Beyond the Black Box
A Current Take on Hormone Therapy.
From hot flashes to disrupted sleep, hormone therapy can often provide significant relief from uncomfortable menopause symptoms. Yet even though this therapy has been used for decades, many women still find its risks and benefits confusing.
“Over the years I’ve been in practice, we’ve seen a huge change in attitudes toward hormone therapy,” said Dr. Wendy Wolfman, Director of the Menopause Clinic and the Premature Ovarian Failure Clinic at Mount Sinai Hospital in Toronto, and professor in the Department of Obstetrics and Gynaecology at the University of Toronto.
Early on, doctors liberally prescribed hormones for their purported heart benefits. Then studies suggesting a link to breast cancer and blood clots brought the widespread use of hormone therapy to a screeching halt. More recently, estrogen has been touted as a safe, anti-aging miracle drug, she noted.
“In the past, it was, ‘Oh, menopausal hormone therapies (MHTs) are bad, they’re going to give you breast cancer and strokes,’” said Dr. M. Natasha Rajah, professor of psychology at Toronto Metropolitan University and Tier 1 Canada Research Chair in Sex, Gender and Diversity in Brain Health, Memory, and Aging. “Now it’s the opposite – ‘MHT is going to cure everything.’”
Changing attitudes led to a 2025 decision by the U.S. Food and Drug Administration to remove the broad “black box” warning from MHT products. The warning remains for “endometrial cancer for systemic estrogen-alone products.”
The warning’s removal left many women wondering about how to weigh MHT’s risks and benefits for themselves.
We spoke with five experts about the current landscape of menopause research and hormone therapies – and what women need to know for their health. Here are the top takeaways.
MOST AGREE THAT REMOVING THE BLACK BOX WARNING WAS THE RIGHT MOVE.
“The issue with hormone therapy and estradiol is that it’s individual. One size does not fit all,” said Dr. Gillian Einstein, professor of psychology at the University of Toronto and the Wilfred and Joyce Posluns Chair in Women’s Brain Health and Aging.
What might be one person’s risk is not a risk for another person.
Dr. Einstein noted that the FDA’s black box warning was originally based on a large 2002 clinical trial released by a research program called the Women’s Health Initiative. Specifically, the study found links between hormone therapy and heart disease, blood clots, and breast cancer.
However, it tested only one kind of hormone therapy – a combination of conjugated equine estrogens and progestin – that is no longer in use, and focused on women in their 60s, well past the age of menopause when most women are treating symptoms.
“I’m glad the study was done, because women should have that kind of research,” Dr. Einstein said. “But in retrospect we can see a lot of flaws, and it shouldn’t have been taken as truth.”
More recent, observational studies have found that many women in their 40s and 50s can safely use hormone therapy to manage hot flashes and other symptoms, she and others said. They added that different formulations, doses, and delivery methods can all affect risk. In particular, vaginal estrogen is widely considered safe for all women, they noted.
Dr. Wolfman said women should consult their own doctors about their individual concerns and risk factors. “A black box warning can be very frightening and make women concerned about using a therapy that can really improve their quality of life and ability to function.”
One expert raising concerns about the FDAs decision to remove the warning is Dr. Pauline Maki, a co-author of Women’s Health Initiative studies on hormone therapy and cognition.
Dr. Maki, professor of psychiatry, psychology and obstetrics & gynecology and Director of the Women’s Mental Health Research Program at the University of Illinois College of Medicine, noted that the FDA didn’t follow an appropriate review process before removing the warning.
She was concerned that proponents of MHT could overstate its benefits and downplay risks, particularly for older women. “It is safe for many women in their 50s who have these bothersome symptoms,” she said. “But its benefits and risks vary by age, and that information was missing in the discussion.”
HORMONE THERAPY SHOULD MAINLY BE USED TO TREAT SYMPTOMS.
“It’s critically important to treat the symptoms of menopause, and that should be women’s health goal,” Dr. Maki said. “There’s so much unnecessary suffering.”
Data suggests that hormone therapy is ‘relatively safe for most people’ when taken within ten years of the last period.
Dr. Rajah also noted that there is also some data linking estrogen use in these early stages with better cardiovascular fitness later in life. “If you don’t have any risk factors, it really is the best treatment for many menopause-related symptoms,” Dr. Rajah said.
Symptoms don’t just cause discomfort; they affect women’s ability to function. “If you’re having ten flashes a day, that’s a lot,” Dr. Wolfman said. “The goal is to improve quality of life so we can function well and contribute to society, to ourselves, to our families, and to the world.” Talk with your doctor about the type of hormone therapy and delivery method that would work best for your symptoms, age, and risk factors, experts said.
MHT ISN’T FOR ANTI-AGING.
If you’re not bothered by menopause symptoms, you shouldn’t take MHT preventatively, experts agreed. “I think we need to get rid of this mindset that hormones are fountains of youth, and realize they are very serious biochemicals that can be beneficial but can also carry risks,” Dr. Einstein said.
Dr. Wolfman was concerned about a new group of online influencers touting estrogen as a kind of wellness treatment to prevent aging.
“Many of these claims do not have an evidence base,” she noted. While treating a woman’s symptoms can offer powerful short- and long-term benefits, the point is not to stop or reverse menopause itself, Dr. Rajah explained. She was concerned that some proponents have even suggested staying on hormone therapy indefinitely, potentially postponing menopause forever.
