Podcast Summary:

The Dr. Gabrielle Lyon Show
Episode: Hormone Replacement Therapy Decoded: Why the FDA Removed the Blackbox Warning on HRT
Host: Dr. Gabrielle Lyon
Guest: Dr. Nick Barringer
Date: December 23, 2025

Overview of the Episode

This episode explores the recent removal of the FDA black box warning from Hormone Replacement Therapy (HRT) for menopause, decoding what this change means for women’s health. Dr. Gabrielle Lyon and Dr. Nick Barringer delve into hormone replacement’s risks and benefits, testosterone use in women, misconceptions, laboratory and clinical markers, and the relevance to both men and women. The discussion is rooted in science and clinical practice, aiming to inform patients and clinicians about the current state and future directions of HRT.

Key Discussion Points & Insights

1. The FDA Black Box Warning Removal on HRT

• Context of the Change:
  The FDA's black box warning on HRT, instated in the early 2000s after the Women’s Health Initiative, led to a dramatic reduction in hormone therapy prescriptions due to fears of increased cancer and cardiovascular risks.
• Current Evidence:
  Recent reviews and studies show significant benefits for appropriate candidates, leading to the warning's removal.
• Key Quote:
  "For the last...since 2003 or so, women have stopped using hormone replacement therapy for risk of breast cancer, cancers, heart disease, stroke. And it's really changed the landscape of health and wellness for women. And we're now entering a new landscape." – Dr. Gabrielle Lyon [03:06]

2. Who Should NOT Take HRT

• Explicit Contraindications ([00:00], [17:10]):

  • Active breast cancer or active cancer
  • Undiagnosed or unworked-up vaginal bleeding
  • Recent stroke

• Special Considerations:

  • Individualized decisions made with a provider
  • The importance of clear red flags and patient-specific risk assessment

• Key Quote:
  "Active breast cancer or active cancers. Undiagnosed, unworked up vaginal bleeding and stroke. Those are the things where you would give you pause." – Dr. Gabrielle Lyon [17:10]

3. Benefits of Hormone Replacement Therapy

• Reductions Reported: [00:00], [17:50]

  • 50% reduction in heart attack risk
  • 64% reduction in cognitive decline
  • 34% lower risk of Alzheimer’s
  • Reduced risk of all-cause mortality and bone fractures

• Impact on Women's Health:

  • Reduced heart disease as estrogen declines in menopause
  • Increased quality of life, bone health, cognitive function

• Notable Quote:
  "Benefits of hormone replacement therapy include a reduced risk of all cause mortality, fractures. HRT has also been associated with a 50% reduction in heart attack risk. Wow, sign me up." – Dr. Gabrielle Lyon [17:50]

4. Testosterone in Women: Myths and Mechanisms

• Common Misconception:

  • Testosterone is assumed to be just for men and linked with virilization (i.e., beard growth, deepening of the voice)
  • In reality, physiological doses in women don’t cause masculinization.

• Clarifying Virilization:

  • Only at supraphysiological doses are side effects like increased body hair or clitoral enlargement likely ([13:08]).

• Clinical Uses:

  • Improves sex drive, energy, lean mass, and more
  • "We think about testosterone and we think about muscle mass, but there are testosterone receptors all over the body. There are estrogen receptors all over the body." – Dr. Gabrielle Lyon [00:24, 12:40, 57:31]

• Testing and Dosing:

  • Gold standard: Liquid chromatography-mass spectrometry for hormone measurement ([04:56])
  • "If you're getting your labs, you should request liquid chromatography." – Dr. Gabrielle Lyon [04:55]
  • Usual clinical doses: 1/10th of typical male dosing, often via topical cream or subcutaneous injection ([26:41], [55:14])

5. Testosterone Reference Ranges

• For Women: ([07:28–10:04])

  • Premenopausal, total: 0.3–1.6 nmol/L (8.7–46 ng/dL)
  • Postmenopausal, total: 0.2–1 nmol/L
  • Premenopausal, free: 5.2–26 pmol/L (1.5–7.5 ng/dL)
  • Postmenopausal, free: 2.5–13 pmol/L (0.7–3.8 ng/dL)

• For Men: ([15:36])

  • Total: 264–916 ng/dL (varies by geography)
  • Free: 184–749 pmol/L

6. Estrogen in Men

• Importance:
  Men need healthy estrogen for bone density and sex drive. Too little = low libido/weak bones; too much = mood changes and low drive ([05:57–07:06]).
• Optimal Range:
  Estrogen in men: 30–50 (units not specified) – keep within this range for best outcomes.

