said.
MOBYUS, which is IRB approved, has a database with data from more than 4000 patients. The consortium has not received any industry funding but plans to pursue grant applications in the future.
The MOBYUS website includes a list of its member institutions and leading investigators and its three proof-of-principle manuscripts published to date. The team identifies new research projects at monthly virtual meetings.
Dr. Lundy said MOBYUS’ main goal is to identify a treatment that will change the avenue available for a couple to get pregnant. For example, he said, if a man has zero sperm in his semen, he often requires surgery to find and remove sperm from the testicle. If medications can produce low sperm counts, sperm found in the ejaculate can be frozen and surgery can be avoided.
Dr. Lundy said MOBYUS’ two publications on medical therapies have changed clinical practice, as he and many others have begun to provide the treatments on more carefully selected patients with good outcomes.
Dr. Nam said patients want to know what they can expect from therapies and these research findings will have “a lot of clinical implications” in counseling them.
The MOBYUS team will be describing the consortium and its goals in an abstract presentation at the American Society for Reproductive Medicine Scientific Congress & Expo, to be held October 19-23 in Denver, Colorado, and in an oral presentation at the Sexual Medicine Society of North America’s annual fall scientific meeting, to be held October 17-20 in Scottsdale, Arizona.
The sources in this story reported no relevant financial conflicts of interest.
A version of this article first appeared on Medscape.com.
Undertreatment of Women With MS Unjustified
COPENHAGEN — , even after accounting for treatment discontinuations during pregnancy and the postpartum period, new research suggested.
“We believe that pregnancy-related considerations probably still explain the major part of this gap,” said Antoine Gavoille, MD, University of Lyon, France, who presented the study at the 2024 ECTRIMS annual meeting.
This is likely due to “factors such as anticipation of pregnancy long before it occurs and fear of exposing women of childbearing age to certain treatments even in the absence of planned pregnancy,” he added.
Caution is warranted when medications are first marketed because there are no data on safety in pregnancy. However, in 2024, “this lesser treatment in women is unacceptable,” said Dr. Gavoille. “We now have several highly effective treatment options which are compatible with pregnancy,” he noted.
The researchers analyzed the French MS registry of 22,657 patients with relapsing MS (74.2% women) between 1997 and 2022 for treatment differences between women and their male counterparts. The results were adjusted for multiple factors including educational level, disease activity, disability levels, and discontinuation of drugs during pregnancy.
They found that over a median follow-up of 11.6 years, women had a significantly lower probability of receiving any disease-modifying treatment (odds ratio [OR], 0.92; 95% CI, 0.87-0.97).
In addition, women were even less likely to receive high-efficacy treatments such as natalizumab, anti-CD20 antibodies, or S1P modulators such as fingolimod (OR, 0.80; 95% CI, 0.74-0.86).
The difference in disease-modifying treatment usage varied across different treatments and over time. Teriflunomide, fingolimod, and anti-CD20 therapies were significantly underused throughout their entire availability (OR, 0.87, 0.78, and 0.80, respectively).
Interferon and natalizumab were initially used less frequently in women, but the use of these medications equalized over time.
In contrast, glatiramer acetate and dimethyl fumarate were initially used equally between genders but eventually became more commonly prescribed to women (OR, 1.27 and 1.17, respectively).
The disparity in treatment emerged after 2 years of disease duration for disease-modifying treatments in general and as early as 1 year for highly effective treatments.
The gender-based treatment gap did not significantly vary with patient age, indicating that therapeutic inertia may persist regardless of a woman’s age.
“Women may not be receiving the most effective therapies at the optimal time, often due to concerns about pregnancy risks that may never materialize,” said the study’s lead investigator Sandra Vukusic, MD, Lyon University Hospital, France.
“The main impact of this therapeutic inertia in women is the less effective control of disease activity, leading to the accumulation of lesions and an increased risk of long-term disability. This represents a real loss of opportunity for women, especially in an era where disease-modifying treatments so effective when used early,” she added.
Dr. Gavoille said that recommendations in France allow the use of moderately active drugs, including interferon and glatiramer acetate, during pregnancy or in women planning a pregnancy. More recently there has been enough data to allow the use of natalizumab up until the second trimester.
In addition, although not in the guidelines, it is thought that the anti-CD20 monoclonal antibodies, such as rituximab or ocrelizumab, may be safe as they are very long acting. Women can be dosed before pregnancy and be covered for the whole pregnancy period without exposing the fetus to the drug, he explained.
“The message is that now we have both moderately and highly effective treatments that are compatible with a pregnancy plan,” Dr. Gavoille said.
First, clinicians have to select a level of treatment based on disease activity and then choose the best option, depending on the woman’s plans with respect to pregnancy.
Drugs that are contraindicated in pregnancy include teriflunomide and S1P modulators such as fingolimod, which have been shown to be harmful to the fetus.
“But they could still be used in women of childbearing years as long as they are not planning a pregnancy and understand the need for contraception,” Dr. Gavoille noted.
He believes both neurologists and patients are afraid of using drugs in pregnancy. “It is, of course, important to be cautious on this issue, but we should not let fear stop these women receiving the best treatments available.”
However, he added, clinical practice is changing, and confidence is gradually building around using highly effective treatments in women of childbearing age.
Dr. Gavoille also called for more research to collate data in pregnant women with MS who are exposed to various treatments, starting with case reports and then academic registries, which he described as “difficult but important work.”
Commenting on the study, Robert Hoepner, MD, University Hospital of Bern, Switzerland, agreed that this treatment disparity between men and women is “unacceptable.”
Dr. Hoepner noted that a recent study showed that women have different relapse symptoms than men, which may also affect treatment choice.
Dr. Gavoille responded that other research has shown that women are less likely to have treatment escalation post-relapse. “This could be because of a difference in symptoms. But this is something we haven’t looked at yet.”
Also commenting on the research, Frauke Zipp, MD, University Medical Center Mainz in Germany, said it would be interesting to follow this cohort over the long term to see if the women do less well several years down the line.
The study authors and commentators reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
COPENHAGEN — , even after accounting for treatment discontinuations during pregnancy and the postpartum period, new research suggested.
“We believe that pregnancy-related considerations probably still explain the major part of this gap,” said Antoine Gavoille, MD, University of Lyon, France, who presented the study at the 2024 ECTRIMS annual meeting.
This is likely due to “factors such as anticipation of pregnancy long before it occurs and fear of exposing women of childbearing age to certain treatments even in the absence of planned pregnancy,” he added.
Caution is warranted when medications are first marketed because there are no data on safety in pregnancy. However, in 2024, “this lesser treatment in women is unacceptable,” said Dr. Gavoille. “We now have several highly effective treatment options which are compatible with pregnancy,” he noted.
The researchers analyzed the French MS registry of 22,657 patients with relapsing MS (74.2% women) between 1997 and 2022 for treatment differences between women and their male counterparts. The results were adjusted for multiple factors including educational level, disease activity, disability levels, and discontinuation of drugs during pregnancy.
They found that over a median follow-up of 11.6 years, women had a significantly lower probability of receiving any disease-modifying treatment (odds ratio [OR], 0.92; 95% CI, 0.87-0.97).
In addition, women were even less likely to receive high-efficacy treatments such as natalizumab, anti-CD20 antibodies, or S1P modulators such as fingolimod (OR, 0.80; 95% CI, 0.74-0.86).
The difference in disease-modifying treatment usage varied across different treatments and over time. Teriflunomide, fingolimod, and anti-CD20 therapies were significantly underused throughout their entire availability (OR, 0.87, 0.78, and 0.80, respectively).
Interferon and natalizumab were initially used less frequently in women, but the use of these medications equalized over time.
In contrast, glatiramer acetate and dimethyl fumarate were initially used equally between genders but eventually became more commonly prescribed to women (OR, 1.27 and 1.17, respectively).
The disparity in treatment emerged after 2 years of disease duration for disease-modifying treatments in general and as early as 1 year for highly effective treatments.
The gender-based treatment gap did not significantly vary with patient age, indicating that therapeutic inertia may persist regardless of a woman’s age.
“Women may not be receiving the most effective therapies at the optimal time, often due to concerns about pregnancy risks that may never materialize,” said the study’s lead investigator Sandra Vukusic, MD, Lyon University Hospital, France.
“The main impact of this therapeutic inertia in women is the less effective control of disease activity, leading to the accumulation of lesions and an increased risk of long-term disability. This represents a real loss of opportunity for women, especially in an era where disease-modifying treatments so effective when used early,” she added.
Dr. Gavoille said that recommendations in France allow the use of moderately active drugs, including interferon and glatiramer acetate, during pregnancy or in women planning a pregnancy. More recently there has been enough data to allow the use of natalizumab up until the second trimester.
In addition, although not in the guidelines, it is thought that the anti-CD20 monoclonal antibodies, such as rituximab or ocrelizumab, may be safe as they are very long acting. Women can be dosed before pregnancy and be covered for the whole pregnancy period without exposing the fetus to the drug, he explained.
“The message is that now we have both moderately and highly effective treatments that are compatible with a pregnancy plan,” Dr. Gavoille said.
First, clinicians have to select a level of treatment based on disease activity and then choose the best option, depending on the woman’s plans with respect to pregnancy.
Drugs that are contraindicated in pregnancy include teriflunomide and S1P modulators such as fingolimod, which have been shown to be harmful to the fetus.
“But they could still be used in women of childbearing years as long as they are not planning a pregnancy and understand the need for contraception,” Dr. Gavoille noted.
He believes both neurologists and patients are afraid of using drugs in pregnancy. “It is, of course, important to be cautious on this issue, but we should not let fear stop these women receiving the best treatments available.”
However, he added, clinical practice is changing, and confidence is gradually building around using highly effective treatments in women of childbearing age.
Dr. Gavoille also called for more research to collate data in pregnant women with MS who are exposed to various treatments, starting with case reports and then academic registries, which he described as “difficult but important work.”
Commenting on the study, Robert Hoepner, MD, University Hospital of Bern, Switzerland, agreed that this treatment disparity between men and women is “unacceptable.”
Dr. Hoepner noted that a recent study showed that women have different relapse symptoms than men, which may also affect treatment choice.
Dr. Gavoille responded that other research has shown that women are less likely to have treatment escalation post-relapse. “This could be because of a difference in symptoms. But this is something we haven’t looked at yet.”
Also commenting on the research, Frauke Zipp, MD, University Medical Center Mainz in Germany, said it would be interesting to follow this cohort over the long term to see if the women do less well several years down the line.
The study authors and commentators reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
COPENHAGEN — , even after accounting for treatment discontinuations during pregnancy and the postpartum period, new research suggested.
“We believe that pregnancy-related considerations probably still explain the major part of this gap,” said Antoine Gavoille, MD, University of Lyon, France, who presented the study at the 2024 ECTRIMS annual meeting.
This is likely due to “factors such as anticipation of pregnancy long before it occurs and fear of exposing women of childbearing age to certain treatments even in the absence of planned pregnancy,” he added.
Caution is warranted when medications are first marketed because there are no data on safety in pregnancy. However, in 2024, “this lesser treatment in women is unacceptable,” said Dr. Gavoille. “We now have several highly effective treatment options which are compatible with pregnancy,” he noted.
The researchers analyzed the French MS registry of 22,657 patients with relapsing MS (74.2% women) between 1997 and 2022 for treatment differences between women and their male counterparts. The results were adjusted for multiple factors including educational level, disease activity, disability levels, and discontinuation of drugs during pregnancy.
They found that over a median follow-up of 11.6 years, women had a significantly lower probability of receiving any disease-modifying treatment (odds ratio [OR], 0.92; 95% CI, 0.87-0.97).
In addition, women were even less likely to receive high-efficacy treatments such as natalizumab, anti-CD20 antibodies, or S1P modulators such as fingolimod (OR, 0.80; 95% CI, 0.74-0.86).
The difference in disease-modifying treatment usage varied across different treatments and over time. Teriflunomide, fingolimod, and anti-CD20 therapies were significantly underused throughout their entire availability (OR, 0.87, 0.78, and 0.80, respectively).
Interferon and natalizumab were initially used less frequently in women, but the use of these medications equalized over time.
In contrast, glatiramer acetate and dimethyl fumarate were initially used equally between genders but eventually became more commonly prescribed to women (OR, 1.27 and 1.17, respectively).
The disparity in treatment emerged after 2 years of disease duration for disease-modifying treatments in general and as early as 1 year for highly effective treatments.
The gender-based treatment gap did not significantly vary with patient age, indicating that therapeutic inertia may persist regardless of a woman’s age.
“Women may not be receiving the most effective therapies at the optimal time, often due to concerns about pregnancy risks that may never materialize,” said the study’s lead investigator Sandra Vukusic, MD, Lyon University Hospital, France.
“The main impact of this therapeutic inertia in women is the less effective control of disease activity, leading to the accumulation of lesions and an increased risk of long-term disability. This represents a real loss of opportunity for women, especially in an era where disease-modifying treatments so effective when used early,” she added.
Dr. Gavoille said that recommendations in France allow the use of moderately active drugs, including interferon and glatiramer acetate, during pregnancy or in women planning a pregnancy. More recently there has been enough data to allow the use of natalizumab up until the second trimester.
In addition, although not in the guidelines, it is thought that the anti-CD20 monoclonal antibodies, such as rituximab or ocrelizumab, may be safe as they are very long acting. Women can be dosed before pregnancy and be covered for the whole pregnancy period without exposing the fetus to the drug, he explained.
“The message is that now we have both moderately and highly effective treatments that are compatible with a pregnancy plan,” Dr. Gavoille said.
First, clinicians have to select a level of treatment based on disease activity and then choose the best option, depending on the woman’s plans with respect to pregnancy.
Drugs that are contraindicated in pregnancy include teriflunomide and S1P modulators such as fingolimod, which have been shown to be harmful to the fetus.
“But they could still be used in women of childbearing years as long as they are not planning a pregnancy and understand the need for contraception,” Dr. Gavoille noted.
He believes both neurologists and patients are afraid of using drugs in pregnancy. “It is, of course, important to be cautious on this issue, but we should not let fear stop these women receiving the best treatments available.”
However, he added, clinical practice is changing, and confidence is gradually building around using highly effective treatments in women of childbearing age.
Dr. Gavoille also called for more research to collate data in pregnant women with MS who are exposed to various treatments, starting with case reports and then academic registries, which he described as “difficult but important work.”
Commenting on the study, Robert Hoepner, MD, University Hospital of Bern, Switzerland, agreed that this treatment disparity between men and women is “unacceptable.”
Dr. Hoepner noted that a recent study showed that women have different relapse symptoms than men, which may also affect treatment choice.
Dr. Gavoille responded that other research has shown that women are less likely to have treatment escalation post-relapse. “This could be because of a difference in symptoms. But this is something we haven’t looked at yet.”
Also commenting on the research, Frauke Zipp, MD, University Medical Center Mainz in Germany, said it would be interesting to follow this cohort over the long term to see if the women do less well several years down the line.
