Beyond the Black Box: What the FDA's Historic Decision Really Means for Women's Health

Written and edited by Sarah Bonza MD, MPH, FAAFP, MSCP, DipABLM, NBC-HWC

The FDA recently announced the removal of black box warnings from menopausal hormone therapy products.

On November 10, 2025, the FDA announced the removal of black box warnings from menopausal hormone therapy products: a decision that FDA Commissioner Dr. Marty Makary called "one of the greatest mistakes in modern medicine" to finally correct[1].

As a physician who specializes in perimenopause and menopause care in Ohio, I've spent years watching qualified women be denied treatment because of outdated fears. This announcement should be cause for celebration. And it is, but with important caveats that every woman and clinician needs to understand.

The Human Cost I've Witnessed

In my practice, I see the devastating consequences of 23 years of fear-based medicine every single week. Women in their early 50s—sharp, accomplished, resilient—come to me after being turned away by their primary care physicians who say hormone therapy is "too dangerous."

These women are struggling with debilitating hot flashes that disrupt their sleep and work performance. They're experiencing brain fog so severe that they worry about early dementia. They're dealing with genitourinary symptoms that destroy their intimate relationships, but feel too embarrassed to discuss with providers who seem dismissive.

The tragedy is that many of these women are ideal candidates for hormone therapy. They're within the optimal 10-year window from menopause onset. They have no contraindications. They're suffering unnecessarily while proven, effective treatment exists.

When I explain that the black box warning was based on flawed interpretation of outdated research, they're often angry—and rightly so. They've lost years of quality of life to medical fearmongering.

The FDA’s removal of the black box warning is monumental because it eliminates a major barrier to evidence-based care.

Why the Black Box Warning Was Wrong

The 2002 Women's Health Initiative study[2] fundamentally shaped how we think about hormone therapy, but its conclusions were deeply flawed:

The participants were the wrong age. The average woman was 63 years old: well past the optimal window for initiating hormone therapy. Subsequent analysis revealed that women who started HRT within 10 years of menopause onset showed cardiovascular protection, not harm.

They used outdated formulations. The study used oral conjugated equine estrogen (CEE) and synthetic medroxyprogesterone acetate (MPA), formulations that are no longer commonly prescribed. Modern transdermal estradiol and micronized progesterone have different risk profiles entirely.

The breast cancer data doesn't hold up. The 26% increased risk in breast cancer incidence corresponded to just one additional case per 1,000 patient-years, and there was no difference in breast cancer mortality. More tellingly, this increase disappeared when looking only at women with no prior HRT use. The estrogen-alone arm actually showed nearly 20% lower breast cancer risk and a 40% reduction in mortality at 20-year follow-up.

The cardiovascular findings were misinterpreted. When properly adjusted for multiple comparisons, stroke risk was statistically equivalent between groups. Moreover, oral estrogens increase blood viscosity slightly, but transdermal formulations—which are now standard—do not carry this risk. A 2015 meta-analysis showed HRT reduced cardiovascular events by 48% when initiated within 10 years of menopause[3-7].

The evidence is clear: for the right woman at the right time with the right formulation, hormone therapy is not just safe: it's profoundly beneficial.

The 2002 Women's Health Initiative study fundamentally shaped how we think about hormone therapy, but its conclusions were deeply flawed.

Why This FDA Decision Matters

The removal of the black box warning is monumental because it eliminates a major barrier to evidence-based care. For 23 years, this warning label has:

• Created institutional bias that discouraged physicians from prescribing HRT even when appropriate

• Frightened millions of women away from considering treatment

• Contributed to insurance denials and access challenges

• Perpetuated outdated beliefs in medical practice[8]

This change means qualified women can finally have honest, nuanced conversations with their providers without the shadow of exaggerated, misrepresented risks.

But Here's Where We Need Nuance

As much as I celebrate this decision, I share some of the concerns raised by experts like Dr. Felice Gersh: not all hormone formulations are the same, and we must avoid replacing blanket fearmongering with blanket celebration.

The FDA's decision removes the black box warning from all estrogen-containing products. This is both a strength and a potential weakness.

Not all hormone formulations are the same, and we must avoid replacing blanket fearmongering with blanket celebration.

What I fully support:

• Removing warnings from transdermal estradiol: extensive evidence supports its safety and efficacy

• Removing warnings from vaginal estrogen: these products act locally with minimal systemic absorption and are incredibly safe

• Eliminating fear-based barriers to treatment for appropriate candidates

Where we need continued vigilance:

• Oral estradiol and conjugated equine estradiol (CEE) do carry different risks than transdermal formulations, particularly regarding clot risk

• Synthetic progestins like MPA have different risk profiles than bioidentical micronized progesterone

• We still need more research on optimal dosing, timing, and formulations for different populations

The mistake of the WHI was treating all hormone therapy as identical. We shouldn't make the inverse mistake now by assuming all formulations carry identical safety profiles[9].

