Xtandi Approved for High-Risk Prostate Cancer
Women In Menopause Are Getting Short Shrift
After a decade working as an obstetrician-gynecologist, Marci Bowers thought she understood menopause. Whenever she saw a patient in her 40s or 50s, she knew to ask about things such as hot flashes, vaginal dryness, mood swings, and memory problems. And no matter what a patient's concern was, Bowers almost always ended up prescribing the same thing. "Our answer was always estrogen," she told me.
Then, in the mid-2000s, Bowers took over a gender-affirmation surgical practice in Colorado. In her new role, she began consultations by asking each patient what they wanted from their body—a question she'd never been trained to ask menopausal women. Over time, she grew comfortable bringing up tricky topics such as pleasure, desire, and sexuality, and prescribing testosterone as well as estrogen. That's when she realized: Women in menopause were getting short shrift.
Menopause is a body-wide hormonal transition that affects virtually every organ, from skin to bones to brain. The same can be said of gender transition, which, like menopause, is often referred to by doctors and transgender patients as "a second puberty": a roller coaster of physical and emotional changes, incited by a dramatic shift in hormones. But medicine has only recently begun connecting the dots. In the past few years, some doctors who typically treat transgender patients—urologists, gender-affirmation surgeons, sexual-medicine specialists—have begun moving into menopause care and bringing with them a new set of tools.
"In many ways, trans care is light-years ahead of women's care," Kelly Casperson, a urologist and certified menopause provider in Washington State, told me. Providers who do both are well versed in the effects of hormones, attuned to concerns about sexual function, and empathetic toward people who have had their symptoms dismissed by providers. If the goal of menopause care isn't just to help women survive but also to allow them to live their fullest life, providers would do well to borrow some insights from a field that has been doing just that for decades.
American women's relationship with estrogen has been a rocky one. In the 1960s, books such as Feminine Forever, written by the gynecologist Robert A. Wilson, framed estrogen as a magical substance that could make women once again attractive and sexually available, rendering the menopausal "much more pleasant to live with." (The New York Times later reported that Wilson was paid by the manufacturer of Premarin, the most popular estrogen treatment at the time.) Later, the pitch switched to lifelong health. By 1992, Premarin was the most prescribed drug in the United States. By the end of the decade, 15 million women were on estrogen therapy, with or without progesterone, to treat their menopause symptoms.
Then, in 2002, a large clinical trial concluded that oral estrogen plus progesterone treatment was linked to an increased risk of stroke, heart disease, and breast cancer. The study was an imperfect measure of safety—it focused on older women rather than on the newly menopausal, and it tested only one type of estrogen—but oral-estrogen prescriptions still plummeted, from nearly a quarter of women over 40 to roughly 5 percent. Despite this blow to the hormone's reputation, evidence has continued to pile up confirming that oral estrogen can help prevent bone loss and treat hot flashes and night sweats, though it can increase the risk of strokes for women over 60. Topical estrogen helps address genital symptoms, including vaginal dryness, irritation, and thinning of the tissues, as well as urinary issues such as chronic UTIs and incontinence.
But estrogen alone can't address every menopause symptom, in part because estrogen is not the only hormone that's in short supply during menopause; testosterone is too. Although researchers lack high-quality research on the role of testosterone in women over age 65, they know that in premenopausal women, it plays a role in bone density, heart health, metabolism, cognition, and the function of the ovaries and bladder. A 2022 review concluded, "Testosterone is a vital hormone in women in maintaining sexual health and function" after menopause.
Yet for decades, standard menopause care mostly ignored testosterone. Part of the reason is regulatory: Although estrogen has enjoyed FDA approval for menopausal symptoms since 1941, the agency has never green-lighted a testosterone treatment for women, largely because of scant research. That means doctors have to be familiar enough with the hormone to prescribe it off-label. And unlike estrogen, testosterone is a Schedule III controlled substance, which means more red tape. Some of Casperson's female patients have had their testosterone prescription withheld by pharmacists; one was asked if she was undergoing gender transition.
