Women's Health

This transcript has been edited for clarity.

I think we’re all aware that Alabama has put itself and the rest of the country into a moral bind when it comes to abortion and the status of human embryos. Back on February 16, 2024, the Alabama Supreme Court rendered a decision in a case called LePage v. Center for Reproductive Medicine, in which the court said that cryopreserved embryos in frozen nitrogen were legally equivalent to children.

They basically said they’re granted the same rights, meaning you certainly can’t destroy them. You certainly could not be in a situation where somebody said, “I’m going to not use them,” because once you create them, you seem to have some duty to make sure they end up in an environment where they can become full-fledged adults.

This decision that embryos in frozen nitrogen — but literally embryos anywhere — are the equivalent of full-bore children put Alabama in a terrible situation if you were a person or a couple seeking in vitro fertilization (IVF).

IVF requires the creation of many eggs. Women have to undergo drug treatment so that they superovulate. It’s too expensive to just go one egg at a time, egg procurement costs too much, and a cycle of IVF could cost as much as $15,000. There are some people who don’t make many eggs, so you want to get as many as you can.

When you get them, you freeze them, as happened in this Alabama case. By the way, what triggered the court case was that somebody in the lab dropped the tray with embryos in it, and they were basically accused not just of a mistake but of murder.

It’s pretty serious when you see this decision and you realize that if you make a multitude of embryos and then you had a child after two tries, but you have six more, you can’t destroy them. What are you going to do with them? Will they be under the governance of the utility company? What’s going to happen?

Many women in Alabama were outraged by the court’s opinion because they want to do IVF. In fact, politically, proponents of thinking that life begins at conception — or fetal personhood as it’s called, and the view that human embryos are children from the minute of conception — were stuck. It’s hard to argue that IVF is not pro-life. It’s hard to argue that people who desperately want to have children should find it difficult to use the technique.

The state has tried to pass a law that exempts IVF clinics from liability if they’re trying to use human embryos to make babies. I do not think this will stand. The court decision is fundamentally wrong, in part because human embryos are not children. They are potential children. They are possible children, but outside of implantation in the environment of a woman’s uterus, they’ll never become anything.

In fact, the court decision is a version of what used to be called preformationism, which sees a tiny baby inside a human embryo. That’s not true. We know today that you’ve got sets of genes that need messages from the mom in order to begin the process of division and development. It isn’t just expanding a tiny, miniature baby into a full-bore baby, as the court in Alabama seems to think.

Dr. Caplan, director, division of medical ethics, New York University Langone Medical Center, New York, has served as a director, officer, partner, employee, adviser, consultant, or trustee for Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position). He is a contributing author and adviser for Medscape.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

I think we’re all aware that Alabama has put itself and the rest of the country into a moral bind when it comes to abortion and the status of human embryos. Back on February 16, 2024, the Alabama Supreme Court rendered a decision in a case called LePage v. Center for Reproductive Medicine, in which the court said that cryopreserved embryos in frozen nitrogen were legally equivalent to children.

They basically said they’re granted the same rights, meaning you certainly can’t destroy them. You certainly could not be in a situation where somebody said, “I’m going to not use them,” because once you create them, you seem to have some duty to make sure they end up in an environment where they can become full-fledged adults.

This decision that embryos in frozen nitrogen — but literally embryos anywhere — are the equivalent of full-bore children put Alabama in a terrible situation if you were a person or a couple seeking in vitro fertilization (IVF).

IVF requires the creation of many eggs. Women have to undergo drug treatment so that they superovulate. It’s too expensive to just go one egg at a time, egg procurement costs too much, and a cycle of IVF could cost as much as $15,000. There are some people who don’t make many eggs, so you want to get as many as you can.

When you get them, you freeze them, as happened in this Alabama case. By the way, what triggered the court case was that somebody in the lab dropped the tray with embryos in it, and they were basically accused not just of a mistake but of murder.

It’s pretty serious when you see this decision and you realize that if you make a multitude of embryos and then you had a child after two tries, but you have six more, you can’t destroy them. What are you going to do with them? Will they be under the governance of the utility company? What’s going to happen?

Many women in Alabama were outraged by the court’s opinion because they want to do IVF. In fact, politically, proponents of thinking that life begins at conception — or fetal personhood as it’s called, and the view that human embryos are children from the minute of conception — were stuck. It’s hard to argue that IVF is not pro-life. It’s hard to argue that people who desperately want to have children should find it difficult to use the technique.

The state has tried to pass a law that exempts IVF clinics from liability if they’re trying to use human embryos to make babies. I do not think this will stand. The court decision is fundamentally wrong, in part because human embryos are not children. They are potential children. They are possible children, but outside of implantation in the environment of a woman’s uterus, they’ll never become anything.

In fact, the court decision is a version of what used to be called preformationism, which sees a tiny baby inside a human embryo. That’s not true. We know today that you’ve got sets of genes that need messages from the mom in order to begin the process of division and development. It isn’t just expanding a tiny, miniature baby into a full-bore baby, as the court in Alabama seems to think.

Dr. Caplan, director, division of medical ethics, New York University Langone Medical Center, New York, has served as a director, officer, partner, employee, adviser, consultant, or trustee for Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position). He is a contributing author and adviser for Medscape.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

I think we’re all aware that Alabama has put itself and the rest of the country into a moral bind when it comes to abortion and the status of human embryos. Back on February 16, 2024, the Alabama Supreme Court rendered a decision in a case called LePage v. Center for Reproductive Medicine, in which the court said that cryopreserved embryos in frozen nitrogen were legally equivalent to children.

They basically said they’re granted the same rights, meaning you certainly can’t destroy them. You certainly could not be in a situation where somebody said, “I’m going to not use them,” because once you create them, you seem to have some duty to make sure they end up in an environment where they can become full-fledged adults.

This decision that embryos in frozen nitrogen — but literally embryos anywhere — are the equivalent of full-bore children put Alabama in a terrible situation if you were a person or a couple seeking in vitro fertilization (IVF).

IVF requires the creation of many eggs. Women have to undergo drug treatment so that they superovulate. It’s too expensive to just go one egg at a time, egg procurement costs too much, and a cycle of IVF could cost as much as $15,000. There are some people who don’t make many eggs, so you want to get as many as you can.

When you get them, you freeze them, as happened in this Alabama case. By the way, what triggered the court case was that somebody in the lab dropped the tray with embryos in it, and they were basically accused not just of a mistake but of murder.

It’s pretty serious when you see this decision and you realize that if you make a multitude of embryos and then you had a child after two tries, but you have six more, you can’t destroy them. What are you going to do with them? Will they be under the governance of the utility company? What’s going to happen?

Many women in Alabama were outraged by the court’s opinion because they want to do IVF. In fact, politically, proponents of thinking that life begins at conception — or fetal personhood as it’s called, and the view that human embryos are children from the minute of conception — were stuck. It’s hard to argue that IVF is not pro-life. It’s hard to argue that people who desperately want to have children should find it difficult to use the technique.

The state has tried to pass a law that exempts IVF clinics from liability if they’re trying to use human embryos to make babies. I do not think this will stand. The court decision is fundamentally wrong, in part because human embryos are not children. They are potential children. They are possible children, but outside of implantation in the environment of a woman’s uterus, they’ll never become anything.

In fact, the court decision is a version of what used to be called preformationism, which sees a tiny baby inside a human embryo. That’s not true. We know today that you’ve got sets of genes that need messages from the mom in order to begin the process of division and development. It isn’t just expanding a tiny, miniature baby into a full-bore baby, as the court in Alabama seems to think.

Dr. Caplan, director, division of medical ethics, New York University Langone Medical Center, New York, has served as a director, officer, partner, employee, adviser, consultant, or trustee for Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position). He is a contributing author and adviser for Medscape.

A version of this article appeared on Medscape.com.

Female bias in autoimmune disease can be profound, with nine females developing lupus for every male affected, and nearly twice that ratio seen in Sjögren disease.

For years, researchers have worked to determine the reasons for sex-linked differences in immune response and autoimmunity, with environmental factors, sex hormones, and X-chromosome inactivation — the process by which a second X chromosome is silenced — all seen as having roles.

More recently, different groups of researchers have homed in on a long noncoding RNA fragment called X-inactive specific transcript, or Xist, as a potential driver of sex bias in autoimmune disease. Xist, which occurs in female mammals, has been known since the 1990s as the master regulator of X-chromosome inactivation, the process by which the second X chromosome is silenced, averting a fatal double dose of X-linked genes.

The inactivation process, which scientists liken to wrapping the extra X with a fluffy cloud of proteins, occurs early in embryonic development. After its initial work silencing the X, Xist is produced throughout the female’s life, allowing X inactivation to be maintained.

But is it possible that Xist, and the many dozens of proteins it recruits to keep that extra X chromosome silent, can also provoke autoimmunity? This is the question that several teams of researchers have been grappling with, resulting in provocative findings and opening exciting new avenues of discovery.
 

Xist Protein Complexes Make Male Mice Vulnerable to Lupus

In February, researchers Howard Chang, MD, PhD, and Diana Dou, PhD, of Stanford University in Stanford, California, made worldwide news when they published results from an experiment using male mice genetically engineered to carry a non-silencing form of Xist on one of their chromosomes.

Xist acts like a scaffold, recruiting multiple protein complexes to help it do its job. Dr. Dou explained in an interview that her team has been eyeing suspiciously for years the dozens of proteins Xist recruits in the process of X-chromosome inactivation, many of which are known autoantigens.

When the mice were injected with pristane, a chemical that induces lupus-like autoimmunity in mice, the Xist-producing males developed symptoms at a rate similar to that of females, while wild-type male mice did not.

By using a male model, the scientists could determine whether Xist could cause an increased vulnerability for autoimmunity absent the influence of female hormones and development. “Everything else about the animal is male,” Dr. Dou commented. “You just add the formation of the Xist ribonucleoprotein particles — Xist RNA plus the associating proteins — to male cells that would not ordinarily have these particles. Is just having the particles present in these animals sufficient to increase their autoimmunity? This is what our paper showed: That just having expression of Xist, the presence of these Xist [ribonucleoproteins], is enough in permissive genetic backgrounds to invoke higher incidence and severity of autoimmune disease development in our pristane-induced lupus model.”

The Stanford group sees the Xist protein complex, which they have studied extensively, as a key to understanding how Xist might provoke autoimmunity. Nonetheless, Dr. Dou said, “It’s important to note that there are other contributing factors, which is why not all females develop autoimmunity, and we had very different results in our autoimmune-resistant mouse strain compared to the more autoimmune-prone strain. Xist is a factor, but many factors are required to subvert the checkpoints in immune balance and allow the progression to full-blown autoimmunity.”
 

Faulty X Inactivation and Gene Escape

The understanding that Xist might be implicated in autoimmune disease — and explain some of its female bias — is not new.

About a decade ago, Montserrat Anguera, PhD, a biologist at the University of Pennsylvania, Philadelphia, began looking at the relationship of X-chromosome inactivation, which by definition involves Xist, and lupus.

University of Pennsylvania

Dr. Anguera hypothesized that imperfect X inactivation allowed for greater escape of genes associated with immunity and autoimmunity. Studying patients with lupus, Dr. Anguera found that the silencing process was abnormal, allowing more of these genes to escape the silenced X — including toll-like receptor 7 (TLR-7) and other genes implicated in the pathogenesis of lupus.

“If you get increased expression of certain genes from the [silenced] X, like TLR-7, it can result in autoimmune disease,” Dr. Anguera said. “So what we think is that in the lupus patients, because the silencing is impacted, you’re going to have more expression happening from the inactive X. And then in conjunction with the active X, that’s going to throw off the dosage [of autoimmunity-linked genes]. You’re changing the dosage of genes, and that’s what’s critical.”

Even among patients with lupus whose symptoms are well controlled with medication, “if you look at their T cells and B cells, they still have messed up X inactivation,” Dr. Anguera said. “The Xist RNA that’s supposed to be tethered to the inactive X in a fluffy cloud is not localized, and instead is dispersed all over the nucleus.”

Dr. Anguera pointed out that autoimmune diseases are complex and can result from a combination of factors. “You also have a host of hormonal and environmental contributors, such as previous viral infections,” she said. And of course men can also develop lupus, meaning that the X chromosome cannot explain everything.

Dr. Anguera said that, while the findings by the Stanford scientists do not explain the full pathogenesis of lupus and related diseases, they still support a strong role for Xist in sex-biased autoimmune diseases. “It’s sort of another take on it,” she said.
 

Is It the Proteins, the RNA, or Both?

The Stanford team points to the proteins recruited by Xist in the process of X-chromosome inactivation as the likely trigger of autoimmunity. However, a group of researchers at Johns Hopkins University in Baltimore, Maryland, made the case in a 2022 paper that Xist RNA itself was dangerous. They found that numerous short RNA sequences within the Xist molecule serve as ligands for TLR-7. And TLR-7 ligation causes plasmacytoid dendritic cells to overproduce type 1 interferon, a classic hallmark of lupus.

Alexander Girgis

“Within rheumatology, the diseases that tend to be most female biased are the ones that are antibody positive and have this presence of upregulated interferon,” explained Brendan Antiochos, MD. “Lupus is an example of that. Sjögren’s syndrome is another. So there’s always been this quest to want to understand the mechanisms that explain why women would have more autoimmunity. And are there specific pathways which could contribute? One of the key pathways that’s been shown in humans and in mice to be important in lupus is toll-like receptor signaling.” Most convincingly, one recent study showed that people who have a gain-of-function mutation in their TLR-7 gene get a spontaneous form of lupus.

Wes Linda

These findings led Erika Darrah, PhD, and her colleague Dr. Antiochos to begin looking more deeply into which RNAs could be triggering this signaling pathway. “We started to think: Well, there is this sex bias. Could it be that women have unique RNAs that could potentially act as triggers for TLR-7 signaling?” Dr. Darrah said.

Dr. Darrah and Dr. Antiochos looked at publicly available genetic data to identify sex-biased sources of self-RNA containing TLR-7 ligands. Xist, they found, was chock full of them. “Every time we analyzed that data, no matter what filter we applied, Xist kept popping out over and over again as the most highly female skewed RNA, the RNA most likely to contain these TLR-7 binding motifs,” Dr. Darrah said. “We started to formulate the hypothesis that Xist was actually promoting responses that were dangerous and pathogenic in lupus.”

That finding led the team to conduct in-vitro experiments that showed different fragments of Xist can activate TLR-7, resulting in higher interferon production. Finally, they looked at blood and kidney cells from women with lupus and found that higher Xist expression correlated with more interferon production, and higher disease activity. “The more Xist, the sicker people were,” Dr. Darrah said.
 

Xist’s Other Functions

Xist was first studied in the 1990s, and most research has centered on its primary role in X-chromosome inactivation. A research group led by Kathrin Plath, PhD, at the University of California, Los Angeles, has been occupied for years with untangling exactly how Xist does what it does. “It’s a very clever RNA, right? It can silence the whole chromosome,” Dr. Plath said in an interview.

In 2021, Dr. Plath and her colleagues established in detail how Xist executes silencing, setting down pairs of molecules in specific spots along the chromosome and building huge protein clouds around them. “We worked on learning where Xist binds and what proteins it binds, drilling down to understand how these proteins and the RNA are coming together.”

Dr. Plath has long suspected that Xist has other functions besides X inactivation, and she and her colleagues are starting to identify them. Early this year they published the surprising finding that Xist can regulate gene expression in autosomes, or non–sex-linked chromosomes, “which it might well also do in cancer cells and lymphocytes,” Dr. Plath said. “And now there is this new evidence of an autoimmune function,” she said. “It’s a super exciting time.”

The different hypotheses surrounding Xist’s role in sex-biased autoimmunity aren’t mutually exclusive, Dr. Plath said. “There’s a tremendous enrichment of proteins occurring” during X inactivation, she said, supporting the Stanford team’s hypothesis that proteins are triggering autoimmunity. As for the Johns Hopkins researchers’ understanding that Xist RNA itself is the trigger, “I’m totally open to that,” she said. “Why can’t it be an autoantigen?”

The other model in the field, Dr. Plath noted, is the one proposed by Dr. Anguera — “that there’s [gene] escape from X-inactivation — that females have more escape expression, and that Xist is more dispersed in the lymphocytes [of patients with lupus]. In fact, Xist becoming a little dispersed might make it a better antigen. So I do think everything is possible.”

The plethora of new findings related to autoimmunity has caused Dr. Plath to consider redirecting her lab’s focus toward more translational work, “because we are obviously good at studying Xist.” Among the mysteries Dr. Plath would like to solve is how some genes manage to escape the Xist cloud.

What is needed, she said, is collaboration. “Everyone will come up with different ideas. So I think it’s good to have more people look at things together. Then the field will achieve a breakthrough treatment.”

Female bias in autoimmune disease can be profound, with nine females developing lupus for every male affected, and nearly twice that ratio seen in Sjögren disease.

For years, researchers have worked to determine the reasons for sex-linked differences in immune response and autoimmunity, with environmental factors, sex hormones, and X-chromosome inactivation — the process by which a second X chromosome is silenced — all seen as having roles.

More recently, different groups of researchers have homed in on a long noncoding RNA fragment called X-inactive specific transcript, or Xist, as a potential driver of sex bias in autoimmune disease. Xist, which occurs in female mammals, has been known since the 1990s as the master regulator of X-chromosome inactivation, the process by which the second X chromosome is silenced, averting a fatal double dose of X-linked genes.

The inactivation process, which scientists liken to wrapping the extra X with a fluffy cloud of proteins, occurs early in embryonic development. After its initial work silencing the X, Xist is produced throughout the female’s life, allowing X inactivation to be maintained.

But is it possible that Xist, and the many dozens of proteins it recruits to keep that extra X chromosome silent, can also provoke autoimmunity? This is the question that several teams of researchers have been grappling with, resulting in provocative findings and opening exciting new avenues of discovery.
 

Xist Protein Complexes Make Male Mice Vulnerable to Lupus

In February, researchers Howard Chang, MD, PhD, and Diana Dou, PhD, of Stanford University in Stanford, California, made worldwide news when they published results from an experiment using male mice genetically engineered to carry a non-silencing form of Xist on one of their chromosomes.

Xist acts like a scaffold, recruiting multiple protein complexes to help it do its job. Dr. Dou explained in an interview that her team has been eyeing suspiciously for years the dozens of proteins Xist recruits in the process of X-chromosome inactivation, many of which are known autoantigens.

When the mice were injected with pristane, a chemical that induces lupus-like autoimmunity in mice, the Xist-producing males developed symptoms at a rate similar to that of females, while wild-type male mice did not.

By using a male model, the scientists could determine whether Xist could cause an increased vulnerability for autoimmunity absent the influence of female hormones and development. “Everything else about the animal is male,” Dr. Dou commented. “You just add the formation of the Xist ribonucleoprotein particles — Xist RNA plus the associating proteins — to male cells that would not ordinarily have these particles. Is just having the particles present in these animals sufficient to increase their autoimmunity? This is what our paper showed: That just having expression of Xist, the presence of these Xist [ribonucleoproteins], is enough in permissive genetic backgrounds to invoke higher incidence and severity of autoimmune disease development in our pristane-induced lupus model.”

The Stanford group sees the Xist protein complex, which they have studied extensively, as a key to understanding how Xist might provoke autoimmunity. Nonetheless, Dr. Dou said, “It’s important to note that there are other contributing factors, which is why not all females develop autoimmunity, and we had very different results in our autoimmune-resistant mouse strain compared to the more autoimmune-prone strain. Xist is a factor, but many factors are required to subvert the checkpoints in immune balance and allow the progression to full-blown autoimmunity.”
 

Faulty X Inactivation and Gene Escape

The understanding that Xist might be implicated in autoimmune disease — and explain some of its female bias — is not new.

About a decade ago, Montserrat Anguera, PhD, a biologist at the University of Pennsylvania, Philadelphia, began looking at the relationship of X-chromosome inactivation, which by definition involves Xist, and lupus.

University of Pennsylvania

Dr. Anguera hypothesized that imperfect X inactivation allowed for greater escape of genes associated with immunity and autoimmunity. Studying patients with lupus, Dr. Anguera found that the silencing process was abnormal, allowing more of these genes to escape the silenced X — including toll-like receptor 7 (TLR-7) and other genes implicated in the pathogenesis of lupus.

“If you get increased expression of certain genes from the [silenced] X, like TLR-7, it can result in autoimmune disease,” Dr. Anguera said. “So what we think is that in the lupus patients, because the silencing is impacted, you’re going to have more expression happening from the inactive X. And then in conjunction with the active X, that’s going to throw off the dosage [of autoimmunity-linked genes]. You’re changing the dosage of genes, and that’s what’s critical.”

Even among patients with lupus whose symptoms are well controlled with medication, “if you look at their T cells and B cells, they still have messed up X inactivation,” Dr. Anguera said. “The Xist RNA that’s supposed to be tethered to the inactive X in a fluffy cloud is not localized, and instead is dispersed all over the nucleus.”

Dr. Anguera pointed out that autoimmune diseases are complex and can result from a combination of factors. “You also have a host of hormonal and environmental contributors, such as previous viral infections,” she said. And of course men can also develop lupus, meaning that the X chromosome cannot explain everything.

Dr. Anguera said that, while the findings by the Stanford scientists do not explain the full pathogenesis of lupus and related diseases, they still support a strong role for Xist in sex-biased autoimmune diseases. “It’s sort of another take on it,” she said.
 

Is It the Proteins, the RNA, or Both?

The Stanford team points to the proteins recruited by Xist in the process of X-chromosome inactivation as the likely trigger of autoimmunity. However, a group of researchers at Johns Hopkins University in Baltimore, Maryland, made the case in a 2022 paper that Xist RNA itself was dangerous. They found that numerous short RNA sequences within the Xist molecule serve as ligands for TLR-7. And TLR-7 ligation causes plasmacytoid dendritic cells to overproduce type 1 interferon, a classic hallmark of lupus.

Alexander Girgis

“Within rheumatology, the diseases that tend to be most female biased are the ones that are antibody positive and have this presence of upregulated interferon,” explained Brendan Antiochos, MD. “Lupus is an example of that. Sjögren’s syndrome is another. So there’s always been this quest to want to understand the mechanisms that explain why women would have more autoimmunity. And are there specific pathways which could contribute? One of the key pathways that’s been shown in humans and in mice to be important in lupus is toll-like receptor signaling.” Most convincingly, one recent study showed that people who have a gain-of-function mutation in their TLR-7 gene get a spontaneous form of lupus.

Wes Linda

These findings led Erika Darrah, PhD, and her colleague Dr. Antiochos to begin looking more deeply into which RNAs could be triggering this signaling pathway. “We started to think: Well, there is this sex bias. Could it be that women have unique RNAs that could potentially act as triggers for TLR-7 signaling?” Dr. Darrah said.

