For more than two decades, many American women entering menopause were told that hormone replacement therapy was dangerous -- a belief rooted in early interpretations of the Women’s Health Initiative (WHI) study and reinforced by prominent FDA boxed warnings.
That messaging reshaped medical practice. Prescriptions dropped. Alternatives such as antidepressants and sleep aids rose. Menopause itself was often framed as something to manage symptom by symptom.
Removing the black box warning
Now, with the Food and Drug Administration moving to remove long-standing boxed warnings on certain estrogen products, clinicians and patients are revisiting the data and the conversation.
Dr. Charles Mok, with Allure Medical, said the initial reaction to the WHI findings changed women’s health care for a generation.
“Probably the biggest disservice to women’s healthcare in the last century was how we responded to this very narrow segment of the women’s health initiative study.”
He argued that early findings involving a specific subgroup -- older women who began certain synthetic hormones years after menopause -- were applied too broadly.
“We reacted to that one subgroup taking a certain synthetic drug at a certain time in her life that we shouldn’t have done,” Dr. Mok said. “We changed the entire face of woman’s health care for 23 years. The FDA responded by putting a black box on estrogen products to say that they cause heart disease, strokes, possible dementia, and breast cancer.”
After that, prescribing patterns shifted dramatically. Mok said menopause was increasingly treated with medications aimed at mood and sleep rather than hormone replacement.
“We started treating menopause like a mental illness versus a hormone deficiency.”
In November 2025, federal officials announced that the FDA would begin removing broad boxed warnings from certain estrogen-containing products after updated evidence reviews and advocacy from major medical societies. Label revisions are being implemented as manufacturers submit updated information.
For many clinicians, the change reflects a more nuanced understanding of hormone therapy -- one that accounts for timing, formulation and patient risk factors, rather than applying a blanket warning to all women.
Who is -- and isn’t -- a good candidate?
Health care professionals do not approach hormone therapy as one-size-fits-all. Instead, they evaluate several factors before recommending HRT.
Age and timing are central. Starting hormone therapy closer to the onset of menopause is generally considered different from beginning therapy 10 to 15 years later. Personal and family history also matter -- particularly a history of breast cancer, blood clots, stroke, liver disease or uncontrolled cardiovascular disease.
Symptom burden is another consideration. Women with severe vasomotor symptoms -- hot flashes, night sweats and sleep disruption -- may derive more immediate quality-of-life benefits than women with minimal symptoms.
Mok described his approach as addressing both symptom relief and long-term health outcomes.
“I look at hormone replacement therapy as a dual track. So, on one hand we have symptoms women have in perimenopause and menopause, and then me as a doctor, what kind of outcomes I want to see, and I want to see you feel better but I want you to be healthier too.”
Clinicians also determine whether a woman has an intact uterus. Estrogen alone can stimulate the uterine lining, so women with a uterus typically require progesterone alongside estrogen to protect against endometrial overgrowth.
Mok emphasized the importance of formulation.
“You should take an actual progesterone versus a synthetic copy. I think that’s not disputable.”
Route of delivery is also part of the evaluation. Estrogen can be taken orally, applied as a skin patch, delivered through topical gels or creams, or administered via subcutaneous pellets. The choice affects how the body processes the hormone.
In Europe, Mok noted, transdermal delivery has long been more common.
“They were more likely to use a skin-based estrogen, which means a patch or a pellet under the skin than oral.”
Oral estrogen is absorbed through the digestive tract and processed first by the liver.
“What happens when you eat your estrogen? It goes to your liver and does something called first pass effect,” Dr. Mok said.
That pathway can increase the production of certain clotting factors and inflammatory markers.
Because transdermal estrogen is absorbed directly into the bloodstream through the skin, it bypasses that initial liver metabolism. Some studies have suggested that transdermal delivery may be associated with a lower risk of blood clots compared with oral estrogen, particularly in women with underlying cardiovascular risk factors. It may also have less impact on triglyceride levels.
That distinction can matter in women with elevated clotting risk, obesity, migraine with aura or other cardiometabolic concerns. For women at low baseline risk, both routes may be appropriate depending on symptom profile and preference.
Clinicians typically weigh convenience, cost, risk profile and patient goals when choosing a delivery method. Oral therapy may be easier to prescribe and more familiar to some providers, while patches or other transdermal forms may offer advantages in certain patients.
Doctors also weigh potential benefits against risks in the context of each woman’s health goals, including bone density protection, cardiometabolic health and cognitive concerns.
Mok referenced data he believes support broader benefits.
“Looking at all estrogens and all progesterones reduce all-cause mortality. In other words, you’re more likely to live on them than off of them.”
He also discussed possible reductions in chronic disease.
“You’re less likely to get heart disease. You’re less likely to get diabetes. Less likely to get colon cancer. You’re less likely to have fractures and you’re less likely to develop Alzheimer’s and dementia.”
Still, hormone therapy is not appropriate for everyone. Women with certain active cancers, unexplained vaginal bleeding or a history of thromboembolic events may be advised against HRT. For others, non-hormonal approaches may be recommended first.
The decision ultimately requires individualized risk assessment.
A shifting conversation
The FDA’s recent updated stance does not eliminate risk, nor does it mean HRT is universally recommended. It does, however, signal a shift away from sweeping warnings that shaped care for more than 20 years.
For Mok, the message is about informed choice.
“Look into it yourself. Do a little deep dive on it and think about being the chief executive of your own health.”
As labeling evolves and newer research continues to emerge, experts say the most important step for women is a thoughtful discussion with a qualified health care provider -- one that considers medical history, personal priorities and the latest evidence.
The conversation around menopause may be changing. For many women, that means revisiting options that were once widely embraced, then widely avoided -- and deciding, with clearer information, what fits their health goals now.
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