The study authors and commentators reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM ECTRIMS 2024
Antidepressants Linked to Improved Verbal Memory
MILAN — , a clinical effect linked to changes in serotonin 4 (5-HT4) receptor levels in the brain, as shown on PET.
These findings suggested there is a role for specifically targeting the 5-HT4 receptor to improve verbal memory in depression, said investigator Vibeke H. Dam, PhD, from Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
“Verbal memory is often impaired in depression, and this has a lot of impact on patients’ ability to work and have a normal life. That’s why we’re so excited about this receptor in particular,” Dr. Dam said.
“If we can find a way to activate it more directly, we’re thinking this could be a way to treat this memory symptom that a lot of patients have and that currently we don’t really have a treatment for,” she added.
The findings were presented at the 37th European College of Neuropsychopharmacology (ECNP) Congress and recently published in Biological Psychiatry .
Largest Trial of Its Kind
The study is the largest single-site PET trial investigating serotonergic neurotransmission in major depressive disorder over the course of antidepressant treatment to date. It included 90 patients with moderate to severe depression who underwent baseline cognitive tests and brain scans to measure 5-HT4 receptor levels before starting their treatment with the selective serotonin reuptake inhibitor escitalopram.
Patients who showed no improvement in depressive symptoms after 4 weeks (n = 14), as assessed by the Hamilton Depression Rating Scale 6 (HAMD6), were switched to the serotonin-norepinephrine reuptake inhibitor duloxetine.
Both escitalopram and duloxetine inhibit the reuptake of 5-HT4, enhancing neurotransmitter activity; escitalopram primarily increases serotonin levels, while duloxetine increases both serotonin and norepinephrine levels.
The primary cognitive outcome measure was change in the Verbal Affective Memory Task 26. Secondary cognitive outcomes were change in working memory, reaction time, emotion recognition bias, and negative social emotion.
After 8 weeks of treatment, a subset of 40 patients repeated PET scans, and at 12 weeks, all patients repeated cognitive testing.
Matching neuroimaging and cognitive data were available for 88 patients at baseline and for 39 patients with rescan.
As expected, the study showed that antidepressant treatment resulted in the downregulation of 5-HT4 receptor levels. “One hypothesis is that if we increase the availability of serotonin [with treatment], downregulation of the receptors might be a response,” said Dr. Dam.
“What was interesting was that this was the effect across all patients, whether they [clinically] responded or not. So we see the medication does what it’s supposed to do in the brain.” But, she said, there was no association between 5-HT4 receptor levels and HAMD6 scores.
Gains in Verbal Memory
Although the downregulation of 5-HT4 did not correlate with somatic or mood symptoms, it did correlate with cognitive symptoms.
Interestingly, while most patients showed improvement in depressive symptoms — many reaching remission or recovery — they also experienced gains in verbal memory. However, these improvements were not correlated. It was possible for one to improve more than the other, with no apparent link between the two, said Dr. Dam.
“What was linked was how the brain responded to the medication for this particular receptor. So even though there is this downregulation of the receptor, there’s still a lot of activation of it, and our thinking is that it’s activation of the receptor that is the important bit.”
Work by other groups has shown that another medication, prucalopride, which is used to treat gastroparesis, can more directly activate the 5-HT4 receptor, and that the treatment of healthy volunteers with this medication can boost memory and learning, said Dr. Dam.
“We could repurpose this drug, and we’re currently looking for funding to test this in a wide variety of different groups such as concussion, diabetes, and depression.”
The study’s coinvestigator, Vibe G. Frokjaer, MD, said more research is required to understand the potential implications of the findings.
“Poor cognitive function is very hard to treat efficiently and may require extra treatment. This work points to the possibility of stimulating this specific receptor so that we can treat cognitive problems, even aside from whether or not the patient has overcome the core symptoms of depression,” she said in a release.
Commenting on the research, Philip Cowen, MD, professor of psychopharmacology at the University of Oxford, England, said in a release that in light of “recent controversies about the role of brain serotonin in clinical depression, it is noteworthy that the PET studies of the Copenhagen Group provide unequivocal evidence that brain 5-HT4 receptors are decreased in unmedicated depressed patients.
“Their work also demonstrates the intimate role of brain 5-HT4 receptors in cognitive function,” he added. “This confirms recent work from Oxford, showing that the 5-HT4 receptor stimulant, prucalopride — a drug licensed for the treatment of constipation — improves memory in both healthy participants and people at risk of depression,” he added.
The study was funded by the Innovation Fund Denmark, Research Fund of the Mental Health Services – Capital Region of Denmark, Independent Research Fund Denmark, Global Justice Foundation, Research Council of Rigshospitalet, Augustinus Foundation, Savværksejer Jeppe Juhl og hustru Ovita Juhls Mindelegat, Lundbeck Foundation, and H. Lundbeck A/S.
Dr. Dam reported serving as a speaker for H. Lundbeck. Frokjaer reported serving as a consultant for Sage Therapeutics and lecturer for H. Lundbeck, Janssen-Cilag, and Gedeon Richter. Study investigator Martin B. Jørgensen has given talks sponsored by Boehringer Ingelheim and Lundbeck Pharma. All other investigators reported no relevant disclosures.
A version of this article appeared on Medscape.com.
MILAN — , a clinical effect linked to changes in serotonin 4 (5-HT4) receptor levels in the brain, as shown on PET.
These findings suggested there is a role for specifically targeting the 5-HT4 receptor to improve verbal memory in depression, said investigator Vibeke H. Dam, PhD, from Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
“Verbal memory is often impaired in depression, and this has a lot of impact on patients’ ability to work and have a normal life. That’s why we’re so excited about this receptor in particular,” Dr. Dam said.
“If we can find a way to activate it more directly, we’re thinking this could be a way to treat this memory symptom that a lot of patients have and that currently we don’t really have a treatment for,” she added.
The findings were presented at the 37th European College of Neuropsychopharmacology (ECNP) Congress and recently published in Biological Psychiatry .
Largest Trial of Its Kind
The study is the largest single-site PET trial investigating serotonergic neurotransmission in major depressive disorder over the course of antidepressant treatment to date. It included 90 patients with moderate to severe depression who underwent baseline cognitive tests and brain scans to measure 5-HT4 receptor levels before starting their treatment with the selective serotonin reuptake inhibitor escitalopram.
Patients who showed no improvement in depressive symptoms after 4 weeks (n = 14), as assessed by the Hamilton Depression Rating Scale 6 (HAMD6), were switched to the serotonin-norepinephrine reuptake inhibitor duloxetine.
Both escitalopram and duloxetine inhibit the reuptake of 5-HT4, enhancing neurotransmitter activity; escitalopram primarily increases serotonin levels, while duloxetine increases both serotonin and norepinephrine levels.
The primary cognitive outcome measure was change in the Verbal Affective Memory Task 26. Secondary cognitive outcomes were change in working memory, reaction time, emotion recognition bias, and negative social emotion.
After 8 weeks of treatment, a subset of 40 patients repeated PET scans, and at 12 weeks, all patients repeated cognitive testing.
Matching neuroimaging and cognitive data were available for 88 patients at baseline and for 39 patients with rescan.
As expected, the study showed that antidepressant treatment resulted in the downregulation of 5-HT4 receptor levels. “One hypothesis is that if we increase the availability of serotonin [with treatment], downregulation of the receptors might be a response,” said Dr. Dam.
“What was interesting was that this was the effect across all patients, whether they [clinically] responded or not. So we see the medication does what it’s supposed to do in the brain.” But, she said, there was no association between 5-HT4 receptor levels and HAMD6 scores.
Gains in Verbal Memory
Although the downregulation of 5-HT4 did not correlate with somatic or mood symptoms, it did correlate with cognitive symptoms.
Interestingly, while most patients showed improvement in depressive symptoms — many reaching remission or recovery — they also experienced gains in verbal memory. However, these improvements were not correlated. It was possible for one to improve more than the other, with no apparent link between the two, said Dr. Dam.
“What was linked was how the brain responded to the medication for this particular receptor. So even though there is this downregulation of the receptor, there’s still a lot of activation of it, and our thinking is that it’s activation of the receptor that is the important bit.”
Work by other groups has shown that another medication, prucalopride, which is used to treat gastroparesis, can more directly activate the 5-HT4 receptor, and that the treatment of healthy volunteers with this medication can boost memory and learning, said Dr. Dam.
“We could repurpose this drug, and we’re currently looking for funding to test this in a wide variety of different groups such as concussion, diabetes, and depression.”
The study’s coinvestigator, Vibe G. Frokjaer, MD, said more research is required to understand the potential implications of the findings.
“Poor cognitive function is very hard to treat efficiently and may require extra treatment. This work points to the possibility of stimulating this specific receptor so that we can treat cognitive problems, even aside from whether or not the patient has overcome the core symptoms of depression,” she said in a release.
Commenting on the research, Philip Cowen, MD, professor of psychopharmacology at the University of Oxford, England, said in a release that in light of “recent controversies about the role of brain serotonin in clinical depression, it is noteworthy that the PET studies of the Copenhagen Group provide unequivocal evidence that brain 5-HT4 receptors are decreased in unmedicated depressed patients.
“Their work also demonstrates the intimate role of brain 5-HT4 receptors in cognitive function,” he added. “This confirms recent work from Oxford, showing that the 5-HT4 receptor stimulant, prucalopride — a drug licensed for the treatment of constipation — improves memory in both healthy participants and people at risk of depression,” he added.
The study was funded by the Innovation Fund Denmark, Research Fund of the Mental Health Services – Capital Region of Denmark, Independent Research Fund Denmark, Global Justice Foundation, Research Council of Rigshospitalet, Augustinus Foundation, Savværksejer Jeppe Juhl og hustru Ovita Juhls Mindelegat, Lundbeck Foundation, and H. Lundbeck A/S.
Dr. Dam reported serving as a speaker for H. Lundbeck. Frokjaer reported serving as a consultant for Sage Therapeutics and lecturer for H. Lundbeck, Janssen-Cilag, and Gedeon Richter. Study investigator Martin B. Jørgensen has given talks sponsored by Boehringer Ingelheim and Lundbeck Pharma. All other investigators reported no relevant disclosures.
A version of this article appeared on Medscape.com.
MILAN — , a clinical effect linked to changes in serotonin 4 (5-HT4) receptor levels in the brain, as shown on PET.
These findings suggested there is a role for specifically targeting the 5-HT4 receptor to improve verbal memory in depression, said investigator Vibeke H. Dam, PhD, from Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
“Verbal memory is often impaired in depression, and this has a lot of impact on patients’ ability to work and have a normal life. That’s why we’re so excited about this receptor in particular,” Dr. Dam said.
“If we can find a way to activate it more directly, we’re thinking this could be a way to treat this memory symptom that a lot of patients have and that currently we don’t really have a treatment for,” she added.
The findings were presented at the 37th European College of Neuropsychopharmacology (ECNP) Congress and recently published in Biological Psychiatry .
Largest Trial of Its Kind
The study is the largest single-site PET trial investigating serotonergic neurotransmission in major depressive disorder over the course of antidepressant treatment to date. It included 90 patients with moderate to severe depression who underwent baseline cognitive tests and brain scans to measure 5-HT4 receptor levels before starting their treatment with the selective serotonin reuptake inhibitor escitalopram.
Patients who showed no improvement in depressive symptoms after 4 weeks (n = 14), as assessed by the Hamilton Depression Rating Scale 6 (HAMD6), were switched to the serotonin-norepinephrine reuptake inhibitor duloxetine.
Both escitalopram and duloxetine inhibit the reuptake of 5-HT4, enhancing neurotransmitter activity; escitalopram primarily increases serotonin levels, while duloxetine increases both serotonin and norepinephrine levels.
The primary cognitive outcome measure was change in the Verbal Affective Memory Task 26. Secondary cognitive outcomes were change in working memory, reaction time, emotion recognition bias, and negative social emotion.
After 8 weeks of treatment, a subset of 40 patients repeated PET scans, and at 12 weeks, all patients repeated cognitive testing.
Matching neuroimaging and cognitive data were available for 88 patients at baseline and for 39 patients with rescan.
As expected, the study showed that antidepressant treatment resulted in the downregulation of 5-HT4 receptor levels. “One hypothesis is that if we increase the availability of serotonin [with treatment], downregulation of the receptors might be a response,” said Dr. Dam.
“What was interesting was that this was the effect across all patients, whether they [clinically] responded or not. So we see the medication does what it’s supposed to do in the brain.” But, she said, there was no association between 5-HT4 receptor levels and HAMD6 scores.
Gains in Verbal Memory
Although the downregulation of 5-HT4 did not correlate with somatic or mood symptoms, it did correlate with cognitive symptoms.
Interestingly, while most patients showed improvement in depressive symptoms — many reaching remission or recovery — they also experienced gains in verbal memory. However, these improvements were not correlated. It was possible for one to improve more than the other, with no apparent link between the two, said Dr. Dam.
“What was linked was how the brain responded to the medication for this particular receptor. So even though there is this downregulation of the receptor, there’s still a lot of activation of it, and our thinking is that it’s activation of the receptor that is the important bit.”
Work by other groups has shown that another medication, prucalopride, which is used to treat gastroparesis, can more directly activate the 5-HT4 receptor, and that the treatment of healthy volunteers with this medication can boost memory and learning, said Dr. Dam.
“We could repurpose this drug, and we’re currently looking for funding to test this in a wide variety of different groups such as concussion, diabetes, and depression.”
The study’s coinvestigator, Vibe G. Frokjaer, MD, said more research is required to understand the potential implications of the findings.
“Poor cognitive function is very hard to treat efficiently and may require extra treatment. This work points to the possibility of stimulating this specific receptor so that we can treat cognitive problems, even aside from whether or not the patient has overcome the core symptoms of depression,” she said in a release.
Commenting on the research, Philip Cowen, MD, professor of psychopharmacology at the University of Oxford, England, said in a release that in light of “recent controversies about the role of brain serotonin in clinical depression, it is noteworthy that the PET studies of the Copenhagen Group provide unequivocal evidence that brain 5-HT4 receptors are decreased in unmedicated depressed patients.
“Their work also demonstrates the intimate role of brain 5-HT4 receptors in cognitive function,” he added. “This confirms recent work from Oxford, showing that the 5-HT4 receptor stimulant, prucalopride — a drug licensed for the treatment of constipation — improves memory in both healthy participants and people at risk of depression,” he added.
The study was funded by the Innovation Fund Denmark, Research Fund of the Mental Health Services – Capital Region of Denmark, Independent Research Fund Denmark, Global Justice Foundation, Research Council of Rigshospitalet, Augustinus Foundation, Savværksejer Jeppe Juhl og hustru Ovita Juhls Mindelegat, Lundbeck Foundation, and H. Lundbeck A/S.
Dr. Dam reported serving as a speaker for H. Lundbeck. Frokjaer reported serving as a consultant for Sage Therapeutics and lecturer for H. Lundbeck, Janssen-Cilag, and Gedeon Richter. Study investigator Martin B. Jørgensen has given talks sponsored by Boehringer Ingelheim and Lundbeck Pharma. All other investigators reported no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM ECNP 2024
Heightened Amygdala Activity Tied to Postpartum Depression
MILAN, ITALY — Pregnant women with heightened amygdala activity have a reduced capacity to regulate emotions and report more symptoms of depression than those with lower activity in this brain region, a new imaging study suggested.