The other hurdle is cultural. These days, providers such as Casperson, as well as menopause-trained gynecologists, might prescribe testosterone to menopausal women experiencing difficulty with libido, arousal, and orgasm. Many women see improvements in these areas after a few months. But first, they have to get used to the idea of taking a hormone they've been told all their lives is for men, at just the time when their femininity can feel most tenuous (see: Feminine Forever). Here, too, experience in trans care can help: Casperson has talked many transmasculine patients through similar hesitations about using genital estrogen cream to balance out the side effects of their high testosterone doses. Taking estrogen, she tells those patients, "doesn't mean you're not who you want to be," just as taking testosterone wouldn't change a menopause patient's gender identity.
Many trans-health providers have also honed their skills in speaking frankly about sexuality. That's especially true for those who do surgeries that will affect a patient's future sex life, Blair Peters, a plastic surgeon at Oregon Health & Science University who performs phalloplasties and vaginoplasties, told me. Experts I spoke with, including urologists and gynecologists with training in sexual health, said that gynecologists can often fall short in this regard. Despite treating vaginas for a living, they can often be uncomfortable bringing up sexual concerns with patients or inexperienced at treating issues beyond vaginal dryness. They can also assume, inaccurately, that concerns about vaginal discomfort always center on penetrative sex with a male partner, Tania Glyde, an LGBTQ+ therapist in London and the founder of the website Queer Menopause, told me. A 2022 survey of OB-GYN residency programs found that less than a third had a dedicated menopause curriculum.
Bowers, who is herself transgender, told me she got comfortable talking about sexuality in a clinical setting only after moving into trans care. If she were to return to gynecology today, she said, she would add some frank questions to her conversations with midlife patients who share that they're having sexual issues: "Tell me about your sexuality. Tell me, are you happy with that? How long does it take you to orgasm? Do you masturbate? What do you use?"
Menopause care has already benefited from decades of effort by queer people, who have pushed doctors to pay more attention to a diversity of experiences. Research dating as far back as the 2000s that included lesbians going through menopause helped show that common menopause stereotypes, such as anxiety over remaining attractive to men and disconnect between members of a couple, were far from universal. Trans people, too, have benefited from advances in menopause care. Because both gender transition and menopause involve a sharp drop in estrogen, many transmasculine men who take testosterone also lose their period, and experience a similar (though more extreme) version of the genital dryness and irritation. That means they can benefit from treatments developed for menopausal women, as Tate Smith, a 25-year-old trans activist in the U.K., realized when he experienced genital pain and spotting after starting testosterone at 20. After he found relief with topical estrogen cream, he made an Instagram post coining the term trans male menopause to make sure more trans men were aware of the connection.
The more menopause and gender care are considered together in medical settings, the better the outcomes will be for everyone involved. Yet menopause studies rarely consider trans men and nonbinary people, along with younger women and girls who experience menopause due to cancer treatment, surgery, or health conditions that affect ovarian function. Although these patient populations represent a small proportion of the patients going through menopause, their experiences can help researchers understand the effects of low estrogen across a range of bodies. Siloing off menopause from other relevant fields of medicine means menopausal women and trans people alike can miss out on knowledge and treatments that already exist.
Unlike gender transition, menopause is generally not chosen. But it, too, can be an opportunity for a person to make choices about what they want out of their changing body. Not all women in menopause are worried about their libido or interested in taking testosterone. Like trans patients, they deserve providers who listen to what they care about and then offer them a full range of options, not just a limited selection based on outdated notions of what menopause is supposed to be.
Experimental Ovarian Tissue Freezing Could Delay Menopause, But Experts Are Weighing The Risks
Hot flashes, insomnia and mood swings are among the difficult symptoms that affect some people experiencing menopause. While symptoms are typically temporary and treatable, menopause can also increase the risk of some chronic illnesses, such as osteoporosis and heart disease. Now a handful of researchers and companies are making a bold claim: collecting and freezing ovarian tissue when one is young and then transplanting it back into the body years later could restore hormone production—putting the onset of menopause on hold, potentially for many years.