The Science We Know vs. The Science We Need

Here's what robust evidence demonstrates for women who initiate HRT within 10 years of menopause onset or before age 60:

Proven Benefits:

• 60-90% reduction in vasomotor symptoms (hot flashes, night sweats)

• 48% reduction in cardiovascular events (when started in the optimal window)

• 64% reduction in cognitive decline

• 35% lower risk of Alzheimer's disease

• 50-60% reduction in bone fractures

• Reduction in all-cause mortality

• Significant improvement in quality of life, sexual function, and urogenital health[3,10,11,12,13]

What We Still Need to Learn:

• Optimal doses for different health outcomes

• Long-term effects of different progestogen formulations

• Cardiovascular and cognitive impacts of various delivery methods

• Personalized approaches based on genetic factors and health profiles

• Safety and efficacy data for diverse populations underrepresented in trials

Dr. Gersh makes a critical point: declaring premature victory could actually slow the research we desperately need. We must balance celebration with continued scientific rigor.

Not all hormone formulations are the same, and we must avoid replacing blanket fearmongering with blanket celebration.

My Perspective: Grounded Optimism with Clinical Wisdom

After years of fighting to get appropriate women access to hormone therapy, I'm thrilled about this FDA decision. But I also recognize that responsible medicine requires nuance.

In my practice, I use a personalized approach:

For most perimenopausal and early menopausal women with symptoms, I prefer:

• Transdermal estradiol (patch, gel, or spray) to minimize clot risk

• Micronized progesterone for women with a uterus (better breast and cardiovascular profile than synthetic progestins)

• Vaginal estrogen for genitourinary symptoms (can be used safely even in women with contraindications to systemic therapy)

• Individualized dosing based on symptoms, age, and health profile

Dr. Bonza uses a personalized approach when prescribing menopause hormone replacement therapy.

I avoid or use extreme caution with:

• Oral estrogens in women with elevated clot risk, migraines with aura, or significant cardiovascular risk factors

• Synthetic progestins when bioidentical options are available

• Initiating systemic HRT in women more than 10 years past menopause without compelling reasons

I absolutely do not prescribe HRT for:

• Women with current or recent breast cancer (with rare exceptions for vaginal estrogen)

• Women with active blood clots or high clot risk

• Women with unexplained vaginal bleeding

• Women with certain liver diseases or estrogen-dependent cancers

This is what evidence-based, patient-centered care looks like: using the best available science while recognizing that each woman's situation is unique.

A thorough evaluation of your medical history, risk factors, symptoms, and goals should guide your decision to use menopause hormone replacement therapy.

What Women Need to Know

If you're experiencing menopause symptoms, here's what this FDA decision means for you:

You deserve accurate information. The outdated black box warning created unnecessary fear. You can now have informed conversations without this barrier, but you still need a provider who understands the nuances.

Timing is critical. The optimal window for initiating systemic HRT is within 10 years of menopause onset or before age 60. If you're in this window and have symptoms affecting your quality of life, explore your options.

Formulation matters. Not all hormone therapy is created equal. Transdermal estradiol has a different risk profile than oral estrogen. Micronized progesterone is not the same as synthetic progestins. Your provider should understand these distinctions.

Individualization is essential. Even with the black box warning removed, HRT isn't right for everyone. A thorough evaluation of your medical history, risk factors, symptoms, and goals should guide the decision.

Access is expanding. Beyond removing the warning, the FDA approved a generic version of Premarin (the first in 30 years) and a new non-hormonal treatment for hot flashes. Options are growing.

Used appropriately in the right women at the right time with the right formulations, hormone replacement therapy can be transformative.

What Clinicians Need to Embrace

To my fellow healthcare providers: it's time to update our practice. The evidence has evolved dramatically since 2003.

• Review current guidelines from the North American Menopause Society and recent literature

• Understand the timing hypothesis: HRT initiated early in menopause has profoundly different effects than late initiation

• Learn the differences between formulations, routes of administration, and progestogen types

• Listen to your patients: when a 52-year-old woman says she can't sleep, can't focus, and feels like herself slipping away, that's a clinical problem deserving intervention

• Refer when appropriate: if you're not comfortable managing menopause, connect patients with specialists who are

No more reflexively saying "hormone therapy is too risky" without understanding the actual evidence. No more dismissing women's suffering as something they should just endure.

Physicians must learn the differences between formulations, routes of administration, and progestogen types

The Path Forward

This FDA decision represents a correction of a 23-year mistake. That's worth celebrating. But celebration shouldn't lead to complacency.

We need:

• More research on optimal formulations, dosing, and timing

• Better training in menopause care across all levels of medical education

• Increased access to menopause specialists

• Insurance coverage that reflects the importance of this care

• Transparency about what we know and what we still need to learn

We went from "hormones are dangerous for everyone" to (hopefully) a more nuanced middle ground. The truth, as always, lies in the details.

Hormone therapy is powerful medicine. Used appropriately in the right women at the right time with the right formulations, it can be transformative. Used carelessly or with blanket recommendations, it carries risks. This isn't about ideology or politics: it's about evidence, individualization, and respect for women's health and autonomy.