Dr. Darrah and Dr. Antiochos looked at publicly available genetic data to identify sex-biased sources of self-RNA containing TLR-7 ligands. Xist, they found, was chock full of them. “Every time we analyzed that data, no matter what filter we applied, Xist kept popping out over and over again as the most highly female skewed RNA, the RNA most likely to contain these TLR-7 binding motifs,” Dr. Darrah said. “We started to formulate the hypothesis that Xist was actually promoting responses that were dangerous and pathogenic in lupus.”

That finding led the team to conduct in-vitro experiments that showed different fragments of Xist can activate TLR-7, resulting in higher interferon production. Finally, they looked at blood and kidney cells from women with lupus and found that higher Xist expression correlated with more interferon production, and higher disease activity. “The more Xist, the sicker people were,” Dr. Darrah said.
 

Xist’s Other Functions

Xist was first studied in the 1990s, and most research has centered on its primary role in X-chromosome inactivation. A research group led by Kathrin Plath, PhD, at the University of California, Los Angeles, has been occupied for years with untangling exactly how Xist does what it does. “It’s a very clever RNA, right? It can silence the whole chromosome,” Dr. Plath said in an interview.

In 2021, Dr. Plath and her colleagues established in detail how Xist executes silencing, setting down pairs of molecules in specific spots along the chromosome and building huge protein clouds around them. “We worked on learning where Xist binds and what proteins it binds, drilling down to understand how these proteins and the RNA are coming together.”

Dr. Plath has long suspected that Xist has other functions besides X inactivation, and she and her colleagues are starting to identify them. Early this year they published the surprising finding that Xist can regulate gene expression in autosomes, or non–sex-linked chromosomes, “which it might well also do in cancer cells and lymphocytes,” Dr. Plath said. “And now there is this new evidence of an autoimmune function,” she said. “It’s a super exciting time.”

The different hypotheses surrounding Xist’s role in sex-biased autoimmunity aren’t mutually exclusive, Dr. Plath said. “There’s a tremendous enrichment of proteins occurring” during X inactivation, she said, supporting the Stanford team’s hypothesis that proteins are triggering autoimmunity. As for the Johns Hopkins researchers’ understanding that Xist RNA itself is the trigger, “I’m totally open to that,” she said. “Why can’t it be an autoantigen?”

The other model in the field, Dr. Plath noted, is the one proposed by Dr. Anguera — “that there’s [gene] escape from X-inactivation — that females have more escape expression, and that Xist is more dispersed in the lymphocytes [of patients with lupus]. In fact, Xist becoming a little dispersed might make it a better antigen. So I do think everything is possible.”

The plethora of new findings related to autoimmunity has caused Dr. Plath to consider redirecting her lab’s focus toward more translational work, “because we are obviously good at studying Xist.” Among the mysteries Dr. Plath would like to solve is how some genes manage to escape the Xist cloud.

What is needed, she said, is collaboration. “Everyone will come up with different ideas. So I think it’s good to have more people look at things together. Then the field will achieve a breakthrough treatment.”

Female bias in autoimmune disease can be profound, with nine females developing lupus for every male affected, and nearly twice that ratio seen in Sjögren disease.

For years, researchers have worked to determine the reasons for sex-linked differences in immune response and autoimmunity, with environmental factors, sex hormones, and X-chromosome inactivation — the process by which a second X chromosome is silenced — all seen as having roles.

More recently, different groups of researchers have homed in on a long noncoding RNA fragment called X-inactive specific transcript, or Xist, as a potential driver of sex bias in autoimmune disease. Xist, which occurs in female mammals, has been known since the 1990s as the master regulator of X-chromosome inactivation, the process by which the second X chromosome is silenced, averting a fatal double dose of X-linked genes.

The inactivation process, which scientists liken to wrapping the extra X with a fluffy cloud of proteins, occurs early in embryonic development. After its initial work silencing the X, Xist is produced throughout the female’s life, allowing X inactivation to be maintained.

But is it possible that Xist, and the many dozens of proteins it recruits to keep that extra X chromosome silent, can also provoke autoimmunity? This is the question that several teams of researchers have been grappling with, resulting in provocative findings and opening exciting new avenues of discovery.
 

Xist Protein Complexes Make Male Mice Vulnerable to Lupus

In February, researchers Howard Chang, MD, PhD, and Diana Dou, PhD, of Stanford University in Stanford, California, made worldwide news when they published results from an experiment using male mice genetically engineered to carry a non-silencing form of Xist on one of their chromosomes.

Xist acts like a scaffold, recruiting multiple protein complexes to help it do its job. Dr. Dou explained in an interview that her team has been eyeing suspiciously for years the dozens of proteins Xist recruits in the process of X-chromosome inactivation, many of which are known autoantigens.

When the mice were injected with pristane, a chemical that induces lupus-like autoimmunity in mice, the Xist-producing males developed symptoms at a rate similar to that of females, while wild-type male mice did not.

By using a male model, the scientists could determine whether Xist could cause an increased vulnerability for autoimmunity absent the influence of female hormones and development. “Everything else about the animal is male,” Dr. Dou commented. “You just add the formation of the Xist ribonucleoprotein particles — Xist RNA plus the associating proteins — to male cells that would not ordinarily have these particles. Is just having the particles present in these animals sufficient to increase their autoimmunity? This is what our paper showed: That just having expression of Xist, the presence of these Xist [ribonucleoproteins], is enough in permissive genetic backgrounds to invoke higher incidence and severity of autoimmune disease development in our pristane-induced lupus model.”

The Stanford group sees the Xist protein complex, which they have studied extensively, as a key to understanding how Xist might provoke autoimmunity. Nonetheless, Dr. Dou said, “It’s important to note that there are other contributing factors, which is why not all females develop autoimmunity, and we had very different results in our autoimmune-resistant mouse strain compared to the more autoimmune-prone strain. Xist is a factor, but many factors are required to subvert the checkpoints in immune balance and allow the progression to full-blown autoimmunity.”
 

Faulty X Inactivation and Gene Escape

The understanding that Xist might be implicated in autoimmune disease — and explain some of its female bias — is not new.

About a decade ago, Montserrat Anguera, PhD, a biologist at the University of Pennsylvania, Philadelphia, began looking at the relationship of X-chromosome inactivation, which by definition involves Xist, and lupus.

University of Pennsylvania

Dr. Anguera hypothesized that imperfect X inactivation allowed for greater escape of genes associated with immunity and autoimmunity. Studying patients with lupus, Dr. Anguera found that the silencing process was abnormal, allowing more of these genes to escape the silenced X — including toll-like receptor 7 (TLR-7) and other genes implicated in the pathogenesis of lupus.

“If you get increased expression of certain genes from the [silenced] X, like TLR-7, it can result in autoimmune disease,” Dr. Anguera said. “So what we think is that in the lupus patients, because the silencing is impacted, you’re going to have more expression happening from the inactive X. And then in conjunction with the active X, that’s going to throw off the dosage [of autoimmunity-linked genes]. You’re changing the dosage of genes, and that’s what’s critical.”

Even among patients with lupus whose symptoms are well controlled with medication, “if you look at their T cells and B cells, they still have messed up X inactivation,” Dr. Anguera said. “The Xist RNA that’s supposed to be tethered to the inactive X in a fluffy cloud is not localized, and instead is dispersed all over the nucleus.”

Dr. Anguera pointed out that autoimmune diseases are complex and can result from a combination of factors. “You also have a host of hormonal and environmental contributors, such as previous viral infections,” she said. And of course men can also develop lupus, meaning that the X chromosome cannot explain everything.

Dr. Anguera said that, while the findings by the Stanford scientists do not explain the full pathogenesis of lupus and related diseases, they still support a strong role for Xist in sex-biased autoimmune diseases. “It’s sort of another take on it,” she said.
 

Is It the Proteins, the RNA, or Both?

The Stanford team points to the proteins recruited by Xist in the process of X-chromosome inactivation as the likely trigger of autoimmunity. However, a group of researchers at Johns Hopkins University in Baltimore, Maryland, made the case in a 2022 paper that Xist RNA itself was dangerous. They found that numerous short RNA sequences within the Xist molecule serve as ligands for TLR-7. And TLR-7 ligation causes plasmacytoid dendritic cells to overproduce type 1 interferon, a classic hallmark of lupus.

Alexander Girgis

“Within rheumatology, the diseases that tend to be most female biased are the ones that are antibody positive and have this presence of upregulated interferon,” explained Brendan Antiochos, MD. “Lupus is an example of that. Sjögren’s syndrome is another. So there’s always been this quest to want to understand the mechanisms that explain why women would have more autoimmunity. And are there specific pathways which could contribute? One of the key pathways that’s been shown in humans and in mice to be important in lupus is toll-like receptor signaling.” Most convincingly, one recent study showed that people who have a gain-of-function mutation in their TLR-7 gene get a spontaneous form of lupus.

Wes Linda

These findings led Erika Darrah, PhD, and her colleague Dr. Antiochos to begin looking more deeply into which RNAs could be triggering this signaling pathway. “We started to think: Well, there is this sex bias. Could it be that women have unique RNAs that could potentially act as triggers for TLR-7 signaling?” Dr. Darrah said.

Dr. Darrah and Dr. Antiochos looked at publicly available genetic data to identify sex-biased sources of self-RNA containing TLR-7 ligands. Xist, they found, was chock full of them. “Every time we analyzed that data, no matter what filter we applied, Xist kept popping out over and over again as the most highly female skewed RNA, the RNA most likely to contain these TLR-7 binding motifs,” Dr. Darrah said. “We started to formulate the hypothesis that Xist was actually promoting responses that were dangerous and pathogenic in lupus.”

That finding led the team to conduct in-vitro experiments that showed different fragments of Xist can activate TLR-7, resulting in higher interferon production. Finally, they looked at blood and kidney cells from women with lupus and found that higher Xist expression correlated with more interferon production, and higher disease activity. “The more Xist, the sicker people were,” Dr. Darrah said.
 

Xist’s Other Functions

Xist was first studied in the 1990s, and most research has centered on its primary role in X-chromosome inactivation. A research group led by Kathrin Plath, PhD, at the University of California, Los Angeles, has been occupied for years with untangling exactly how Xist does what it does. “It’s a very clever RNA, right? It can silence the whole chromosome,” Dr. Plath said in an interview.

In 2021, Dr. Plath and her colleagues established in detail how Xist executes silencing, setting down pairs of molecules in specific spots along the chromosome and building huge protein clouds around them. “We worked on learning where Xist binds and what proteins it binds, drilling down to understand how these proteins and the RNA are coming together.”

Dr. Plath has long suspected that Xist has other functions besides X inactivation, and she and her colleagues are starting to identify them. Early this year they published the surprising finding that Xist can regulate gene expression in autosomes, or non–sex-linked chromosomes, “which it might well also do in cancer cells and lymphocytes,” Dr. Plath said. “And now there is this new evidence of an autoimmune function,” she said. “It’s a super exciting time.”

The different hypotheses surrounding Xist’s role in sex-biased autoimmunity aren’t mutually exclusive, Dr. Plath said. “There’s a tremendous enrichment of proteins occurring” during X inactivation, she said, supporting the Stanford team’s hypothesis that proteins are triggering autoimmunity. As for the Johns Hopkins researchers’ understanding that Xist RNA itself is the trigger, “I’m totally open to that,” she said. “Why can’t it be an autoantigen?”

The other model in the field, Dr. Plath noted, is the one proposed by Dr. Anguera — “that there’s [gene] escape from X-inactivation — that females have more escape expression, and that Xist is more dispersed in the lymphocytes [of patients with lupus]. In fact, Xist becoming a little dispersed might make it a better antigen. So I do think everything is possible.”

The plethora of new findings related to autoimmunity has caused Dr. Plath to consider redirecting her lab’s focus toward more translational work, “because we are obviously good at studying Xist.” Among the mysteries Dr. Plath would like to solve is how some genes manage to escape the Xist cloud.

What is needed, she said, is collaboration. “Everyone will come up with different ideas. So I think it’s good to have more people look at things together. Then the field will achieve a breakthrough treatment.”

Disparities and geographical variations in cervical cancer outcomes appear to be related to social determinants of health, including socioeconomic status, race or ethnicity, and proximity to facilities skilled at early-stage diagnosis and treatment.

These findings come from analyses of insurance data gathered via the Cervical Cancer Geo-Analyzer tool, a publicly available online instrument designed to provide visual representation of recurrent or metastatic cervical cancer burden across metropolitan statistical areas in the United States over multiple years.

[Reporting the findings of] “this study is the first step to optimize healthcare resources allocations, advocate for policy changes that will minimize access barriers, and tailor education for modern treatment options to help reduce and improve outcomes for cervical cancer in US patients,” said Tara Castellano, MD, an author and presenter of this new research, at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer, held in San Diego.

Seeing Cancer Cases

Dr. Castellano and colleagues previously reported that the Geo-Analyzer tool effectively provides quantified evidence of cervical cancer disease burden and graphic representation of geographical variations across the United States for both incident and recurrent/metastatic cervical cancer.

In the current analysis, Dr. Castellano, of Louisiana State University School of Medicine in New Orleans, discussed potential factors related to cervical cancer incidence and geographic variations.

The study builds on previous studies that have shown that Black and Hispanic women have longer time to treatment and worse cervical cancer outcomes than White women.

For example, in a study published in the International Journal of Gynecologic Cancer, Marilyn Huang, MD, and colleagues from the University of Miami Miller School of Medicine, Miami, Florida, and other centers in Miami looked at time to treatment in a diverse population of 274 women starting therapy for cervical cancer.

They found that insurance type (private, public, or none) contributed to delay in treatment initiation regardless of the treatment modality, and that the patient’s language and institution of diagnosis also influenced time to treatment.

In a separate scientific poster presented at SGO 2024, Dr. Castellano and colleagues reported that, among women with newly diagnosed endometrial cancer, the median time to treatment was 7 days longer for both Hispanic and Black women, compared with non-Hispanic White women. In addition, Black women had a 7-day longer time to receiving their first therapy for advanced disease. All of these differences were statistically significant.

Dr. Castellano told this news organization that the time-to-treatment disparities in the endometrial cancer study were determined by diagnostic codes and the timing of insurance claims.

Reasons for the disparities may include more limited access to care and structural and systemic biases in the healthcare systems where the majority of Black and Hispanic patients live, she said.

Insurance Database

In the new study on cervical cancer, Dr. Castellano and her team defined cervical cancer burden as prevalent cervical cancer diagnosis per 100,000 eligible women enrolled in a commercial insurance plan, Medicaid, or Medicare Advantage. Recurrent or metastatic cancer was determined to be the proportion of patients with cervical cancer who initiated systemic therapy.

The goals of the study were to provide a visualization of geographical distribution of cervical cancer in the US, and to quantify associations between early or advanced cancers with screening rates, poverty level, race/ethnicity, and access to brachytherapy.

The administrative claims database queried for the study included information on 75,521 women (median age 53) with a first diagnosis of cervical cancer from 2015 through 2022, and 14,033 women with recurrent or metastatic malignancies (median age 59 years).

Distribution of cases was higher in the South compared with in other US regions (37% vs approximately 20% for other regions).

Looking at the association between screening rates and disease burden from 2017 through 2022, the Geo-Analyzer showed that higher screening rates were significantly associated with decreased burden of new cases only in the South, whereas higher screening rates were associated with lower recurrent/metastatic disease burden in the Midwest and South, but a higher disease burden in the West.

In all regions, there was a significant association between decreased early cancer burden in areas with high percentages of women of Asian heritage, and significantly increased burden in areas with large populations of women of Hispanic origin.

The only significant association of race/ethnicity with recurrent/metastatic burden was a decrease in the Midwest in populations with large Asian populations.

An analysis of the how poverty levels affected screening and disease burden showed that in areas with a high percentage of low-income households there were significant associations with decreased cervical cancer screening and higher burden of newly diagnosed cases.

Poverty levels were significantly associated with recurrent/metastatic cancers only in the South.

The investigators also found that the presence of one or more brachytherapy centers within a ZIP-3 region (that is, a large geographic area designated by the first 3 digits of ZIP codes rather than 5-digit city codes) was associated with a 2.7% reduction in recurrent or metastatic cervical cancer burden (P less than .001).

Demographic Marker?

Reasons for disparities are complex and may involve a combination of inadequate health literacy and social and economic circumstances, said Cesar Castro, MD, commenting on the new cervical cancer study.

He noted in an interview that “the concept that a single Pap smear is often insufficient to capture precancerous changes, and hence the need for serial testing every 3 years, can be lost on individuals who also have competing challenges securing paychecks and/or dependent care. Historical barriers such as perceptions of the underlying cause of cervical cancer, the HPV virus, being a sexually transmitted disease and hence a taboo subject, also underpin decision-making. These sentiments have also fueled resistance towards HPV vaccination in young girls and boys.”

Dr. Castro, who is Program Director for Gynecologic Oncology at the Mass General Cancer Center in Boston, pointed out that treatments for cervical cancer often involve surgery or a combination of chemotherapy and radiation, and that side effects from these interventions may be especially disruptive to the lives of women who are breadwinners or caregivers for their families.

“These are the shackles that poverty places on many Black and Hispanic women notably in under-resourced regions domestically and globally,” he said.

The study was supported by Seagen and Genmab. Dr. Castellano disclosed consulting fees from GSK and Nykode and grant support from BMS. Dr. Castro reported no relevant conflicts of interest and was not involved in either of the studies presented at the meeting.

Disparities and geographical variations in cervical cancer outcomes appear to be related to social determinants of health, including socioeconomic status, race or ethnicity, and proximity to facilities skilled at early-stage diagnosis and treatment.

These findings come from analyses of insurance data gathered via the Cervical Cancer Geo-Analyzer tool, a publicly available online instrument designed to provide visual representation of recurrent or metastatic cervical cancer burden across metropolitan statistical areas in the United States over multiple years.

[Reporting the findings of] “this study is the first step to optimize healthcare resources allocations, advocate for policy changes that will minimize access barriers, and tailor education for modern treatment options to help reduce and improve outcomes for cervical cancer in US patients,” said Tara Castellano, MD, an author and presenter of this new research, at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer, held in San Diego.

Seeing Cancer Cases

Dr. Castellano and colleagues previously reported that the Geo-Analyzer tool effectively provides quantified evidence of cervical cancer disease burden and graphic representation of geographical variations across the United States for both incident and recurrent/metastatic cervical cancer.

In the current analysis, Dr. Castellano, of Louisiana State University School of Medicine in New Orleans, discussed potential factors related to cervical cancer incidence and geographic variations.

The study builds on previous studies that have shown that Black and Hispanic women have longer time to treatment and worse cervical cancer outcomes than White women.

For example, in a study published in the International Journal of Gynecologic Cancer, Marilyn Huang, MD, and colleagues from the University of Miami Miller School of Medicine, Miami, Florida, and other centers in Miami looked at time to treatment in a diverse population of 274 women starting therapy for cervical cancer.

They found that insurance type (private, public, or none) contributed to delay in treatment initiation regardless of the treatment modality, and that the patient’s language and institution of diagnosis also influenced time to treatment.

In a separate scientific poster presented at SGO 2024, Dr. Castellano and colleagues reported that, among women with newly diagnosed endometrial cancer, the median time to treatment was 7 days longer for both Hispanic and Black women, compared with non-Hispanic White women. In addition, Black women had a 7-day longer time to receiving their first therapy for advanced disease. All of these differences were statistically significant.

Dr. Castellano told this news organization that the time-to-treatment disparities in the endometrial cancer study were determined by diagnostic codes and the timing of insurance claims.

Reasons for the disparities may include more limited access to care and structural and systemic biases in the healthcare systems where the majority of Black and Hispanic patients live, she said.

Insurance Database

In the new study on cervical cancer, Dr. Castellano and her team defined cervical cancer burden as prevalent cervical cancer diagnosis per 100,000 eligible women enrolled in a commercial insurance plan, Medicaid, or Medicare Advantage. Recurrent or metastatic cancer was determined to be the proportion of patients with cervical cancer who initiated systemic therapy.

The goals of the study were to provide a visualization of geographical distribution of cervical cancer in the US, and to quantify associations between early or advanced cancers with screening rates, poverty level, race/ethnicity, and access to brachytherapy.

The administrative claims database queried for the study included information on 75,521 women (median age 53) with a first diagnosis of cervical cancer from 2015 through 2022, and 14,033 women with recurrent or metastatic malignancies (median age 59 years).

Distribution of cases was higher in the South compared with in other US regions (37% vs approximately 20% for other regions).

Looking at the association between screening rates and disease burden from 2017 through 2022, the Geo-Analyzer showed that higher screening rates were significantly associated with decreased burden of new cases only in the South, whereas higher screening rates were associated with lower recurrent/metastatic disease burden in the Midwest and South, but a higher disease burden in the West.

In all regions, there was a significant association between decreased early cancer burden in areas with high percentages of women of Asian heritage, and significantly increased burden in areas with large populations of women of Hispanic origin.

The only significant association of race/ethnicity with recurrent/metastatic burden was a decrease in the Midwest in populations with large Asian populations.

An analysis of the how poverty levels affected screening and disease burden showed that in areas with a high percentage of low-income households there were significant associations with decreased cervical cancer screening and higher burden of newly diagnosed cases.

Poverty levels were significantly associated with recurrent/metastatic cancers only in the South.

The investigators also found that the presence of one or more brachytherapy centers within a ZIP-3 region (that is, a large geographic area designated by the first 3 digits of ZIP codes rather than 5-digit city codes) was associated with a 2.7% reduction in recurrent or metastatic cervical cancer burden (P less than .001).

Demographic Marker?

Reasons for disparities are complex and may involve a combination of inadequate health literacy and social and economic circumstances, said Cesar Castro, MD, commenting on the new cervical cancer study.

He noted in an interview that “the concept that a single Pap smear is often insufficient to capture precancerous changes, and hence the need for serial testing every 3 years, can be lost on individuals who also have competing challenges securing paychecks and/or dependent care. Historical barriers such as perceptions of the underlying cause of cervical cancer, the HPV virus, being a sexually transmitted disease and hence a taboo subject, also underpin decision-making. These sentiments have also fueled resistance towards HPV vaccination in young girls and boys.”

Dr. Castro, who is Program Director for Gynecologic Oncology at the Mass General Cancer Center in Boston, pointed out that treatments for cervical cancer often involve surgery or a combination of chemotherapy and radiation, and that side effects from these interventions may be especially disruptive to the lives of women who are breadwinners or caregivers for their families.

“These are the shackles that poverty places on many Black and Hispanic women notably in under-resourced regions domestically and globally,” he said.

The study was supported by Seagen and Genmab. Dr. Castellano disclosed consulting fees from GSK and Nykode and grant support from BMS. Dr. Castro reported no relevant conflicts of interest and was not involved in either of the studies presented at the meeting.

Disparities and geographical variations in cervical cancer outcomes appear to be related to social determinants of health, including socioeconomic status, race or ethnicity, and proximity to facilities skilled at early-stage diagnosis and treatment.