The fact that there are few treatment options for menopause had led some clinicians to propose the unconventional intervention—a technique typically used to restore fertility in people who undergo chemotherapy or who have entered menopause prematurely. A recent modeling study in the American Journal of Obstetrics and Gynecology estimates that reimplanting bits of one's own frozen ovaries every few years could maintain the cyclical hormonal fluctuations that cause menstruation. This could delay normal onset of menopause potentially for several decades if started in people younger than age 40.
Outside experts have raised concerns about using this technique to delay menopause in healthy individuals and question whether that goal is necessary in the first place. They say that the potential to reduce the risk of health conditions is oversold. Scientists have also said that existing treatments for menopause symptoms are simpler and safer than this elective procedure, which would require surgically extracting tissue from people in their 20s or 30s, freezing and storing the tissue for decades, and performing multiple surgeries to implant tissue with the goal of maintaining premenopausal hormonal function.
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Still, proponents of the technique say there is a need for new treatment options and that people are already interested. Kutluk Oktay, a reproductive biologist at Yale University and senior author of the nonclinical modeling study, says that about 20 "carefully screened" individuals have opted to store ovarian tissue at his clinic in anticipation of potentially delaying menopause. Those people qualified for select health reasons, including a family history of early menopause and a high risk for menopause-related illnesses. Others who initially banked the tissue for fertility reasons are leaving the option open to use the tissue for menopause delay. "As more proof comes in, it could be that we're doing it for these general benefits for everybody," Oktay says. "But initially, I think we're being more selective."
In 2019 more than 100 women from multiple countries seeking menopause and fertility treatments were added to a waiting list to preserve their ovarian tissue for future transplantation, offered by then newly launched company ProFaM Health, based in Ireland. Regulatory delays as well as the pandemic have since stalled the company from enrolling people. "This is very new; I understand that," says Christiani Amorim, ProFaM Health's chief scientific officer and a fertility researcher at the Catholic University of Louvain in Belgium. Amorim, who has worked both animal and human ovarian cryopreservation, started to consider the procedure's benefits for humans after witnessing her mother experience severe menopausal symptoms.
In 2019 more than 100 women from multiple countries seeking menopause and fertility treatments were added to a waiting list to preserve their ovarian tissue for future transplantation, offered by then newly launched company ProFaM Health, based in Ireland. Regulatory delays as well as the pandemic have since stalled the company from enrolling people. "This is very new; I understand that," says Christiani Amorim, ProFaM Health's chief scientific officer and a fertility researcher at the Catholic University of Louvain in Belgium. Amorim, who has worked/researched both animal and human ovarian cryopreservation, started to consider the procedure's benefits for humans after witnessing her mother experience severe menopausal symptoms.
Maintaining premenopausal hormonal production—the basis of the ovarian tissue transplant technique—could potentially avert some health issues. The procedure relies on primordial follicles for producing those hormones. Female babies are born with a fixed number of immature eggs in the primordial follicles in their ovaries. The ovaries usually eject one egg for potential fertilization each month—using, in a lifetime, only about 500 eggs out of a million or so available. "If you do the math, 99.9 percent are wasted," Oktay says. "They're reserve." The body produces estrogen when a primordial follicle begins to mature an egg, and then it produces progesterone after ovulation occurs. Whether or not follicles release an egg, their number declines over time as they are used or naturally degenerate with age. People reach menopause when the body goes a full year without a period—typically around age 50. By the time of menopause, very few follicles remain, and hormone production has plummeted.
When someone is younger than age 40, those follicles can be extracted and later transplanted back into the body where they can release mature eggs that could be fertilized—and hormones that could prevent menopausal symptoms. Oktay's research suggests that beyond age 40, the procedure is unlikely to prevent the onset of menopause.