If validated, these findings could pave the way for identifying women at higher risk for postpartum depression, said lead researcher Franziska Weinmar, MSc, from the University of Tübingen in Germany.
The study was presented at the 37th European College of Neuropsychopharmacology Congress.
Differences in Brain Activity
During pregnancy and the peripartum period, rising hormone levels create a “psychoneuroendocrinological window of vulnerability” for mental health in which 80% of women can develop transitory “baby blues,” and about one in seven develop more serious postpartum depression, Ms. Weinmar told this news organization.
The study included 47 women — 15 pregnant women and 32 nonpregnant controls. The nonpregnant women had normal menstrual cycles; 16 were in the early follicular phase with low estradiol levels (231.7 pmol/L), and 16 had high estradiol levels (516.6 pmol/L) after administration of estradiol.
To examine brain activity, participants were asked to view negative emotional images while undergoing functional MRI. They were then asked to use cognitive reappraisal to regulate their emotional response to the images.
The findings showed that both pregnant and nonpregnant women were equally successful at emotional regulation, but this process involved different brain activity in pregnant vs their nonpregnant counterpart.
All women had increased left middle frontal gyrus activity when regulating their emotions, but there was a difference in the amygdala between the pregnancy group and controls, Ms. Weinmar noted.
This suggests that pregnant women may have to exert more neural effort in emotional regulation, she said. “And pregnant women with higher amygdala activity were less able to regulate their emotions successfully compared to those with less amygdala activity.”
Linear regression analyses were performed to assess the relation of brain activity during down-regulation, regulation success, and self-reported depression scores, and this showed that higher amygdala activity was also associated with higher depression scores.
“We need to be cautious in interpreting this,” said Ms. Weinmar. “This is a small sample, and we are the first to undertake this work.”
Nonetheless, she said that if the findings are confirmed by larger studies, pregnant women could be assessed “in the waiting room” using existing questionnaires that evaluate emotional regulation.
If a woman has difficulties with emotion regulation, “there are adaptive strategies, like cognitive reappraisal that a counseling psychotherapist can help with,” said Ms. Weinmar.
“I could also imagine group sessions, for example, or online courses,” she said, adding that obstetricians could also be trained to identify these women.
Commenting on the findings in a press release, Susana Carmona, PhD, from Gregorio Marañón Hospital in Madrid, Spain, said research like this is crucial for gaining insight into one of the most intense physiological processes a human can undergo: pregnancy. It’s remarkable how much remains unknown.
“Recently, the FDA [Food and Drug Administration] approved the first treatment for postpartum depression. However, we still have a long way to go in characterizing what happens in the brain during pregnancy, identifying biomarkers that can indicate the risk of developing perinatal mental disorders, and designing strategies to prevent mother and infant suffering during the delicate and critical peripartum period,” Dr. Carmona added.
The study was supported by the Center for Integrative Neuroscience in Tübingen, Germany, and the International Research Training Group “Women’s Mental Health Across the Reproductive Years” (IRTG 2804). Ms. Weinmar and Dr. Carmona reported no relevant disclosures.
A version of this article appeared on Medscape.com.
MILAN, ITALY — Pregnant women with heightened amygdala activity have a reduced capacity to regulate emotions and report more symptoms of depression than those with lower activity in this brain region, a new imaging study suggested.
If validated, these findings could pave the way for identifying women at higher risk for postpartum depression, said lead researcher Franziska Weinmar, MSc, from the University of Tübingen in Germany.
The study was presented at the 37th European College of Neuropsychopharmacology Congress.
Differences in Brain Activity
During pregnancy and the peripartum period, rising hormone levels create a “psychoneuroendocrinological window of vulnerability” for mental health in which 80% of women can develop transitory “baby blues,” and about one in seven develop more serious postpartum depression, Ms. Weinmar told this news organization.
The study included 47 women — 15 pregnant women and 32 nonpregnant controls. The nonpregnant women had normal menstrual cycles; 16 were in the early follicular phase with low estradiol levels (231.7 pmol/L), and 16 had high estradiol levels (516.6 pmol/L) after administration of estradiol.
To examine brain activity, participants were asked to view negative emotional images while undergoing functional MRI. They were then asked to use cognitive reappraisal to regulate their emotional response to the images.
The findings showed that both pregnant and nonpregnant women were equally successful at emotional regulation, but this process involved different brain activity in pregnant vs their nonpregnant counterpart.
All women had increased left middle frontal gyrus activity when regulating their emotions, but there was a difference in the amygdala between the pregnancy group and controls, Ms. Weinmar noted.
This suggests that pregnant women may have to exert more neural effort in emotional regulation, she said. “And pregnant women with higher amygdala activity were less able to regulate their emotions successfully compared to those with less amygdala activity.”
Linear regression analyses were performed to assess the relation of brain activity during down-regulation, regulation success, and self-reported depression scores, and this showed that higher amygdala activity was also associated with higher depression scores.
“We need to be cautious in interpreting this,” said Ms. Weinmar. “This is a small sample, and we are the first to undertake this work.”
Nonetheless, she said that if the findings are confirmed by larger studies, pregnant women could be assessed “in the waiting room” using existing questionnaires that evaluate emotional regulation.
If a woman has difficulties with emotion regulation, “there are adaptive strategies, like cognitive reappraisal that a counseling psychotherapist can help with,” said Ms. Weinmar.
“I could also imagine group sessions, for example, or online courses,” she said, adding that obstetricians could also be trained to identify these women.
Commenting on the findings in a press release, Susana Carmona, PhD, from Gregorio Marañón Hospital in Madrid, Spain, said research like this is crucial for gaining insight into one of the most intense physiological processes a human can undergo: pregnancy. It’s remarkable how much remains unknown.
“Recently, the FDA [Food and Drug Administration] approved the first treatment for postpartum depression. However, we still have a long way to go in characterizing what happens in the brain during pregnancy, identifying biomarkers that can indicate the risk of developing perinatal mental disorders, and designing strategies to prevent mother and infant suffering during the delicate and critical peripartum period,” Dr. Carmona added.
The study was supported by the Center for Integrative Neuroscience in Tübingen, Germany, and the International Research Training Group “Women’s Mental Health Across the Reproductive Years” (IRTG 2804). Ms. Weinmar and Dr. Carmona reported no relevant disclosures.
A version of this article appeared on Medscape.com.
MILAN, ITALY — Pregnant women with heightened amygdala activity have a reduced capacity to regulate emotions and report more symptoms of depression than those with lower activity in this brain region, a new imaging study suggested.
If validated, these findings could pave the way for identifying women at higher risk for postpartum depression, said lead researcher Franziska Weinmar, MSc, from the University of Tübingen in Germany.
The study was presented at the 37th European College of Neuropsychopharmacology Congress.
Differences in Brain Activity
During pregnancy and the peripartum period, rising hormone levels create a “psychoneuroendocrinological window of vulnerability” for mental health in which 80% of women can develop transitory “baby blues,” and about one in seven develop more serious postpartum depression, Ms. Weinmar told this news organization.
The study included 47 women — 15 pregnant women and 32 nonpregnant controls. The nonpregnant women had normal menstrual cycles; 16 were in the early follicular phase with low estradiol levels (231.7 pmol/L), and 16 had high estradiol levels (516.6 pmol/L) after administration of estradiol.
To examine brain activity, participants were asked to view negative emotional images while undergoing functional MRI. They were then asked to use cognitive reappraisal to regulate their emotional response to the images.
The findings showed that both pregnant and nonpregnant women were equally successful at emotional regulation, but this process involved different brain activity in pregnant vs their nonpregnant counterpart.
All women had increased left middle frontal gyrus activity when regulating their emotions, but there was a difference in the amygdala between the pregnancy group and controls, Ms. Weinmar noted.
This suggests that pregnant women may have to exert more neural effort in emotional regulation, she said. “And pregnant women with higher amygdala activity were less able to regulate their emotions successfully compared to those with less amygdala activity.”
Linear regression analyses were performed to assess the relation of brain activity during down-regulation, regulation success, and self-reported depression scores, and this showed that higher amygdala activity was also associated with higher depression scores.
“We need to be cautious in interpreting this,” said Ms. Weinmar. “This is a small sample, and we are the first to undertake this work.”
Nonetheless, she said that if the findings are confirmed by larger studies, pregnant women could be assessed “in the waiting room” using existing questionnaires that evaluate emotional regulation.
If a woman has difficulties with emotion regulation, “there are adaptive strategies, like cognitive reappraisal that a counseling psychotherapist can help with,” said Ms. Weinmar.
“I could also imagine group sessions, for example, or online courses,” she said, adding that obstetricians could also be trained to identify these women.
Commenting on the findings in a press release, Susana Carmona, PhD, from Gregorio Marañón Hospital in Madrid, Spain, said research like this is crucial for gaining insight into one of the most intense physiological processes a human can undergo: pregnancy. It’s remarkable how much remains unknown.
“Recently, the FDA [Food and Drug Administration] approved the first treatment for postpartum depression. However, we still have a long way to go in characterizing what happens in the brain during pregnancy, identifying biomarkers that can indicate the risk of developing perinatal mental disorders, and designing strategies to prevent mother and infant suffering during the delicate and critical peripartum period,” Dr. Carmona added.
The study was supported by the Center for Integrative Neuroscience in Tübingen, Germany, and the International Research Training Group “Women’s Mental Health Across the Reproductive Years” (IRTG 2804). Ms. Weinmar and Dr. Carmona reported no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM ECNP 2024
Heat-Related Pediatric ED Visits More Than Double
ORLANDO – according to research presented at the annual meeting of the American Academy of Pediatrics (AAP).
“Our study really highlights the adverse effects that can come from extreme heat, and how increasing heat-related illness is affecting our children,” Taylor Merritt, MD, a pediatric resident at the University of Texas Southwestern Medical Center and Children’s Health in Dallas, said during a press briefing.
Underestimating the Problem?
Lori Byron, MD, a pediatrician from Red Lodge, Montana, who heads the AAP Chapter Climate Advocates program and was not involved in this research, was not surprised by the findings. “If anything, we’re vastly underestimating it because when people come in with heat exhaustion or heat smoke, that gets coded correctly, but when people come in with heart attacks, asthma attacks, strokes, and other exacerbations of chronic disease, it very rarely gets coded as a heat-related illness.”
Record-breaking summer temperatures from the changing climate have led to increased heat-related morbidity and mortality. Past research suggests that children and teens make up nearly half of all those affected by heat-related illnesses, she noted. 2023, for example, was the hottest year on record, and 2024 is predicted to be hotter, Dr. Merritt said.
A Sharp Increase in Cases
The retrospective study examined emergency department diagnoses during May-September from 2012-2023 at two large children’s hospitals within a north Texas pediatric health care system. The researchers compared heat-specific conditions with rhabdomyolysis encounters based on ICD-10 coding.
Heat-specific conditions include heatstroke/sunstroke, exertion heatstroke, heat syncope, heat crap, heat exhaustion, heat fatigue, heat edema, and exposure to excessive natural heat. Rhabdomyolysis encounters included both exertional and nonexertional rhabdomyolysis as well as non-traumatic rhabdomyolysis and elevated creatine kinase (CK) levels.
Among 542 heat-related encounters, 77% had heat-specific diagnoses and 24% had a rhabdomyolysis diagnosis. Combined, heat-related encounters increased 170% from 2012 to 2023, from 4.3 per 10,000 to 11.6 per 10,000 (P = .1). Summer months with higher peak temperatures were also associated with higher heat-related volume in the emergency department (P < .001).
Teenage boys were most likely to have rhabdomyolysis, with 82% of the cases occurring in boys and 70% in ages 12-18 (P < .001). “Compared to the rhabdomyolysis group, the heat-specific group was more likely to be younger, Hispanic, use government-based insurance, and live in an area with a lower Child Opportunity Index,” Dr. Merritt reported. “Most heat-specific encounters resulted in an ED discharge (96%), while most rhabdomyolysis encounters resulted in hospital admission (63%)” (P < .001).
”Thankfully, pediatric heat-related illness is still relatively rare,” Dr. Merritt said. “However, given the context of increasing temperatures, this is important for us all to know, anyone who cares for children, whether that be families or parents or pediatricians.”
Prevention Is Key
Dr. Byron noted that about half of AAP chapters now have climate committees, many of which have created educational materials on heat and wildfire smoke and on talking with athletes about risk of heat-related illnesses.
“A lot of the state high school sports associations are actually now adopting guidelines on when it’s safe to practice and when it’s safe to play for heat and for smoke, so that’s definitely something that we can talk to parents about and kids about,” Dr. Byron said. “Otherwise, you still have a lot of coaches and a lot of kids out there that think you’re just supposed to be tough and barrel through it.”
Rhabdomyolysis and heat stroke are both potentially deadly illnesses, so the biggest focus needs to be on prevention, Dr. Byron said. “Not just working with individuals in your office, but working within your school or within your state high school sports association is totally within the lane of a pediatrician to get involved.”
The research had no external funding. Dr. Merritt and Dr. Byron had no disclosures.
ORLANDO – according to research presented at the annual meeting of the American Academy of Pediatrics (AAP).
“Our study really highlights the adverse effects that can come from extreme heat, and how increasing heat-related illness is affecting our children,” Taylor Merritt, MD, a pediatric resident at the University of Texas Southwestern Medical Center and Children’s Health in Dallas, said during a press briefing.
Underestimating the Problem?
Lori Byron, MD, a pediatrician from Red Lodge, Montana, who heads the AAP Chapter Climate Advocates program and was not involved in this research, was not surprised by the findings. “If anything, we’re vastly underestimating it because when people come in with heat exhaustion or heat smoke, that gets coded correctly, but when people come in with heart attacks, asthma attacks, strokes, and other exacerbations of chronic disease, it very rarely gets coded as a heat-related illness.”
Record-breaking summer temperatures from the changing climate have led to increased heat-related morbidity and mortality. Past research suggests that children and teens make up nearly half of all those affected by heat-related illnesses, she noted. 2023, for example, was the hottest year on record, and 2024 is predicted to be hotter, Dr. Merritt said.
A Sharp Increase in Cases
The retrospective study examined emergency department diagnoses during May-September from 2012-2023 at two large children’s hospitals within a north Texas pediatric health care system. The researchers compared heat-specific conditions with rhabdomyolysis encounters based on ICD-10 coding.
Heat-specific conditions include heatstroke/sunstroke, exertion heatstroke, heat syncope, heat crap, heat exhaustion, heat fatigue, heat edema, and exposure to excessive natural heat. Rhabdomyolysis encounters included both exertional and nonexertional rhabdomyolysis as well as non-traumatic rhabdomyolysis and elevated creatine kinase (CK) levels.
Among 542 heat-related encounters, 77% had heat-specific diagnoses and 24% had a rhabdomyolysis diagnosis. Combined, heat-related encounters increased 170% from 2012 to 2023, from 4.3 per 10,000 to 11.6 per 10,000 (P = .1). Summer months with higher peak temperatures were also associated with higher heat-related volume in the emergency department (P < .001).