These findings come from analyses of insurance data gathered via the Cervical Cancer Geo-Analyzer tool, a publicly available online instrument designed to provide visual representation of recurrent or metastatic cervical cancer burden across metropolitan statistical areas in the United States over multiple years.

[Reporting the findings of] “this study is the first step to optimize healthcare resources allocations, advocate for policy changes that will minimize access barriers, and tailor education for modern treatment options to help reduce and improve outcomes for cervical cancer in US patients,” said Tara Castellano, MD, an author and presenter of this new research, at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer, held in San Diego.

Seeing Cancer Cases

Dr. Castellano and colleagues previously reported that the Geo-Analyzer tool effectively provides quantified evidence of cervical cancer disease burden and graphic representation of geographical variations across the United States for both incident and recurrent/metastatic cervical cancer.

In the current analysis, Dr. Castellano, of Louisiana State University School of Medicine in New Orleans, discussed potential factors related to cervical cancer incidence and geographic variations.

The study builds on previous studies that have shown that Black and Hispanic women have longer time to treatment and worse cervical cancer outcomes than White women.

For example, in a study published in the International Journal of Gynecologic Cancer, Marilyn Huang, MD, and colleagues from the University of Miami Miller School of Medicine, Miami, Florida, and other centers in Miami looked at time to treatment in a diverse population of 274 women starting therapy for cervical cancer.

They found that insurance type (private, public, or none) contributed to delay in treatment initiation regardless of the treatment modality, and that the patient’s language and institution of diagnosis also influenced time to treatment.

In a separate scientific poster presented at SGO 2024, Dr. Castellano and colleagues reported that, among women with newly diagnosed endometrial cancer, the median time to treatment was 7 days longer for both Hispanic and Black women, compared with non-Hispanic White women. In addition, Black women had a 7-day longer time to receiving their first therapy for advanced disease. All of these differences were statistically significant.

Dr. Castellano told this news organization that the time-to-treatment disparities in the endometrial cancer study were determined by diagnostic codes and the timing of insurance claims.

Reasons for the disparities may include more limited access to care and structural and systemic biases in the healthcare systems where the majority of Black and Hispanic patients live, she said.

Insurance Database

In the new study on cervical cancer, Dr. Castellano and her team defined cervical cancer burden as prevalent cervical cancer diagnosis per 100,000 eligible women enrolled in a commercial insurance plan, Medicaid, or Medicare Advantage. Recurrent or metastatic cancer was determined to be the proportion of patients with cervical cancer who initiated systemic therapy.

The goals of the study were to provide a visualization of geographical distribution of cervical cancer in the US, and to quantify associations between early or advanced cancers with screening rates, poverty level, race/ethnicity, and access to brachytherapy.

The administrative claims database queried for the study included information on 75,521 women (median age 53) with a first diagnosis of cervical cancer from 2015 through 2022, and 14,033 women with recurrent or metastatic malignancies (median age 59 years).

Distribution of cases was higher in the South compared with in other US regions (37% vs approximately 20% for other regions).

Looking at the association between screening rates and disease burden from 2017 through 2022, the Geo-Analyzer showed that higher screening rates were significantly associated with decreased burden of new cases only in the South, whereas higher screening rates were associated with lower recurrent/metastatic disease burden in the Midwest and South, but a higher disease burden in the West.

In all regions, there was a significant association between decreased early cancer burden in areas with high percentages of women of Asian heritage, and significantly increased burden in areas with large populations of women of Hispanic origin.

The only significant association of race/ethnicity with recurrent/metastatic burden was a decrease in the Midwest in populations with large Asian populations.

An analysis of the how poverty levels affected screening and disease burden showed that in areas with a high percentage of low-income households there were significant associations with decreased cervical cancer screening and higher burden of newly diagnosed cases.

Poverty levels were significantly associated with recurrent/metastatic cancers only in the South.

The investigators also found that the presence of one or more brachytherapy centers within a ZIP-3 region (that is, a large geographic area designated by the first 3 digits of ZIP codes rather than 5-digit city codes) was associated with a 2.7% reduction in recurrent or metastatic cervical cancer burden (P less than .001).

Demographic Marker?

Reasons for disparities are complex and may involve a combination of inadequate health literacy and social and economic circumstances, said Cesar Castro, MD, commenting on the new cervical cancer study.

He noted in an interview that “the concept that a single Pap smear is often insufficient to capture precancerous changes, and hence the need for serial testing every 3 years, can be lost on individuals who also have competing challenges securing paychecks and/or dependent care. Historical barriers such as perceptions of the underlying cause of cervical cancer, the HPV virus, being a sexually transmitted disease and hence a taboo subject, also underpin decision-making. These sentiments have also fueled resistance towards HPV vaccination in young girls and boys.”

Dr. Castro, who is Program Director for Gynecologic Oncology at the Mass General Cancer Center in Boston, pointed out that treatments for cervical cancer often involve surgery or a combination of chemotherapy and radiation, and that side effects from these interventions may be especially disruptive to the lives of women who are breadwinners or caregivers for their families.

“These are the shackles that poverty places on many Black and Hispanic women notably in under-resourced regions domestically and globally,” he said.

The study was supported by Seagen and Genmab. Dr. Castellano disclosed consulting fees from GSK and Nykode and grant support from BMS. Dr. Castro reported no relevant conflicts of interest and was not involved in either of the studies presented at the meeting.

Teen pregnancy is associated with a higher risk for premature mortality, both among those who carry the pregnancies to term and those who miscarry, according to a new study.

Among 2.2 million female teenagers in Ontario, Canada, the risk for premature death by age 31 years was 1.5 times higher among those who had one teen pregnancy and 2.1 times higher among those with two or more teen pregnancies.

“No person should die during childhood or early adulthood. Such deaths, unexpected and tragic, are often from preventable causes, including intentional injury,” lead author Joel Ray, MD, an obstetric medicine specialist and epidemiologist at St. Michael’s Hospital in Toronto, told this news organization. 

“Women who experience teen pregnancy appear more vulnerable, often having experienced a history of adverse experiences in childhood, including abuse and economic challenges,” he said.

The study was published online in JAMA Network Open.
 

Analyzing Pregnancy Associations

The investigators conducted a population-based cohort study of all girls who were alive at age 12 years from April 1991 to March 2021 in Ontario. They evaluated the risk for all-cause mortality from age 12 years onward in association with the number of teen pregnancies between ages 12 and 19 years and the age at first pregnancy. The investigators adjusted the hazard ratios for year of birth, comorbidities at ages 9-11 years, area-level education, income level, and rural status.

Among more than 2.2 million teens, 163,124 (7.3%) had a pregnancy at a median age of 18 years, including 121,276 (74.3%) who had one pregnancy and 41,848 (25.6%) who had two or more. These teens were more likely to live in the lowest neighborhood income quintile and in an area with a lower rate of high school completion. They also had a higher prevalence of self-harm history between ages 12 and 19 years but not a higher prevalence of physical or mental comorbidities.

Among all teens who had a pregnancy, 60,037 (36.8%) ended in a birth, including 59,485 (99.1%) live births. A further 106,135 (65.1%) ended in induced abortion, and 17,945 (11%) ended in miscarriage or ectopic pregnancy.

Overall, there were 6030 premature deaths among those without a teen pregnancy, or 1.9 per 10,000 person-years. There were 701 deaths among those with one teen pregnancy (4.1 per 10,000 person-years) and 345 deaths among those with two or more teen pregnancies (6.1 per 10,000 person-years).

The adjusted hazard ratios (AHRs) for mortality were 1.51 for those with one pregnancy and 2.14 for those with two or more pregnancies. Compared with no teen pregnancy, the AHRs for premature death were 1.41 if the first teen pregnancy ended in an induced abortion and 2.10 if it ended in a miscarriage or birth.

Comparing those with a teen pregnancy and those without, the AHRs for premature death were 1.25 from noninjury, 2.06 from unintentional injury, and 2.02 from intentional injury. Among patients with teen pregnancy, noninjury-related premature mortality was more common, at 2.0 per 10,000 person-years, than unintentional and intentional injuries, at 1.0 per 10,000 person-years and 0.4 per 10,000 person-years, respectively.

A teen pregnancy before age 16 years entailed the highest associated risk for premature death, with an AHR of 2.00.
 

Next Research Steps

“We were not surprised by our findings, but it was new to us to see that the risk for premature death was higher for women who had an induced abortion in their teen years,” said Dr. Ray. “It was even higher in those whose pregnancy ended in a birth or miscarriage.”

The investigators plan to evaluate whether the future risk for premature death after teen pregnancy differs by the type of induced abortion, such as procedural or pharmaceutical, or by whether the pregnancy ended in a live birth, stillbirth, or miscarriage. Among those with a live birth, the researchers will also analyze the risk for premature death in relation to whether the newborn was taken into custody by child protection services in Canada.

Other factors associated with teen pregnancy and overall mortality, particularly adverse childhood experiences, may point to the reasons for premature mortality and should be studied further, the authors wrote. Structural and systems-related factors should be considered as well.
 

Stigmatization and Isolation 

“Some teens choose to become pregnant, but most teen pregnancies are unintended, which exposes shortcomings in the systems that exist to educate, guide, and support young people,” said Elizabeth Cook, a research scientist at Child Trends in Rockville, Maryland.

Dr. Cook, who wasn’t involved with this study, wrote an accompanying editorial in JAMA Network Open. She conducts studies of sexual and reproductive health for Child Trends.

“Teens who become pregnant often experience stigmatization and isolation that can make it more difficult to thrive in adulthood, especially if they lack the necessary support to navigate such a significant decision,” she said. “Fortunately, the systems that youths encounter, such as healthcare, education, and child welfare, are taking on a larger role in prevention efforts than they have in the past.”

These systems are shifting the burden of unintended teen pregnancy from the teens themselves and their behaviors to the health and education systems, Dr. Cook noted, though more work is needed around local policies and lack of access to healthcare facilities. 

“Teen pregnancy may offer an opportunity to intervene in the lives of people at higher risk for premature death, but knowing how best to offer support requires an understanding of the context of their lives,” she said. “As a starting point, we must celebrate and listen to all pregnant young people so they can tell us what they need to live long, fulfilled lives.”

The study was funded by grants from the PSI Foundation and the Canadian Institutes of Health Research, as well as ICES, which is funded by the Ontario Ministry of Health and the Ministry of Long-Term Care. Dr. Ray and Dr. Cook reported no relevant disclosures. 

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

Teen pregnancy is associated with a higher risk for premature mortality, both among those who carry the pregnancies to term and those who miscarry, according to a new study.

Among 2.2 million female teenagers in Ontario, Canada, the risk for premature death by age 31 years was 1.5 times higher among those who had one teen pregnancy and 2.1 times higher among those with two or more teen pregnancies.

“No person should die during childhood or early adulthood. Such deaths, unexpected and tragic, are often from preventable causes, including intentional injury,” lead author Joel Ray, MD, an obstetric medicine specialist and epidemiologist at St. Michael’s Hospital in Toronto, told this news organization. 

“Women who experience teen pregnancy appear more vulnerable, often having experienced a history of adverse experiences in childhood, including abuse and economic challenges,” he said.

The study was published online in JAMA Network Open.
 

Analyzing Pregnancy Associations

The investigators conducted a population-based cohort study of all girls who were alive at age 12 years from April 1991 to March 2021 in Ontario. They evaluated the risk for all-cause mortality from age 12 years onward in association with the number of teen pregnancies between ages 12 and 19 years and the age at first pregnancy. The investigators adjusted the hazard ratios for year of birth, comorbidities at ages 9-11 years, area-level education, income level, and rural status.

Among more than 2.2 million teens, 163,124 (7.3%) had a pregnancy at a median age of 18 years, including 121,276 (74.3%) who had one pregnancy and 41,848 (25.6%) who had two or more. These teens were more likely to live in the lowest neighborhood income quintile and in an area with a lower rate of high school completion. They also had a higher prevalence of self-harm history between ages 12 and 19 years but not a higher prevalence of physical or mental comorbidities.

Among all teens who had a pregnancy, 60,037 (36.8%) ended in a birth, including 59,485 (99.1%) live births. A further 106,135 (65.1%) ended in induced abortion, and 17,945 (11%) ended in miscarriage or ectopic pregnancy.

Overall, there were 6030 premature deaths among those without a teen pregnancy, or 1.9 per 10,000 person-years. There were 701 deaths among those with one teen pregnancy (4.1 per 10,000 person-years) and 345 deaths among those with two or more teen pregnancies (6.1 per 10,000 person-years).

The adjusted hazard ratios (AHRs) for mortality were 1.51 for those with one pregnancy and 2.14 for those with two or more pregnancies. Compared with no teen pregnancy, the AHRs for premature death were 1.41 if the first teen pregnancy ended in an induced abortion and 2.10 if it ended in a miscarriage or birth.

Comparing those with a teen pregnancy and those without, the AHRs for premature death were 1.25 from noninjury, 2.06 from unintentional injury, and 2.02 from intentional injury. Among patients with teen pregnancy, noninjury-related premature mortality was more common, at 2.0 per 10,000 person-years, than unintentional and intentional injuries, at 1.0 per 10,000 person-years and 0.4 per 10,000 person-years, respectively.

A teen pregnancy before age 16 years entailed the highest associated risk for premature death, with an AHR of 2.00.
 

Next Research Steps

“We were not surprised by our findings, but it was new to us to see that the risk for premature death was higher for women who had an induced abortion in their teen years,” said Dr. Ray. “It was even higher in those whose pregnancy ended in a birth or miscarriage.”

The investigators plan to evaluate whether the future risk for premature death after teen pregnancy differs by the type of induced abortion, such as procedural or pharmaceutical, or by whether the pregnancy ended in a live birth, stillbirth, or miscarriage. Among those with a live birth, the researchers will also analyze the risk for premature death in relation to whether the newborn was taken into custody by child protection services in Canada.

Other factors associated with teen pregnancy and overall mortality, particularly adverse childhood experiences, may point to the reasons for premature mortality and should be studied further, the authors wrote. Structural and systems-related factors should be considered as well.
 

Stigmatization and Isolation 

“Some teens choose to become pregnant, but most teen pregnancies are unintended, which exposes shortcomings in the systems that exist to educate, guide, and support young people,” said Elizabeth Cook, a research scientist at Child Trends in Rockville, Maryland.

Dr. Cook, who wasn’t involved with this study, wrote an accompanying editorial in JAMA Network Open. She conducts studies of sexual and reproductive health for Child Trends.

“Teens who become pregnant often experience stigmatization and isolation that can make it more difficult to thrive in adulthood, especially if they lack the necessary support to navigate such a significant decision,” she said. “Fortunately, the systems that youths encounter, such as healthcare, education, and child welfare, are taking on a larger role in prevention efforts than they have in the past.”

These systems are shifting the burden of unintended teen pregnancy from the teens themselves and their behaviors to the health and education systems, Dr. Cook noted, though more work is needed around local policies and lack of access to healthcare facilities. 

“Teen pregnancy may offer an opportunity to intervene in the lives of people at higher risk for premature death, but knowing how best to offer support requires an understanding of the context of their lives,” she said. “As a starting point, we must celebrate and listen to all pregnant young people so they can tell us what they need to live long, fulfilled lives.”

The study was funded by grants from the PSI Foundation and the Canadian Institutes of Health Research, as well as ICES, which is funded by the Ontario Ministry of Health and the Ministry of Long-Term Care. Dr. Ray and Dr. Cook reported no relevant disclosures. 

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

Teen pregnancy is associated with a higher risk for premature mortality, both among those who carry the pregnancies to term and those who miscarry, according to a new study.

Among 2.2 million female teenagers in Ontario, Canada, the risk for premature death by age 31 years was 1.5 times higher among those who had one teen pregnancy and 2.1 times higher among those with two or more teen pregnancies.

“No person should die during childhood or early adulthood. Such deaths, unexpected and tragic, are often from preventable causes, including intentional injury,” lead author Joel Ray, MD, an obstetric medicine specialist and epidemiologist at St. Michael’s Hospital in Toronto, told this news organization. 

“Women who experience teen pregnancy appear more vulnerable, often having experienced a history of adverse experiences in childhood, including abuse and economic challenges,” he said.

The study was published online in JAMA Network Open.
 

Analyzing Pregnancy Associations

The investigators conducted a population-based cohort study of all girls who were alive at age 12 years from April 1991 to March 2021 in Ontario. They evaluated the risk for all-cause mortality from age 12 years onward in association with the number of teen pregnancies between ages 12 and 19 years and the age at first pregnancy. The investigators adjusted the hazard ratios for year of birth, comorbidities at ages 9-11 years, area-level education, income level, and rural status.

Among more than 2.2 million teens, 163,124 (7.3%) had a pregnancy at a median age of 18 years, including 121,276 (74.3%) who had one pregnancy and 41,848 (25.6%) who had two or more. These teens were more likely to live in the lowest neighborhood income quintile and in an area with a lower rate of high school completion. They also had a higher prevalence of self-harm history between ages 12 and 19 years but not a higher prevalence of physical or mental comorbidities.

Among all teens who had a pregnancy, 60,037 (36.8%) ended in a birth, including 59,485 (99.1%) live births. A further 106,135 (65.1%) ended in induced abortion, and 17,945 (11%) ended in miscarriage or ectopic pregnancy.

Overall, there were 6030 premature deaths among those without a teen pregnancy, or 1.9 per 10,000 person-years. There were 701 deaths among those with one teen pregnancy (4.1 per 10,000 person-years) and 345 deaths among those with two or more teen pregnancies (6.1 per 10,000 person-years).

The adjusted hazard ratios (AHRs) for mortality were 1.51 for those with one pregnancy and 2.14 for those with two or more pregnancies. Compared with no teen pregnancy, the AHRs for premature death were 1.41 if the first teen pregnancy ended in an induced abortion and 2.10 if it ended in a miscarriage or birth.

Comparing those with a teen pregnancy and those without, the AHRs for premature death were 1.25 from noninjury, 2.06 from unintentional injury, and 2.02 from intentional injury. Among patients with teen pregnancy, noninjury-related premature mortality was more common, at 2.0 per 10,000 person-years, than unintentional and intentional injuries, at 1.0 per 10,000 person-years and 0.4 per 10,000 person-years, respectively.

A teen pregnancy before age 16 years entailed the highest associated risk for premature death, with an AHR of 2.00.
 

Next Research Steps

“We were not surprised by our findings, but it was new to us to see that the risk for premature death was higher for women who had an induced abortion in their teen years,” said Dr. Ray. “It was even higher in those whose pregnancy ended in a birth or miscarriage.”

The investigators plan to evaluate whether the future risk for premature death after teen pregnancy differs by the type of induced abortion, such as procedural or pharmaceutical, or by whether the pregnancy ended in a live birth, stillbirth, or miscarriage. Among those with a live birth, the researchers will also analyze the risk for premature death in relation to whether the newborn was taken into custody by child protection services in Canada.

Other factors associated with teen pregnancy and overall mortality, particularly adverse childhood experiences, may point to the reasons for premature mortality and should be studied further, the authors wrote. Structural and systems-related factors should be considered as well.
 

Stigmatization and Isolation 

“Some teens choose to become pregnant, but most teen pregnancies are unintended, which exposes shortcomings in the systems that exist to educate, guide, and support young people,” said Elizabeth Cook, a research scientist at Child Trends in Rockville, Maryland.

Dr. Cook, who wasn’t involved with this study, wrote an accompanying editorial in JAMA Network Open. She conducts studies of sexual and reproductive health for Child Trends.

“Teens who become pregnant often experience stigmatization and isolation that can make it more difficult to thrive in adulthood, especially if they lack the necessary support to navigate such a significant decision,” she said. “Fortunately, the systems that youths encounter, such as healthcare, education, and child welfare, are taking on a larger role in prevention efforts than they have in the past.”

These systems are shifting the burden of unintended teen pregnancy from the teens themselves and their behaviors to the health and education systems, Dr. Cook noted, though more work is needed around local policies and lack of access to healthcare facilities. 

“Teen pregnancy may offer an opportunity to intervene in the lives of people at higher risk for premature death, but knowing how best to offer support requires an understanding of the context of their lives,” she said. “As a starting point, we must celebrate and listen to all pregnant young people so they can tell us what they need to live long, fulfilled lives.”

The study was funded by grants from the PSI Foundation and the Canadian Institutes of Health Research, as well as ICES, which is funded by the Ontario Ministry of Health and the Ministry of Long-Term Care. Dr. Ray and Dr. Cook reported no relevant disclosures. 

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

TOPLINE:

Despite concerns about malpractice risk among physicians, investigators found no successful malpractice litigation related to active surveillance as a management strategy for low-risk cancers.

METHODOLOGY:

• Although practice guidelines from the National Comprehensive Cancer Network consider active surveillance an effective strategy for managing low-risk cancers, some physicians have been hesitant to incorporate it into their practice because of concerns about potential litigation.
• Researchers used Westlaw Edge and LexisNexis Advance databases to identify malpractice trends involving active surveillance related to thyroid, prostate, kidney, and  or  from 1990 to 2022.
• Data included unpublished cases, trial orders, jury verdicts, and administrative decisions.
• Researchers identified 201 malpractice cases across all low-risk cancers in the initial screening. Out of these, only five cases, all , involved active surveillance as the point of allegation.

TAKEAWAY:

• Out of the five prostate cancer cases, two involved incarcerated patients with Gleason 6 very-low-risk prostate adenocarcinoma that was managed with active surveillance by their urologists.
• In these two cases, the patients claimed that active surveillance violated their 8th Amendment right to be free from cruel or unusual punishment. In both cases, there was no metastasis or spread detected and the court determined active surveillance management was performed under national standards.
• The other three cases involved litigation claiming that active surveillance was not explicitly recommended as a treatment option for patients who all had very-low-risk prostate adenocarcinoma and had reported negligence from an intervention ( or cryoablation). However, all cases had documented informed consent for active surveillance.
• No relevant cases were found relating to active surveillance in any other type of cancer, whether in an initial diagnosis or recurrence.

IN PRACTICE:

“This data should bolster physicians’ confidence in recommending active surveillance for their patients when it is an appropriate option,” study coauthor Timothy Daskivich, MD, assistant professor of surgery at Cedars-Sinai Medical Center, Los Angeles, said in a statement . “Active surveillance maximizes quality of life and avoids unnecessary overtreatment, and it does not increase medicolegal liability to physicians, as detailed in the case dismissals identified in this study.”

SOURCE:

This study, led by Samuel Chang, JD, with Athene Law LLP, San Francisco, was recently published in Annals of Surgery.

LIMITATIONS:

The Westlaw and Lexis databases may not contain all cases or decisions issued by a state regulatory agency, like a medical board. Federal and state decisions from lower courts may not be published and available. Also, settlements outside of court or suits filed and not pursued were not included in the data.

