The FDA’s Historic Reversal on Estrogen Therapy: What The Black Box Warning Removal Means for You

Picture this: You're 48 years old. You haven't slept through the night in months because night sweats jolt you awake. Your brain feels foggy during important presentations at work. Hot flashes interrupt client meetings. You're gaining weight despite eating the same way you always have. Your joints ache. You finally work up the courage to ask your doctor about hormone therapy.

"It's too risky," you're told. "The side effects are too dangerous. You'll just have to deal with it."

For 23 years, this has been the story for millions of American women. Until November 11, 2025, when everything changed.

What Happened?

On November 11, 2025, the FDA removed the black box warnings for cardiovascular disease, breast cancer, and dementia from estrogen products that had been in place since 2003.

Before 2002, hormones were widely prescribed to women in menopause and considered safe and beneficial. Multiple observational studies showed reductions in heart disease, osteoporosis, cognitive decline, cancer, and mortality in women on estrogen therapy.

The Women’s Health Initiative (WHI) was a randomized controlled trial designed to test the impact of hormone therapy on major postmenopausal health issues. The study was stopped early due to concerns for increased risk of breast cancer, heart attack, blood clots, and stroke. Influenced by this report, the FDA placed a black box warning on all estrogen products, cautioning women of the risk of cancer, heart disease, and dementia with use. 

This created fear and panic among doctors and patients alike and effectively halted prescribing menopausal hormone therapy in the United States, leaving women with scarce options for treating the symptoms of menopause, as well as the health impacts associated with it – osteoporosis, cardiovascular disease, and cognitive decline.

Why Was There a Change in Opinion?

The decision to update the FDA’s position follows a comprehensive review of the medical literature, including a reanalysis of the original WHI data. We now know that the risks associated with hormone therapy are not uniform and depend on patient factors, delivery method, and formulation. The average age of women in the study was 63, well past the onset of menopause, and a significant percentage had health problems, including hypertension, obesity, and smoking. 

The women in the study were given one pill at one dose - similar to a birth control pill. The hormones used were Premarin (estrogen from pregnant horses) and MPA (a synthetic progesterone). 

Prescribing practices have changed, and data show better outcomes with physiologic (rather than high) doses, vaginal or transdermal administration (rather than oral), and bioidentical formulations (rather than synthetic).

The WHI was inadequately designed, evaluated, and reported - the study was based on the wrong women at the wrong time, given the wrong hormones at the wrong doses.

What the Science Actually Shows

There were multiple problems with the WHI: the data was misinterpreted, and rampant misinformation followed. Women on estrogen alone actually had a decreased risk of getting and dying from breast cancer. When the data was further dissected, the reported increased risk of cancer was associated with the use of estrogen combined with the synthetic progestin, but even this was exaggerated. The data showed the absolute risk of breast cancer was 0.1% - for every 1,000 women on combined hormone therapy, one additional woman was diagnosed with breast cancer compared to women not taking hormone therapy.

The formulation of hormone therapy matters. The WHI used a hormone combination that is no longer commonly used, a combination pill of synthetic estrogen and synthetic progestin. The current practice is prescribing bioidentical hormone therapy - hormones that have the same structure as those naturally produced by our body.

The route of administration affects risk. There is an increased risk of blood clots with orally administered estrogen, but transdermal or vaginal estrogen does not carry an increased risk.

The timing of hormone therapy is also a critical factor when discussing risk. Here's why: Estrogen supports nitric oxide production, which helps keep your cardiovascular system functioning optimally. When you have continuous estrogen, either from your ovaries or from hormone therapy, your blood vessels stay soft and healthy. If there is a period (> 10 years) during which your blood vessels are without estrogen, they are likely already beginning to harden and narrow, and starting hormone therapy after this long lapse can destabilize existing plaque.

Researchers have defined a “critical window” for the initiation of hormone therapy, within 10 years of menopause or less than age 60. Hormone therapy initiated in this window confers significant protection while minimizing potential risks.

