Podcast Summary: "BONUS Episode! Historic FDA Label Change!"

You Are Not Broken Podcast – Episode 344 (November 11, 2025)

Host: Dr. Kelly Casperson, MD
Guests: Dr. Rachel Rubin, Dr. Marty Makary (FDA Commissioner)
Main Theme:
A landmark discussion of the FDA’s historic decision to remove the black box warning from vaginal estrogen products and to update boxed warnings for systemic hormone therapy—effectively correcting decades of misinformation and fear around hormone replacement therapy (HRT) for women in perimenopause and menopause.

Episode Overview

This episode centers on the FDA’s recent and unprecedented move to update the labeling on hormone replacement therapies (HRT), including the complete removal of the black box warning for vaginal estrogen products. Dr. Kelly Casperson is joined by Dr. Rachel Rubin, a sexual medicine specialist, and FDA Commissioner Dr. Marty Makary to explore the evidence behind these changes, the damage caused by two decades of fear-based HRT messaging, and the broad implications for women’s health, medical education, and public policy.

Key Discussion Points & Insights

1. What Changed: The FDA Decision

• The FDA removed the black box warning from vaginal estrogen products and modified warnings for systemic HRT based on a comprehensive review of scientific literature, addressing outdated fears linked to breast cancer and cardiovascular risk.
  • Dr. Makary (05:04): “We are getting rid of that fear machine black box warning on hormone replacement therapy that is estrogen or estrogen plus progesterone.”
• This revision reflects substantial evidence that previous risks were misconstrued due to flaws in the Women's Health Initiative (WHI) study and subsequent "groupthink" in medicine.

2. Background: The Women’s Health Initiative and Its Damage

• In 2002, the WHI study results were hastily publicized, sparking fears of HRT causing breast cancer and heart disease—prior to the publication and full assessment of data.
  • Dr. Rubin (07:31): “The catastrophic event that happens because of that is an entire generation of clinicians have no idea how to talk to their patients about this or how to write prescriptions... This must be changed.”
• Subsequent analysis found:
  • The average age in the study was 63 (not the typical candidate for HRT).
  • The formulation used (oral horse estrogen) is different from modern HRT (estradiol).
  • No statistically significant increase in breast cancer for the general HRT group; in fact, the estrogen-only group had a decreased risk.
  • Dr. Rubin (09:51): “If you didn’t have a uterus... the risk was reduced.”

3. How Fear Became Policy

• The FDA's black box warning institutionalized misinformation, creating a generation of clinicians and patients terrified of HRT.
• Lack of training in medical residency about menopause and HRT compounded the issue.
  • Dr. Rubin (12:34): “Clinicians don’t know the safety and benefits of hormone therapy... Even gynecologists do not get this training routinely.”

4. Evidence-Based Benefits of HRT

• Dr. Makary emphasizes that the benefits are both short- and long-term:
  • Short-Term: Relief from vasomotor symptoms (hot flashes, night sweats), mood improvement, improvement in sexual function.
  • Long-Term:
    • Heart Disease: Reduced risk of fatal heart events by 25–50% (28:47)
    • Cognitive Decline: Reduced risk of Alzheimer's and other forms of dementia by up to 64%
    • Bone Health: Over 50% reduction in bone fractures, osteoporosis prevention
    • Colon Cancer, Diabetes, Depression: Notable reductions in risk in various studies (22:22)
  • Dr. Casperson (29:07): “There’s more hospitalizations in America every year from bone fracture, hip fracture than stroke and heart attack combined.”

5. Vaginal Estrogen: Microdosing, Maximal Safety

• Advocates stress the difference between local/vaginal estrogen (microdose, local action) and systemic HRT—yet historically, both carried the same strict warnings.
• Dr. Rubin (14:59): “The revolutionary thing... is that they changed the labeling so that vaginal hormones... are very different than whole body systemic hormones.”
• Even in women with a history of breast cancer, data favor mortality benefit with vaginal estrogen (37:28).

6. Barriers & Next Steps: Education and Access

• The WHI fallout means most clinicians today lack basic knowledge on menopause management.
  • Dr. Casperson (18:21): “Ten years after [WHI], about 10% of women in this country were on hormones... Twenty years after, only 5% were.”
• Women frequently see 5–6 doctors before receiving menopause treatment (32:48).
• Educational efforts must address both patients’ and clinicians’ knowledge gaps, emphasizing individualized, informed choice over fear-driven medicine.
  • Dr. Rubin (31:43): “There is not enough, here’s how to write the prescription, here’s how to counsel your patient... when I go to the doctor, it’s a 10-minute visit.”

Notable Quotes & Memorable Moments

• Dr. Makary (03:53): “Maybe one of the greatest screw ups of modern medicine in recent time.”
• Dr. Rubin (11:35): “Clinicians don’t know this... Even gynecologists do not get this training routinely and systematically.”
• Dr. Casperson (14:22): “[A husband said] It’s okay, honey, our sex life is not that important. It’s not worth you dying over.”
• Dr. Makary (21:52): “If there was a drug you could take in prediabetes... decreases risk of getting diabetes by 30%. That’s an estrogen patch.”
• Dr. Rubin (34:08): “He just wants to connect with the woman who he has loved for 35 years... It’s her biology that is affecting their biopsychosocial relationship.”
• Dr. Casperson (38:54): “I’m not here to tell you what to do. Women are smart... I want you to make your decision based upon education and not fear.”
• Dr. Makary (43:47): “The boxed warnings... are now gone. The fear machine is hopefully going to end, and we are going to now usher in a new era of education and research.”

Timestamps for Major Segments

• 00:00–03:34: Introduction, summary of historic FDA decision, context of boxed warning.
• 03:53–07:31: How the FDA made the decision and the background of boxed warnings.
• 07:31–11:35: WHI study flaws, media and policy missteps, difference in hormone formulations.
• 14:22–16:03: Real-world impact: patient confusion/fear, vaginal estrogen labeling revolution.
• 18:21–21:52: Medical training gap; population-level impacts.
• 21:52–25:43: Comprehensive review: HRT's benefits across organ systems, insurance and FDA approval.
• 28:47–31:35: Enumerating long-term outcomes: heart, bone, brain health.
• 34:08–35:57: Patient stories highlighting quality-of-life, relationship, and access issues.
• 36:49–38:54: Policy impact, public health economics, and the necessity for informed patient choice.
• 43:47–44:28: Conclusion and outlook for the future.

Takeaways for Listeners

• The FDA’s new labeling means more truthful, evidence-based information is now available regarding HRT and vaginal estrogen, potentially opening access to millions currently denied effective therapy due to outdated fears.
• A major shift is now needed in medical education and clinical practice to ensure clinicians are equipped to offer nuanced HRT counseling and care.
• Women (and their clinicians) should approach HRT decisions with up-to-date knowledge, focusing on personalized risk/benefit, and shift away from decade-old scare tactics.
• Advocacy and further research are needed, but the existing evidence already strongly supports the benefits of HRT for symptom relief and long-term health.

If you or someone you know is navigating perimenopause, menopause, or interested in HRT, this episode is a must-listen and marks a turning point in women’s health advocacy.