A Final Thought

The removal of the black box warning matters not just because of what it changes about labels, but because of what it represents: a healthcare system finally paying attention to the needs of menopausal women, correcting outdated science, and removing barriers to evidence-based care.

But our work isn't finished. We must resist the temptation to swing from one extreme (all hormones are dangerous) to another (all hormones are miracle drugs). Women deserve better than pendulum medicine. They deserve nuance, evidence, individualization, and respect.

Dr. Sarah Bonza is a board-certified family physician and Menopause Society Certified Practitioner who founded Bonza Health, specializing in evidence-based perimenopause and menopause care. She offers telemedicine consultations for women in Ohio, Michigan, Washington, and Kentucky, using a personalized, functional medicine approach that honors both scientific evidence and individual needs.

In my practice at Bonza Health, I've always provided personalized, evidence-based hormone therapy when appropriate—using the formulations supported by the best science, at the right time, for the right women. This FDA decision affirms what I've known all along: that for many women, carefully selected hormone therapy isn't just safe: it's life-changing.

If you've been told hormone therapy is too risky, if you've been suffering without adequate support, if you want to explore whether modern, evidence-based hormone therapy might be right for you, I invite you to schedule a consultation. Together, we'll review your complete medical picture, discuss your symptoms and goals, and create a truly personalized plan.

The era of one-size-fits-all fear is ending. The era of evidence-based, individualized menopause care is here.

Ready to explore your options with a provider who understands the nuances? Schedule your consultation at www.bonzahealth.com.

References

[1] “Updated Labeling for Menopausal Hormone Therapy,” JAMA, Nov. 2025, https://doi.org/10.1001/jama.2025.22259

[2] J. E. Rossouw et al., “Risks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal Women: Principal Results From the Women’s Health Initiative Randomized Controlled Trial,” JAMA, vol. 288, no. 3, p. 321, Jul. 2002, https://doi.org/10.1001/jama.288.3.321

[3] L. Cho et al., “Rethinking Menopausal Hormone Therapy: For Whom, What, When, and How Long?,” Circulation, vol. 147, no. 7. Lippincott Williams & Wilkins, p. 597, Feb. 13, 2023. https://doi.org/10.1161/circulationaha.122.061559

[4] R. A. Løbo, “Estrogen and Cardiovascular Disease,” Annals of the New York Academy of Sciences, vol. 592, no. 1. Wiley, p. 286, Jun. 01, 1990. https://doi.org/10.1111/j.1749-6632.1990.tb30340.x

[5] L. Vogel, “Trial overstated HRT risk for younger women,” Canadian Medical Association Journal, vol. 189, no. 17, Apr. 2017, https://doi.org/10.1503/cmaj.1095421

[6] J. Mehta, J. M. Kling, and J. E. Manson, “Risks, Benefits, and Treatment Modalities of Menopausal Hormone Therapy: Current Concepts,” Frontiers in Endocrinology, vol. 12. Frontiers Media, Mar. 26, 2021. https://doi.org/10.3389/fendo.2021.564781

[7] P. Stute, J. Marsden, N. Salih, and A. Cagnacci, “Reappraising 21 years of the WHI study: Putting the findings in context for clinical practice,” Maturitas, vol. 174. Elsevier BV, p. 8, May 11, 2023. https://doi.org/10.1016/j.maturitas.2023.04.271

[8] A. Z. Bluming and C. Tavris, “Hormone Replacement Therapy: Real Concerns and False Alarms,” The Cancer Journal, vol. 15, no. 2. Lippincott Williams & Wilkins, p. 93, Mar. 01, 2009. https://doi.org/10.1097/ppo.0b013e31819e332a

[9] S. Graham, D. F. Archer, J. A. Simon, K. M. Ohleth, and B. Bernick, “Review of menopausal hormone therapy with estradiol and progesterone versus other estrogens and progestins,” Gynecological Endocrinology, vol. 38, no. 11. Informa, p. 891, Sep. 08, 2022. https://doi.org/10.1080/09513590.2022.2118254

[10] S. S. Faubion et al., “The 2022 hormone therapy position statement of The North American Menopause Society,” Menopause The Journal of The North American Menopause Society, vol. 29, no. 7, p. 767, Jul. 2022, https://doi.org/10.1097/gme.0000000000002028

[11] L. A. K. Kaltoft, E. Christensen, and M. Kassem, “Postmenopausal Hormone Replacement Therapy for Health Maintenance during Aging,” in Obstetrics and gynecology., 2024. https://doi.org/10.5772/intechopen.114846

[12] V. A. Flores, L. Pal, and J. E. Manson, “Hormone Therapy in Menopause: Concepts, Controversies, and Approach to Treatment,” Endocrine Reviews, vol. 42, no. 6. Oxford University Press, p. 720, Apr. 15, 2021. https://doi.org/10.1210/endrev/bnab011

[13] G. Devi, C. Creatura, and V. Devi-Chou, “Hormone Therapy for Postmenopausal Women,” New England Journal of Medicine, vol. 382, no. 24, Massachusetts Medical Society, Jun. 10, 2020. https://doi.org/10.1056/nejmc2005199