When the dust settled and researchers re-analyzed the data, this time separating younger, recently menopausal women from older participants, a completely different picture emerged.

Brain

Women suffer from cognitive decline and dementia at a disproportionate rate compared to their male counterparts. Two-thirds of those living with Alzheimer’s disease are women. 

Estrogen receptors in your brain, especially receptors crucial for cognitive function, degrade over time when they're not activated by estrogen. Start hormone therapy during the menopausal transition when these receptors are still healthy, and you may protect against cognitive decline. In fact, studies show that women who start hormone therapy in midlife have a lower risk of developing dementia compared to women who never started hormones.

Bone

The risk of osteoporosis spikes during perimenopause and after menopause. Within the first five years after menopause, women can lose up to 20% of their bone density. Hip fractures carry serious consequences, 20% of women who fracture a hip will die within a year, and 50% will never regain their previous level of independence.

Hormone therapy's bone-protective effects have never been controversial. Multiple studies confirm that estrogen reduces fracture risk at all bone sites by 20-40%.

Significantly, hormone therapy is the only osteoporosis treatment proven effective regardless of baseline fracture risk, even women at low risk benefit from estrogen's bone-protective effects.

Heart

Cardiovascular disease is consistently the top cause of death in postmenopausal women. Up to ten times more women die of cardiovascular disease than breast cancer, yet most women fear cancer more than heart disease. The sharp rise in cardiovascular risk after menopause is driven by estrogen loss, which leads to hypertension, vascular stiffness, and insulin resistance.

For women who start hormone therapy before age 60 or within 10 years of menopause, the cardiovascular benefits are remarkable. Studies show a 48% decline in fatal heart attacks and a 30% decline in all-cause mortality when hormone therapy is started during this critical window. 

This isn't about vanity or comfort; this is about potentially adding years to your life.

What This Means for You

Every year, 47 million women in the United States enter menopause. If you are in your 30s to 50s and experiencing perimenopause or early menopause symptoms, you are in the window where hormone therapy offers the clearest benefits with the lowest risks. The goal of prescribing HRT should not only be the alleviation of the many symptoms of menopause, but also to maintain memory, mobility, and function for women in midlife and beyond. 

For 23 years, women have been told that hormone therapy is too dangerous, based on flawed data from women who were the wrong age, taking the wrong formulations, starting at the wrong time.

The FDA's reversal acknowledges that science has evolved. Women deserve treatment approaches that reflect current evidence, not two-decade-old fears.

If you're struggling through perimenopause or menopause, you have options. You don't have to suffer through symptoms that affect your work, relationships, and quality of life. And you may be able to protect your long-term health in the process.

The key is being informed, finding a provider who understands the nuances of hormone therapy, and making decisions based on your individual health profile and risk factors.

You deserve to feel like yourself again. And now, the science (and the FDA) finally support giving you that option.

Amanda Jordan, MD, is a board-certified physician specializing in functional and longevity medicine with a focus on women’s health. She helps women reclaim their spark: restorative sleep, mental clarity, sustainable energy, and the vitality to show up fully in their careers and relationships. Through her Las Vegas-based virtual practice, she serves women throughout Nevada who refuse to accept that feeling exhausted, foggy, and unlike themselves is simply "part of getting older."

Her approach integrates traditional medical expertise with whole-person, precision care - including comprehensive functional testing, bioidentical hormone therapy, peptide protocols, and the kind of ongoing physician partnership that allows for truly individualized treatment. This isn't about managing symptoms with band-aid solutions. It's about addressing root causes and optimizing your health for the decades ahead.

If you're ready to feel like yourself again - to wake up rested, think clearly, and have the energy to actually enjoy your life - Dr. Jordan offers complimentary discovery calls to discuss your symptoms and explore whether hormone optimization is right for you.

Visit dramandajordan.com to learn more or schedule your complimentary consultation.