Teenage boys were most likely to have rhabdomyolysis, with 82% of the cases occurring in boys and 70% in ages 12-18 (P < .001). “Compared to the rhabdomyolysis group, the heat-specific group was more likely to be younger, Hispanic, use government-based insurance, and live in an area with a lower Child Opportunity Index,” Dr. Merritt reported. “Most heat-specific encounters resulted in an ED discharge (96%), while most rhabdomyolysis encounters resulted in hospital admission (63%)” (P < .001).
”Thankfully, pediatric heat-related illness is still relatively rare,” Dr. Merritt said. “However, given the context of increasing temperatures, this is important for us all to know, anyone who cares for children, whether that be families or parents or pediatricians.”
Prevention Is Key
Dr. Byron noted that about half of AAP chapters now have climate committees, many of which have created educational materials on heat and wildfire smoke and on talking with athletes about risk of heat-related illnesses.
“A lot of the state high school sports associations are actually now adopting guidelines on when it’s safe to practice and when it’s safe to play for heat and for smoke, so that’s definitely something that we can talk to parents about and kids about,” Dr. Byron said. “Otherwise, you still have a lot of coaches and a lot of kids out there that think you’re just supposed to be tough and barrel through it.”
Rhabdomyolysis and heat stroke are both potentially deadly illnesses, so the biggest focus needs to be on prevention, Dr. Byron said. “Not just working with individuals in your office, but working within your school or within your state high school sports association is totally within the lane of a pediatrician to get involved.”
The research had no external funding. Dr. Merritt and Dr. Byron had no disclosures.
ORLANDO – according to research presented at the annual meeting of the American Academy of Pediatrics (AAP).
“Our study really highlights the adverse effects that can come from extreme heat, and how increasing heat-related illness is affecting our children,” Taylor Merritt, MD, a pediatric resident at the University of Texas Southwestern Medical Center and Children’s Health in Dallas, said during a press briefing.
Underestimating the Problem?
Lori Byron, MD, a pediatrician from Red Lodge, Montana, who heads the AAP Chapter Climate Advocates program and was not involved in this research, was not surprised by the findings. “If anything, we’re vastly underestimating it because when people come in with heat exhaustion or heat smoke, that gets coded correctly, but when people come in with heart attacks, asthma attacks, strokes, and other exacerbations of chronic disease, it very rarely gets coded as a heat-related illness.”
Record-breaking summer temperatures from the changing climate have led to increased heat-related morbidity and mortality. Past research suggests that children and teens make up nearly half of all those affected by heat-related illnesses, she noted. 2023, for example, was the hottest year on record, and 2024 is predicted to be hotter, Dr. Merritt said.
A Sharp Increase in Cases
The retrospective study examined emergency department diagnoses during May-September from 2012-2023 at two large children’s hospitals within a north Texas pediatric health care system. The researchers compared heat-specific conditions with rhabdomyolysis encounters based on ICD-10 coding.
Heat-specific conditions include heatstroke/sunstroke, exertion heatstroke, heat syncope, heat crap, heat exhaustion, heat fatigue, heat edema, and exposure to excessive natural heat. Rhabdomyolysis encounters included both exertional and nonexertional rhabdomyolysis as well as non-traumatic rhabdomyolysis and elevated creatine kinase (CK) levels.
Among 542 heat-related encounters, 77% had heat-specific diagnoses and 24% had a rhabdomyolysis diagnosis. Combined, heat-related encounters increased 170% from 2012 to 2023, from 4.3 per 10,000 to 11.6 per 10,000 (P = .1). Summer months with higher peak temperatures were also associated with higher heat-related volume in the emergency department (P < .001).
Teenage boys were most likely to have rhabdomyolysis, with 82% of the cases occurring in boys and 70% in ages 12-18 (P < .001). “Compared to the rhabdomyolysis group, the heat-specific group was more likely to be younger, Hispanic, use government-based insurance, and live in an area with a lower Child Opportunity Index,” Dr. Merritt reported. “Most heat-specific encounters resulted in an ED discharge (96%), while most rhabdomyolysis encounters resulted in hospital admission (63%)” (P < .001).
”Thankfully, pediatric heat-related illness is still relatively rare,” Dr. Merritt said. “However, given the context of increasing temperatures, this is important for us all to know, anyone who cares for children, whether that be families or parents or pediatricians.”
Prevention Is Key
Dr. Byron noted that about half of AAP chapters now have climate committees, many of which have created educational materials on heat and wildfire smoke and on talking with athletes about risk of heat-related illnesses.
“A lot of the state high school sports associations are actually now adopting guidelines on when it’s safe to practice and when it’s safe to play for heat and for smoke, so that’s definitely something that we can talk to parents about and kids about,” Dr. Byron said. “Otherwise, you still have a lot of coaches and a lot of kids out there that think you’re just supposed to be tough and barrel through it.”
Rhabdomyolysis and heat stroke are both potentially deadly illnesses, so the biggest focus needs to be on prevention, Dr. Byron said. “Not just working with individuals in your office, but working within your school or within your state high school sports association is totally within the lane of a pediatrician to get involved.”
The research had no external funding. Dr. Merritt and Dr. Byron had no disclosures.
FROM AAP 2024
Aspects of the Skin Microbiome Remain Elusive
SAN DIEGO — Although it has been known for several years that
In one review of the topic, researchers from the National Institutes of Health wrote that the skin is composed of 1.8 million diverse habitats with an abundance of folds, invaginations, and specialized niches that support a wide range of microorganisms. “Many of these microorganisms are harmless and, in some cases, provide vital functions for us to live and they have not evolved over time,” Jill S. Waibel, MD, medical director of the Miami Dermatology and Laser Institute, said at the annual Masters of Aesthetics Symposium.
“This is complex ecosystem that we don’t really talk about,” she said. “There is wide topographical distribution of bacteria on skin sites. The bacteria we have on our head and neck area is different from that on our feet. There is also a lot of interpersonal variation of the skin microbiome, so one person may have a lot of one type of bacteria and not as much of another.”
A Shield From Foreign Pathogens
At its core, Dr. Waibel continued, the skin microbiome functions as an interface between the human body and the environment, a physical barrier that prevents the invasion of foreign pathogens. The skin also provides a home to commensal microbiota. She likened the skin’s landscape to that of the tundra: “It’s desiccated, has poor nutrients, and it’s very acidic, thus pathogens have a hard time living on it,” she said. “However, our skin microorganisms have adapted to utilize the sparse nutrients available on the skin. That’s why I tell my patients, ‘don’t use a sugar scrub because you’re potentially feeding these bad bacteria.’ ”
According to more recent research, the skin microbiota in healthy adults remains stable over time, despite environmental perturbations, and they have important roles in educating the innate and adaptive arms of the cutaneous immune system. “Some skin diseases are associated with an altered microbial state: dysbiosis,” said Dr. Waibel, subsection chief of dermatology at Baptist Health South Florida, Miami Beach. “Reversion of this may help prevent or treat the disease.”
She cited the following factors that influence the skin microbiome:
- Genetics affects the skin microbiome considerably. Individuals with autoimmune predispositions have different microbiota compared with those who don’t.
- Climate, pollution, and hygiene practices the other influencing factors. “Even clothing can impact the microbiome, by causing the transfer of microorganisms,” she said.
- Age and hormonal changes (particularly during puberty) and senescence alter the microbial landscape.
- Systemic health conditions such as diabetes mellitus and irritable bowel disease, as well as cutaneous conditions like psoriasis and atopic dermatitis can also disrupt the skin microbiome.
Ingredients contained in soaps, antibiotics, and cosmetics can also cause skin dysbiosis, Dr. Waibel said. However, the integrity of the skin’s microbiome following dermatological procedures such as excisions, dermabrasion, laser therapy, and other physical procedures is less understood, according to a recent review of the topic. Phototherapy appears to be the most extensively studied, “and shows an increase in microbial diversity post-treatment,” she said. “Light treatments have been found to kill bacteria by inducing DNA damage. More studies need to be performed on specific wavelengths of light used, conditions being treated and individual patient differences.”
According to the review’s authors, no change in the microbiome was observed in studies of debridement. “That was surprising, as it is a method to remove unhealthy tissue that often contains pathogenic bacteria,” Dr. Waibel said. “The big take-home message is that we need more research.”
Dr. Waibel disclosed that she has conducted clinical trials for several device and pharmaceutical companies.
A version of this article first appeared on Medscape.com.
SAN DIEGO — Although it has been known for several years that
In one review of the topic, researchers from the National Institutes of Health wrote that the skin is composed of 1.8 million diverse habitats with an abundance of folds, invaginations, and specialized niches that support a wide range of microorganisms. “Many of these microorganisms are harmless and, in some cases, provide vital functions for us to live and they have not evolved over time,” Jill S. Waibel, MD, medical director of the Miami Dermatology and Laser Institute, said at the annual Masters of Aesthetics Symposium.
“This is complex ecosystem that we don’t really talk about,” she said. “There is wide topographical distribution of bacteria on skin sites. The bacteria we have on our head and neck area is different from that on our feet. There is also a lot of interpersonal variation of the skin microbiome, so one person may have a lot of one type of bacteria and not as much of another.”
A Shield From Foreign Pathogens
At its core, Dr. Waibel continued, the skin microbiome functions as an interface between the human body and the environment, a physical barrier that prevents the invasion of foreign pathogens. The skin also provides a home to commensal microbiota. She likened the skin’s landscape to that of the tundra: “It’s desiccated, has poor nutrients, and it’s very acidic, thus pathogens have a hard time living on it,” she said. “However, our skin microorganisms have adapted to utilize the sparse nutrients available on the skin. That’s why I tell my patients, ‘don’t use a sugar scrub because you’re potentially feeding these bad bacteria.’ ”
According to more recent research, the skin microbiota in healthy adults remains stable over time, despite environmental perturbations, and they have important roles in educating the innate and adaptive arms of the cutaneous immune system. “Some skin diseases are associated with an altered microbial state: dysbiosis,” said Dr. Waibel, subsection chief of dermatology at Baptist Health South Florida, Miami Beach. “Reversion of this may help prevent or treat the disease.”
She cited the following factors that influence the skin microbiome:
- Genetics affects the skin microbiome considerably. Individuals with autoimmune predispositions have different microbiota compared with those who don’t.
- Climate, pollution, and hygiene practices the other influencing factors. “Even clothing can impact the microbiome, by causing the transfer of microorganisms,” she said.
- Age and hormonal changes (particularly during puberty) and senescence alter the microbial landscape.
- Systemic health conditions such as diabetes mellitus and irritable bowel disease, as well as cutaneous conditions like psoriasis and atopic dermatitis can also disrupt the skin microbiome.
Ingredients contained in soaps, antibiotics, and cosmetics can also cause skin dysbiosis, Dr. Waibel said. However, the integrity of the skin’s microbiome following dermatological procedures such as excisions, dermabrasion, laser therapy, and other physical procedures is less understood, according to a recent review of the topic. Phototherapy appears to be the most extensively studied, “and shows an increase in microbial diversity post-treatment,” she said. “Light treatments have been found to kill bacteria by inducing DNA damage. More studies need to be performed on specific wavelengths of light used, conditions being treated and individual patient differences.”
According to the review’s authors, no change in the microbiome was observed in studies of debridement. “That was surprising, as it is a method to remove unhealthy tissue that often contains pathogenic bacteria,” Dr. Waibel said. “The big take-home message is that we need more research.”
Dr. Waibel disclosed that she has conducted clinical trials for several device and pharmaceutical companies.
A version of this article first appeared on Medscape.com.
SAN DIEGO — Although it has been known for several years that
In one review of the topic, researchers from the National Institutes of Health wrote that the skin is composed of 1.8 million diverse habitats with an abundance of folds, invaginations, and specialized niches that support a wide range of microorganisms. “Many of these microorganisms are harmless and, in some cases, provide vital functions for us to live and they have not evolved over time,” Jill S. Waibel, MD, medical director of the Miami Dermatology and Laser Institute, said at the annual Masters of Aesthetics Symposium.
“This is complex ecosystem that we don’t really talk about,” she said. “There is wide topographical distribution of bacteria on skin sites. The bacteria we have on our head and neck area is different from that on our feet. There is also a lot of interpersonal variation of the skin microbiome, so one person may have a lot of one type of bacteria and not as much of another.”
A Shield From Foreign Pathogens
At its core, Dr. Waibel continued, the skin microbiome functions as an interface between the human body and the environment, a physical barrier that prevents the invasion of foreign pathogens. The skin also provides a home to commensal microbiota. She likened the skin’s landscape to that of the tundra: “It’s desiccated, has poor nutrients, and it’s very acidic, thus pathogens have a hard time living on it,” she said. “However, our skin microorganisms have adapted to utilize the sparse nutrients available on the skin. That’s why I tell my patients, ‘don’t use a sugar scrub because you’re potentially feeding these bad bacteria.’ ”
According to more recent research, the skin microbiota in healthy adults remains stable over time, despite environmental perturbations, and they have important roles in educating the innate and adaptive arms of the cutaneous immune system. “Some skin diseases are associated with an altered microbial state: dysbiosis,” said Dr. Waibel, subsection chief of dermatology at Baptist Health South Florida, Miami Beach. “Reversion of this may help prevent or treat the disease.”
She cited the following factors that influence the skin microbiome:
- Genetics affects the skin microbiome considerably. Individuals with autoimmune predispositions have different microbiota compared with those who don’t.
- Climate, pollution, and hygiene practices the other influencing factors. “Even clothing can impact the microbiome, by causing the transfer of microorganisms,” she said.
- Age and hormonal changes (particularly during puberty) and senescence alter the microbial landscape.
- Systemic health conditions such as diabetes mellitus and irritable bowel disease, as well as cutaneous conditions like psoriasis and atopic dermatitis can also disrupt the skin microbiome.
Ingredients contained in soaps, antibiotics, and cosmetics can also cause skin dysbiosis, Dr. Waibel said. However, the integrity of the skin’s microbiome following dermatological procedures such as excisions, dermabrasion, laser therapy, and other physical procedures is less understood, according to a recent review of the topic. Phototherapy appears to be the most extensively studied, “and shows an increase in microbial diversity post-treatment,” she said. “Light treatments have been found to kill bacteria by inducing DNA damage. More studies need to be performed on specific wavelengths of light used, conditions being treated and individual patient differences.”
According to the review’s authors, no change in the microbiome was observed in studies of debridement. “That was surprising, as it is a method to remove unhealthy tissue that often contains pathogenic bacteria,” Dr. Waibel said. “The big take-home message is that we need more research.”
Dr. Waibel disclosed that she has conducted clinical trials for several device and pharmaceutical companies.
A version of this article first appeared on Medscape.com.
FROM THE 2024 MASTERS OF AESTHETICS SYMPOSIUM
Myeloma: Daratumumab Plus Lenalidomide Improves MRD Outcomes
“To date, no randomized trial has directly compared daratumumab-based maintenance therapy vs standard of care lenalidomide maintenance, which is the focus of our trial,” said first author Ashraf Z. Badros, MD, a professor of medicine at the Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland Medical Center, Baltimore, in presenting the findings at the International Myeloma Society (IMS) 2024.