DISCLOSURES:

The researchers did not provide any disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Despite concerns about malpractice risk among physicians, investigators found no successful malpractice litigation related to active surveillance as a management strategy for low-risk cancers.

METHODOLOGY:

• Although practice guidelines from the National Comprehensive Cancer Network consider active surveillance an effective strategy for managing low-risk cancers, some physicians have been hesitant to incorporate it into their practice because of concerns about potential litigation.
• Researchers used Westlaw Edge and LexisNexis Advance databases to identify malpractice trends involving active surveillance related to thyroid, prostate, kidney, and  or  from 1990 to 2022.
• Data included unpublished cases, trial orders, jury verdicts, and administrative decisions.
• Researchers identified 201 malpractice cases across all low-risk cancers in the initial screening. Out of these, only five cases, all , involved active surveillance as the point of allegation.

TAKEAWAY:

• Out of the five prostate cancer cases, two involved incarcerated patients with Gleason 6 very-low-risk prostate adenocarcinoma that was managed with active surveillance by their urologists.
• In these two cases, the patients claimed that active surveillance violated their 8th Amendment right to be free from cruel or unusual punishment. In both cases, there was no metastasis or spread detected and the court determined active surveillance management was performed under national standards.
• The other three cases involved litigation claiming that active surveillance was not explicitly recommended as a treatment option for patients who all had very-low-risk prostate adenocarcinoma and had reported negligence from an intervention ( or cryoablation). However, all cases had documented informed consent for active surveillance.
• No relevant cases were found relating to active surveillance in any other type of cancer, whether in an initial diagnosis or recurrence.

IN PRACTICE:

“This data should bolster physicians’ confidence in recommending active surveillance for their patients when it is an appropriate option,” study coauthor Timothy Daskivich, MD, assistant professor of surgery at Cedars-Sinai Medical Center, Los Angeles, said in a statement . “Active surveillance maximizes quality of life and avoids unnecessary overtreatment, and it does not increase medicolegal liability to physicians, as detailed in the case dismissals identified in this study.”

SOURCE:

This study, led by Samuel Chang, JD, with Athene Law LLP, San Francisco, was recently published in Annals of Surgery.

LIMITATIONS:

The Westlaw and Lexis databases may not contain all cases or decisions issued by a state regulatory agency, like a medical board. Federal and state decisions from lower courts may not be published and available. Also, settlements outside of court or suits filed and not pursued were not included in the data.

DISCLOSURES:

The researchers did not provide any disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Despite concerns about malpractice risk among physicians, investigators found no successful malpractice litigation related to active surveillance as a management strategy for low-risk cancers.

METHODOLOGY:

• Although practice guidelines from the National Comprehensive Cancer Network consider active surveillance an effective strategy for managing low-risk cancers, some physicians have been hesitant to incorporate it into their practice because of concerns about potential litigation.
• Researchers used Westlaw Edge and LexisNexis Advance databases to identify malpractice trends involving active surveillance related to thyroid, prostate, kidney, and  or  from 1990 to 2022.
• Data included unpublished cases, trial orders, jury verdicts, and administrative decisions.
• Researchers identified 201 malpractice cases across all low-risk cancers in the initial screening. Out of these, only five cases, all , involved active surveillance as the point of allegation.

TAKEAWAY:

• Out of the five prostate cancer cases, two involved incarcerated patients with Gleason 6 very-low-risk prostate adenocarcinoma that was managed with active surveillance by their urologists.
• In these two cases, the patients claimed that active surveillance violated their 8th Amendment right to be free from cruel or unusual punishment. In both cases, there was no metastasis or spread detected and the court determined active surveillance management was performed under national standards.
• The other three cases involved litigation claiming that active surveillance was not explicitly recommended as a treatment option for patients who all had very-low-risk prostate adenocarcinoma and had reported negligence from an intervention ( or cryoablation). However, all cases had documented informed consent for active surveillance.
• No relevant cases were found relating to active surveillance in any other type of cancer, whether in an initial diagnosis or recurrence.

IN PRACTICE:

“This data should bolster physicians’ confidence in recommending active surveillance for their patients when it is an appropriate option,” study coauthor Timothy Daskivich, MD, assistant professor of surgery at Cedars-Sinai Medical Center, Los Angeles, said in a statement . “Active surveillance maximizes quality of life and avoids unnecessary overtreatment, and it does not increase medicolegal liability to physicians, as detailed in the case dismissals identified in this study.”

SOURCE:

This study, led by Samuel Chang, JD, with Athene Law LLP, San Francisco, was recently published in Annals of Surgery.

LIMITATIONS:

The Westlaw and Lexis databases may not contain all cases or decisions issued by a state regulatory agency, like a medical board. Federal and state decisions from lower courts may not be published and available. Also, settlements outside of court or suits filed and not pursued were not included in the data.

DISCLOSURES:

The researchers did not provide any disclosures.

A version of this article appeared on Medscape.com.

Many women with cancer want advice for managing sexual function issues, and clinicians are tuning in, new studies suggest.

Decreased sexual function is a side effect of many types of cancer, notably uterine, cervical, ovarian, and breast cancer, that often goes unaddressed, according to the authors of several studies presented at the Society of Gynecologic Oncology (SGO)’s Annual Meeting on Women’s Cancer.

Patients want to talk about sex, but not necessarily at the start of their diagnosis or treatment, suggest the findings of a study presented at the meeting. Jesse T. Brewer of Weill Cornell Medicine in New York City and colleagues enrolled 63 patients who underwent surgery with documented hereditary breast cancer, ovarian cancer, or Lynch syndrome in a cross-sectional survey.

Overall, 86% said that sexuality and intimacy were very or somewhat important, and 78% said that the healthcare team addressing the issue was very or somewhat important, the researchers found. However, only 40% of the respondents said that they wanted to discuss sexuality at the time of diagnosis because the idea was too overwhelming.

Oncologists are more aware of sexual side effects and the potential for sexual issues that persist long after treatment, but many patients may not have opportunities to talk about sexual concerns, said Don S. Dizon, MD, an oncologist specializing in women’s cancers at Brown University, Providence, Rhode Island, in an interview.

“It is important that we [oncologists] be the ones to open the door to these conversations; people with cancer will not bring it up spontaneously, for fear of making their provider uncomfortable, especially if they’ve never been asked about it before,” Dr. Dizon said in an interview.

He advised clinicians to find a network within their health systems so they can refer patients to specialized services, such as sex therapy, couples counseling, pelvic rehabilitation, or menopausal experts as needed.

In another study presented at the meeting, Naaman Mehta, MD, of NYU Langone Health, and colleagues reviewed data from 166 healthcare providers who completed a 23-item survey about evaluating and managing sexual health concerns of their patients. Most of the respondents were gynecologic oncologists (93.4%), but one radiation oncologist and 10 other healthcare providers also completed the survey.

Overall, approximately 60% of the respondents routinely asked about the sexual health concerns of their patients, and 98% of these said they believed that sexual health discussions should be held with a gynecologic oncologist. Just over half (54%) also said that the patient should be the one to initiate a discussion of sexual health concerns.

Female providers were significantly more likely to discuss sexual health with patients, compared with male providers, after controlling for the hospital setting and training level, the researchers noted (odds ratio, 1.4;P < .01).

The results suggest a need for more ways to integrate sexual health screening into gynecologic oncologic clinics, the researchers concluded.

The provider survey findings are similar to the results of a survey conducted by Dr. Dizon and colleagues in 2007. In that study, less than half of respondents took a sexual history, but 80% felt there was insufficient time to explore sexual issues.

“It is critical to understand that people with cancer do not expect their oncologists to be sexual health experts, but as with all other side effects caused by treatment and the diagnosis, we can be the ones who recognize it,” Dr. Dizon noted, in an interview.
 

Common Complaints and Causes

In Dr. Dizon’s experience, local symptoms including vaginal dryness, pain with penetration, and vaginal thinning, are common sexual complaints in women with cancer, as are systemic issues such as lack of interest and menopause-type symptoms.

“For those undergoing radiation, the vaginal tunnel can actually develop adhesions, and if not treated proactively this can lead to vaginal stenosis,” said Dr. Dizon, who was not involved in the studies presented at the meeting.

Comorbidities such as diabetes, cardiovascular disease, and musculoskeletal conditions can contribute to sexual issues in women with cancer, according to Nora Lersch, DNP, FNP-BC, AOCNP, and Nicole Dreibelbis, CRNP, the authors of other research presented at the meeting.

Culture, religion, fitness level, history of sexual violence, and gender spectrum health also play a role, as do anxiety and depression, dementia, and substance abuse disorders, the authors wrote in their presentation, “Prioritizing Sexual Health in Gynecological Oncology Care.”

Low libido is a frequent complaint across all cancer types, Ms. Dreibelbis, a nurse practitioner specializing in gynecologic oncology at the UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, said in an interview.

“Breast cancer patients, especially those on [aromatase inhibitor] therapy, often experience vaginal dryness and therefore dyspareunia,” she added.

The pelvic floor muscles, with their important role in sexual response, can be weakened by cancer treatment or surgery, and the pudendal nerves, which are the primary nerves responsible for sexual response in women, can be affected as well, Dr. Lersch and Ms. Dreibelbis wrote.
 

Taking Sex Seriously

Researchers are exploring the impact of different cancer prevention treatments for women to mitigate sexual side effects, as illustrated by another study presented at the meeting.

Dr. Barbara Norquist, MD, a gynecologic oncologist at the University of Washington, Seattle, and colleagues compared the sexual function and menopausal symptoms of patients at high risk of ovarian carcinoma who underwent either interval salpingectomy/delayed oophorectomy (ISDO) or risk-reducing salpingo-oophorectomy (RRSO).

“For patients at high risk for ovarian cancer, surgical removal of the tubes and ovaries is the mainstay of prevention, as screening is not effective at reducing death from ovarian cancer. As a result of surgery, many patients become suddenly postmenopausal from losing their ovaries,” Dr. Norquist said in an interview.

Some patients delay surgery out of concern for health and quality of life, including sexual function, she said.

In the study (known as the WISP trial) the researchers compared data from 166 patients who underwent immediate removal of the fallopian tubes and ovaries and 171 who underwent fallopian tube removal and delayed oophorectomy. All patients completed questionnaires about sexual function. The primary outcome was change in sexual function based on the sexual function index (FSFI) from baseline to 6 months after surgery.

Overall, changes in sexual function were significantly greater in the immediate oophorectomy group, compared with the delayed oophorectomy group at 6 months (33% vs 17%) and also at 12 months (43% vs 20%).

A further review of patients using hormone therapy showed that those in the immediate oophorectomy group still had greater decreases in sexual function, compared with the delayed group, though the difference between groups of patients using hormone therapy was less dramatic.

“I was surprised that, even with hormone replacement therapy, patients undergoing removal of the ovaries still had significant detrimental changes to sexual function when compared to those having the tubes removed, although this was even worse in those who could not take HRT,” Dr. Norquist said, in an interview. “I was reassured that menopausal symptoms in general were well managed with HRT, as these patients did not score differently on menopause symptoms, compared with those having their tubes removed,” she said.

Patients deserve accurate information about predicted changes in menopausal symptoms and sexual function as a result of ovary removal, and HRT should be provided when there is no contraindication, Dr. Norquist told this news organization.

Dr. Norquist and colleagues are awaiting the results of clinical trials investigating the safety of salpingectomy with delayed oophorectomy in terms of ovarian cancer prevention, but more research is needed to identify optimal management of the menopausal and sexual side effects associated with surgical menopause, she noted.

“Findings from the WISP study show the importance of hormones in women undergoing prophylactic surgery,” Dr. Dizon said. The findings indicate that salpingectomy has less of a negative influence on sexual function compared to removal of the ovaries, and the impact of hormone therapy and the relatively young age of the patients who took hormones reinforces current knowledge about hormones and sex, he added.
 

Barriers and Solutions

Barriers to asking women with cancer about sexual issues reported by providers include limited time, lack of training in sexual health, a desire to avoid offending the patient or making them uncomfortable, and uncertainty about how to answer the questions, Dr. Lersch and Ms. Dreibelbis wrote in their presentation.

Barriers to asking healthcare providers about their sexual issues reported by patients include the beliefs that the clinician should initiate the discussion, that sexual function will not be taken seriously, and that they might make the provider uncomfortable.

“Fortunately, more information and research has been done on sexual health and gynecological cancer in recent years, so oncologists are becoming more aware of the issues women may have,” said Dr. Lersch who is an oncology nurse practitioner at Providence Franz Cancer Institute in Portland, Oregon, in an interview.

Telling patients early in their cancer treatment about potential sexual side effects and opportunities for help is essential, she added.

Although oncologists have become more aware of the importance of sexual health and well-being for their patients, “I think there has historically been a disconnect in including sexual health education in medical training,” Ms. Dreibelbis said in an interview.

Dr. Lersch and Ms. Dreibelbis advised a multidimensional approach to managing sexual problems in cancer patients that includes consideration of biological and psychological symptoms, but also social, cultural, and interpersonal factors, in their presentation.

Their suggestions include discussing dyspareunia with their patients, asking for details such as whether the pain is internal or external, whether it occurs with activities outside of sex including masturbation, and whether bleeding is present.

Oncology therapies and surgeries can decrease or eliminate an individual’s ability to produce their own lubricant; for example, removal of the cervix eliminates cervical mucous, which helps with internal lubrication, they wrote in their presentation.

For patients with dyspareunia, Dr. Lersch and Ms. Dreibelbis recommend a vaginal moisturizer especially formulated for vaginal tissue that can be absorbed by the mucosal tissue of the vagina. Use of this type of product can increase the effectiveness of lubricants and help restore integrity of the vaginal tissue. Such moisturizers are available as gels, creams, or suppositories over the counter, and do not contain hormones.

Vaginal estrogen can be helpful for burning, itching, irritation, tissue fragility, and pain with sex, according to Dr. Lersch and Ms. Dreibelbis. Adequate estrogen therapy can promote normalization of vaginal pH and microflora, as well increase vaginal secretion and reduce pain and dryness with intercourse, the presenters stated in their presentation. In addition, dilator therapy can be used to help prevent vaginal stenosis, and penetration bumpers can help relieve discomfort during intercourse, they wrote.

Looking ahead, more research is needed to serve a wider patient population, Ms. Dreibelbis said, in an interview.

“LGBTQIA [individuals] have not been included in sexual health research and there are more people than ever who identify within this group of people. I know there has also been some very early work on shielding the clitoris from the impacts of radiation, and I believe this is extremely important up-and-coming research,” she said.

Dr. Lersch, Ms. Dreibelbi, Dr. Dizon, Dr. Norquist, Ms. Brewer, and Dr. Mehta had no financial conflicts to disclose.

Many women with cancer want advice for managing sexual function issues, and clinicians are tuning in, new studies suggest.

Decreased sexual function is a side effect of many types of cancer, notably uterine, cervical, ovarian, and breast cancer, that often goes unaddressed, according to the authors of several studies presented at the Society of Gynecologic Oncology (SGO)’s Annual Meeting on Women’s Cancer.

Patients want to talk about sex, but not necessarily at the start of their diagnosis or treatment, suggest the findings of a study presented at the meeting. Jesse T. Brewer of Weill Cornell Medicine in New York City and colleagues enrolled 63 patients who underwent surgery with documented hereditary breast cancer, ovarian cancer, or Lynch syndrome in a cross-sectional survey.

Overall, 86% said that sexuality and intimacy were very or somewhat important, and 78% said that the healthcare team addressing the issue was very or somewhat important, the researchers found. However, only 40% of the respondents said that they wanted to discuss sexuality at the time of diagnosis because the idea was too overwhelming.

Oncologists are more aware of sexual side effects and the potential for sexual issues that persist long after treatment, but many patients may not have opportunities to talk about sexual concerns, said Don S. Dizon, MD, an oncologist specializing in women’s cancers at Brown University, Providence, Rhode Island, in an interview.

“It is important that we [oncologists] be the ones to open the door to these conversations; people with cancer will not bring it up spontaneously, for fear of making their provider uncomfortable, especially if they’ve never been asked about it before,” Dr. Dizon said in an interview.

He advised clinicians to find a network within their health systems so they can refer patients to specialized services, such as sex therapy, couples counseling, pelvic rehabilitation, or menopausal experts as needed.

In another study presented at the meeting, Naaman Mehta, MD, of NYU Langone Health, and colleagues reviewed data from 166 healthcare providers who completed a 23-item survey about evaluating and managing sexual health concerns of their patients. Most of the respondents were gynecologic oncologists (93.4%), but one radiation oncologist and 10 other healthcare providers also completed the survey.

Overall, approximately 60% of the respondents routinely asked about the sexual health concerns of their patients, and 98% of these said they believed that sexual health discussions should be held with a gynecologic oncologist. Just over half (54%) also said that the patient should be the one to initiate a discussion of sexual health concerns.

Female providers were significantly more likely to discuss sexual health with patients, compared with male providers, after controlling for the hospital setting and training level, the researchers noted (odds ratio, 1.4;P < .01).

The results suggest a need for more ways to integrate sexual health screening into gynecologic oncologic clinics, the researchers concluded.

The provider survey findings are similar to the results of a survey conducted by Dr. Dizon and colleagues in 2007. In that study, less than half of respondents took a sexual history, but 80% felt there was insufficient time to explore sexual issues.

“It is critical to understand that people with cancer do not expect their oncologists to be sexual health experts, but as with all other side effects caused by treatment and the diagnosis, we can be the ones who recognize it,” Dr. Dizon noted, in an interview.
 

Common Complaints and Causes

In Dr. Dizon’s experience, local symptoms including vaginal dryness, pain with penetration, and vaginal thinning, are common sexual complaints in women with cancer, as are systemic issues such as lack of interest and menopause-type symptoms.

“For those undergoing radiation, the vaginal tunnel can actually develop adhesions, and if not treated proactively this can lead to vaginal stenosis,” said Dr. Dizon, who was not involved in the studies presented at the meeting.

Comorbidities such as diabetes, cardiovascular disease, and musculoskeletal conditions can contribute to sexual issues in women with cancer, according to Nora Lersch, DNP, FNP-BC, AOCNP, and Nicole Dreibelbis, CRNP, the authors of other research presented at the meeting.

Culture, religion, fitness level, history of sexual violence, and gender spectrum health also play a role, as do anxiety and depression, dementia, and substance abuse disorders, the authors wrote in their presentation, “Prioritizing Sexual Health in Gynecological Oncology Care.”

Low libido is a frequent complaint across all cancer types, Ms. Dreibelbis, a nurse practitioner specializing in gynecologic oncology at the UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, said in an interview.

“Breast cancer patients, especially those on [aromatase inhibitor] therapy, often experience vaginal dryness and therefore dyspareunia,” she added.

The pelvic floor muscles, with their important role in sexual response, can be weakened by cancer treatment or surgery, and the pudendal nerves, which are the primary nerves responsible for sexual response in women, can be affected as well, Dr. Lersch and Ms. Dreibelbis wrote.
 

Taking Sex Seriously

Researchers are exploring the impact of different cancer prevention treatments for women to mitigate sexual side effects, as illustrated by another study presented at the meeting.

Dr. Barbara Norquist, MD, a gynecologic oncologist at the University of Washington, Seattle, and colleagues compared the sexual function and menopausal symptoms of patients at high risk of ovarian carcinoma who underwent either interval salpingectomy/delayed oophorectomy (ISDO) or risk-reducing salpingo-oophorectomy (RRSO).

“For patients at high risk for ovarian cancer, surgical removal of the tubes and ovaries is the mainstay of prevention, as screening is not effective at reducing death from ovarian cancer. As a result of surgery, many patients become suddenly postmenopausal from losing their ovaries,” Dr. Norquist said in an interview.

Some patients delay surgery out of concern for health and quality of life, including sexual function, she said.

In the study (known as the WISP trial) the researchers compared data from 166 patients who underwent immediate removal of the fallopian tubes and ovaries and 171 who underwent fallopian tube removal and delayed oophorectomy. All patients completed questionnaires about sexual function. The primary outcome was change in sexual function based on the sexual function index (FSFI) from baseline to 6 months after surgery.

Overall, changes in sexual function were significantly greater in the immediate oophorectomy group, compared with the delayed oophorectomy group at 6 months (33% vs 17%) and also at 12 months (43% vs 20%).

A further review of patients using hormone therapy showed that those in the immediate oophorectomy group still had greater decreases in sexual function, compared with the delayed group, though the difference between groups of patients using hormone therapy was less dramatic.

“I was surprised that, even with hormone replacement therapy, patients undergoing removal of the ovaries still had significant detrimental changes to sexual function when compared to those having the tubes removed, although this was even worse in those who could not take HRT,” Dr. Norquist said, in an interview. “I was reassured that menopausal symptoms in general were well managed with HRT, as these patients did not score differently on menopause symptoms, compared with those having their tubes removed,” she said.

Patients deserve accurate information about predicted changes in menopausal symptoms and sexual function as a result of ovary removal, and HRT should be provided when there is no contraindication, Dr. Norquist told this news organization.

Dr. Norquist and colleagues are awaiting the results of clinical trials investigating the safety of salpingectomy with delayed oophorectomy in terms of ovarian cancer prevention, but more research is needed to identify optimal management of the menopausal and sexual side effects associated with surgical menopause, she noted.

“Findings from the WISP study show the importance of hormones in women undergoing prophylactic surgery,” Dr. Dizon said. The findings indicate that salpingectomy has less of a negative influence on sexual function compared to removal of the ovaries, and the impact of hormone therapy and the relatively young age of the patients who took hormones reinforces current knowledge about hormones and sex, he added.
 

Barriers and Solutions

Barriers to asking women with cancer about sexual issues reported by providers include limited time, lack of training in sexual health, a desire to avoid offending the patient or making them uncomfortable, and uncertainty about how to answer the questions, Dr. Lersch and Ms. Dreibelbis wrote in their presentation.

Barriers to asking healthcare providers about their sexual issues reported by patients include the beliefs that the clinician should initiate the discussion, that sexual function will not be taken seriously, and that they might make the provider uncomfortable.

“Fortunately, more information and research has been done on sexual health and gynecological cancer in recent years, so oncologists are becoming more aware of the issues women may have,” said Dr. Lersch who is an oncology nurse practitioner at Providence Franz Cancer Institute in Portland, Oregon, in an interview.

Telling patients early in their cancer treatment about potential sexual side effects and opportunities for help is essential, she added.

Although oncologists have become more aware of the importance of sexual health and well-being for their patients, “I think there has historically been a disconnect in including sexual health education in medical training,” Ms. Dreibelbis said in an interview.

Dr. Lersch and Ms. Dreibelbis advised a multidimensional approach to managing sexual problems in cancer patients that includes consideration of biological and psychological symptoms, but also social, cultural, and interpersonal factors, in their presentation.

