Beyond the black box: What women deserve to know about menopause hormone therapy

What the updated guidance on menopause hormone therapy means for safety, symptoms, and informed care

Last week, the FDA announced it has initiated the process of removing the black box warning from menopause hormone therapy (MHT; often called hormone replacement therapy or HRT) products. The announcement was rife with falsehoods and failed to follow the appropriate processes, but that, sadly, is no longer surprising.

Beneath the surface lies something important: menopause, a universal biological transition, remains deeply misunderstood in medicine, and millions of women have suffered because of it. There are signs that the tide may finally be turning toward more evidence-based, compassionate care, but we still have a long way to go.

To unpack how we got here and what women still deserve to know, I called in Nikki Sapiro Vinckier—OBGYN PA-C and reproductive health educator—to walk through the evidence, the uncertainties, and how individual history shapes each woman’s risk–benefit picture.

How we got here: What we used to believe and how it changed

The history of hormone therapy is nearly 85 years of swinging between enthusiasm, fear, and recalibration.

After decades of being used primarily for symptomatic relief, hormone therapy in the 1980s began to be prescribed to prevent chronic disease. This shift was driven by observational studies suggesting lower rates of heart disease and even hinting that women with existing heart disease had fewer second heart attacks while on hormones.

Why did this seem plausible? Because decreases in estrogen have wide-reaching effects across nearly every major organ system. As estrogen falls blood vessels stiffen, cholesterol worsens, bones weaken, metabolism shifts toward greater abdominal fat and insulin resistance, and brain and urogenital tissues lose important support.

These biologically plausible pathways helped fuel enthusiasm, but the studies weren’t designed to measure cause and effect.

This ultimately led to the initiation of a study by the Women’s Health Initiative (WHI)—the largest randomized controlled trial involving more than 27,000 post-menopausal women, designed to test whether MHT could prevent chronic diseases such as heart disease. The study found no cardiovascular benefit and an increase in strokes and breast cancer (24% increase or about 8 extra breast cancer cases per 10,000 women per year). The trial was stopped early in mid-2002 because of emerging risk signals.

Almost overnight, MHT was seen not as preventive medicine but as potentially dangerous. Suddenly, the treatment was no longer routinely recommended, and FDA put a black box warning on estrogen-containing therapies—the strictest warning label, meant to draw attention to drugs with potentially life-threatening risks.

This impacted behavior and usage dropped significantly: from 27% in 1999 to 5% in 2020. Millions of women were told to “just deal with” their menopausal symptoms.

Figure 1: Prevalence of Hormone Therapy Usage. Figure from Yang et al., JAMA

What we now understand

With time, it became clear that the Women’s Health Initiative study carried important blind spots. Most participants were well past the menopausal transition, and the hormone regimen tested doesn’t reflect the options commonly used today: women were older (mid-60s on average) and were given higher-dose oral formulations that are now rarely prescribed. These factors alone skewed results toward higher risk.

In the years since the WHI study, the science has evolved and there is a clearer understanding that the risks linked to MHT—particularly risks for breast cancer, stroke, and blood clots—depend heavily on age, timing, type of hormone, dose, delivery route, and individual health history. It is not a simple yes/no calculation.

Here’s what the evidence now shows:

1. Formulation and route. The type of hormone and the way it enters the body significantly shape risks for blood clots, stroke, and breast cancer. Oral pills circulate systemically raising clotting risk, while local vaginal estrogen (such as creams, rings, or tablets) targets symptoms like dryness or pain with minimal absorption into the bloodstream. Research also suggests that body-identical options—estradiol (found in patches, gels, or oral estradiol) and micronized progesterone (Prometrium) may have lower clotting and cardiovascular risks than older synthetic formulations once used in the WHI study.

2. Timing. Women who initiate MHT within approximately 10 years of menopause or before age 60 may experience better cardiac outcomes compared to starting later. This doesn’t mean everyone over 60 has to stop MHT immediately, though. In fact, vaginal estrogen shows no risk regardless of whether you are 50 or 80 years old.