“These results support the addition of daratumumab not only to induction/consolidation but also to standard of care lenalidomide maintenance for these patients,” he said of the study, which was published concurrently in the journal Blood.
Despite ongoing advancements in regimens for induction, consolidation, and maintenance posttransplant, most patients with MM eventually relapse, driving continuing efforts to optimize treatment strategies and improve long-term outcomes.
While daratumumab, an anti-CD38 monoclonal antibody, is approved in induction and consolidation with ASCT for patients with newly diagnosed MM, the authors sought to investigate the potential benefits of adding it to the standard-of-care therapy lenalidomide in maintenance therapy.
For the phase 3 AURIGA trial, they recruited 200 patients with newly diagnosed MM within 12 months of induction therapy and 6 months of ASCT.
The patients, who were all anti-CD38 naive, received at least four induction cycles, had at least a very good partial response, and were MRD positive following ASCT.
They were randomized 1:1 to receive 28-day lenalidomide maintenance cycles either with (n = 99) or without (n = 101) subcutaneous daratumumab for at least 36 cycles or until disease progression, unacceptable toxicity, or withdrawal.
The patients had similar baseline demographic characteristics; their median age was about 62 years, and 25.3% in the daratumumab and 23.5% in the no-daratumumab group had ISS stage III disease. At the time of diagnosis, 23.9% and 16.9%, respectively, had high cytogenic risk.
Overall, patients received a median of five induction cycles prior to entering the study.
For the primary endpoint, the rate of conversion from MRD positive to MRD negative (at a sensitivity of 10-5 using next-generation sequencing) by 12 months was significantly higher in the daratumumab group than in the lenalidomide-only group, at 50.5% vs 18.8% (odds ratio [OR], 4.51; P < .0001).
A similar benefit with the daratumumab group was observed across all clinically relevant subgroups, including patients with high-risk disease.
The MRD-negative conversion rate was similar at the 10-6 threshold (23.2% vs 5%; OR, 5.97; P = .0002).
At a median follow-up of 32.3 months, the overall rates of MRD negativity were 60.6% and 27.7%, with and without daratumumab, respectively (OR, 4.12; P < .0001)
The achievement of complete response or better also was significantly greater with daratumumab (75.8% vs 61.4%; OR, 2.00; P = .0255).
Likewise, PFS favored daratumumab (hazard ratio, 0.53), and the estimated 30-month PFS rates were 82.7% and 66.4%, respectively.
The daratumumab group received more maintenance cycles than the lenalidomide-only group (median of 33 vs 21.5), and it had higher rates of completion of 12 cycles (88.5% vs 78.6%). Dr. Badros noted that the main reason for discontinuation of therapy in the no-daratumumab arm was disease progression.
Consistent with previous studies, daratumumab was associated with more grade 3/4 treatment-emergent adverse events (TEAEs), occurring in 74.0% patients vs 67.3% patients not receiving daratumumab, including infections (18.8% vs 13.3%), cytopenia (54.2% vs 46.9%), and neutropenia (46.9% vs 41.8%). Dr. Badros noted the significantly longer time of treatment in the daratumumab arm (30 months vs 20 months).
Serious TEAEs occurred in 30.2% daratumumab patients and 22.4% no-daratumumab patients, and fatal TEAEs occurred in 2.1% and 1.0% patients, respectively.
“Overall, there were no new safety concerns for daratumumab,” he said.
The authors noted that the requirement that patients be anti-CD38 naive was partially because of “the D-VRd [daratumumab combined with bortezomib, lenalidomide, and dexamethasone] regimen gaining popularity and increased utilization in the myeloma community for transplant-eligible patients with NDMM, even before the publication of the long-term results of the randomized GRIFFIN and PERSEUS studies.”
A key question, remarked Joseph Mikhael, MD, who is chief medical officer of the International Myeloma Foundation, from the audience, is how applicable the findings are in the modern environment, where most patients now have indeed had prior anti-CD38 treatment.
In response, Dr. Badros explained that “I think this is an important study because it is probably one of the few studies that separates the impact of daratumumab-lenalidomide without prior daratumumab use.”
Dr. Badros noted that results from the PERSEUS trial, of D-VRd, show MRD-positive to MRD-negative conversion rates that are similar to the current trial; “therefore, I really don’t think that using daratumumab up front will prevent using it as maintenance,” he said. “If anything, it actually improves outcomes.”
The findings from continuous treatment “are an important reminder that high-risk patients do not do well if you stop treatment,” he said.
Further commenting on the research at the meeting, María-Victoria Mateos, MD, PhD, an associate professor of medicine at the University of Salamanca in Spain, noted that “the unmet need in maintenance is to upgrade the quality of the response and to increase the conversion of MRD-positivity to MRD negative in order to delay the progression of the disease and prolong the overall survival.”
Regarding the AURIGA trial, “this is very interesting data about the role of daratumumab-lenalidomide maintenance in patients who are MRD positive after autologous stem cell transplantation.”
“What is more important is we are progressing in response-adaptive therapy, and we are generating very useful information to possibly make the majority of patients become MRD negative.
“Developing early endpoints as surrogate markers for long-term outcomes and overall survival is critically important,” she added. “Otherwise, trials may continue for more than 15 years.”
The study was sponsored by Janssen Biotech. Dr. Badros reported relationships with Bristol-Myers Squibb, BeiGene, Roche, Jansen, and GSK. Mateos disclosed ties with AbbVie, Amgen, Bristol-Myers Squibb, GSK, Kite, Johnson & Johnson, Oncopeptides, Pfizer, Regeneron, Roche, and Sanofi.
A version of this article first appeared on Medscape.com.
“To date, no randomized trial has directly compared daratumumab-based maintenance therapy vs standard of care lenalidomide maintenance, which is the focus of our trial,” said first author Ashraf Z. Badros, MD, a professor of medicine at the Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland Medical Center, Baltimore, in presenting the findings at the International Myeloma Society (IMS) 2024.
“These results support the addition of daratumumab not only to induction/consolidation but also to standard of care lenalidomide maintenance for these patients,” he said of the study, which was published concurrently in the journal Blood.
Despite ongoing advancements in regimens for induction, consolidation, and maintenance posttransplant, most patients with MM eventually relapse, driving continuing efforts to optimize treatment strategies and improve long-term outcomes.
While daratumumab, an anti-CD38 monoclonal antibody, is approved in induction and consolidation with ASCT for patients with newly diagnosed MM, the authors sought to investigate the potential benefits of adding it to the standard-of-care therapy lenalidomide in maintenance therapy.
For the phase 3 AURIGA trial, they recruited 200 patients with newly diagnosed MM within 12 months of induction therapy and 6 months of ASCT.
The patients, who were all anti-CD38 naive, received at least four induction cycles, had at least a very good partial response, and were MRD positive following ASCT.
They were randomized 1:1 to receive 28-day lenalidomide maintenance cycles either with (n = 99) or without (n = 101) subcutaneous daratumumab for at least 36 cycles or until disease progression, unacceptable toxicity, or withdrawal.
The patients had similar baseline demographic characteristics; their median age was about 62 years, and 25.3% in the daratumumab and 23.5% in the no-daratumumab group had ISS stage III disease. At the time of diagnosis, 23.9% and 16.9%, respectively, had high cytogenic risk.
Overall, patients received a median of five induction cycles prior to entering the study.
For the primary endpoint, the rate of conversion from MRD positive to MRD negative (at a sensitivity of 10-5 using next-generation sequencing) by 12 months was significantly higher in the daratumumab group than in the lenalidomide-only group, at 50.5% vs 18.8% (odds ratio [OR], 4.51; P < .0001).
A similar benefit with the daratumumab group was observed across all clinically relevant subgroups, including patients with high-risk disease.
The MRD-negative conversion rate was similar at the 10-6 threshold (23.2% vs 5%; OR, 5.97; P = .0002).
At a median follow-up of 32.3 months, the overall rates of MRD negativity were 60.6% and 27.7%, with and without daratumumab, respectively (OR, 4.12; P < .0001)
The achievement of complete response or better also was significantly greater with daratumumab (75.8% vs 61.4%; OR, 2.00; P = .0255).
Likewise, PFS favored daratumumab (hazard ratio, 0.53), and the estimated 30-month PFS rates were 82.7% and 66.4%, respectively.
The daratumumab group received more maintenance cycles than the lenalidomide-only group (median of 33 vs 21.5), and it had higher rates of completion of 12 cycles (88.5% vs 78.6%). Dr. Badros noted that the main reason for discontinuation of therapy in the no-daratumumab arm was disease progression.
Consistent with previous studies, daratumumab was associated with more grade 3/4 treatment-emergent adverse events (TEAEs), occurring in 74.0% patients vs 67.3% patients not receiving daratumumab, including infections (18.8% vs 13.3%), cytopenia (54.2% vs 46.9%), and neutropenia (46.9% vs 41.8%). Dr. Badros noted the significantly longer time of treatment in the daratumumab arm (30 months vs 20 months).
Serious TEAEs occurred in 30.2% daratumumab patients and 22.4% no-daratumumab patients, and fatal TEAEs occurred in 2.1% and 1.0% patients, respectively.
“Overall, there were no new safety concerns for daratumumab,” he said.
The authors noted that the requirement that patients be anti-CD38 naive was partially because of “the D-VRd [daratumumab combined with bortezomib, lenalidomide, and dexamethasone] regimen gaining popularity and increased utilization in the myeloma community for transplant-eligible patients with NDMM, even before the publication of the long-term results of the randomized GRIFFIN and PERSEUS studies.”
A key question, remarked Joseph Mikhael, MD, who is chief medical officer of the International Myeloma Foundation, from the audience, is how applicable the findings are in the modern environment, where most patients now have indeed had prior anti-CD38 treatment.
In response, Dr. Badros explained that “I think this is an important study because it is probably one of the few studies that separates the impact of daratumumab-lenalidomide without prior daratumumab use.”
Dr. Badros noted that results from the PERSEUS trial, of D-VRd, show MRD-positive to MRD-negative conversion rates that are similar to the current trial; “therefore, I really don’t think that using daratumumab up front will prevent using it as maintenance,” he said. “If anything, it actually improves outcomes.”
The findings from continuous treatment “are an important reminder that high-risk patients do not do well if you stop treatment,” he said.
Further commenting on the research at the meeting, María-Victoria Mateos, MD, PhD, an associate professor of medicine at the University of Salamanca in Spain, noted that “the unmet need in maintenance is to upgrade the quality of the response and to increase the conversion of MRD-positivity to MRD negative in order to delay the progression of the disease and prolong the overall survival.”
Regarding the AURIGA trial, “this is very interesting data about the role of daratumumab-lenalidomide maintenance in patients who are MRD positive after autologous stem cell transplantation.”
“What is more important is we are progressing in response-adaptive therapy, and we are generating very useful information to possibly make the majority of patients become MRD negative.
“Developing early endpoints as surrogate markers for long-term outcomes and overall survival is critically important,” she added. “Otherwise, trials may continue for more than 15 years.”
The study was sponsored by Janssen Biotech. Dr. Badros reported relationships with Bristol-Myers Squibb, BeiGene, Roche, Jansen, and GSK. Mateos disclosed ties with AbbVie, Amgen, Bristol-Myers Squibb, GSK, Kite, Johnson & Johnson, Oncopeptides, Pfizer, Regeneron, Roche, and Sanofi.
A version of this article first appeared on Medscape.com.
“To date, no randomized trial has directly compared daratumumab-based maintenance therapy vs standard of care lenalidomide maintenance, which is the focus of our trial,” said first author Ashraf Z. Badros, MD, a professor of medicine at the Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland Medical Center, Baltimore, in presenting the findings at the International Myeloma Society (IMS) 2024.
“These results support the addition of daratumumab not only to induction/consolidation but also to standard of care lenalidomide maintenance for these patients,” he said of the study, which was published concurrently in the journal Blood.
Despite ongoing advancements in regimens for induction, consolidation, and maintenance posttransplant, most patients with MM eventually relapse, driving continuing efforts to optimize treatment strategies and improve long-term outcomes.
While daratumumab, an anti-CD38 monoclonal antibody, is approved in induction and consolidation with ASCT for patients with newly diagnosed MM, the authors sought to investigate the potential benefits of adding it to the standard-of-care therapy lenalidomide in maintenance therapy.
For the phase 3 AURIGA trial, they recruited 200 patients with newly diagnosed MM within 12 months of induction therapy and 6 months of ASCT.
The patients, who were all anti-CD38 naive, received at least four induction cycles, had at least a very good partial response, and were MRD positive following ASCT.
They were randomized 1:1 to receive 28-day lenalidomide maintenance cycles either with (n = 99) or without (n = 101) subcutaneous daratumumab for at least 36 cycles or until disease progression, unacceptable toxicity, or withdrawal.
The patients had similar baseline demographic characteristics; their median age was about 62 years, and 25.3% in the daratumumab and 23.5% in the no-daratumumab group had ISS stage III disease. At the time of diagnosis, 23.9% and 16.9%, respectively, had high cytogenic risk.
Overall, patients received a median of five induction cycles prior to entering the study.
For the primary endpoint, the rate of conversion from MRD positive to MRD negative (at a sensitivity of 10-5 using next-generation sequencing) by 12 months was significantly higher in the daratumumab group than in the lenalidomide-only group, at 50.5% vs 18.8% (odds ratio [OR], 4.51; P < .0001).
A similar benefit with the daratumumab group was observed across all clinically relevant subgroups, including patients with high-risk disease.
The MRD-negative conversion rate was similar at the 10-6 threshold (23.2% vs 5%; OR, 5.97; P = .0002).
At a median follow-up of 32.3 months, the overall rates of MRD negativity were 60.6% and 27.7%, with and without daratumumab, respectively (OR, 4.12; P < .0001)
The achievement of complete response or better also was significantly greater with daratumumab (75.8% vs 61.4%; OR, 2.00; P = .0255).
Likewise, PFS favored daratumumab (hazard ratio, 0.53), and the estimated 30-month PFS rates were 82.7% and 66.4%, respectively.
The daratumumab group received more maintenance cycles than the lenalidomide-only group (median of 33 vs 21.5), and it had higher rates of completion of 12 cycles (88.5% vs 78.6%). Dr. Badros noted that the main reason for discontinuation of therapy in the no-daratumumab arm was disease progression.
Consistent with previous studies, daratumumab was associated with more grade 3/4 treatment-emergent adverse events (TEAEs), occurring in 74.0% patients vs 67.3% patients not receiving daratumumab, including infections (18.8% vs 13.3%), cytopenia (54.2% vs 46.9%), and neutropenia (46.9% vs 41.8%). Dr. Badros noted the significantly longer time of treatment in the daratumumab arm (30 months vs 20 months).
Serious TEAEs occurred in 30.2% daratumumab patients and 22.4% no-daratumumab patients, and fatal TEAEs occurred in 2.1% and 1.0% patients, respectively.