Their suggestions include discussing dyspareunia with their patients, asking for details such as whether the pain is internal or external, whether it occurs with activities outside of sex including masturbation, and whether bleeding is present.

Oncology therapies and surgeries can decrease or eliminate an individual’s ability to produce their own lubricant; for example, removal of the cervix eliminates cervical mucous, which helps with internal lubrication, they wrote in their presentation.

For patients with dyspareunia, Dr. Lersch and Ms. Dreibelbis recommend a vaginal moisturizer especially formulated for vaginal tissue that can be absorbed by the mucosal tissue of the vagina. Use of this type of product can increase the effectiveness of lubricants and help restore integrity of the vaginal tissue. Such moisturizers are available as gels, creams, or suppositories over the counter, and do not contain hormones.

Vaginal estrogen can be helpful for burning, itching, irritation, tissue fragility, and pain with sex, according to Dr. Lersch and Ms. Dreibelbis. Adequate estrogen therapy can promote normalization of vaginal pH and microflora, as well increase vaginal secretion and reduce pain and dryness with intercourse, the presenters stated in their presentation. In addition, dilator therapy can be used to help prevent vaginal stenosis, and penetration bumpers can help relieve discomfort during intercourse, they wrote.

Looking ahead, more research is needed to serve a wider patient population, Ms. Dreibelbis said, in an interview.

“LGBTQIA [individuals] have not been included in sexual health research and there are more people than ever who identify within this group of people. I know there has also been some very early work on shielding the clitoris from the impacts of radiation, and I believe this is extremely important up-and-coming research,” she said.

Dr. Lersch, Ms. Dreibelbi, Dr. Dizon, Dr. Norquist, Ms. Brewer, and Dr. Mehta had no financial conflicts to disclose.

Many women with cancer want advice for managing sexual function issues, and clinicians are tuning in, new studies suggest.

Decreased sexual function is a side effect of many types of cancer, notably uterine, cervical, ovarian, and breast cancer, that often goes unaddressed, according to the authors of several studies presented at the Society of Gynecologic Oncology (SGO)’s Annual Meeting on Women’s Cancer.

Patients want to talk about sex, but not necessarily at the start of their diagnosis or treatment, suggest the findings of a study presented at the meeting. Jesse T. Brewer of Weill Cornell Medicine in New York City and colleagues enrolled 63 patients who underwent surgery with documented hereditary breast cancer, ovarian cancer, or Lynch syndrome in a cross-sectional survey.

Overall, 86% said that sexuality and intimacy were very or somewhat important, and 78% said that the healthcare team addressing the issue was very or somewhat important, the researchers found. However, only 40% of the respondents said that they wanted to discuss sexuality at the time of diagnosis because the idea was too overwhelming.

Oncologists are more aware of sexual side effects and the potential for sexual issues that persist long after treatment, but many patients may not have opportunities to talk about sexual concerns, said Don S. Dizon, MD, an oncologist specializing in women’s cancers at Brown University, Providence, Rhode Island, in an interview.

“It is important that we [oncologists] be the ones to open the door to these conversations; people with cancer will not bring it up spontaneously, for fear of making their provider uncomfortable, especially if they’ve never been asked about it before,” Dr. Dizon said in an interview.

He advised clinicians to find a network within their health systems so they can refer patients to specialized services, such as sex therapy, couples counseling, pelvic rehabilitation, or menopausal experts as needed.

In another study presented at the meeting, Naaman Mehta, MD, of NYU Langone Health, and colleagues reviewed data from 166 healthcare providers who completed a 23-item survey about evaluating and managing sexual health concerns of their patients. Most of the respondents were gynecologic oncologists (93.4%), but one radiation oncologist and 10 other healthcare providers also completed the survey.

Overall, approximately 60% of the respondents routinely asked about the sexual health concerns of their patients, and 98% of these said they believed that sexual health discussions should be held with a gynecologic oncologist. Just over half (54%) also said that the patient should be the one to initiate a discussion of sexual health concerns.

Female providers were significantly more likely to discuss sexual health with patients, compared with male providers, after controlling for the hospital setting and training level, the researchers noted (odds ratio, 1.4;P < .01).

The results suggest a need for more ways to integrate sexual health screening into gynecologic oncologic clinics, the researchers concluded.

The provider survey findings are similar to the results of a survey conducted by Dr. Dizon and colleagues in 2007. In that study, less than half of respondents took a sexual history, but 80% felt there was insufficient time to explore sexual issues.

“It is critical to understand that people with cancer do not expect their oncologists to be sexual health experts, but as with all other side effects caused by treatment and the diagnosis, we can be the ones who recognize it,” Dr. Dizon noted, in an interview.
 

Common Complaints and Causes

In Dr. Dizon’s experience, local symptoms including vaginal dryness, pain with penetration, and vaginal thinning, are common sexual complaints in women with cancer, as are systemic issues such as lack of interest and menopause-type symptoms.

“For those undergoing radiation, the vaginal tunnel can actually develop adhesions, and if not treated proactively this can lead to vaginal stenosis,” said Dr. Dizon, who was not involved in the studies presented at the meeting.

Comorbidities such as diabetes, cardiovascular disease, and musculoskeletal conditions can contribute to sexual issues in women with cancer, according to Nora Lersch, DNP, FNP-BC, AOCNP, and Nicole Dreibelbis, CRNP, the authors of other research presented at the meeting.

Culture, religion, fitness level, history of sexual violence, and gender spectrum health also play a role, as do anxiety and depression, dementia, and substance abuse disorders, the authors wrote in their presentation, “Prioritizing Sexual Health in Gynecological Oncology Care.”

Low libido is a frequent complaint across all cancer types, Ms. Dreibelbis, a nurse practitioner specializing in gynecologic oncology at the UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, said in an interview.

“Breast cancer patients, especially those on [aromatase inhibitor] therapy, often experience vaginal dryness and therefore dyspareunia,” she added.

The pelvic floor muscles, with their important role in sexual response, can be weakened by cancer treatment or surgery, and the pudendal nerves, which are the primary nerves responsible for sexual response in women, can be affected as well, Dr. Lersch and Ms. Dreibelbis wrote.
 

Taking Sex Seriously

Researchers are exploring the impact of different cancer prevention treatments for women to mitigate sexual side effects, as illustrated by another study presented at the meeting.

Dr. Barbara Norquist, MD, a gynecologic oncologist at the University of Washington, Seattle, and colleagues compared the sexual function and menopausal symptoms of patients at high risk of ovarian carcinoma who underwent either interval salpingectomy/delayed oophorectomy (ISDO) or risk-reducing salpingo-oophorectomy (RRSO).

“For patients at high risk for ovarian cancer, surgical removal of the tubes and ovaries is the mainstay of prevention, as screening is not effective at reducing death from ovarian cancer. As a result of surgery, many patients become suddenly postmenopausal from losing their ovaries,” Dr. Norquist said in an interview.

Some patients delay surgery out of concern for health and quality of life, including sexual function, she said.

In the study (known as the WISP trial) the researchers compared data from 166 patients who underwent immediate removal of the fallopian tubes and ovaries and 171 who underwent fallopian tube removal and delayed oophorectomy. All patients completed questionnaires about sexual function. The primary outcome was change in sexual function based on the sexual function index (FSFI) from baseline to 6 months after surgery.

Overall, changes in sexual function were significantly greater in the immediate oophorectomy group, compared with the delayed oophorectomy group at 6 months (33% vs 17%) and also at 12 months (43% vs 20%).

A further review of patients using hormone therapy showed that those in the immediate oophorectomy group still had greater decreases in sexual function, compared with the delayed group, though the difference between groups of patients using hormone therapy was less dramatic.

“I was surprised that, even with hormone replacement therapy, patients undergoing removal of the ovaries still had significant detrimental changes to sexual function when compared to those having the tubes removed, although this was even worse in those who could not take HRT,” Dr. Norquist said, in an interview. “I was reassured that menopausal symptoms in general were well managed with HRT, as these patients did not score differently on menopause symptoms, compared with those having their tubes removed,” she said.

Patients deserve accurate information about predicted changes in menopausal symptoms and sexual function as a result of ovary removal, and HRT should be provided when there is no contraindication, Dr. Norquist told this news organization.

Dr. Norquist and colleagues are awaiting the results of clinical trials investigating the safety of salpingectomy with delayed oophorectomy in terms of ovarian cancer prevention, but more research is needed to identify optimal management of the menopausal and sexual side effects associated with surgical menopause, she noted.

“Findings from the WISP study show the importance of hormones in women undergoing prophylactic surgery,” Dr. Dizon said. The findings indicate that salpingectomy has less of a negative influence on sexual function compared to removal of the ovaries, and the impact of hormone therapy and the relatively young age of the patients who took hormones reinforces current knowledge about hormones and sex, he added.
 

Barriers and Solutions

Barriers to asking women with cancer about sexual issues reported by providers include limited time, lack of training in sexual health, a desire to avoid offending the patient or making them uncomfortable, and uncertainty about how to answer the questions, Dr. Lersch and Ms. Dreibelbis wrote in their presentation.

Barriers to asking healthcare providers about their sexual issues reported by patients include the beliefs that the clinician should initiate the discussion, that sexual function will not be taken seriously, and that they might make the provider uncomfortable.

“Fortunately, more information and research has been done on sexual health and gynecological cancer in recent years, so oncologists are becoming more aware of the issues women may have,” said Dr. Lersch who is an oncology nurse practitioner at Providence Franz Cancer Institute in Portland, Oregon, in an interview.

Telling patients early in their cancer treatment about potential sexual side effects and opportunities for help is essential, she added.

Although oncologists have become more aware of the importance of sexual health and well-being for their patients, “I think there has historically been a disconnect in including sexual health education in medical training,” Ms. Dreibelbis said in an interview.

Dr. Lersch and Ms. Dreibelbis advised a multidimensional approach to managing sexual problems in cancer patients that includes consideration of biological and psychological symptoms, but also social, cultural, and interpersonal factors, in their presentation.

Their suggestions include discussing dyspareunia with their patients, asking for details such as whether the pain is internal or external, whether it occurs with activities outside of sex including masturbation, and whether bleeding is present.

Oncology therapies and surgeries can decrease or eliminate an individual’s ability to produce their own lubricant; for example, removal of the cervix eliminates cervical mucous, which helps with internal lubrication, they wrote in their presentation.

For patients with dyspareunia, Dr. Lersch and Ms. Dreibelbis recommend a vaginal moisturizer especially formulated for vaginal tissue that can be absorbed by the mucosal tissue of the vagina. Use of this type of product can increase the effectiveness of lubricants and help restore integrity of the vaginal tissue. Such moisturizers are available as gels, creams, or suppositories over the counter, and do not contain hormones.

Vaginal estrogen can be helpful for burning, itching, irritation, tissue fragility, and pain with sex, according to Dr. Lersch and Ms. Dreibelbis. Adequate estrogen therapy can promote normalization of vaginal pH and microflora, as well increase vaginal secretion and reduce pain and dryness with intercourse, the presenters stated in their presentation. In addition, dilator therapy can be used to help prevent vaginal stenosis, and penetration bumpers can help relieve discomfort during intercourse, they wrote.

Looking ahead, more research is needed to serve a wider patient population, Ms. Dreibelbis said, in an interview.

“LGBTQIA [individuals] have not been included in sexual health research and there are more people than ever who identify within this group of people. I know there has also been some very early work on shielding the clitoris from the impacts of radiation, and I believe this is extremely important up-and-coming research,” she said.

Dr. Lersch, Ms. Dreibelbi, Dr. Dizon, Dr. Norquist, Ms. Brewer, and Dr. Mehta had no financial conflicts to disclose.

Introduction: Imaging for Endometriosis — A Necessary Prerequisite

While the gold standard in the diagnosis of endometriosis remains laparoscopy, it is now recognized that thorough evaluation via ultrasound offers an acceptable, less expensive, and less invasive alternative. It is especially useful for the diagnosis of deep infiltrative disease, which penetrates more than 5 mm into the peritoneum, ovarian endometrioma, and when anatomic distortion occurs, such as to the path of the ureter.

Besides establishing the diagnosis, ultrasound imaging has become, along with MRI, the most important aid for proper preoperative planning. Not only does imaging provide the surgeon and patient with knowledge regarding the extent of the upcoming procedure, but it also allows the minimally invasive gynecologic (MIG) surgeon to involve colleagues, such as colorectal surgeons or urologists. For example, deep infiltrative endometriosis penetrating into the bowel mucosa will require a discoid or segmental bowel resection.

While many endometriosis experts rely on MRI, many MIG surgeons are dependent on ultrasound. I would not consider taking a patient with signs and symptoms suggestive of endometriosis to surgery without 2D/3D transvaginal ultrasound. If the patient possesses a uterus, a saline-infused sonogram is performed to potentially diagnose adenomyosis.

It is a pleasure and honor to welcome Professor Caterina Exacoustos MD, PhD, associate professor of ob.gyn. at the University of Rome “Tor Vergata,” to this edition of the Master Class in Gynecologic Surgery to discuss “Ultrasound and Its Role in the Diagnosis of and Management of Endometriosis, Including DIE.”

Prof. Exacoustos’ main areas of interest are endometriosis and benign diseases including uterine pathology and infertility. Her extensive body of work comprises over 120 scientific publications and numerous book chapters both in English and in Italian.

Prof. Exacoustos continues to be one of the most well respected lecturers speaking about ultrasound throughout the world.
 

Dr. Miller is professor of obstetrics and gynecology, department of clinical sciences, Rosalind Franklin University of Medicine and Science, North Chicago. Dr. Miller has no conflicts of interest to report.

Ultrasound and Its Role In Diagnosing and Managing Endometriosis

Endometriosis affects approximately 10%-20% of premenopausal women worldwide. It is the leading cause of chronic pelvic pain, is often associated with infertility, and has a significant impact on quality of life. Although the natural history of endometriosis remains unknown, emerging evidence suggests that the pathophysiological steps of initiation and development of endometriosis must occur earlier in the lifespan. Most notably, the onset of endometriosis-associated pain symptoms is often reported during adolescence and young adulthood.¹

While many patients with endometriosis are referred with dysmenorrhea at a young age, at age ≤ 25 years,² symptoms are often highly underestimated and considered to be normal and transient.^3,4 Clinical and pelvic exams are often negative in young women, and delays in endometriosis diagnosis are well known.

The presentation of primary dysmenorrhea with no anatomical cause embodies the paradigm that dysmenorrhea in adolescents is most often an insignificant disorder. This perspective is probably a root cause of delayed endometriosis diagnosis in young patients. However, another issue behind delayed diagnosis is the reluctance of the physician to perform a diagnostic laparoscopy — historically the gold standard for diagnosing endometriosis — for seemingly common symptoms such as dysmenorrhea in young patients.

Today we know that there are typical aspects of ultrasound imaging that identify endometriosis in the pelvis, and notably, the 2022 European Society for Human Reproduction and Embryology (ESHRE) endometriosis guideline⁵ recognizes imaging (ultrasound or MRI) as the standard for endometriosis diagnosis without requiring laparoscopic or histological confirmation.

An early and noninvasive method of diagnosis aids in timely diagnosis and provides for the timely initiation of medical management to improve quality of life and prevent progression of disease (Figure 1).

Dr. Exacoustos

(A. Transvaginal ultrasound appearance of a small ovarian endometrioma in a 16-year-old girl. Note the unilocular cyst with ground glass echogenicity surrounded by multifollicular ovarian tissue. B. Ultrasound image of a retroverted uterus of an 18-year-old girl with focal adenomyosis of the posterior wall. Note the round cystic anechoic areas in the inner myometrium or junctional zone. The small intra-myometrial cyst is surrounded by a hyperechoic ring).

Indeed, the typical appearance of endometriotic pelvic lesions on transvaginal sonography, such as endometriomas and rectal deep infiltrating endometriosis (DIE) — as well as adenomyosis – can be medically treated without histologic confirmation .

When surgery is advisable, ultrasound findings also play a valuable role in presurgical staging, planning, and counseling for patients of all ages. Determining the extent and location of DIE preoperatively, for instance, facilitates the engagement of the appropriate surgical specialists so that multiple surgeries can be avoided. It also enables patients to be optimally informed before surgery of possible outcomes and complications.

Moreover, in the context of infertility, ultrasound can be a valuable tool for understanding uterine pathology and assessing for adenomyosis so that affected patients may be treated surgically or medically before turning to assisted reproductive technology.
 

Uniformity, Standardization in the Sonographic Assessment

In Europe, as in the United States, transvaginal sonography (TVS) is the first-line imaging tool for the diagnosis and management of endometriosis. In Europe, many ob.gyns. perform ultrasound themselves, as do treating surgeons. When diagnostic findings are negative but clinical suspicion is high, MRI is often utilized. Laparoscopy may then be considered in patients with negative imaging results.

Efforts to standardize terms, definitions, measurements, and sonographic features of different types of endometriosis have been made to make it easier for physicians to share data and communicate with each other. A lack of uniformity has contributed to variability in the reported diagnostic accuracy of TVS.

About 10 years ago, in one such effort, we assessed the accuracy of TVS for DIE by comparing TVS results with laparoscopic/histologic findings, and developed an ultrasound mapping system to accurately record the location, size and depth of lesions visualized by TVS. The accuracy of TVS ranged from 76% for the diagnosis of vaginal endometriosis to 97% for the diagnosis of bladder lesions and posterior cul-de-sac obliteration. Accuracy was 93% and 91% for detecting ureteral involvement (right and left); 87% for uterosacral ligament endometriotic lesions; and 87% for parametrial involvement.⁶

Shortly after, with a focus on DIE, expert sonographers and physician-sonographers from across Europe — as well as some experts from Australia, Japan, Brazil, Chile, and the United States (Y. Osuga from Brigham and Women’s Hospital and Harvard Medical School) — came together to agree on a uniform approach to the sonographic evaluation for suspected endometriosis and a standardization of terminology.

The consensus opinion from the International Deep Endometriosis Analysis (IDEA) group details four steps for examining women with suspected DIE: 1) Evaluation of the uterus and adnexa, 2) evaluation of transvaginal sonographic “soft markers” (ie. site-specific tenderness and ovarian mobility), 3) assessment of the status of the posterior cul-de-sac using real-time ultrasound-based “sliding sign,” and 4) assessment for DIE nodules in the anterior and posterior compartments.⁷

Our paper describing a mapping system and the IDEA paper describe how to detect deep endometriosis in the pelvis by utilizing an ultrasound view of normal anatomy and pelvic organ structure to provide landmarks for accurately defining the site of DIE lesions (Figure 2).

Dr. Exacoustos

(A. Ultrasound appearance of a small DIE lesion of the retrocervical area [white arrows], which involved the torus uterinum and the right uterosacral ligament [USL]. The lesion appears as hypoechoic tissue with irregular margins caused by the fibrosis induced by the DIE. B. TVS appearance of small nodules of DIE of the left USL. Note the small retrocervical DIE lesion [white arrows], which appears hypoechoic due to the infiltration of the hyperechoic USL. C) Ultrasound appearance of a DIE nodule of the recto-sigmoid wall. Note the hypoechoic thickening of the muscular layers of the bowel wall attached to the corpus of the uterus and the adenomyosis of the posterior wall. The retrocervical area is free. D. TVS appearance of nodules of DIE of the lower rectal wall. Note the hypoechoic lesion [white arrows] of the rectum is attached to a retrocervical DIE fibrosis of the torus and USL [white dotted line]).

So-called rectovaginal endometriosis can be well assessed, for instance, since the involvement of the rectum, sigmoid colon, vaginal wall, rectovaginal septum, and posterior cul-de-sac uterosacral ligament can be seen by ultrasound as a single structure, making the location, size, and depth of any lesions discernible.

Again, this evaluation of the extent of disease is important for presurgical assessment so the surgeon can organize the right team and time of surgery and so the patient can be counseled on the advantages and possible complications of the treatment.

Notably, an accurate ultrasound description of pelvic endometriosis is helpful for accurate classification of disease. Endometriosis classification systems such as that of the American Association of Gynecologic Laparoscopists (AAGL)⁸ and the American Society of Reproductive Medicine (ASRM),⁹ as well as the #Enzian surgical description system,¹⁰ have been adapted to cover findings from ultrasound as well as MRI imaging.
 

A Systematic Evaluation

In keeping with the IDEA consensus opinion and based on our years of experience at the University of Rome, I advise that patients with typical pain symptoms of endometriosis or infertility undergo an accurate sonographic assessment of the pelvis with particular evaluation not only of the uterus and ovaries but of all pelvic retroperitoneal spaces.

The TVS examination should start with a slightly filled bladder, which permits a better evaluation of the bladder walls and the presence of endometriotic nodules. These nodules appear as hyperechoic linear or spherical lesions bulging toward the lumen and involving the serosa, muscularis, or (sub)mucosa of the bladder.

Then, an accurate evaluation of the uterus in 2D and 3D permits the diagnosis of adenomyosis. 3D sonographic evaluation of the myometrium and of the junctional zone are important; alteration and infiltration of the junctional zone and the presence of small adenomyotic cysts in the inner or outer myometrium are direct, specific signs of adenomyosis and should be ruled out in patients with dysmenorrhea, heavy menstrual bleeding, infertility, and pregnancy complications.

Endometriomas of the ovaries can be easily detected as having the typical appearance of a cyst with ground glass content. Adhesions of the ovaries and the uterus also should be evaluated with a dynamic ultrasound approach that utilizes the sliding sign and mobilization by palpation of the organs during the TVS scan.

Finally, the posterior and lateral retroperitoneal compartments should be carefully evaluated, with symptoms guiding the TVS examination whenever possible. Deep endometriotic nodules of the rectum appear as hypoechoic lesions or linear or nodular retroperitoneal thickening with irregular borders, penetrating into the intestinal wall and distorting its normal structure. In young patients, it seems very important to assess for small lesions below the peritoneum between the vagina and rectum, and in the parametria and around the ureter and nerves — lesions that, notably, would not be seen by diagnostic laparoscopy.
 

The Evaluation of Young Patients

In adolescent and young patients, endometriosis and adenomyosis are often present with small lesions and shallow tissue invasion, making a very careful and experienced approach to ultrasound essential for detection. Endometriomas are often of small diameter, and DIE is not always easily diagnosed because retroperitoneal lesions are similarly very small.

In a series of 270 adolescents (ages 12-20) who were referred to our outpatient gynecologic ultrasound unit over a 5-year period for various indications, at least one ultrasound feature of endometriosis was observed in 13.3%. In those with dysmenorrhea, the detection of endometriosis increased to 21%. Endometrioma was the most common type of endometriosis we found in the study, but DIE and adenomyosis were found in 4%-11%.

Although endometriotic lesions typically are small in young patients, they are often associated with severe pain symptoms, including chronic pelvic pain, dysmenorrhea, dyspareunia, dysuria, and dyschezia, all of which can have a serious effect on the quality of life of these young women. These symptoms keep them away from school during menstruation, away from sports, and cause painful intercourse and infertility. In young patients, an accurate TVS can provide a lot of information, and the ability to detect retroperitoneal endometriotic lesions and adenomyosis is probably better than with purely diagnostic laparoscopy, which would evaluate only superficial lesions.