3. Medical history. Systemic MHT of any kind is not recommended for women with a history of breast cancer because it can increase recurrence risk—particularly in hormone-receptor-positive disease, the most common breast cancer subtype. However, local vaginal estrogen may be considered in coordination with an oncology team to improve comfort and quality of life. A 2023 analysis of nearly 50,000 breast cancer survivors confirmed that vaginal estrogen doesn’t increase the risk of breast cancer recurrence or mortality.

In short: risk exists, but it is not uniform. It depends on who you are, what symptoms you have, your age, when you start, and what formulation you use.

What remains uncertain

Even after two decades of research, several important questions about hormone therapy remain unanswered:

• How long—and for whom? Risk of breast cancer appears to rise with longer use, while short-term use (less than five years) has not been associated with an increased risk. Long-term outcomes beyond 10–15 years are largely unknown.

• Cognition remains contested. Research on the impact of MHT on dementia is mixed. Some studies have found potential protective benefits for dementia and cognitive function when MHT begins near menopause. While four clinical trials show no benefit on cognition in early menopause, other studies, like one among people who started MHT at 65+, suggest increased dementia risk. Researchers continue to study how timing, dose, and hormone type influence these outcomes. For now, MHT should be prescribed for symptom management, not dementia prevention.

• Does one size fit all? Study participants are primarily white and healthy at baseline. We need more research on how hormone therapy affects women from different racial, genetic, and health backgrounds and whether risks differ by those factors.

Menopause care has fallen behind.

Even as the science evolves, the system hasn’t kept pace. Menopause is universal but remains one of the most misunderstood health transitions in medicine. Symptoms vary wildly, timelines differ, and treatment options have changed dramatically over the past two decades—yet clinical training hasn’t kept pace.

Historically, medical education focused overwhelmingly on male physiology, leaving conditions specific to women undertaught. Menopause was treated as an afterthought, and as a result, most clinicians were never meaningfully trained to recognize or manage it, especially as newer formulations and safer delivery methods emerged.

And the fallout from the WHI study only deepened those gaps. For decades, clinicians were trained in the shadow of that study—taught that MHT was dangerous and to be avoided, rather than when and how to use it safely. Most never received an updated education once science evolved. The result is a generation of providers who carry outdated fears rather than current evidence.

The current health system structure isn’t helping. Even clinicians who want to do better are working within a system that rewards volume and procedures over conversation. Appointments are short, insurance codes are rigid, and nuanced discussions about hormones, risks, and quality of life rarely fit into a 10-minute visit.

This results in something predictable: women don’t get the care that they need and deserve.

Bottom line

The removal of the black box is an important course correction that affirms what modern evidence and practice have made clear: when used thoughtfully and individually, hormone therapy can be both safe and life-changing. Critical gaps remain in how we communicate risks, tailor treatment, and support women through menopause. Still, this moment is ultimately a testament to the clinicians, researchers, advocates, and women who pushed for clarity long before it arrived.

Love, YLE and NSV

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Nikki Sapiro Vinckier, PA-C, is an OB/GYN Physician Assistant, reproductive health advocate, and founder of Take Back Trust—a national platform offering tools and education to help people navigate reproductive care. With over a decade of clinical experience and a fast-growing digital presence, she works at the intersection of medicine, media, and movement. Her first book, We Deserve More, will be released in May 2025.

Your Local Epidemiologist (YLE) is founded and operated by Dr. Katelyn Jetelina, MPH PhD—an epidemiologist, wife, and mom of two little girls. YLE is a public health newsletter that reaches over 400,000 people in more than 132 countries, with one goal: to translate the ever-evolving public health science so that people are well-equipped to make evidence-based decisions. This newsletter is free to everyone, thanks to the generous support of fellow YLE community members.