“Overall, there were no new safety concerns for daratumumab,” he said.
The authors noted that the requirement that patients be anti-CD38 naive was partially because of “the D-VRd [daratumumab combined with bortezomib, lenalidomide, and dexamethasone] regimen gaining popularity and increased utilization in the myeloma community for transplant-eligible patients with NDMM, even before the publication of the long-term results of the randomized GRIFFIN and PERSEUS studies.”
A key question, remarked Joseph Mikhael, MD, who is chief medical officer of the International Myeloma Foundation, from the audience, is how applicable the findings are in the modern environment, where most patients now have indeed had prior anti-CD38 treatment.
In response, Dr. Badros explained that “I think this is an important study because it is probably one of the few studies that separates the impact of daratumumab-lenalidomide without prior daratumumab use.”
Dr. Badros noted that results from the PERSEUS trial, of D-VRd, show MRD-positive to MRD-negative conversion rates that are similar to the current trial; “therefore, I really don’t think that using daratumumab up front will prevent using it as maintenance,” he said. “If anything, it actually improves outcomes.”
The findings from continuous treatment “are an important reminder that high-risk patients do not do well if you stop treatment,” he said.
Further commenting on the research at the meeting, María-Victoria Mateos, MD, PhD, an associate professor of medicine at the University of Salamanca in Spain, noted that “the unmet need in maintenance is to upgrade the quality of the response and to increase the conversion of MRD-positivity to MRD negative in order to delay the progression of the disease and prolong the overall survival.”
Regarding the AURIGA trial, “this is very interesting data about the role of daratumumab-lenalidomide maintenance in patients who are MRD positive after autologous stem cell transplantation.”
“What is more important is we are progressing in response-adaptive therapy, and we are generating very useful information to possibly make the majority of patients become MRD negative.
“Developing early endpoints as surrogate markers for long-term outcomes and overall survival is critically important,” she added. “Otherwise, trials may continue for more than 15 years.”
The study was sponsored by Janssen Biotech. Dr. Badros reported relationships with Bristol-Myers Squibb, BeiGene, Roche, Jansen, and GSK. Mateos disclosed ties with AbbVie, Amgen, Bristol-Myers Squibb, GSK, Kite, Johnson & Johnson, Oncopeptides, Pfizer, Regeneron, Roche, and Sanofi.
A version of this article first appeared on Medscape.com.
FROM IMS 2024
Diabetic Kidney Disease Therapies Keep on FLOWing
Further data from the FLOW study were presented during the 2024 congress of the European Association for the Study of Diabetes (EASD) in Madrid. The FLOW study was originally presented in May at the European Renal Association’s 2024 congress in Stockholm. It was the first dedicated kidney outcomes trial to examine a GLP-1 receptor agonist.
The FLOW study demonstrated significant kidney, cardiovascular, and mortality benefits with semaglutide 1 mg once weekly in patients with type 2 diabetes and chronic kidney disease (CKD). This study has elevated semaglutide to a new pillar of care for the management of diabetic kidney disease (DKD) alongside RAAS inhibitors, SGLT2 inhibitors, and finerenone.
At first, whether the benefits of semaglutide were independent of baseline SGLT2 inhibitor use was uncertain. The data presented at the EASD congress, however, appeared to confirm the additive benefits of semaglutide, when combined with SGLT2 inhibitor use, in patients with DKD. The authors did acknowledge that study power was limited, given the low use of SGLT2 inhibitors at trial recruitment (no licensed SGLT2 inhibitor was available for CKD at that point), so small, clinically relevant interactions may not have been detected.
So, what are the implications of the FLOW study for primary care?
DKD is a common clinical challenge in primary care; a national diabetes audit in the United Kingdom suggested that over 40% of patients with type 2 diabetes had kidney disease. Moreover, DKD is the most common cause of kidney failure in adults starting renal replacement therapy in the United Kingdom.
Residual renal risk in patients with DKD persists despite optimal use of guideline-directed medical therapy (GDMT) with RAAS inhibitors, SGLT2 inhibitors, and finerenone, as demonstrated in the many landmark kidney outcomes trials over the past 25 years.
So, a new pillar of GDMT is welcome, but I am worried that this widened choice of therapies may worsen therapeutic inertia; baseline use of the newer DKD therapies (specifically SGLT2 inhibitors and finerenone) remains low.
In addition, during the EASD FLOW session, Katherine Tuttle, MD, executive director for research at Providence Inland Northwest Health Services in Spokane, Washington, presented data from the US CURE-CKD registry study showing that baseline ACE inhibitor/ARB use of about 70% dropped to 50% after just 90 days. Baseline use of SGLT2 inhibitors was only about 6% and dropped to 5% after 90 days.
I suspect that much of this reduction in prescribing of ACE inhibitors/ARBs will have been in response to an acute dip in estimated glomerular filtration rate (eGFR) or hyperkalemia, which has been a perennial challenge with RAAS inhibitor use in primary care. Ongoing education in primary care is required to manage hyperkalemia and reductions in eGFR after RAAS inhibitor initiation to prevent premature cessation of these foundational therapies.
On a positive note, there was no acute dip in eGFR after prescribing semaglutide in DKD. This observation will be reassuring for primary care and hopefully prevent unnecessary cessation of therapy.
Also reassuring was the lack of difference in diabetic retinopathy adverse events between the semaglutide and placebo groups. These events raised concerns about semaglutide following the SUSTAIN-6 CVOT study and have affected attitudes in primary care. But the rapidity and magnitude of improvement in glycemic control with semaglutide was believed to be the underlying issue, rather than semaglutide itself. A similar phenomenon has been observed with insulin. The ongoing FOCUS study is exploring the long-term effects of semaglutide on diabetic retinopathy in patients with type 2 diabetes. This study will hopefully provide a definite answer to this issue.
Another useful message from the FLOW study for primary care is the utility of semaglutide for glucose-lowering in the context of CKD. A1c was 0.81% lower in the semaglutide group compared with the placebo group in participants with eGFRs as low as 25 mL/min/1.73 m2. It is well established that SGLT2 inhibitors have negligible glucose-lowering effects once eGFR drops below 45 mL/min/1.73 m2. Indeed, my usual practice in CKD, if additional glucose-lowering is required once renal protection has been established with an SGLT2 inhibitor, was to add a GLP-1 receptor agonist. It is reassuring to have my clinical practice ratified by the FLOW study.
Semaglutide also helpfully provides an alternative therapeutic option for patients who do not tolerate SGLT2 inhibitors because of, for example, recurrent mycotic genital infections or polyuria, or for those in whom SGLT2 inhibitors are contraindicated, such as patients who have experienced an unprovoked episode of diabetic ketoacidosis. Many of these patients still require cardiovascular and kidney protection, so the FLOW study gives me a viable evidence-based alternative.
As a class, semaglutide and GLP-1 receptor agonists are, of course, not without side effects. Gastrointestinal side effects are the most common, and this finding was echoed in the FLOW study. Gastrointestinal disorders led to permanent treatment discontinuation in 4.5% of the semaglutide group compared with 1.1% of the placebo group. The overall safety profile of semaglutide was favorable, however.
Gastrointestinal side effects can be particularly concerning in the context of CKD because of the possibility of clinical dehydration and acute kidney injury with persistent vomiting or diarrhea. Patient education is particularly important when using GLP-1 receptor agonists in this group of individuals. Reassuringly, there was no imbalance in dehydration and acute kidney injury between trial arms in the FLOW study.
Notably, past studies have suggested that patients with CKD are more likely to experience gastrointestinal side effects with GLP-1 receptor agonists; in these patients, the usual mantra of GLP-1 receptor agonist prescribing is particularly important: Start low, go slow.
Finally, medication adherence is a challenge with multiple pillars of GDMT: These evidence-based disease-modifying therapies work only if our patients take them regularly. My senior partner had a lovely turn of phrase when reviewing patients with multiple long-term conditions; he would always start the consultation by asking individuals which medications they were not taking regularly.
Overall, the FLOW study confirms semaglutide’s position as a new therapeutic pillar for DKD. This treatment will help address the residual renal risk for patients with DKD despite optimal use of GDMT. However, education and support will be required in primary care to prevent worsening therapeutic inertia.
Kevin Fernando, general practitioner partner, North Berwick Health Centre, North Berwick, UK, has disclosed the following relevant financial relationships: Received speaker fees from: Amarin; Amgen; AstraZeneca; Bayer; Boehringer Ingelheim; Dexcom; Daiichi Sankyo; Lilly; Menarini; Novartis; Novo Nordisk; Roche Diagnostics; Embecta; Roche Diabetes Care. Received honoraria for participation in advisory boards from: Amarin; Amgen; AstraZen
A version of this article first appeared on Medscape.com.
Further data from the FLOW study were presented during the 2024 congress of the European Association for the Study of Diabetes (EASD) in Madrid. The FLOW study was originally presented in May at the European Renal Association’s 2024 congress in Stockholm. It was the first dedicated kidney outcomes trial to examine a GLP-1 receptor agonist.
The FLOW study demonstrated significant kidney, cardiovascular, and mortality benefits with semaglutide 1 mg once weekly in patients with type 2 diabetes and chronic kidney disease (CKD). This study has elevated semaglutide to a new pillar of care for the management of diabetic kidney disease (DKD) alongside RAAS inhibitors, SGLT2 inhibitors, and finerenone.
At first, whether the benefits of semaglutide were independent of baseline SGLT2 inhibitor use was uncertain. The data presented at the EASD congress, however, appeared to confirm the additive benefits of semaglutide, when combined with SGLT2 inhibitor use, in patients with DKD. The authors did acknowledge that study power was limited, given the low use of SGLT2 inhibitors at trial recruitment (no licensed SGLT2 inhibitor was available for CKD at that point), so small, clinically relevant interactions may not have been detected.
So, what are the implications of the FLOW study for primary care?
DKD is a common clinical challenge in primary care; a national diabetes audit in the United Kingdom suggested that over 40% of patients with type 2 diabetes had kidney disease. Moreover, DKD is the most common cause of kidney failure in adults starting renal replacement therapy in the United Kingdom.
Residual renal risk in patients with DKD persists despite optimal use of guideline-directed medical therapy (GDMT) with RAAS inhibitors, SGLT2 inhibitors, and finerenone, as demonstrated in the many landmark kidney outcomes trials over the past 25 years.
So, a new pillar of GDMT is welcome, but I am worried that this widened choice of therapies may worsen therapeutic inertia; baseline use of the newer DKD therapies (specifically SGLT2 inhibitors and finerenone) remains low.
In addition, during the EASD FLOW session, Katherine Tuttle, MD, executive director for research at Providence Inland Northwest Health Services in Spokane, Washington, presented data from the US CURE-CKD registry study showing that baseline ACE inhibitor/ARB use of about 70% dropped to 50% after just 90 days. Baseline use of SGLT2 inhibitors was only about 6% and dropped to 5% after 90 days.
I suspect that much of this reduction in prescribing of ACE inhibitors/ARBs will have been in response to an acute dip in estimated glomerular filtration rate (eGFR) or hyperkalemia, which has been a perennial challenge with RAAS inhibitor use in primary care. Ongoing education in primary care is required to manage hyperkalemia and reductions in eGFR after RAAS inhibitor initiation to prevent premature cessation of these foundational therapies.
On a positive note, there was no acute dip in eGFR after prescribing semaglutide in DKD. This observation will be reassuring for primary care and hopefully prevent unnecessary cessation of therapy.
Also reassuring was the lack of difference in diabetic retinopathy adverse events between the semaglutide and placebo groups. These events raised concerns about semaglutide following the SUSTAIN-6 CVOT study and have affected attitudes in primary care. But the rapidity and magnitude of improvement in glycemic control with semaglutide was believed to be the underlying issue, rather than semaglutide itself. A similar phenomenon has been observed with insulin. The ongoing FOCUS study is exploring the long-term effects of semaglutide on diabetic retinopathy in patients with type 2 diabetes. This study will hopefully provide a definite answer to this issue.
Another useful message from the FLOW study for primary care is the utility of semaglutide for glucose-lowering in the context of CKD. A1c was 0.81% lower in the semaglutide group compared with the placebo group in participants with eGFRs as low as 25 mL/min/1.73 m2. It is well established that SGLT2 inhibitors have negligible glucose-lowering effects once eGFR drops below 45 mL/min/1.73 m2. Indeed, my usual practice in CKD, if additional glucose-lowering is required once renal protection has been established with an SGLT2 inhibitor, was to add a GLP-1 receptor agonist. It is reassuring to have my clinical practice ratified by the FLOW study.
Semaglutide also helpfully provides an alternative therapeutic option for patients who do not tolerate SGLT2 inhibitors because of, for example, recurrent mycotic genital infections or polyuria, or for those in whom SGLT2 inhibitors are contraindicated, such as patients who have experienced an unprovoked episode of diabetic ketoacidosis. Many of these patients still require cardiovascular and kidney protection, so the FLOW study gives me a viable evidence-based alternative.
As a class, semaglutide and GLP-1 receptor agonists are, of course, not without side effects. Gastrointestinal side effects are the most common, and this finding was echoed in the FLOW study. Gastrointestinal disorders led to permanent treatment discontinuation in 4.5% of the semaglutide group compared with 1.1% of the placebo group. The overall safety profile of semaglutide was favorable, however.
Gastrointestinal side effects can be particularly concerning in the context of CKD because of the possibility of clinical dehydration and acute kidney injury with persistent vomiting or diarrhea. Patient education is particularly important when using GLP-1 receptor agonists in this group of individuals. Reassuringly, there was no imbalance in dehydration and acute kidney injury between trial arms in the FLOW study.
Notably, past studies have suggested that patients with CKD are more likely to experience gastrointestinal side effects with GLP-1 receptor agonists; in these patients, the usual mantra of GLP-1 receptor agonist prescribing is particularly important: Start low, go slow.
Finally, medication adherence is a challenge with multiple pillars of GDMT: These evidence-based disease-modifying therapies work only if our patients take them regularly. My senior partner had a lovely turn of phrase when reviewing patients with multiple long-term conditions; he would always start the consultation by asking individuals which medications they were not taking regularly.
Overall, the FLOW study confirms semaglutide’s position as a new therapeutic pillar for DKD. This treatment will help address the residual renal risk for patients with DKD despite optimal use of GDMT. However, education and support will be required in primary care to prevent worsening therapeutic inertia.
Kevin Fernando, general practitioner partner, North Berwick Health Centre, North Berwick, UK, has disclosed the following relevant financial relationships: Received speaker fees from: Amarin; Amgen; AstraZeneca; Bayer; Boehringer Ingelheim; Dexcom; Daiichi Sankyo; Lilly; Menarini; Novartis; Novo Nordisk; Roche Diagnostics; Embecta; Roche Diabetes Care. Received honoraria for participation in advisory boards from: Amarin; Amgen; AstraZen
A version of this article first appeared on Medscape.com.
Further data from the FLOW study were presented during the 2024 congress of the European Association for the Study of Diabetes (EASD) in Madrid. The FLOW study was originally presented in May at the European Renal Association’s 2024 congress in Stockholm. It was the first dedicated kidney outcomes trial to examine a GLP-1 receptor agonist.