TVS or, when needed, transrectal ultrasound, can enable adequate treatment and follow-up of the disease and its symptoms. There are no guidelines recommending adequate follow-up times to evaluate the effectiveness of medical therapy in patients with ultrasound signs of endometriosis. (Likewise, there are no indications for follow-up in patients with severe dysmenorrhea without ultrasound signs of endometriosis.) Certainly, our studies suggest careful evaluation over time of young patients with severe dysmenorrhea by serial ultrasound scans. With such follow-up, disease progress can be monitored and the medical or surgical treatment approach modified if needed.

The diagnosis of endometriosis at a young age has significant benefits not only in avoiding or reducing progression of the disease, but also in improving quality of life and aiding women in their desire for pregnancy.
 

Dr. Exacoustos is associate professor of ob.gyn. at the University of Rome “Tor Vergata.” She has no conflicts of interest to report.

References

1. Zondervan KT et al. N Engl J Med. 2020;382:1244-56.

2. Greene R et al. Fertil Steril. 2009;91:32-9.

3. Chapron C et al. J Pediatr Adolesc Gynecol. 2011;24:S7-12.

4. Randhawa AE et al. J Pediatr Adolesc Gynecol. 2021;34:643-8.

5. Becker CM et al. Hum Reprod Open. 2022(2):hoac009.

6. Exacoustos C et al. Fertil Steril. 2014;102:143-9. 7. Guerriero S et al. Ultrasound Obstet Gynecol. 2016;48(3):318-32.

8. Abrao MS et al. J Minim Invasive Gynecol. 2021;28:1941-50.9. Revised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil Steril. 1997;67:817-21. 10. Keckstein J et al. Acta Obstet Gynecol Scand. 2021;100:1165-75.

11. Martire FG et al. Fertil Steril. 2020;114(5):1049-57.

Introduction: Imaging for Endometriosis — A Necessary Prerequisite

While the gold standard in the diagnosis of endometriosis remains laparoscopy, it is now recognized that thorough evaluation via ultrasound offers an acceptable, less expensive, and less invasive alternative. It is especially useful for the diagnosis of deep infiltrative disease, which penetrates more than 5 mm into the peritoneum, ovarian endometrioma, and when anatomic distortion occurs, such as to the path of the ureter.

Besides establishing the diagnosis, ultrasound imaging has become, along with MRI, the most important aid for proper preoperative planning. Not only does imaging provide the surgeon and patient with knowledge regarding the extent of the upcoming procedure, but it also allows the minimally invasive gynecologic (MIG) surgeon to involve colleagues, such as colorectal surgeons or urologists. For example, deep infiltrative endometriosis penetrating into the bowel mucosa will require a discoid or segmental bowel resection.

While many endometriosis experts rely on MRI, many MIG surgeons are dependent on ultrasound. I would not consider taking a patient with signs and symptoms suggestive of endometriosis to surgery without 2D/3D transvaginal ultrasound. If the patient possesses a uterus, a saline-infused sonogram is performed to potentially diagnose adenomyosis.

It is a pleasure and honor to welcome Professor Caterina Exacoustos MD, PhD, associate professor of ob.gyn. at the University of Rome “Tor Vergata,” to this edition of the Master Class in Gynecologic Surgery to discuss “Ultrasound and Its Role in the Diagnosis of and Management of Endometriosis, Including DIE.”

Prof. Exacoustos’ main areas of interest are endometriosis and benign diseases including uterine pathology and infertility. Her extensive body of work comprises over 120 scientific publications and numerous book chapters both in English and in Italian.

Prof. Exacoustos continues to be one of the most well respected lecturers speaking about ultrasound throughout the world.
 

Dr. Miller is professor of obstetrics and gynecology, department of clinical sciences, Rosalind Franklin University of Medicine and Science, North Chicago. Dr. Miller has no conflicts of interest to report.

Ultrasound and Its Role In Diagnosing and Managing Endometriosis

Endometriosis affects approximately 10%-20% of premenopausal women worldwide. It is the leading cause of chronic pelvic pain, is often associated with infertility, and has a significant impact on quality of life. Although the natural history of endometriosis remains unknown, emerging evidence suggests that the pathophysiological steps of initiation and development of endometriosis must occur earlier in the lifespan. Most notably, the onset of endometriosis-associated pain symptoms is often reported during adolescence and young adulthood.¹

While many patients with endometriosis are referred with dysmenorrhea at a young age, at age ≤ 25 years,² symptoms are often highly underestimated and considered to be normal and transient.^3,4 Clinical and pelvic exams are often negative in young women, and delays in endometriosis diagnosis are well known.

The presentation of primary dysmenorrhea with no anatomical cause embodies the paradigm that dysmenorrhea in adolescents is most often an insignificant disorder. This perspective is probably a root cause of delayed endometriosis diagnosis in young patients. However, another issue behind delayed diagnosis is the reluctance of the physician to perform a diagnostic laparoscopy — historically the gold standard for diagnosing endometriosis — for seemingly common symptoms such as dysmenorrhea in young patients.

Today we know that there are typical aspects of ultrasound imaging that identify endometriosis in the pelvis, and notably, the 2022 European Society for Human Reproduction and Embryology (ESHRE) endometriosis guideline⁵ recognizes imaging (ultrasound or MRI) as the standard for endometriosis diagnosis without requiring laparoscopic or histological confirmation.

An early and noninvasive method of diagnosis aids in timely diagnosis and provides for the timely initiation of medical management to improve quality of life and prevent progression of disease (Figure 1).

Dr. Exacoustos

(A. Transvaginal ultrasound appearance of a small ovarian endometrioma in a 16-year-old girl. Note the unilocular cyst with ground glass echogenicity surrounded by multifollicular ovarian tissue. B. Ultrasound image of a retroverted uterus of an 18-year-old girl with focal adenomyosis of the posterior wall. Note the round cystic anechoic areas in the inner myometrium or junctional zone. The small intra-myometrial cyst is surrounded by a hyperechoic ring).

Indeed, the typical appearance of endometriotic pelvic lesions on transvaginal sonography, such as endometriomas and rectal deep infiltrating endometriosis (DIE) — as well as adenomyosis – can be medically treated without histologic confirmation .

When surgery is advisable, ultrasound findings also play a valuable role in presurgical staging, planning, and counseling for patients of all ages. Determining the extent and location of DIE preoperatively, for instance, facilitates the engagement of the appropriate surgical specialists so that multiple surgeries can be avoided. It also enables patients to be optimally informed before surgery of possible outcomes and complications.

Moreover, in the context of infertility, ultrasound can be a valuable tool for understanding uterine pathology and assessing for adenomyosis so that affected patients may be treated surgically or medically before turning to assisted reproductive technology.
 

Uniformity, Standardization in the Sonographic Assessment

In Europe, as in the United States, transvaginal sonography (TVS) is the first-line imaging tool for the diagnosis and management of endometriosis. In Europe, many ob.gyns. perform ultrasound themselves, as do treating surgeons. When diagnostic findings are negative but clinical suspicion is high, MRI is often utilized. Laparoscopy may then be considered in patients with negative imaging results.

Efforts to standardize terms, definitions, measurements, and sonographic features of different types of endometriosis have been made to make it easier for physicians to share data and communicate with each other. A lack of uniformity has contributed to variability in the reported diagnostic accuracy of TVS.

About 10 years ago, in one such effort, we assessed the accuracy of TVS for DIE by comparing TVS results with laparoscopic/histologic findings, and developed an ultrasound mapping system to accurately record the location, size and depth of lesions visualized by TVS. The accuracy of TVS ranged from 76% for the diagnosis of vaginal endometriosis to 97% for the diagnosis of bladder lesions and posterior cul-de-sac obliteration. Accuracy was 93% and 91% for detecting ureteral involvement (right and left); 87% for uterosacral ligament endometriotic lesions; and 87% for parametrial involvement.⁶

Shortly after, with a focus on DIE, expert sonographers and physician-sonographers from across Europe — as well as some experts from Australia, Japan, Brazil, Chile, and the United States (Y. Osuga from Brigham and Women’s Hospital and Harvard Medical School) — came together to agree on a uniform approach to the sonographic evaluation for suspected endometriosis and a standardization of terminology.

The consensus opinion from the International Deep Endometriosis Analysis (IDEA) group details four steps for examining women with suspected DIE: 1) Evaluation of the uterus and adnexa, 2) evaluation of transvaginal sonographic “soft markers” (ie. site-specific tenderness and ovarian mobility), 3) assessment of the status of the posterior cul-de-sac using real-time ultrasound-based “sliding sign,” and 4) assessment for DIE nodules in the anterior and posterior compartments.⁷

Our paper describing a mapping system and the IDEA paper describe how to detect deep endometriosis in the pelvis by utilizing an ultrasound view of normal anatomy and pelvic organ structure to provide landmarks for accurately defining the site of DIE lesions (Figure 2).

Dr. Exacoustos

(A. Ultrasound appearance of a small DIE lesion of the retrocervical area [white arrows], which involved the torus uterinum and the right uterosacral ligament [USL]. The lesion appears as hypoechoic tissue with irregular margins caused by the fibrosis induced by the DIE. B. TVS appearance of small nodules of DIE of the left USL. Note the small retrocervical DIE lesion [white arrows], which appears hypoechoic due to the infiltration of the hyperechoic USL. C) Ultrasound appearance of a DIE nodule of the recto-sigmoid wall. Note the hypoechoic thickening of the muscular layers of the bowel wall attached to the corpus of the uterus and the adenomyosis of the posterior wall. The retrocervical area is free. D. TVS appearance of nodules of DIE of the lower rectal wall. Note the hypoechoic lesion [white arrows] of the rectum is attached to a retrocervical DIE fibrosis of the torus and USL [white dotted line]).

So-called rectovaginal endometriosis can be well assessed, for instance, since the involvement of the rectum, sigmoid colon, vaginal wall, rectovaginal septum, and posterior cul-de-sac uterosacral ligament can be seen by ultrasound as a single structure, making the location, size, and depth of any lesions discernible.

Again, this evaluation of the extent of disease is important for presurgical assessment so the surgeon can organize the right team and time of surgery and so the patient can be counseled on the advantages and possible complications of the treatment.

Notably, an accurate ultrasound description of pelvic endometriosis is helpful for accurate classification of disease. Endometriosis classification systems such as that of the American Association of Gynecologic Laparoscopists (AAGL)⁸ and the American Society of Reproductive Medicine (ASRM),⁹ as well as the #Enzian surgical description system,¹⁰ have been adapted to cover findings from ultrasound as well as MRI imaging.
 

A Systematic Evaluation

In keeping with the IDEA consensus opinion and based on our years of experience at the University of Rome, I advise that patients with typical pain symptoms of endometriosis or infertility undergo an accurate sonographic assessment of the pelvis with particular evaluation not only of the uterus and ovaries but of all pelvic retroperitoneal spaces.

The TVS examination should start with a slightly filled bladder, which permits a better evaluation of the bladder walls and the presence of endometriotic nodules. These nodules appear as hyperechoic linear or spherical lesions bulging toward the lumen and involving the serosa, muscularis, or (sub)mucosa of the bladder.

Then, an accurate evaluation of the uterus in 2D and 3D permits the diagnosis of adenomyosis. 3D sonographic evaluation of the myometrium and of the junctional zone are important; alteration and infiltration of the junctional zone and the presence of small adenomyotic cysts in the inner or outer myometrium are direct, specific signs of adenomyosis and should be ruled out in patients with dysmenorrhea, heavy menstrual bleeding, infertility, and pregnancy complications.

Endometriomas of the ovaries can be easily detected as having the typical appearance of a cyst with ground glass content. Adhesions of the ovaries and the uterus also should be evaluated with a dynamic ultrasound approach that utilizes the sliding sign and mobilization by palpation of the organs during the TVS scan.

Finally, the posterior and lateral retroperitoneal compartments should be carefully evaluated, with symptoms guiding the TVS examination whenever possible. Deep endometriotic nodules of the rectum appear as hypoechoic lesions or linear or nodular retroperitoneal thickening with irregular borders, penetrating into the intestinal wall and distorting its normal structure. In young patients, it seems very important to assess for small lesions below the peritoneum between the vagina and rectum, and in the parametria and around the ureter and nerves — lesions that, notably, would not be seen by diagnostic laparoscopy.
 

The Evaluation of Young Patients

In adolescent and young patients, endometriosis and adenomyosis are often present with small lesions and shallow tissue invasion, making a very careful and experienced approach to ultrasound essential for detection. Endometriomas are often of small diameter, and DIE is not always easily diagnosed because retroperitoneal lesions are similarly very small.

In a series of 270 adolescents (ages 12-20) who were referred to our outpatient gynecologic ultrasound unit over a 5-year period for various indications, at least one ultrasound feature of endometriosis was observed in 13.3%. In those with dysmenorrhea, the detection of endometriosis increased to 21%. Endometrioma was the most common type of endometriosis we found in the study, but DIE and adenomyosis were found in 4%-11%.

Although endometriotic lesions typically are small in young patients, they are often associated with severe pain symptoms, including chronic pelvic pain, dysmenorrhea, dyspareunia, dysuria, and dyschezia, all of which can have a serious effect on the quality of life of these young women. These symptoms keep them away from school during menstruation, away from sports, and cause painful intercourse and infertility. In young patients, an accurate TVS can provide a lot of information, and the ability to detect retroperitoneal endometriotic lesions and adenomyosis is probably better than with purely diagnostic laparoscopy, which would evaluate only superficial lesions.

TVS or, when needed, transrectal ultrasound, can enable adequate treatment and follow-up of the disease and its symptoms. There are no guidelines recommending adequate follow-up times to evaluate the effectiveness of medical therapy in patients with ultrasound signs of endometriosis. (Likewise, there are no indications for follow-up in patients with severe dysmenorrhea without ultrasound signs of endometriosis.) Certainly, our studies suggest careful evaluation over time of young patients with severe dysmenorrhea by serial ultrasound scans. With such follow-up, disease progress can be monitored and the medical or surgical treatment approach modified if needed.

The diagnosis of endometriosis at a young age has significant benefits not only in avoiding or reducing progression of the disease, but also in improving quality of life and aiding women in their desire for pregnancy.
 

Dr. Exacoustos is associate professor of ob.gyn. at the University of Rome “Tor Vergata.” She has no conflicts of interest to report.

References

1. Zondervan KT et al. N Engl J Med. 2020;382:1244-56.

2. Greene R et al. Fertil Steril. 2009;91:32-9.

3. Chapron C et al. J Pediatr Adolesc Gynecol. 2011;24:S7-12.

4. Randhawa AE et al. J Pediatr Adolesc Gynecol. 2021;34:643-8.

5. Becker CM et al. Hum Reprod Open. 2022(2):hoac009.

6. Exacoustos C et al. Fertil Steril. 2014;102:143-9. 7. Guerriero S et al. Ultrasound Obstet Gynecol. 2016;48(3):318-32.

8. Abrao MS et al. J Minim Invasive Gynecol. 2021;28:1941-50.9. Revised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil Steril. 1997;67:817-21. 10. Keckstein J et al. Acta Obstet Gynecol Scand. 2021;100:1165-75.

11. Martire FG et al. Fertil Steril. 2020;114(5):1049-57.

Introduction: Imaging for Endometriosis — A Necessary Prerequisite

While the gold standard in the diagnosis of endometriosis remains laparoscopy, it is now recognized that thorough evaluation via ultrasound offers an acceptable, less expensive, and less invasive alternative. It is especially useful for the diagnosis of deep infiltrative disease, which penetrates more than 5 mm into the peritoneum, ovarian endometrioma, and when anatomic distortion occurs, such as to the path of the ureter.

Besides establishing the diagnosis, ultrasound imaging has become, along with MRI, the most important aid for proper preoperative planning. Not only does imaging provide the surgeon and patient with knowledge regarding the extent of the upcoming procedure, but it also allows the minimally invasive gynecologic (MIG) surgeon to involve colleagues, such as colorectal surgeons or urologists. For example, deep infiltrative endometriosis penetrating into the bowel mucosa will require a discoid or segmental bowel resection.

While many endometriosis experts rely on MRI, many MIG surgeons are dependent on ultrasound. I would not consider taking a patient with signs and symptoms suggestive of endometriosis to surgery without 2D/3D transvaginal ultrasound. If the patient possesses a uterus, a saline-infused sonogram is performed to potentially diagnose adenomyosis.

It is a pleasure and honor to welcome Professor Caterina Exacoustos MD, PhD, associate professor of ob.gyn. at the University of Rome “Tor Vergata,” to this edition of the Master Class in Gynecologic Surgery to discuss “Ultrasound and Its Role in the Diagnosis of and Management of Endometriosis, Including DIE.”

Prof. Exacoustos’ main areas of interest are endometriosis and benign diseases including uterine pathology and infertility. Her extensive body of work comprises over 120 scientific publications and numerous book chapters both in English and in Italian.

Prof. Exacoustos continues to be one of the most well respected lecturers speaking about ultrasound throughout the world.
 

Dr. Miller is professor of obstetrics and gynecology, department of clinical sciences, Rosalind Franklin University of Medicine and Science, North Chicago. Dr. Miller has no conflicts of interest to report.

Ultrasound and Its Role In Diagnosing and Managing Endometriosis

Endometriosis affects approximately 10%-20% of premenopausal women worldwide. It is the leading cause of chronic pelvic pain, is often associated with infertility, and has a significant impact on quality of life. Although the natural history of endometriosis remains unknown, emerging evidence suggests that the pathophysiological steps of initiation and development of endometriosis must occur earlier in the lifespan. Most notably, the onset of endometriosis-associated pain symptoms is often reported during adolescence and young adulthood.¹

While many patients with endometriosis are referred with dysmenorrhea at a young age, at age ≤ 25 years,² symptoms are often highly underestimated and considered to be normal and transient.^3,4 Clinical and pelvic exams are often negative in young women, and delays in endometriosis diagnosis are well known.

The presentation of primary dysmenorrhea with no anatomical cause embodies the paradigm that dysmenorrhea in adolescents is most often an insignificant disorder. This perspective is probably a root cause of delayed endometriosis diagnosis in young patients. However, another issue behind delayed diagnosis is the reluctance of the physician to perform a diagnostic laparoscopy — historically the gold standard for diagnosing endometriosis — for seemingly common symptoms such as dysmenorrhea in young patients.

Today we know that there are typical aspects of ultrasound imaging that identify endometriosis in the pelvis, and notably, the 2022 European Society for Human Reproduction and Embryology (ESHRE) endometriosis guideline⁵ recognizes imaging (ultrasound or MRI) as the standard for endometriosis diagnosis without requiring laparoscopic or histological confirmation.

An early and noninvasive method of diagnosis aids in timely diagnosis and provides for the timely initiation of medical management to improve quality of life and prevent progression of disease (Figure 1).

Dr. Exacoustos

(A. Transvaginal ultrasound appearance of a small ovarian endometrioma in a 16-year-old girl. Note the unilocular cyst with ground glass echogenicity surrounded by multifollicular ovarian tissue. B. Ultrasound image of a retroverted uterus of an 18-year-old girl with focal adenomyosis of the posterior wall. Note the round cystic anechoic areas in the inner myometrium or junctional zone. The small intra-myometrial cyst is surrounded by a hyperechoic ring).

Indeed, the typical appearance of endometriotic pelvic lesions on transvaginal sonography, such as endometriomas and rectal deep infiltrating endometriosis (DIE) — as well as adenomyosis – can be medically treated without histologic confirmation .

When surgery is advisable, ultrasound findings also play a valuable role in presurgical staging, planning, and counseling for patients of all ages. Determining the extent and location of DIE preoperatively, for instance, facilitates the engagement of the appropriate surgical specialists so that multiple surgeries can be avoided. It also enables patients to be optimally informed before surgery of possible outcomes and complications.

Moreover, in the context of infertility, ultrasound can be a valuable tool for understanding uterine pathology and assessing for adenomyosis so that affected patients may be treated surgically or medically before turning to assisted reproductive technology.
 

Uniformity, Standardization in the Sonographic Assessment

In Europe, as in the United States, transvaginal sonography (TVS) is the first-line imaging tool for the diagnosis and management of endometriosis. In Europe, many ob.gyns. perform ultrasound themselves, as do treating surgeons. When diagnostic findings are negative but clinical suspicion is high, MRI is often utilized. Laparoscopy may then be considered in patients with negative imaging results.

Efforts to standardize terms, definitions, measurements, and sonographic features of different types of endometriosis have been made to make it easier for physicians to share data and communicate with each other. A lack of uniformity has contributed to variability in the reported diagnostic accuracy of TVS.

About 10 years ago, in one such effort, we assessed the accuracy of TVS for DIE by comparing TVS results with laparoscopic/histologic findings, and developed an ultrasound mapping system to accurately record the location, size and depth of lesions visualized by TVS. The accuracy of TVS ranged from 76% for the diagnosis of vaginal endometriosis to 97% for the diagnosis of bladder lesions and posterior cul-de-sac obliteration. Accuracy was 93% and 91% for detecting ureteral involvement (right and left); 87% for uterosacral ligament endometriotic lesions; and 87% for parametrial involvement.⁶

Shortly after, with a focus on DIE, expert sonographers and physician-sonographers from across Europe — as well as some experts from Australia, Japan, Brazil, Chile, and the United States (Y. Osuga from Brigham and Women’s Hospital and Harvard Medical School) — came together to agree on a uniform approach to the sonographic evaluation for suspected endometriosis and a standardization of terminology.

The consensus opinion from the International Deep Endometriosis Analysis (IDEA) group details four steps for examining women with suspected DIE: 1) Evaluation of the uterus and adnexa, 2) evaluation of transvaginal sonographic “soft markers” (ie. site-specific tenderness and ovarian mobility), 3) assessment of the status of the posterior cul-de-sac using real-time ultrasound-based “sliding sign,” and 4) assessment for DIE nodules in the anterior and posterior compartments.⁷

Our paper describing a mapping system and the IDEA paper describe how to detect deep endometriosis in the pelvis by utilizing an ultrasound view of normal anatomy and pelvic organ structure to provide landmarks for accurately defining the site of DIE lesions (Figure 2).

Dr. Exacoustos

(A. Ultrasound appearance of a small DIE lesion of the retrocervical area [white arrows], which involved the torus uterinum and the right uterosacral ligament [USL]. The lesion appears as hypoechoic tissue with irregular margins caused by the fibrosis induced by the DIE. B. TVS appearance of small nodules of DIE of the left USL. Note the small retrocervical DIE lesion [white arrows], which appears hypoechoic due to the infiltration of the hyperechoic USL. C) Ultrasound appearance of a DIE nodule of the recto-sigmoid wall. Note the hypoechoic thickening of the muscular layers of the bowel wall attached to the corpus of the uterus and the adenomyosis of the posterior wall. The retrocervical area is free. D. TVS appearance of nodules of DIE of the lower rectal wall. Note the hypoechoic lesion [white arrows] of the rectum is attached to a retrocervical DIE fibrosis of the torus and USL [white dotted line]).