The process involves a keyhole surgery through the belly button to strip off part of an ovary's glistening, pearl-like "skin"—a millimeter-thick cortex containing the primordial follicles. This is "like peeling an orange," Oktay explains. The tissue is then sliced into thin slivers, bathed in antifreeze substances in test tubes and preserved in liquid nitrogen, where it awaits transplantation back into the body years later. Oktay says there is no practical limit for how long the tissue can be preserved and still remain effective. The process is ultimately the same for those seeking to restore fertility as it would be for those seeking to delay menopause. To prevent the risk of pregnancy in the latter group, however, the tissue could be grafted to the forearm or abdominal wall instead of in the pelvis, where it could still release hormones into the bloodstream but avoid releasing an egg that could encounter sperm and become fertilized. The procedure would also prolong menstruation, which few people anticipating menopause would welcome.
Since Oktay performed the first successful ovarian tissue transplant in 1999, the procedure has become an established fertility option for young people about to undergo chemotherapy, which can damage eggs and reduce blood flow to the ovaries. More than 200 babies have been born using the technique—about a 28 percent success rate for live births, according to a recent review. Data on the procedure's effects on menopause and hormone restoration are limited to people who have had the transplant after undergoing treatment for serious illnesses. The efficacy of the transplant in healthy people remains unclear.
Even though menopause itself is not a disease, "it brings a lot of complications with it," Oktay says. For instance, perimenopause (the years leading up to menopause) "can be quite nasty for some women to go through," says Kirsten Louise Tryde Macklon, an oncofertility specialist at Copenhagen University Hospital. Perimenopause can cause life-disrupting sleep problems and hot flashes—sudden, sometimes debilitating surges of a heat sensation in the upper body. One UK-based survey found that one in 10 people left a job because of menopause symptoms.
People in menopause may face a higher risk of developing cardiovascular disease as levels of estrogen—which helps protect the heart—start to drop off. Estrogen also promotes bone health, which means that lower levels in menopause can raise the risk of osteoporosis. Some studies have found a link between early menopause (typically defined as occurring before age 45) and a higher risk of dementia.
Many experts, including Macklon and her colleague Stine Gry Kristensen, a reproductive biologist at Copenhagen University Hospital, question the need for ovarian tissue transplantation, given that hormone replacement therapy, or HRT, is already an effective and readily accessible intervention to manage menopause symptoms. HRT replenishes hormones with estrogen patches or pills, often combined with progesterone. This relieves symptoms such as hot flashes and sleep disturbances, and strong evidence suggests it helps prevent osteoporosis. Research on its effects on other chronic conditions is mixed. Some research suggest HRT can help reduce the risk of heart disease, stroke and cognitive decline, while other studies suggest it increases risk or has no effect.
Only a small proportion of women undergo hormone replacement therapy because of its controversial history, however, says Clarisa Gracia, chair of the practice committee of the American Society for Reproductive Medicine and a reproductive endocrinologist at Penn Medicine. Findings from the Women's Health Initiative study in the early 2000s suggested HRT has potential links to breast cancer, heart disease and stroke. The study had significant limitations, but still "the pendulum swung," Gracia says, "and we stopped prescribing it to women."
Ovarian tissue transplants also produce hormones and may come with similar risks as HRT, but there are not enough data to know for sure. Oktay says naturally producing hormones in this way could be more beneficial than the synthetic hormones used in the current therapies; he says his patients tell him they feel better and more "like themselves" when their own hormones kick in after the transplant, compared with when they were on synthetic hormones. But Kristensen says there isn't substantive evidence to back that comparison. "It sounds nice; it sounds better; but we have no data, really," she says.
The success of the procedure, both for fertility and menopause, depends largely on the tissue's survival rate. This process is not like a typical transplant, which connects an organ to existing blood vessels, explains Michael von Wolff, a reproductive endocrinologist at the University Hospital of Bern in Switzerland, who previously published a critique on the method. The ovarian tissue has to form new blood vessels and re-establish blood supply, which can take approximately 10 days. Additionally, restoring hormone production takes up to several months, von Wolff says. About 60 percent of the follicles die during the time the tissue is thawed, transplanted and reconnected to surrounding blood vessels. Over the long run, the tissue tends to last for two and a half years on average in the body. Oktay's model estimates that a person who has a quarter of their ovarian reserve removed at age 30 could delay menopause for about 10 years. He is optimistic that better grafting can boost the tissue survival rate in the future, but other experts such as Macklon argue that "it's simply too premature to say that."