The FLOW study demonstrated significant kidney, cardiovascular, and mortality benefits with semaglutide 1 mg once weekly in patients with type 2 diabetes and chronic kidney disease (CKD). This study has elevated semaglutide to a new pillar of care for the management of diabetic kidney disease (DKD) alongside RAAS inhibitors, SGLT2 inhibitors, and finerenone.
At first, whether the benefits of semaglutide were independent of baseline SGLT2 inhibitor use was uncertain. The data presented at the EASD congress, however, appeared to confirm the additive benefits of semaglutide, when combined with SGLT2 inhibitor use, in patients with DKD. The authors did acknowledge that study power was limited, given the low use of SGLT2 inhibitors at trial recruitment (no licensed SGLT2 inhibitor was available for CKD at that point), so small, clinically relevant interactions may not have been detected.
So, what are the implications of the FLOW study for primary care?
DKD is a common clinical challenge in primary care; a national diabetes audit in the United Kingdom suggested that over 40% of patients with type 2 diabetes had kidney disease. Moreover, DKD is the most common cause of kidney failure in adults starting renal replacement therapy in the United Kingdom.
Residual renal risk in patients with DKD persists despite optimal use of guideline-directed medical therapy (GDMT) with RAAS inhibitors, SGLT2 inhibitors, and finerenone, as demonstrated in the many landmark kidney outcomes trials over the past 25 years.
So, a new pillar of GDMT is welcome, but I am worried that this widened choice of therapies may worsen therapeutic inertia; baseline use of the newer DKD therapies (specifically SGLT2 inhibitors and finerenone) remains low.
In addition, during the EASD FLOW session, Katherine Tuttle, MD, executive director for research at Providence Inland Northwest Health Services in Spokane, Washington, presented data from the US CURE-CKD registry study showing that baseline ACE inhibitor/ARB use of about 70% dropped to 50% after just 90 days. Baseline use of SGLT2 inhibitors was only about 6% and dropped to 5% after 90 days.
I suspect that much of this reduction in prescribing of ACE inhibitors/ARBs will have been in response to an acute dip in estimated glomerular filtration rate (eGFR) or hyperkalemia, which has been a perennial challenge with RAAS inhibitor use in primary care. Ongoing education in primary care is required to manage hyperkalemia and reductions in eGFR after RAAS inhibitor initiation to prevent premature cessation of these foundational therapies.
On a positive note, there was no acute dip in eGFR after prescribing semaglutide in DKD. This observation will be reassuring for primary care and hopefully prevent unnecessary cessation of therapy.
Also reassuring was the lack of difference in diabetic retinopathy adverse events between the semaglutide and placebo groups. These events raised concerns about semaglutide following the SUSTAIN-6 CVOT study and have affected attitudes in primary care. But the rapidity and magnitude of improvement in glycemic control with semaglutide was believed to be the underlying issue, rather than semaglutide itself. A similar phenomenon has been observed with insulin. The ongoing FOCUS study is exploring the long-term effects of semaglutide on diabetic retinopathy in patients with type 2 diabetes. This study will hopefully provide a definite answer to this issue.
Another useful message from the FLOW study for primary care is the utility of semaglutide for glucose-lowering in the context of CKD. A1c was 0.81% lower in the semaglutide group compared with the placebo group in participants with eGFRs as low as 25 mL/min/1.73 m2. It is well established that SGLT2 inhibitors have negligible glucose-lowering effects once eGFR drops below 45 mL/min/1.73 m2. Indeed, my usual practice in CKD, if additional glucose-lowering is required once renal protection has been established with an SGLT2 inhibitor, was to add a GLP-1 receptor agonist. It is reassuring to have my clinical practice ratified by the FLOW study.
Semaglutide also helpfully provides an alternative therapeutic option for patients who do not tolerate SGLT2 inhibitors because of, for example, recurrent mycotic genital infections or polyuria, or for those in whom SGLT2 inhibitors are contraindicated, such as patients who have experienced an unprovoked episode of diabetic ketoacidosis. Many of these patients still require cardiovascular and kidney protection, so the FLOW study gives me a viable evidence-based alternative.
As a class, semaglutide and GLP-1 receptor agonists are, of course, not without side effects. Gastrointestinal side effects are the most common, and this finding was echoed in the FLOW study. Gastrointestinal disorders led to permanent treatment discontinuation in 4.5% of the semaglutide group compared with 1.1% of the placebo group. The overall safety profile of semaglutide was favorable, however.
Gastrointestinal side effects can be particularly concerning in the context of CKD because of the possibility of clinical dehydration and acute kidney injury with persistent vomiting or diarrhea. Patient education is particularly important when using GLP-1 receptor agonists in this group of individuals. Reassuringly, there was no imbalance in dehydration and acute kidney injury between trial arms in the FLOW study.
Notably, past studies have suggested that patients with CKD are more likely to experience gastrointestinal side effects with GLP-1 receptor agonists; in these patients, the usual mantra of GLP-1 receptor agonist prescribing is particularly important: Start low, go slow.
Finally, medication adherence is a challenge with multiple pillars of GDMT: These evidence-based disease-modifying therapies work only if our patients take them regularly. My senior partner had a lovely turn of phrase when reviewing patients with multiple long-term conditions; he would always start the consultation by asking individuals which medications they were not taking regularly.
Overall, the FLOW study confirms semaglutide’s position as a new therapeutic pillar for DKD. This treatment will help address the residual renal risk for patients with DKD despite optimal use of GDMT. However, education and support will be required in primary care to prevent worsening therapeutic inertia.
Kevin Fernando, general practitioner partner, North Berwick Health Centre, North Berwick, UK, has disclosed the following relevant financial relationships: Received speaker fees from: Amarin; Amgen; AstraZeneca; Bayer; Boehringer Ingelheim; Dexcom; Daiichi Sankyo; Lilly; Menarini; Novartis; Novo Nordisk; Roche Diagnostics; Embecta; Roche Diabetes Care. Received honoraria for participation in advisory boards from: Amarin; Amgen; AstraZen
A version of this article first appeared on Medscape.com.
FROM EASD 2024
Can Hormones Guide Sex-Specific Treatments for Alcohol Use Disorder?
MILAN — Specific combinations of hormonal and biochemical factors were associated with different clinical characteristics and treatment outcomes of alcohol use disorder (AUD) between men and women.
“These hormones and proteins are known to have an influence on behavior, and indeed we see an association between different levels of these compounds and different behavioral aspects of [AUD], although we can’t for sure say that one directly causes another,” said lead researcher Victor M. Karpyak, MD, PhD, professor of psychiatry at the Mayo Clinic, in a release.
The findings were presented at the 37th European College of Neuropsychopharmacology (ECNP) Congress.
Sex Hormone Signatures
Previous research has highlighted differences in symptoms including cravings, withdrawal, consumption patterns, depression, and anxiety between men and women with AUD, said Dr. Karpyak. Differences in hormones and biochemicals have also been observed between individuals with and without AUD.
However, specific biochemical and hormonal “signatures” associated with male and female responses to treatment have thus far not been explored, he told this news organization.
The study included 400 treatment-seeking individuals (132 women and 268 men; mean age, 41.8 years; 93% White) who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for AUD and were enrolled in a clinical trial of acamprosate.
Baseline assessment included psychiatric comorbidities and substance use with the Psychiatric Research Interview for Substance and Mental Disorders, alcohol consumption pattern over the past 90 days by Timeline Follow-Back calendar, recent craving on the Penn Alcohol Craving Scale (PACS), situations at the risk of drinking on the Inventory of Drug-Taking Situation, recent depression severity on the Patient Health Questionnaire 9 (PHQ-9), and recent anxiety severity on the Generalized Anxiety Disorder 7 scale.
Plasma sex-related hormone and protein measurements were taken at baseline — after detoxification but before treatment. These included total testosterone, estradiol, estrone, progesterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone–binding globulin (SHBG), and albumin.
“The important thing is that these measurements were taken during sobriety,” said Dr. Karpyak. Study participants were already in residential treatment programs, and the average time since their last drink was approximately 3 weeks. Relapse was defined as any alcohol consumption during the first 3 months.
What Works for Men May Not Work for Women
Results showed that men with symptoms of depression and a higher craving for alcohol, as shown on baseline PHQ-9 and PACS scores, had lower baseline levels of testosterone, estrone, estradiol, and SHBG than those without these symptoms (P = .0102 and P = .0014, respectively).
In addition, a combination of higher progesterone and lower albumin was associated with a lower risk for relapse during the first 3 months (odds ratio [OR], 0.518; P = .0079).
In women, a combination of lower estrone and estradiol and higher FSH and LH levels was associated with higher maximum number of drinks per day (P = .035).
In addition, women who were more likely to relapse during the first 3 months of treatment had higher baseline levels of testosterone, SHBG, and albumin than those at lower relapse risk (OR, 4.536; P = .0057).
Dr. Karpyak noted that these “hormone signatures” were associative and not predictive.
What this means, he said, “is that if you are treating a man and a woman for alcoholism, you are dealing with different biochemical and psychological starting points. This implies that what works for a man may not work for a woman, and vice versa.”
Toward Gender Equity
The findings may eventually lead to a way to predict treatment responses in patients with AUD, Dr. Karpyak added, but cautioned that despite statistical significance, these are preliminary findings.
Before these results can be integrated into clinical practice, they need to be replicated. Dr. Karpyak emphasized the need for follow-up research that builds on these findings, using them as preliminary data to determine whether prediction holds real significance.
“Given that many of these differences are related to sex hormones, we particularly want to see how the dramatic hormonal change women experience during the menstrual cycle and at menopause may affect the biochemistry of alcoholism and guide treatment efforts,” he said.
In a statement, Erika Comasco, PhD, associate professor in molecular psychiatry, Uppsala University, Sweden, said the research “is an important step forward to gender equity in medicine.”
“The findings provide an important first insight into the relationship between sex hormones and alcohol use disorder treatment,” she explained. “While sex differences in the way the disorder manifests itself are known, these results suggest that sex hormones may modulate treatment response, potentially supporting sex-specific pharmacological intervention.”
Dr. Comasco shares Dr. Karpyak’s view that hormonal fluctuations linked to the menstrual cycle may influence alcohol misuse and believes more research is needed to explore their impact on treatment and relapse outcomes in female patients.
This study was funded by the National Institute on Alcohol Abuse and Alcoholism (National Institutes of Health) and the Samuel C. Johnson Genomics of Addiction Program at Mayo Clinic. Dr. Karpyak and Dr. Comasco reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
MILAN — Specific combinations of hormonal and biochemical factors were associated with different clinical characteristics and treatment outcomes of alcohol use disorder (AUD) between men and women.
“These hormones and proteins are known to have an influence on behavior, and indeed we see an association between different levels of these compounds and different behavioral aspects of [AUD], although we can’t for sure say that one directly causes another,” said lead researcher Victor M. Karpyak, MD, PhD, professor of psychiatry at the Mayo Clinic, in a release.
The findings were presented at the 37th European College of Neuropsychopharmacology (ECNP) Congress.
Sex Hormone Signatures
Previous research has highlighted differences in symptoms including cravings, withdrawal, consumption patterns, depression, and anxiety between men and women with AUD, said Dr. Karpyak. Differences in hormones and biochemicals have also been observed between individuals with and without AUD.
However, specific biochemical and hormonal “signatures” associated with male and female responses to treatment have thus far not been explored, he told this news organization.
The study included 400 treatment-seeking individuals (132 women and 268 men; mean age, 41.8 years; 93% White) who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for AUD and were enrolled in a clinical trial of acamprosate.
Baseline assessment included psychiatric comorbidities and substance use with the Psychiatric Research Interview for Substance and Mental Disorders, alcohol consumption pattern over the past 90 days by Timeline Follow-Back calendar, recent craving on the Penn Alcohol Craving Scale (PACS), situations at the risk of drinking on the Inventory of Drug-Taking Situation, recent depression severity on the Patient Health Questionnaire 9 (PHQ-9), and recent anxiety severity on the Generalized Anxiety Disorder 7 scale.
Plasma sex-related hormone and protein measurements were taken at baseline — after detoxification but before treatment. These included total testosterone, estradiol, estrone, progesterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone–binding globulin (SHBG), and albumin.
“The important thing is that these measurements were taken during sobriety,” said Dr. Karpyak. Study participants were already in residential treatment programs, and the average time since their last drink was approximately 3 weeks. Relapse was defined as any alcohol consumption during the first 3 months.
What Works for Men May Not Work for Women
Results showed that men with symptoms of depression and a higher craving for alcohol, as shown on baseline PHQ-9 and PACS scores, had lower baseline levels of testosterone, estrone, estradiol, and SHBG than those without these symptoms (P = .0102 and P = .0014, respectively).
In addition, a combination of higher progesterone and lower albumin was associated with a lower risk for relapse during the first 3 months (odds ratio [OR], 0.518; P = .0079).
In women, a combination of lower estrone and estradiol and higher FSH and LH levels was associated with higher maximum number of drinks per day (P = .035).
In addition, women who were more likely to relapse during the first 3 months of treatment had higher baseline levels of testosterone, SHBG, and albumin than those at lower relapse risk (OR, 4.536; P = .0057).
Dr. Karpyak noted that these “hormone signatures” were associative and not predictive.
What this means, he said, “is that if you are treating a man and a woman for alcoholism, you are dealing with different biochemical and psychological starting points. This implies that what works for a man may not work for a woman, and vice versa.”
Toward Gender Equity
The findings may eventually lead to a way to predict treatment responses in patients with AUD, Dr. Karpyak added, but cautioned that despite statistical significance, these are preliminary findings.
Before these results can be integrated into clinical practice, they need to be replicated. Dr. Karpyak emphasized the need for follow-up research that builds on these findings, using them as preliminary data to determine whether prediction holds real significance.
“Given that many of these differences are related to sex hormones, we particularly want to see how the dramatic hormonal change women experience during the menstrual cycle and at menopause may affect the biochemistry of alcoholism and guide treatment efforts,” he said.
In a statement, Erika Comasco, PhD, associate professor in molecular psychiatry, Uppsala University, Sweden, said the research “is an important step forward to gender equity in medicine.”
“The findings provide an important first insight into the relationship between sex hormones and alcohol use disorder treatment,” she explained. “While sex differences in the way the disorder manifests itself are known, these results suggest that sex hormones may modulate treatment response, potentially supporting sex-specific pharmacological intervention.”
Dr. Comasco shares Dr. Karpyak’s view that hormonal fluctuations linked to the menstrual cycle may influence alcohol misuse and believes more research is needed to explore their impact on treatment and relapse outcomes in female patients.
This study was funded by the National Institute on Alcohol Abuse and Alcoholism (National Institutes of Health) and the Samuel C. Johnson Genomics of Addiction Program at Mayo Clinic. Dr. Karpyak and Dr. Comasco reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
MILAN — Specific combinations of hormonal and biochemical factors were associated with different clinical characteristics and treatment outcomes of alcohol use disorder (AUD) between men and women.