“Just as a feminist, I find that perspective interesting,” Dr. Rajah said. “Are we trying to 'fix' women by preventing them from experiencing menopause? That has a different implication to me.”
MHT ISN’T ONE-SIZE-FITS-ALL.
“One thing we don’t take into account enough is the incredible individuality around response to hormone therapy,” Dr. Einstein said.
Dr. Liisa Galea, the womenmind Treliving Family Chair in Women’s Mental Health at the Centre for Addiction and Mental Health in Toronto, agreed. Just look at how different women react to hormonal birth control, she noted.
Women typically try several different formulas and delivery methods before finding birth control that works well for them and doesn’t cause side effects, so it makes sense that the same would be true with menopausal hormone therapy, she said.
There are many forms of hormone therapies, not just one, and they all do
different things.
Dr. Galea said. “And how you take your hormones, whether through an IUD, a patch, a gel, or orally all have distinct effects on your health. We’re all individuals,” Dr. Galea continued.
Different women will also have different risk factors, Dr. Wolfman noted. While many women can take menopausal hormone therapy safely, it may not be recommended in women with a history of blood clots or breast cancer, for example.
Age matters, too – the same hormone therapy that offers health benefits to women in their 40s and 50s might increase risk of stroke or breast cancer in older women, Dr. Maki said.
The important takeaway is that every woman should talk with their doctor about their individual risks and benefits, as well as the type of therapy that might work best for them. “Women deserve precision medicine just like everyone else,” Dr. Einstein said.
THE LINK BETWEEN MENOPAUSE, HORMONES, AND DEMENTIA IS STILL NOT CLEAR.
“No doctor will prescribe you menopausal hormone therapy for dementia prevention, because it’s not for that,” Dr. Rajah said. Randomized controlled trials are still “very mixed” on whether hormone therapy protects brain health, Dr. Einstein noted.
There are some that find it’s beneficial for cognition,and others that find it has no effect at all.
Some studies now suggest that it’s actually the symptoms of menopause, like hot flashes and mood changes, that are most important in increasing the risk of conditions like dementia, not the hormone changes themselves.
“We believe that for symptomatic women, relieving symptoms is probably one of the most beneficial ways it improves brain health,” Dr. Wolfman said.
For women who are unable to take hormonal therapies, that means non-hormonal options could still offer benefits, Dr. Maki noted. “You don’t have to treat the loss of estrogen, you can treat the presence of symptoms,” she said.
More research is needed to better understand how menopause affects brain health and what interventions might help, experts agreed, adding that it might take years or decades to understand long-term outcomes.
One important exception: for women who go through menopausal changes prematurely, such as because of ovarian removal, cancer treatment, or other reasons, there’s already enough evidence to suggest that hormonal therapy can have a protective effect, Dr. Einstein said. “That’s not a small subset of women,” she noted.
MENOPAUSE ITSELF ISN’T A PROBLEM – IT’S NORMAL.
“Menopause isn’t something to fix,” Dr. Rajah said. “But we can still help treat symptoms.”
She noted that women go through hormonal changes at different times in life, including puberty and pregnancy, and it’s not considered a problem.
“Why do we treat menopause so differently? It’s a natural phase,” she said.
Dr. Maki agreed. “We need to tailor our approach to the symptoms, not to the idea that the loss of estrogen is some type of catastrophic event,” she said. “That really pathologizes it.”
In fact, it’s possible to look at menopause as an opportunity, Dr. Rajah noted. “The way I think of menopause: it’s a change. It’s a time of neuroplasticity. Your entire system is reorganizing itself to a decline of estrogens and other hormones. There’s a lot going on,” she said.
That means positive changes made at mid-life – like a commitment to eating well, exercising, and managing stress – can lead to significant long-term benefits.
“I think there’s an upside, and I want to get there,” she said.
WOMEN NEED TO ADVOCATE FOR THEMSELVES WHEN IT COMES TO MANAGING MENOPAUSE.
“Don’t assume your GP or even your gynecologist understands the nuances of hormone therapy,” Dr. Galea said. That’s not to blame healthcare providers. Research is lacking, and most doctors don’t get extensive training on menopause, she noted. In fact, she added, women are already experts on an important part of the equation: their own bodies.
By the time a woman gets to menopause, she likely has a wealth of experience navigating hormonal changes like puberty, birth control, and pregnancy. That’s why it’s important to engage in a dialogue with your doctor about treatment options.
We already know so much about how our bodies react to hormones. We should be using this information to inform our decisions later on in life.
Women should work with their doctors to make an individual assessment of their risks and potential benefits, Dr. Wolfman said. This should include an assessment of the woman’s general health, medical history including past clots or breast cancer, any contraindications, and family history with menopause.
“I personally believe there should be a menopausal women’s health assessment to identify risk factors as people get older, to improve the quality of aging so that we have healthier lives, not just longer lives,” Dr. Wolfman said.
It’s also important to take symptoms seriously, and “not to trivialize them,” Dr. Wolfman said. She said women shouldn’t wait until they’re really suffering to get help. “Women are the backbone of this country, and when we function well, we can do anything,” she said.
While research over the past decades has advanced our understanding of menopause and its effects on health, more work needs to be done, experts agreed. Future studies could help answer questions like how long it’s safe for women to take hormone therapy, when they should start, and what individual differences determine a woman’s potential benefits and risks, Dr. Einstein said.
They could also shed more light on how menopause, hormones, and other factors affect the brain over long spans of time. “The important take-home message is that women deserve the best science possible,” she said.
Source: Mind Over Matter 22