Age may also be a barrier. The transplant would be most effective if one has the tissue removed and frozen in their 20s. "I have a very hard time believing that a 25-, 30- or 35-year-old woman is even thinking about menopause," Gracia says.
Despite the procedure's limitations, momentum for the overall idea of restoring hormone production through ovarian tissue seems to be building. Oktay's clinic and Amorim's ProFaM Health are exploring this procedure, and other labs are investigating the use of drugs such as rapamycin to delay menopause by slowing down ovaries' aging process. Kristensen says she's engineering another version of ovarian tissue transplantation—a small, synthetic device that houses hormone-producing cells and could be implanted into the body. This field of research has "huge potential because so many women, [who make up] half of the human population, could benefit from this," she says.
Olivia Munn Opens Up About Being Medically Induced Into Menopause Amid Cancer Diagnosis
Published Apr 17, 2024, 17:11:43 GMT+1Last updated Apr 17, 2024, 17:11:41 GMT+1
Olivia Munn has opened up about being medically induced into menopause amid her breast cancer diagnosis.
Last month, the 43-year-old explained she'd been diagnosed with breast cancer the previous year.
Olivia spoke about her diagnosis. (Instagram/@oliviamunn)Speaking about her diagnosis, Olivia explained how she came to discover the cancer, which is a bilateral cancer called luminal B.
"In February of 2023, in an effort to be more proactive about my health, I took a genetic test that checks you for 90 cancer genes. I tested negative for all, including BRCA (the most well-known breast cancer gene)," she began.
"My sister Sara had just tested negative as well. We called each other and high-fived over the phone. The same winter I also had a negative mammogram.
"Two months later I was diagnosed with breast cancer."
Speaking about her treatment so far, Olivia added: "In the past ten months I have had four surgeries, so many days spent in bed I can't even count and have learned more about cancer, cancer treatment and hormones than I could ever have imagined.
"Surprisingly, I've only cried twice. I guess I haven't felt like there was time to cry. My focus narrowed and I tabled my emotions that I felt would interfere with my ability to stay clearheaded.
"I've tended to let people see me when I have energy, when I can get dressed and get out of the house, when I can take my baby boy to the park. I've kept the diagnosis and the worry and the recovery and the pain medicine and the paper gowns private.
"I needed to catch my breath and get through some of the hardest parts before sharing."
While Olivia didn't need to have radiation or chemotherapy, she did undergo a lymph node dissection, a nipple delay procedure and a double mastectomy.
She also began a hormone suppressing therapy in November.
Olivia said she was put into a medically-induced coma. (Instagram/@oliviamunn)The treatment essentially put her into a medically induced menopause.
"I'm constantly thinking it's hot, my hair is thinning, and I'm tired a lot," she told People.
Speaking about her son Malcolm, she added: "When I'm with him it's the only time my brain doesn't think about being sick. I'm just so happy with him. And it puts a lot of stuff into perspective.
"Because if my body changes, I'm still his mom. If I have hot flashes, I'm still his mom. If I lose my hair, I'm still his mom. That's really what matters the most to me. I get to be here for him."
Olivia caught her cancer after her doctor recommended she calculate her lifetime breast cancer risk score, using the Tyrer-Cuzick risk assessment calculator.
After she scored 37.3, she was given an MRI scan which discovered the cancer.
Olivia said she was 'lucky' it was caught 'with enough time' that she had 'options'.
"I want the same for any woman who might have to face this one day," she urged.
"Ask your doctor to calculate your Breast Cancer Risk Assessment Score. Dr. Aliabadi says that If the number is greater than 20 percent, you need annual mammograms and breast MRIs starting at age 30."
If you've been affected by any of these issues and want to speak to someone in confidence, contact Macmillan's Cancer Support Line on 0808 808 00 00, 8am–8pm seven days a week.
Featured Image Credit: Instagram/oliviamunnTopics: Celebrity, Health
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