So-called rectovaginal endometriosis can be well assessed, for instance, since the involvement of the rectum, sigmoid colon, vaginal wall, rectovaginal septum, and posterior cul-de-sac uterosacral ligament can be seen by ultrasound as a single structure, making the location, size, and depth of any lesions discernible.

Again, this evaluation of the extent of disease is important for presurgical assessment so the surgeon can organize the right team and time of surgery and so the patient can be counseled on the advantages and possible complications of the treatment.

Notably, an accurate ultrasound description of pelvic endometriosis is helpful for accurate classification of disease. Endometriosis classification systems such as that of the American Association of Gynecologic Laparoscopists (AAGL)⁸ and the American Society of Reproductive Medicine (ASRM),⁹ as well as the #Enzian surgical description system,¹⁰ have been adapted to cover findings from ultrasound as well as MRI imaging.
 

A Systematic Evaluation

In keeping with the IDEA consensus opinion and based on our years of experience at the University of Rome, I advise that patients with typical pain symptoms of endometriosis or infertility undergo an accurate sonographic assessment of the pelvis with particular evaluation not only of the uterus and ovaries but of all pelvic retroperitoneal spaces.

The TVS examination should start with a slightly filled bladder, which permits a better evaluation of the bladder walls and the presence of endometriotic nodules. These nodules appear as hyperechoic linear or spherical lesions bulging toward the lumen and involving the serosa, muscularis, or (sub)mucosa of the bladder.

Then, an accurate evaluation of the uterus in 2D and 3D permits the diagnosis of adenomyosis. 3D sonographic evaluation of the myometrium and of the junctional zone are important; alteration and infiltration of the junctional zone and the presence of small adenomyotic cysts in the inner or outer myometrium are direct, specific signs of adenomyosis and should be ruled out in patients with dysmenorrhea, heavy menstrual bleeding, infertility, and pregnancy complications.

Endometriomas of the ovaries can be easily detected as having the typical appearance of a cyst with ground glass content. Adhesions of the ovaries and the uterus also should be evaluated with a dynamic ultrasound approach that utilizes the sliding sign and mobilization by palpation of the organs during the TVS scan.

Finally, the posterior and lateral retroperitoneal compartments should be carefully evaluated, with symptoms guiding the TVS examination whenever possible. Deep endometriotic nodules of the rectum appear as hypoechoic lesions or linear or nodular retroperitoneal thickening with irregular borders, penetrating into the intestinal wall and distorting its normal structure. In young patients, it seems very important to assess for small lesions below the peritoneum between the vagina and rectum, and in the parametria and around the ureter and nerves — lesions that, notably, would not be seen by diagnostic laparoscopy.
 

The Evaluation of Young Patients

In adolescent and young patients, endometriosis and adenomyosis are often present with small lesions and shallow tissue invasion, making a very careful and experienced approach to ultrasound essential for detection. Endometriomas are often of small diameter, and DIE is not always easily diagnosed because retroperitoneal lesions are similarly very small.

In a series of 270 adolescents (ages 12-20) who were referred to our outpatient gynecologic ultrasound unit over a 5-year period for various indications, at least one ultrasound feature of endometriosis was observed in 13.3%. In those with dysmenorrhea, the detection of endometriosis increased to 21%. Endometrioma was the most common type of endometriosis we found in the study, but DIE and adenomyosis were found in 4%-11%.

Although endometriotic lesions typically are small in young patients, they are often associated with severe pain symptoms, including chronic pelvic pain, dysmenorrhea, dyspareunia, dysuria, and dyschezia, all of which can have a serious effect on the quality of life of these young women. These symptoms keep them away from school during menstruation, away from sports, and cause painful intercourse and infertility. In young patients, an accurate TVS can provide a lot of information, and the ability to detect retroperitoneal endometriotic lesions and adenomyosis is probably better than with purely diagnostic laparoscopy, which would evaluate only superficial lesions.

TVS or, when needed, transrectal ultrasound, can enable adequate treatment and follow-up of the disease and its symptoms. There are no guidelines recommending adequate follow-up times to evaluate the effectiveness of medical therapy in patients with ultrasound signs of endometriosis. (Likewise, there are no indications for follow-up in patients with severe dysmenorrhea without ultrasound signs of endometriosis.) Certainly, our studies suggest careful evaluation over time of young patients with severe dysmenorrhea by serial ultrasound scans. With such follow-up, disease progress can be monitored and the medical or surgical treatment approach modified if needed.

The diagnosis of endometriosis at a young age has significant benefits not only in avoiding or reducing progression of the disease, but also in improving quality of life and aiding women in their desire for pregnancy.
 

Dr. Exacoustos is associate professor of ob.gyn. at the University of Rome “Tor Vergata.” She has no conflicts of interest to report.

References

1. Zondervan KT et al. N Engl J Med. 2020;382:1244-56.

2. Greene R et al. Fertil Steril. 2009;91:32-9.

3. Chapron C et al. J Pediatr Adolesc Gynecol. 2011;24:S7-12.

4. Randhawa AE et al. J Pediatr Adolesc Gynecol. 2021;34:643-8.

5. Becker CM et al. Hum Reprod Open. 2022(2):hoac009.

6. Exacoustos C et al. Fertil Steril. 2014;102:143-9. 7. Guerriero S et al. Ultrasound Obstet Gynecol. 2016;48(3):318-32.

8. Abrao MS et al. J Minim Invasive Gynecol. 2021;28:1941-50.9. Revised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil Steril. 1997;67:817-21. 10. Keckstein J et al. Acta Obstet Gynecol Scand. 2021;100:1165-75.

11. Martire FG et al. Fertil Steril. 2020;114(5):1049-57.

A recent analysis identified significant disparities in survival outcomes as well as clinical and genetic features between Black and White women with a common subtype of endometrial cancer.

In addition to observing differences in clinical and molecular characteristics, the analysis of real-world registries and clinical trials revealed that Black patients with endometrioid endometrial carcinoma had about a twofold higher risk for cancer-related deaths than White patients.

“Even with propensity-score matching, Black patients had a significantly increased risk of death,” Zachary Kopelman, DO, with Walter Reed National Military Medical Center, Bethesda, Maryland, noted in a presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

Importantly, Dr. Kopelman added, the analysis also confirmed “dramatic” underrepresentation of Black patients with endometrioid endometrial carcinoma in clinical trials.

Endometrial cancer is one of the most common cancers among women in the United States, with data showing rising incidence and mortality rates. “Worryingly, endometrial cancer is estimated to overtake ovarian cancer as the deadliest gynecologic malignancy this year,” Dr. Kopelman told attendees.

Previous studies have shown that Black patients with endometrial cancer consistently are more likely to have aggressive histologic subtypes, high-grade tumors, and advanced-stage disease and are twice as likely to die from the disease as White patients, he noted.

Within endometrial cancer, the most common histologic subtype is endometrioid, comprising 65%-75% of cases. In other studies examining racial disparities, the endometrioid histology is often combined with other subtypes, such as aggressive uterine serous carcinoma, which may influence study outcomes, Dr. Kopelman explained.

Dr. Kopelman and colleagues focused their analyses on Black and White women with endometrioid endometrial carcinoma, with the goal of identifying disparities in cancer-related and non-cancer deaths, as well as clinical and molecular features in this patient population.

All women included in the analysis had undergone hysterectomy with or without adjuvant treatment. The researchers used a four-pronged approach incorporating data from the SEER program (2004-2016), the National Cancer Database (2004-2017), eight National Cancer Institute-sponsored randomized phase 3 clinical trials, and the Genomics Evidence Neoplasia Information Exchange project.

Dr. Kopelman and colleagues then performed propensity score matching in the National Cancer Database and exact matching in the randomized controlled trials.

When comparing 47,959 White patients with 4397 Black patients in the SEER dataset, Dr. Kopelman and colleagues found that Black patients had more than two times the risk of dying from their cancer (hazard ratio [HR], 2.04) and a 22% greater risk for a non-cancer death compared with White patients (HR, 1.22).

In the overall National Cancer Database cohort comparing 155,706 White and 13,468 Black patients, Black patients had a 52% greater risk of dying from any cause (HR, 1.52). In the propensity score-matched cohort of 13,468 White and 13,468 Black patients, survival among Black patients remained significantly worse, with a 29% greater risk of dying from any cause (HR, 1.29).

When looking at clinical trial data, Black patients were more likely than White patients to have worse performance status and a higher grade or recurrent disease, Dr. Kopelman noted.

Black patients in the clinical trials also had significantly worse progression-free survival in both the original cohort (HR, 2.05) and the matched cohort (adjusted HR [aHR], 1.22), which matched patients for grade, stage, and treatment arm within each trial and balanced age and performance status. Black patients also had worse overall survival in the original cohort (HR, 2.19) and matched cohort (aHR, 1.32).

Looking at molecular features, Black patients had significantly fewer mutations in a handful of cancer-related gene pathways, including PTEN, PIK3R1, FBXW7, NF1, mTOR, CCND1, and PI3K pathways.

One caveat, said Dr. Kopelman, is that mutations in PTEN are still present in a high percentage of both Black (62%) and White (72%), which «offers a potential attractive therapeutic opportunity.»

The analysis also revealed a major gap in the number of Black vs White patients enrolled in randomized clinical trials, which is a major “problem,” said Dr. Kopelman.

The study confirms “ongoing disparities in enrollment and underrepresentation of minorities in gynecologic cancer clinical trials, as well as poor outcomes, and should really promote us to enhance research in these areas,” said study discussant Mariam AlHilli, MD, with Cleveland Clinic Lerner College of Medicine and Case Western Reserve University, Cleveland, Ohio.

David M. O’Malley, MD, who gave a separate talk during the same session on practical considerations for implication of clinical trials, encouraged clinicians to “just ask.”

“Just ask the patient in front of you — no matter what their ethnicity, their race, or where they’re coming from — are they interested in participating in a clinical trial?” Or better yet, “I have a clinical trial now which I’m excited about for you,” said Dr. O’Malley, with The Ohio State University, James Comprehensive Cancer Center, Columbus, Ohio.The study had no commercial funding. Dr. Kopelman, Dr. O’Malley, and Dr. AlHilli had no relevant disclosures.

A version of this article appeared on Medscape.com .

A recent analysis identified significant disparities in survival outcomes as well as clinical and genetic features between Black and White women with a common subtype of endometrial cancer.

In addition to observing differences in clinical and molecular characteristics, the analysis of real-world registries and clinical trials revealed that Black patients with endometrioid endometrial carcinoma had about a twofold higher risk for cancer-related deaths than White patients.

“Even with propensity-score matching, Black patients had a significantly increased risk of death,” Zachary Kopelman, DO, with Walter Reed National Military Medical Center, Bethesda, Maryland, noted in a presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

Importantly, Dr. Kopelman added, the analysis also confirmed “dramatic” underrepresentation of Black patients with endometrioid endometrial carcinoma in clinical trials.

Endometrial cancer is one of the most common cancers among women in the United States, with data showing rising incidence and mortality rates. “Worryingly, endometrial cancer is estimated to overtake ovarian cancer as the deadliest gynecologic malignancy this year,” Dr. Kopelman told attendees.

Previous studies have shown that Black patients with endometrial cancer consistently are more likely to have aggressive histologic subtypes, high-grade tumors, and advanced-stage disease and are twice as likely to die from the disease as White patients, he noted.

Within endometrial cancer, the most common histologic subtype is endometrioid, comprising 65%-75% of cases. In other studies examining racial disparities, the endometrioid histology is often combined with other subtypes, such as aggressive uterine serous carcinoma, which may influence study outcomes, Dr. Kopelman explained.

Dr. Kopelman and colleagues focused their analyses on Black and White women with endometrioid endometrial carcinoma, with the goal of identifying disparities in cancer-related and non-cancer deaths, as well as clinical and molecular features in this patient population.

All women included in the analysis had undergone hysterectomy with or without adjuvant treatment. The researchers used a four-pronged approach incorporating data from the SEER program (2004-2016), the National Cancer Database (2004-2017), eight National Cancer Institute-sponsored randomized phase 3 clinical trials, and the Genomics Evidence Neoplasia Information Exchange project.

Dr. Kopelman and colleagues then performed propensity score matching in the National Cancer Database and exact matching in the randomized controlled trials.

When comparing 47,959 White patients with 4397 Black patients in the SEER dataset, Dr. Kopelman and colleagues found that Black patients had more than two times the risk of dying from their cancer (hazard ratio [HR], 2.04) and a 22% greater risk for a non-cancer death compared with White patients (HR, 1.22).

In the overall National Cancer Database cohort comparing 155,706 White and 13,468 Black patients, Black patients had a 52% greater risk of dying from any cause (HR, 1.52). In the propensity score-matched cohort of 13,468 White and 13,468 Black patients, survival among Black patients remained significantly worse, with a 29% greater risk of dying from any cause (HR, 1.29).

When looking at clinical trial data, Black patients were more likely than White patients to have worse performance status and a higher grade or recurrent disease, Dr. Kopelman noted.

Black patients in the clinical trials also had significantly worse progression-free survival in both the original cohort (HR, 2.05) and the matched cohort (adjusted HR [aHR], 1.22), which matched patients for grade, stage, and treatment arm within each trial and balanced age and performance status. Black patients also had worse overall survival in the original cohort (HR, 2.19) and matched cohort (aHR, 1.32).

Looking at molecular features, Black patients had significantly fewer mutations in a handful of cancer-related gene pathways, including PTEN, PIK3R1, FBXW7, NF1, mTOR, CCND1, and PI3K pathways.

One caveat, said Dr. Kopelman, is that mutations in PTEN are still present in a high percentage of both Black (62%) and White (72%), which «offers a potential attractive therapeutic opportunity.»

The analysis also revealed a major gap in the number of Black vs White patients enrolled in randomized clinical trials, which is a major “problem,” said Dr. Kopelman.

The study confirms “ongoing disparities in enrollment and underrepresentation of minorities in gynecologic cancer clinical trials, as well as poor outcomes, and should really promote us to enhance research in these areas,” said study discussant Mariam AlHilli, MD, with Cleveland Clinic Lerner College of Medicine and Case Western Reserve University, Cleveland, Ohio.

David M. O’Malley, MD, who gave a separate talk during the same session on practical considerations for implication of clinical trials, encouraged clinicians to “just ask.”

“Just ask the patient in front of you — no matter what their ethnicity, their race, or where they’re coming from — are they interested in participating in a clinical trial?” Or better yet, “I have a clinical trial now which I’m excited about for you,” said Dr. O’Malley, with The Ohio State University, James Comprehensive Cancer Center, Columbus, Ohio.The study had no commercial funding. Dr. Kopelman, Dr. O’Malley, and Dr. AlHilli had no relevant disclosures.

A version of this article appeared on Medscape.com .

A recent analysis identified significant disparities in survival outcomes as well as clinical and genetic features between Black and White women with a common subtype of endometrial cancer.

In addition to observing differences in clinical and molecular characteristics, the analysis of real-world registries and clinical trials revealed that Black patients with endometrioid endometrial carcinoma had about a twofold higher risk for cancer-related deaths than White patients.

“Even with propensity-score matching, Black patients had a significantly increased risk of death,” Zachary Kopelman, DO, with Walter Reed National Military Medical Center, Bethesda, Maryland, noted in a presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

Importantly, Dr. Kopelman added, the analysis also confirmed “dramatic” underrepresentation of Black patients with endometrioid endometrial carcinoma in clinical trials.

Endometrial cancer is one of the most common cancers among women in the United States, with data showing rising incidence and mortality rates. “Worryingly, endometrial cancer is estimated to overtake ovarian cancer as the deadliest gynecologic malignancy this year,” Dr. Kopelman told attendees.

Previous studies have shown that Black patients with endometrial cancer consistently are more likely to have aggressive histologic subtypes, high-grade tumors, and advanced-stage disease and are twice as likely to die from the disease as White patients, he noted.

Within endometrial cancer, the most common histologic subtype is endometrioid, comprising 65%-75% of cases. In other studies examining racial disparities, the endometrioid histology is often combined with other subtypes, such as aggressive uterine serous carcinoma, which may influence study outcomes, Dr. Kopelman explained.

Dr. Kopelman and colleagues focused their analyses on Black and White women with endometrioid endometrial carcinoma, with the goal of identifying disparities in cancer-related and non-cancer deaths, as well as clinical and molecular features in this patient population.

All women included in the analysis had undergone hysterectomy with or without adjuvant treatment. The researchers used a four-pronged approach incorporating data from the SEER program (2004-2016), the National Cancer Database (2004-2017), eight National Cancer Institute-sponsored randomized phase 3 clinical trials, and the Genomics Evidence Neoplasia Information Exchange project.

Dr. Kopelman and colleagues then performed propensity score matching in the National Cancer Database and exact matching in the randomized controlled trials.

When comparing 47,959 White patients with 4397 Black patients in the SEER dataset, Dr. Kopelman and colleagues found that Black patients had more than two times the risk of dying from their cancer (hazard ratio [HR], 2.04) and a 22% greater risk for a non-cancer death compared with White patients (HR, 1.22).

In the overall National Cancer Database cohort comparing 155,706 White and 13,468 Black patients, Black patients had a 52% greater risk of dying from any cause (HR, 1.52). In the propensity score-matched cohort of 13,468 White and 13,468 Black patients, survival among Black patients remained significantly worse, with a 29% greater risk of dying from any cause (HR, 1.29).

When looking at clinical trial data, Black patients were more likely than White patients to have worse performance status and a higher grade or recurrent disease, Dr. Kopelman noted.

Black patients in the clinical trials also had significantly worse progression-free survival in both the original cohort (HR, 2.05) and the matched cohort (adjusted HR [aHR], 1.22), which matched patients for grade, stage, and treatment arm within each trial and balanced age and performance status. Black patients also had worse overall survival in the original cohort (HR, 2.19) and matched cohort (aHR, 1.32).

Looking at molecular features, Black patients had significantly fewer mutations in a handful of cancer-related gene pathways, including PTEN, PIK3R1, FBXW7, NF1, mTOR, CCND1, and PI3K pathways.

One caveat, said Dr. Kopelman, is that mutations in PTEN are still present in a high percentage of both Black (62%) and White (72%), which «offers a potential attractive therapeutic opportunity.»

The analysis also revealed a major gap in the number of Black vs White patients enrolled in randomized clinical trials, which is a major “problem,” said Dr. Kopelman.

The study confirms “ongoing disparities in enrollment and underrepresentation of minorities in gynecologic cancer clinical trials, as well as poor outcomes, and should really promote us to enhance research in these areas,” said study discussant Mariam AlHilli, MD, with Cleveland Clinic Lerner College of Medicine and Case Western Reserve University, Cleveland, Ohio.

David M. O’Malley, MD, who gave a separate talk during the same session on practical considerations for implication of clinical trials, encouraged clinicians to “just ask.”

“Just ask the patient in front of you — no matter what their ethnicity, their race, or where they’re coming from — are they interested in participating in a clinical trial?” Or better yet, “I have a clinical trial now which I’m excited about for you,” said Dr. O’Malley, with The Ohio State University, James Comprehensive Cancer Center, Columbus, Ohio.The study had no commercial funding. Dr. Kopelman, Dr. O’Malley, and Dr. AlHilli had no relevant disclosures.

A version of this article appeared on Medscape.com .

One in seven women will die within 2 months of being diagnosed with ovarian cancer, a new report from the United Kingdom states. But if diagnosed at the earliest stage, 9 in 10 women will survive. Two thirds of women are now diagnosed late, when the cancer is harder to treat.

Diagnosis is difficult for many reasons, among them that women sometimes think symptoms are a natural part of menopause and don’t acknowledge or report them. Clinicians may mistake abdominal symptoms for those of a bowel condition or bladder problem. Almost half of GPs (46%) in the UK mistakenly believe that ovarian cancer symptoms present in only the later stages of the disease.

Cervical Screening Does Not Detect Ovarian Cancer

Additionally, there are misconceptions regarding cervical cancer screening — one study found that “40% of women in the general public mistakenly believe that cervical screening detects ovarian cancer.” But there is no current screening program for ovarian cancer in the UK or United States.

During a pelvic exam, the physician feels the ovaries and uterus for size, shape, and consistency and that can be useful in finding some cancers early, but most early ovarian tumors are difficult or impossible to feel, the American Cancer Society notes.

Recognizing the Red Flags

Victoria Barber, MBBS, a general practitioner in Northamptonshire and a Primary Care Advisory Board member with the Target Ovarian Cancer program in the UK published a paper in the British Journal of Nursing (2024 Mar 7. doi: 10.12968/bjon.2024.33.5.S16) on the program’s efforts to urge clinicians to recognize ovarian cancer red flags and to “never diagnose new-onset irritable bowel syndrome or overactive bladder in women over 50 without ruling out ovarian cancer.”

She says nurses should be involved to help with earlier diagnosis of ovarian cancer as they are often involved in evaluating urine samples. Nurse practitioners, she notes, are typically included in consultations for abdominal symptoms and potential urinary tract infections.

“If the woman is recurrently presenting with urinary symptoms, sterile midstream urine samples should raise alarm,” she says. “The woman may have diabetes, an overactive bladder, or interstitial cystitis; however, urgency and frequency are some of the symptoms of ovarian cancer, and they need investigation.”

Persistent Systems Over Age 50

The paper lists ovarian cancer symptoms from the UK’s National Institute for Health and Care Excellence and notes that among red flags are having any of the following persistently/frequently (particularly more than 12 times per month and especially if the woman is 50 years or older):

• Early satiety and/or loss of appetite
• Abdominal bloating
• Pelvic or abdominal pain
• Urinary urgency/frequency

Other symptoms could include:

• Changes in bowel habits (e.g., diarrhea or constipation)
• Extreme fatigue
• Unexplained weight loss

Diagnosis Challenges Similar in US

Ernst Lengyel, MD, PhD, UChicago Medicine’s Chairman of the Department of Obstetrics and Gynecology in Chicago, Illinois, who was not involved with the paper, said the situation in the United States is similar to that described in the UK.

“The diagnosis is delayed because the symptoms are unspecific. The problem is that ovarian cancer is so rare, and primary care physicians or nurse practitioners have to consider over 100 differential diagnoses,” he says.

In the US, he says, it is likely easier to get in and see a physician because of the private insurance options and because there are more gynecologic oncologists in large urban areas. Getting imaging approved — such as ultrasound and computed tomography scans — is also easier in the US.

Still, “there is no effective way to diagnose ovarian cancer early,” he says. “No single test or combination of symptoms can be used as a screening test.”