“These hormones and proteins are known to have an influence on behavior, and indeed we see an association between different levels of these compounds and different behavioral aspects of [AUD], although we can’t for sure say that one directly causes another,” said lead researcher Victor M. Karpyak, MD, PhD, professor of psychiatry at the Mayo Clinic, in a release.
The findings were presented at the 37th European College of Neuropsychopharmacology (ECNP) Congress.
Sex Hormone Signatures
Previous research has highlighted differences in symptoms including cravings, withdrawal, consumption patterns, depression, and anxiety between men and women with AUD, said Dr. Karpyak. Differences in hormones and biochemicals have also been observed between individuals with and without AUD.
However, specific biochemical and hormonal “signatures” associated with male and female responses to treatment have thus far not been explored, he told this news organization.
The study included 400 treatment-seeking individuals (132 women and 268 men; mean age, 41.8 years; 93% White) who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for AUD and were enrolled in a clinical trial of acamprosate.
Baseline assessment included psychiatric comorbidities and substance use with the Psychiatric Research Interview for Substance and Mental Disorders, alcohol consumption pattern over the past 90 days by Timeline Follow-Back calendar, recent craving on the Penn Alcohol Craving Scale (PACS), situations at the risk of drinking on the Inventory of Drug-Taking Situation, recent depression severity on the Patient Health Questionnaire 9 (PHQ-9), and recent anxiety severity on the Generalized Anxiety Disorder 7 scale.
Plasma sex-related hormone and protein measurements were taken at baseline — after detoxification but before treatment. These included total testosterone, estradiol, estrone, progesterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone–binding globulin (SHBG), and albumin.
“The important thing is that these measurements were taken during sobriety,” said Dr. Karpyak. Study participants were already in residential treatment programs, and the average time since their last drink was approximately 3 weeks. Relapse was defined as any alcohol consumption during the first 3 months.
What Works for Men May Not Work for Women
Results showed that men with symptoms of depression and a higher craving for alcohol, as shown on baseline PHQ-9 and PACS scores, had lower baseline levels of testosterone, estrone, estradiol, and SHBG than those without these symptoms (P = .0102 and P = .0014, respectively).
In addition, a combination of higher progesterone and lower albumin was associated with a lower risk for relapse during the first 3 months (odds ratio [OR], 0.518; P = .0079).
In women, a combination of lower estrone and estradiol and higher FSH and LH levels was associated with higher maximum number of drinks per day (P = .035).
In addition, women who were more likely to relapse during the first 3 months of treatment had higher baseline levels of testosterone, SHBG, and albumin than those at lower relapse risk (OR, 4.536; P = .0057).
Dr. Karpyak noted that these “hormone signatures” were associative and not predictive.
What this means, he said, “is that if you are treating a man and a woman for alcoholism, you are dealing with different biochemical and psychological starting points. This implies that what works for a man may not work for a woman, and vice versa.”
Toward Gender Equity
The findings may eventually lead to a way to predict treatment responses in patients with AUD, Dr. Karpyak added, but cautioned that despite statistical significance, these are preliminary findings.
Before these results can be integrated into clinical practice, they need to be replicated. Dr. Karpyak emphasized the need for follow-up research that builds on these findings, using them as preliminary data to determine whether prediction holds real significance.
“Given that many of these differences are related to sex hormones, we particularly want to see how the dramatic hormonal change women experience during the menstrual cycle and at menopause may affect the biochemistry of alcoholism and guide treatment efforts,” he said.
In a statement, Erika Comasco, PhD, associate professor in molecular psychiatry, Uppsala University, Sweden, said the research “is an important step forward to gender equity in medicine.”
“The findings provide an important first insight into the relationship between sex hormones and alcohol use disorder treatment,” she explained. “While sex differences in the way the disorder manifests itself are known, these results suggest that sex hormones may modulate treatment response, potentially supporting sex-specific pharmacological intervention.”
Dr. Comasco shares Dr. Karpyak’s view that hormonal fluctuations linked to the menstrual cycle may influence alcohol misuse and believes more research is needed to explore their impact on treatment and relapse outcomes in female patients.
This study was funded by the National Institute on Alcohol Abuse and Alcoholism (National Institutes of Health) and the Samuel C. Johnson Genomics of Addiction Program at Mayo Clinic. Dr. Karpyak and Dr. Comasco reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM ECNP 2024
Head and Neck Cancer: Should Patients Get PEG Access Prior to Therapy? VA pilot study could help clinicians make better-informed decisions to head off malnutrition
Research conducted at the US Department of Veterans Affairs (VA) could offer crucial insight into the hotly debated question of whether patients with head and neck cancer should have access to percutaneous endoscopic gastrostomy (PEG) before they develop malnutrition.
While no definitive conclusions can be drawn until a complete study is performed, early findings of a pilot trial are intriguing, said advanced practice oncology dietitian Katherine Petersen, MS, RDN, CSO, of the Phoenix VA Health Care System, who spoke in an interview with Federal Practitioner and at the annual meeting of the Association of VA Hematology/Oncology.
So far, the 12 patients with head and neck cancer who agreed to the placement of prophylactic feeding tubes prior to chemoradiation have had worse outcomes in some areas compared to the 9 patients who had tubes inserted when clinically indicated and the 12 who didn't need feeding tubes.
Petersen cautioned that the study is small and underpowered at this point. Still, she noted, "We're seeing a hint of exactly the opposite of what I expected. Those who get a tube prophylactically are doing worse than those who are getting it reactively or not at all, If that's the case, that's a really important outcome."
As Petersen explained, the placement of PEG feeding tubes is a hot topic in head and neck cancer care. Malnutrition affects about 80% of these patients and can contribute to mortality, raising the question of whether they should have access to feeding tubes placed prior to treatment in case enteral nutrition is needed.
In some patients with head and neck cancer, malnutrition may arise when tumors block food intake or prevent patients from swallowing. "But in my clinical experience, most often it's from the adverse effects of radiation and chemotherapy. Radiation creates burns inside their throat that make it hard to swallow. Or they have taste changes or really dry mouth," Petersen said.
"On top of these problems, chemotherapy can cause nausea and vomiting," she said. Placing feeding tube access may seem like a smart strategy to head off malnutrition as soon as it occurs. But, as Petersen noted, feeding tube use can lead to dependency as patients lose their ability to swallow. "There's a theory that if we give people feeding tubes, they'll go with the easier route of using a feeding tube and not keep swallowing. Then those swallowing muscles would weaken, and patients would end up permanently on a feeding tube."
In 2020, a retrospective VA study linked feeding tube dependence to lower overall survival in head and neck cancer patients. There are also risks to feeding tube placement, such as infection, pain, leakage, and inflammation.
But what if feeding tube valves are inserted prophylactically so they can be used for nutrition if needed? "We just haven't had any prospective studies to get to the heart of the matter and answer the question," she said. "It's hard to recruit. How do you convince somebody to randomly be assigned to have a hole poked in their stomach?"
For the new pilot study, researchers in Phoenix decided not to randomize patients. Instead, they asked them whether they'd accept the placement of feeding tube valves on a prophylactic basis.
Thirty-six veterans enrolled in 3 years, 33% of those were eligible. Twelve have died, 1 withdrew, and 2 were lost to follow-up.
Those in the prophylactic group had worse physical function and muscle strength over time, while those who received feeding tubes when needed had more adverse events.
Why might some outcomes be worse for patients who chose the prophylactic approach? "The answer is unclear," Petersen said. "Although one possibility is that those patients had higher-risk tumors and were more clued into their own risk."
"The goal now is to get funding for an expanded, multicenter study within the VA," Petersen said. The big question that she hopes to answer is: Does a prophylactic approach work? "Does it make a difference for patients in terms of how quickly they go back to living a full, meaningful life and be able to do all the things that they normally would do?"
A complete study would likely last 7 years, but helpful results may come earlier. "We are starting to see significant differences in terms of our main outcomes of physical function," Petersen said. "We only need 1 to 2 years of data for each patient to get to the heart of that."
The study is not funded, and Petersen reported no disclosures.
Research conducted at the US Department of Veterans Affairs (VA) could offer crucial insight into the hotly debated question of whether patients with head and neck cancer should have access to percutaneous endoscopic gastrostomy (PEG) before they develop malnutrition.
While no definitive conclusions can be drawn until a complete study is performed, early findings of a pilot trial are intriguing, said advanced practice oncology dietitian Katherine Petersen, MS, RDN, CSO, of the Phoenix VA Health Care System, who spoke in an interview with Federal Practitioner and at the annual meeting of the Association of VA Hematology/Oncology.
So far, the 12 patients with head and neck cancer who agreed to the placement of prophylactic feeding tubes prior to chemoradiation have had worse outcomes in some areas compared to the 9 patients who had tubes inserted when clinically indicated and the 12 who didn't need feeding tubes.
Petersen cautioned that the study is small and underpowered at this point. Still, she noted, "We're seeing a hint of exactly the opposite of what I expected. Those who get a tube prophylactically are doing worse than those who are getting it reactively or not at all, If that's the case, that's a really important outcome."
As Petersen explained, the placement of PEG feeding tubes is a hot topic in head and neck cancer care. Malnutrition affects about 80% of these patients and can contribute to mortality, raising the question of whether they should have access to feeding tubes placed prior to treatment in case enteral nutrition is needed.
In some patients with head and neck cancer, malnutrition may arise when tumors block food intake or prevent patients from swallowing. "But in my clinical experience, most often it's from the adverse effects of radiation and chemotherapy. Radiation creates burns inside their throat that make it hard to swallow. Or they have taste changes or really dry mouth," Petersen said.
"On top of these problems, chemotherapy can cause nausea and vomiting," she said. Placing feeding tube access may seem like a smart strategy to head off malnutrition as soon as it occurs. But, as Petersen noted, feeding tube use can lead to dependency as patients lose their ability to swallow. "There's a theory that if we give people feeding tubes, they'll go with the easier route of using a feeding tube and not keep swallowing. Then those swallowing muscles would weaken, and patients would end up permanently on a feeding tube."
In 2020, a retrospective VA study linked feeding tube dependence to lower overall survival in head and neck cancer patients. There are also risks to feeding tube placement, such as infection, pain, leakage, and inflammation.
But what if feeding tube valves are inserted prophylactically so they can be used for nutrition if needed? "We just haven't had any prospective studies to get to the heart of the matter and answer the question," she said. "It's hard to recruit. How do you convince somebody to randomly be assigned to have a hole poked in their stomach?"
For the new pilot study, researchers in Phoenix decided not to randomize patients. Instead, they asked them whether they'd accept the placement of feeding tube valves on a prophylactic basis.
Thirty-six veterans enrolled in 3 years, 33% of those were eligible. Twelve have died, 1 withdrew, and 2 were lost to follow-up.
Those in the prophylactic group had worse physical function and muscle strength over time, while those who received feeding tubes when needed had more adverse events.
Why might some outcomes be worse for patients who chose the prophylactic approach? "The answer is unclear," Petersen said. "Although one possibility is that those patients had higher-risk tumors and were more clued into their own risk."
"The goal now is to get funding for an expanded, multicenter study within the VA," Petersen said. The big question that she hopes to answer is: Does a prophylactic approach work? "Does it make a difference for patients in terms of how quickly they go back to living a full, meaningful life and be able to do all the things that they normally would do?"
A complete study would likely last 7 years, but helpful results may come earlier. "We are starting to see significant differences in terms of our main outcomes of physical function," Petersen said. "We only need 1 to 2 years of data for each patient to get to the heart of that."
The study is not funded, and Petersen reported no disclosures.
Research conducted at the US Department of Veterans Affairs (VA) could offer crucial insight into the hotly debated question of whether patients with head and neck cancer should have access to percutaneous endoscopic gastrostomy (PEG) before they develop malnutrition.
While no definitive conclusions can be drawn until a complete study is performed, early findings of a pilot trial are intriguing, said advanced practice oncology dietitian Katherine Petersen, MS, RDN, CSO, of the Phoenix VA Health Care System, who spoke in an interview with Federal Practitioner and at the annual meeting of the Association of VA Hematology/Oncology.
So far, the 12 patients with head and neck cancer who agreed to the placement of prophylactic feeding tubes prior to chemoradiation have had worse outcomes in some areas compared to the 9 patients who had tubes inserted when clinically indicated and the 12 who didn't need feeding tubes.
Petersen cautioned that the study is small and underpowered at this point. Still, she noted, "We're seeing a hint of exactly the opposite of what I expected. Those who get a tube prophylactically are doing worse than those who are getting it reactively or not at all, If that's the case, that's a really important outcome."
As Petersen explained, the placement of PEG feeding tubes is a hot topic in head and neck cancer care. Malnutrition affects about 80% of these patients and can contribute to mortality, raising the question of whether they should have access to feeding tubes placed prior to treatment in case enteral nutrition is needed.
In some patients with head and neck cancer, malnutrition may arise when tumors block food intake or prevent patients from swallowing. "But in my clinical experience, most often it's from the adverse effects of radiation and chemotherapy. Radiation creates burns inside their throat that make it hard to swallow. Or they have taste changes or really dry mouth," Petersen said.
"On top of these problems, chemotherapy can cause nausea and vomiting," she said. Placing feeding tube access may seem like a smart strategy to head off malnutrition as soon as it occurs. But, as Petersen noted, feeding tube use can lead to dependency as patients lose their ability to swallow. "There's a theory that if we give people feeding tubes, they'll go with the easier route of using a feeding tube and not keep swallowing. Then those swallowing muscles would weaken, and patients would end up permanently on a feeding tube."
In 2020, a retrospective VA study linked feeding tube dependence to lower overall survival in head and neck cancer patients. There are also risks to feeding tube placement, such as infection, pain, leakage, and inflammation.
But what if feeding tube valves are inserted prophylactically so they can be used for nutrition if needed? "We just haven't had any prospective studies to get to the heart of the matter and answer the question," she said. "It's hard to recruit. How do you convince somebody to randomly be assigned to have a hole poked in their stomach?"
For the new pilot study, researchers in Phoenix decided not to randomize patients. Instead, they asked them whether they'd accept the placement of feeding tube valves on a prophylactic basis.
Thirty-six veterans enrolled in 3 years, 33% of those were eligible. Twelve have died, 1 withdrew, and 2 were lost to follow-up.
Those in the prophylactic group had worse physical function and muscle strength over time, while those who received feeding tubes when needed had more adverse events.
Why might some outcomes be worse for patients who chose the prophylactic approach? "The answer is unclear," Petersen said. "Although one possibility is that those patients had higher-risk tumors and were more clued into their own risk."
"The goal now is to get funding for an expanded, multicenter study within the VA," Petersen said. The big question that she hopes to answer is: Does a prophylactic approach work? "Does it make a difference for patients in terms of how quickly they go back to living a full, meaningful life and be able to do all the things that they normally would do?"
A complete study would likely last 7 years, but helpful results may come earlier. "We are starting to see significant differences in terms of our main outcomes of physical function," Petersen said. "We only need 1 to 2 years of data for each patient to get to the heart of that."
The study is not funded, and Petersen reported no disclosures.