The CA-125 blood test measures proteins that can be linked with ovarian cancer, but is not a screening test, he notes.

“Large UK and US studies have not been able to show a survival benefit with ultrasound, serial CA-125, or a combination thereof,” Dr. Lengyel said.

Weight Gain May Also be a Sign

A broad range of clinicians should be aware of the symptoms the author mentions, he says, especially primary care physicians, nurse practitioners, and obstetrician/gynecologists.

“Too often, symptoms that women report are ignored and treated as unspecific or psychosomatic,” Dr. Lengyel says. “It is easy to disregard recurrent complaints and move on instead of being vigilant and working them up. Ironically, women with ovarian cancer can initially gain weight, which is counterintuitive as most doctors believe that patients with cancer lose weight. However, if they develop abdominal fluid, a patient often gains weight.”

Dr. Barber and Dr. Lengyel report no relevant financial relationships.

One in seven women will die within 2 months of being diagnosed with ovarian cancer, a new report from the United Kingdom states. But if diagnosed at the earliest stage, 9 in 10 women will survive. Two thirds of women are now diagnosed late, when the cancer is harder to treat.

Diagnosis is difficult for many reasons, among them that women sometimes think symptoms are a natural part of menopause and don’t acknowledge or report them. Clinicians may mistake abdominal symptoms for those of a bowel condition or bladder problem. Almost half of GPs (46%) in the UK mistakenly believe that ovarian cancer symptoms present in only the later stages of the disease.

Cervical Screening Does Not Detect Ovarian Cancer

Additionally, there are misconceptions regarding cervical cancer screening — one study found that “40% of women in the general public mistakenly believe that cervical screening detects ovarian cancer.” But there is no current screening program for ovarian cancer in the UK or United States.

During a pelvic exam, the physician feels the ovaries and uterus for size, shape, and consistency and that can be useful in finding some cancers early, but most early ovarian tumors are difficult or impossible to feel, the American Cancer Society notes.

Recognizing the Red Flags

Victoria Barber, MBBS, a general practitioner in Northamptonshire and a Primary Care Advisory Board member with the Target Ovarian Cancer program in the UK published a paper in the British Journal of Nursing (2024 Mar 7. doi: 10.12968/bjon.2024.33.5.S16) on the program’s efforts to urge clinicians to recognize ovarian cancer red flags and to “never diagnose new-onset irritable bowel syndrome or overactive bladder in women over 50 without ruling out ovarian cancer.”

She says nurses should be involved to help with earlier diagnosis of ovarian cancer as they are often involved in evaluating urine samples. Nurse practitioners, she notes, are typically included in consultations for abdominal symptoms and potential urinary tract infections.

“If the woman is recurrently presenting with urinary symptoms, sterile midstream urine samples should raise alarm,” she says. “The woman may have diabetes, an overactive bladder, or interstitial cystitis; however, urgency and frequency are some of the symptoms of ovarian cancer, and they need investigation.”

Persistent Systems Over Age 50

The paper lists ovarian cancer symptoms from the UK’s National Institute for Health and Care Excellence and notes that among red flags are having any of the following persistently/frequently (particularly more than 12 times per month and especially if the woman is 50 years or older):

• Early satiety and/or loss of appetite
• Abdominal bloating
• Pelvic or abdominal pain
• Urinary urgency/frequency

Other symptoms could include:

• Changes in bowel habits (e.g., diarrhea or constipation)
• Extreme fatigue
• Unexplained weight loss

Diagnosis Challenges Similar in US

Ernst Lengyel, MD, PhD, UChicago Medicine’s Chairman of the Department of Obstetrics and Gynecology in Chicago, Illinois, who was not involved with the paper, said the situation in the United States is similar to that described in the UK.

“The diagnosis is delayed because the symptoms are unspecific. The problem is that ovarian cancer is so rare, and primary care physicians or nurse practitioners have to consider over 100 differential diagnoses,” he says.

In the US, he says, it is likely easier to get in and see a physician because of the private insurance options and because there are more gynecologic oncologists in large urban areas. Getting imaging approved — such as ultrasound and computed tomography scans — is also easier in the US.

Still, “there is no effective way to diagnose ovarian cancer early,” he says. “No single test or combination of symptoms can be used as a screening test.”

The CA-125 blood test measures proteins that can be linked with ovarian cancer, but is not a screening test, he notes.

“Large UK and US studies have not been able to show a survival benefit with ultrasound, serial CA-125, or a combination thereof,” Dr. Lengyel said.

Weight Gain May Also be a Sign

A broad range of clinicians should be aware of the symptoms the author mentions, he says, especially primary care physicians, nurse practitioners, and obstetrician/gynecologists.

“Too often, symptoms that women report are ignored and treated as unspecific or psychosomatic,” Dr. Lengyel says. “It is easy to disregard recurrent complaints and move on instead of being vigilant and working them up. Ironically, women with ovarian cancer can initially gain weight, which is counterintuitive as most doctors believe that patients with cancer lose weight. However, if they develop abdominal fluid, a patient often gains weight.”

Dr. Barber and Dr. Lengyel report no relevant financial relationships.

One in seven women will die within 2 months of being diagnosed with ovarian cancer, a new report from the United Kingdom states. But if diagnosed at the earliest stage, 9 in 10 women will survive. Two thirds of women are now diagnosed late, when the cancer is harder to treat.

Diagnosis is difficult for many reasons, among them that women sometimes think symptoms are a natural part of menopause and don’t acknowledge or report them. Clinicians may mistake abdominal symptoms for those of a bowel condition or bladder problem. Almost half of GPs (46%) in the UK mistakenly believe that ovarian cancer symptoms present in only the later stages of the disease.

Cervical Screening Does Not Detect Ovarian Cancer

Additionally, there are misconceptions regarding cervical cancer screening — one study found that “40% of women in the general public mistakenly believe that cervical screening detects ovarian cancer.” But there is no current screening program for ovarian cancer in the UK or United States.

During a pelvic exam, the physician feels the ovaries and uterus for size, shape, and consistency and that can be useful in finding some cancers early, but most early ovarian tumors are difficult or impossible to feel, the American Cancer Society notes.

Recognizing the Red Flags

Victoria Barber, MBBS, a general practitioner in Northamptonshire and a Primary Care Advisory Board member with the Target Ovarian Cancer program in the UK published a paper in the British Journal of Nursing (2024 Mar 7. doi: 10.12968/bjon.2024.33.5.S16) on the program’s efforts to urge clinicians to recognize ovarian cancer red flags and to “never diagnose new-onset irritable bowel syndrome or overactive bladder in women over 50 without ruling out ovarian cancer.”

She says nurses should be involved to help with earlier diagnosis of ovarian cancer as they are often involved in evaluating urine samples. Nurse practitioners, she notes, are typically included in consultations for abdominal symptoms and potential urinary tract infections.

“If the woman is recurrently presenting with urinary symptoms, sterile midstream urine samples should raise alarm,” she says. “The woman may have diabetes, an overactive bladder, or interstitial cystitis; however, urgency and frequency are some of the symptoms of ovarian cancer, and they need investigation.”

Persistent Systems Over Age 50

The paper lists ovarian cancer symptoms from the UK’s National Institute for Health and Care Excellence and notes that among red flags are having any of the following persistently/frequently (particularly more than 12 times per month and especially if the woman is 50 years or older):

• Early satiety and/or loss of appetite
• Abdominal bloating
• Pelvic or abdominal pain
• Urinary urgency/frequency

Other symptoms could include:

• Changes in bowel habits (e.g., diarrhea or constipation)
• Extreme fatigue
• Unexplained weight loss

Diagnosis Challenges Similar in US

Ernst Lengyel, MD, PhD, UChicago Medicine’s Chairman of the Department of Obstetrics and Gynecology in Chicago, Illinois, who was not involved with the paper, said the situation in the United States is similar to that described in the UK.

“The diagnosis is delayed because the symptoms are unspecific. The problem is that ovarian cancer is so rare, and primary care physicians or nurse practitioners have to consider over 100 differential diagnoses,” he says.

In the US, he says, it is likely easier to get in and see a physician because of the private insurance options and because there are more gynecologic oncologists in large urban areas. Getting imaging approved — such as ultrasound and computed tomography scans — is also easier in the US.

Still, “there is no effective way to diagnose ovarian cancer early,” he says. “No single test or combination of symptoms can be used as a screening test.”

The CA-125 blood test measures proteins that can be linked with ovarian cancer, but is not a screening test, he notes.

“Large UK and US studies have not been able to show a survival benefit with ultrasound, serial CA-125, or a combination thereof,” Dr. Lengyel said.

Weight Gain May Also be a Sign

A broad range of clinicians should be aware of the symptoms the author mentions, he says, especially primary care physicians, nurse practitioners, and obstetrician/gynecologists.

“Too often, symptoms that women report are ignored and treated as unspecific or psychosomatic,” Dr. Lengyel says. “It is easy to disregard recurrent complaints and move on instead of being vigilant and working them up. Ironically, women with ovarian cancer can initially gain weight, which is counterintuitive as most doctors believe that patients with cancer lose weight. However, if they develop abdominal fluid, a patient often gains weight.”

Dr. Barber and Dr. Lengyel report no relevant financial relationships.

The number of women with perinatal mood and anxiety disorder (PMAD) has spiked sharply in the United States. A new study explores trends by state and time period.

Between 2008 and 2020, in a national cohort of 750,004 commercially insured women with a live birth, nearly 1 in 5 (144,037 [19.2%]) were diagnosed with PMAD, according to a paper published in Health Affairs. PMAD diagnoses among privately insured women increased by 93.3% over those years, wrote lead author Kara Zivin, PhD, of the University of Michigan, Veterans Affairs Ann Arbor Healthcare System, and colleagues.

PMAD describes a spectrum of emotional complications with mild to severe symptoms that can affect women while pregnant and through the first year after giving birth.

The total number of perinatal women decreased from a high of 64,842 in 2008 to a low of 52,479 in 2020, a 19.1% decrease, but over the same time, women with diagnosed PMAD increased 56.4% from 9,520 in 2008 to 14,890 in 2020. Prevalence of PMAD doubled from 1,468 per 10,000 deliveries to 2,837 per 10,000 deliveries in 2020, according to the analysis.
 

Differences by State

Increases differed substantially by state. Though average annual changes across all states reached 109 additional PMAD diagnoses per 10,000 deliveries, Iowa had the greatest increase with an additional 163 PMAD diagnoses per 10,000 deliveries annually. New Mexico had the smallest annual growth, at an additional 49 per 10,000 deliveries.

The increases were accompanied by maternal health improvement efforts. The Affordable Care Act (ACA) required insurance companies to cover maternity and preventive services, which likely increased PMAD screening and detection, the researchers noted.

“Diagnosis of PMAD is rising due to increased awareness and in all likelihood, decrease in stigma, but availability of providers is so challenging,” said Lee S. Cohen, MD, who was not part of the study. Dr. Cohen is director of the Ammon-Pinizzotto Center for Women’s Mental Health and Perinatal and Reproductive Psychiatry at Massachusetts General Hospital in Boston. “The navigation to providers by women who are suffering is beyond challenging,” he said.

The authors reported that all states except Vermont saw increasing rates of PMAD diagnoses post-ACA vs. pre-ACA. The researchers also found that relative to the period from 2008 to 2014, psychotherapy rates continued rising from 2015 to 2020 and suicidality (suicidal ideation or self-harm diagnoses) rates declined.
 

States’ Suicidality Rates Vary Widely

“Overall, access to psychotherapy may have stemmed suicidality despite increasing PMAD diagnoses. But although more PMAD diagnoses may have led to increased psychotherapy, therapy access depends on provider availability, which varies by geographic region and insurance coverage network,” the authors wrote.

Suicidality rates differed greatly by state. Louisiana’s annual rate of increase was greatest, at 22 per 10,000 while Maryland had the greatest negative annual rate of change, at −15 per 10,000 deliveries, the authors explained.

“Observed trends in PMAD diagnoses among privately insured people during 2008-2020 and in associated suicidality and psychotherapy use suggest an increasingly rapid worsening of US maternal mental health,” the authors wrote.

The authors noted that this study did not include those on public insurance, a group that may experience disproportionate maternal morbidity and mortality burden, and urged that future studies include them.
 

Strengths of Study

Kimberly McKee, PhD, MPH, assistant professor in the department of family medicine at University of Michigan in Ann Arbor, who was not part of this research, said this paper gives a broader look than prior work because it includes the year before and after birth, rather than delivery and hospitalization.

“It’s really important to look out at least 12 months postpartum,” she noted.

Another strength is that the study was able to look at use of services such as psychotherapy before and post ACA. She noted the increased use of psychotherapy and the decrease in suicidal ideation was an association, but said, “I think it’s reasonable to assume that there was a benefit.”

She noted that these data go through 2020 and the COVID-19 pandemic has even further stressed the healthcare system, which could affect these numbers.

Primary Care’s Role

“The opportunity for primary care to really be the medical home for reproductive-age women is key here,” Dr. McKee said, adding that primary care can provide the continuity if women go off and on insurance around pregnancy and make sure the women get follow-up care and referrals to specialty care.

Models that integrate behavioral health and primary care are particularly promising, she said. Inclusion of social workers at the point of care can also help meet needs regarding social determinants of health.

Telehealth is another avenue for expansion extending the reach for following perinatal women, she said. “Using every tool we have to reach individuals where they are can allow for more frequent check-ins, which is really important here.”

Dr. McKee said the paper highlights an important reality: Mental health is a leading cause and contributor to maternal mortality, which “is 100% preventable.” Yet, current literature continues to show increases.

“This is a fairly common problem that affects not just women, but the fetus, their children, their families,” she noted.

The authors and Dr. Cohen and Dr. McKee reported no relevant financial relationships.

The number of women with perinatal mood and anxiety disorder (PMAD) has spiked sharply in the United States. A new study explores trends by state and time period.

Between 2008 and 2020, in a national cohort of 750,004 commercially insured women with a live birth, nearly 1 in 5 (144,037 [19.2%]) were diagnosed with PMAD, according to a paper published in Health Affairs. PMAD diagnoses among privately insured women increased by 93.3% over those years, wrote lead author Kara Zivin, PhD, of the University of Michigan, Veterans Affairs Ann Arbor Healthcare System, and colleagues.

PMAD describes a spectrum of emotional complications with mild to severe symptoms that can affect women while pregnant and through the first year after giving birth.

The total number of perinatal women decreased from a high of 64,842 in 2008 to a low of 52,479 in 2020, a 19.1% decrease, but over the same time, women with diagnosed PMAD increased 56.4% from 9,520 in 2008 to 14,890 in 2020. Prevalence of PMAD doubled from 1,468 per 10,000 deliveries to 2,837 per 10,000 deliveries in 2020, according to the analysis.
 

Differences by State

Increases differed substantially by state. Though average annual changes across all states reached 109 additional PMAD diagnoses per 10,000 deliveries, Iowa had the greatest increase with an additional 163 PMAD diagnoses per 10,000 deliveries annually. New Mexico had the smallest annual growth, at an additional 49 per 10,000 deliveries.

The increases were accompanied by maternal health improvement efforts. The Affordable Care Act (ACA) required insurance companies to cover maternity and preventive services, which likely increased PMAD screening and detection, the researchers noted.

“Diagnosis of PMAD is rising due to increased awareness and in all likelihood, decrease in stigma, but availability of providers is so challenging,” said Lee S. Cohen, MD, who was not part of the study. Dr. Cohen is director of the Ammon-Pinizzotto Center for Women’s Mental Health and Perinatal and Reproductive Psychiatry at Massachusetts General Hospital in Boston. “The navigation to providers by women who are suffering is beyond challenging,” he said.

The authors reported that all states except Vermont saw increasing rates of PMAD diagnoses post-ACA vs. pre-ACA. The researchers also found that relative to the period from 2008 to 2014, psychotherapy rates continued rising from 2015 to 2020 and suicidality (suicidal ideation or self-harm diagnoses) rates declined.
 

States’ Suicidality Rates Vary Widely

“Overall, access to psychotherapy may have stemmed suicidality despite increasing PMAD diagnoses. But although more PMAD diagnoses may have led to increased psychotherapy, therapy access depends on provider availability, which varies by geographic region and insurance coverage network,” the authors wrote.

Suicidality rates differed greatly by state. Louisiana’s annual rate of increase was greatest, at 22 per 10,000 while Maryland had the greatest negative annual rate of change, at −15 per 10,000 deliveries, the authors explained.

“Observed trends in PMAD diagnoses among privately insured people during 2008-2020 and in associated suicidality and psychotherapy use suggest an increasingly rapid worsening of US maternal mental health,” the authors wrote.

The authors noted that this study did not include those on public insurance, a group that may experience disproportionate maternal morbidity and mortality burden, and urged that future studies include them.
 

Strengths of Study

Kimberly McKee, PhD, MPH, assistant professor in the department of family medicine at University of Michigan in Ann Arbor, who was not part of this research, said this paper gives a broader look than prior work because it includes the year before and after birth, rather than delivery and hospitalization.

“It’s really important to look out at least 12 months postpartum,” she noted.

Another strength is that the study was able to look at use of services such as psychotherapy before and post ACA. She noted the increased use of psychotherapy and the decrease in suicidal ideation was an association, but said, “I think it’s reasonable to assume that there was a benefit.”

She noted that these data go through 2020 and the COVID-19 pandemic has even further stressed the healthcare system, which could affect these numbers.

Primary Care’s Role

“The opportunity for primary care to really be the medical home for reproductive-age women is key here,” Dr. McKee said, adding that primary care can provide the continuity if women go off and on insurance around pregnancy and make sure the women get follow-up care and referrals to specialty care.

Models that integrate behavioral health and primary care are particularly promising, she said. Inclusion of social workers at the point of care can also help meet needs regarding social determinants of health.

Telehealth is another avenue for expansion extending the reach for following perinatal women, she said. “Using every tool we have to reach individuals where they are can allow for more frequent check-ins, which is really important here.”

Dr. McKee said the paper highlights an important reality: Mental health is a leading cause and contributor to maternal mortality, which “is 100% preventable.” Yet, current literature continues to show increases.

“This is a fairly common problem that affects not just women, but the fetus, their children, their families,” she noted.

The authors and Dr. Cohen and Dr. McKee reported no relevant financial relationships.

The number of women with perinatal mood and anxiety disorder (PMAD) has spiked sharply in the United States. A new study explores trends by state and time period.

Between 2008 and 2020, in a national cohort of 750,004 commercially insured women with a live birth, nearly 1 in 5 (144,037 [19.2%]) were diagnosed with PMAD, according to a paper published in Health Affairs. PMAD diagnoses among privately insured women increased by 93.3% over those years, wrote lead author Kara Zivin, PhD, of the University of Michigan, Veterans Affairs Ann Arbor Healthcare System, and colleagues.

PMAD describes a spectrum of emotional complications with mild to severe symptoms that can affect women while pregnant and through the first year after giving birth.

The total number of perinatal women decreased from a high of 64,842 in 2008 to a low of 52,479 in 2020, a 19.1% decrease, but over the same time, women with diagnosed PMAD increased 56.4% from 9,520 in 2008 to 14,890 in 2020. Prevalence of PMAD doubled from 1,468 per 10,000 deliveries to 2,837 per 10,000 deliveries in 2020, according to the analysis.
 

Differences by State

Increases differed substantially by state. Though average annual changes across all states reached 109 additional PMAD diagnoses per 10,000 deliveries, Iowa had the greatest increase with an additional 163 PMAD diagnoses per 10,000 deliveries annually. New Mexico had the smallest annual growth, at an additional 49 per 10,000 deliveries.

The increases were accompanied by maternal health improvement efforts. The Affordable Care Act (ACA) required insurance companies to cover maternity and preventive services, which likely increased PMAD screening and detection, the researchers noted.

“Diagnosis of PMAD is rising due to increased awareness and in all likelihood, decrease in stigma, but availability of providers is so challenging,” said Lee S. Cohen, MD, who was not part of the study. Dr. Cohen is director of the Ammon-Pinizzotto Center for Women’s Mental Health and Perinatal and Reproductive Psychiatry at Massachusetts General Hospital in Boston. “The navigation to providers by women who are suffering is beyond challenging,” he said.

The authors reported that all states except Vermont saw increasing rates of PMAD diagnoses post-ACA vs. pre-ACA. The researchers also found that relative to the period from 2008 to 2014, psychotherapy rates continued rising from 2015 to 2020 and suicidality (suicidal ideation or self-harm diagnoses) rates declined.
 

States’ Suicidality Rates Vary Widely

“Overall, access to psychotherapy may have stemmed suicidality despite increasing PMAD diagnoses. But although more PMAD diagnoses may have led to increased psychotherapy, therapy access depends on provider availability, which varies by geographic region and insurance coverage network,” the authors wrote.

Suicidality rates differed greatly by state. Louisiana’s annual rate of increase was greatest, at 22 per 10,000 while Maryland had the greatest negative annual rate of change, at −15 per 10,000 deliveries, the authors explained.

“Observed trends in PMAD diagnoses among privately insured people during 2008-2020 and in associated suicidality and psychotherapy use suggest an increasingly rapid worsening of US maternal mental health,” the authors wrote.

The authors noted that this study did not include those on public insurance, a group that may experience disproportionate maternal morbidity and mortality burden, and urged that future studies include them.
 

Strengths of Study

Kimberly McKee, PhD, MPH, assistant professor in the department of family medicine at University of Michigan in Ann Arbor, who was not part of this research, said this paper gives a broader look than prior work because it includes the year before and after birth, rather than delivery and hospitalization.

“It’s really important to look out at least 12 months postpartum,” she noted.

Another strength is that the study was able to look at use of services such as psychotherapy before and post ACA. She noted the increased use of psychotherapy and the decrease in suicidal ideation was an association, but said, “I think it’s reasonable to assume that there was a benefit.”

She noted that these data go through 2020 and the COVID-19 pandemic has even further stressed the healthcare system, which could affect these numbers.

Primary Care’s Role

“The opportunity for primary care to really be the medical home for reproductive-age women is key here,” Dr. McKee said, adding that primary care can provide the continuity if women go off and on insurance around pregnancy and make sure the women get follow-up care and referrals to specialty care.

Models that integrate behavioral health and primary care are particularly promising, she said. Inclusion of social workers at the point of care can also help meet needs regarding social determinants of health.

Telehealth is another avenue for expansion extending the reach for following perinatal women, she said. “Using every tool we have to reach individuals where they are can allow for more frequent check-ins, which is really important here.”

Dr. McKee said the paper highlights an important reality: Mental health is a leading cause and contributor to maternal mortality, which “is 100% preventable.” Yet, current literature continues to show increases.

“This is a fairly common problem that affects not just women, but the fetus, their children, their families,” she noted.

The authors and Dr. Cohen and Dr. McKee reported no relevant financial relationships.