7. Risks and Side Effects of Testosterone

• Hematocrit & Hemoglobin Increase:
  • Testosterone, especially with intramuscular injections, can increase red blood cells ([36:52–39:39]).
  • High hematocrit: Possible recommendations for blood donation
  • Clinical pearl: Can mask conditions like pernicious anemia ([43:58–45:15])
  • "If someone goes on testosterone, it can mask underlying causes of anemia." – Dr. Gabrielle Lyon [43:53]
• Lipids: ([46:43–49:20])
  • Oral testosterone (via the liver): can decrease “good” HDL cholesterol
  • Transdermal/injectable testosterone: at physiological doses, no significant negative effect on HDL
  • Review full lipid panel, not just numbers—look at particle quality and function

8. Menopause, Surgical Menopause, and HRT

• Special Scenarios: ([22:58–23:54])
  • Early loss of ovarian hormones (e.g., total hysterectomy) increases risk for Alzheimer's, osteoporosis, and cardiovascular disease.
  • HRT is especially important for these women.

9. Testosterone Study in Young Women

• Study Review:
  48 physically active women (18–35), 10mg testosterone cream daily for 10 weeks. ([24:56–28:58])

• Findings:

  • Serum testosterone increased from 0.9 to 4.3 nmol/L
  • Time to exhaustion rose by 21 seconds (8.5% improvement)
  • Lean mass increased by ~923g, legs specifically by ~400g
  • No significant change in vertical jump/squat, but marked effect on endurance and body composition.

• Key Quotes:
  "It was a randomized control trial in young healthy women to show the short term testosterone administration led to significant increase in total lean mass." – Dr. Gabrielle Lyon [32:56] "That could be the difference between being on a podium and not." – Dr. Nick Barringer [28:14]

10. Delivery Methods and Optimization

• Topical Creams:
  Common in practice, starting as low as 0.5mg/day and moving up as needed ([26:41]).
• IM vs. SQ Injections:
  IM gives a spike in testosterone (raises hematocrit), SQ more stable levels
• Oral Lymphatic Delivery:
  Bypasses the liver, less impact on cholesterol ([41:50])

11. Clinical Practice Insights

• Testing Schedule: ([52:19–53:20])
  • Baseline labs
  • Recheck at 4 weeks after starting
  • At 3 months
  • Then every 4–6 months
• Labs to Order:
  Free and total testosterone, SHBG, estradiol, progesterone, LH, FSH, thyroid panel, iron, ferritin

12. Outcomes & Transformative Stories

• Notable Case:
  60-year-old woman with muscle loss, low libido, joint pain. With optimized testosterone, estrogen, progesterone, and low-dose tirzepatide, her health and body composition transformed; body fat dropped to 16%, and mental freedom from food and body image obsession achieved ([53:38–57:01]).

• Memorable Quote:
  "Her body transformation was unbelievable. This was a woman who never wanted to get on the scale ever. She’s like running ultras. Her body fat percentage is 16 now." – Dr. Gabrielle Lyon [55:14]

13. DHEA as an Alternative or Adjunct

• Supplemental Use:
  DHEA (50mg+) may increase estradiol and testosterone moderately, especially for those unwilling to use prescription hormones ([59:13–61:33]).
• In Practice:
  Dr. Lyon uses DHEA mostly as adjunct in women on testosterone who experience declines in DHEA sulfate.

14. Vaginal Testosterone, Estrogen, and Progesterone

• Local Therapy:
  Important for tissue health and prevention of atrophy/UTIs in aging women: "This tissue atrophies and nobody wants that... increases risks of urinary tract infections." – Dr. Gabrielle Lyon [58:10]

Notable Quotes & Moments (with Timestamps)

• "The FDA just removed the black box warning on HRT for menopause... Hormone replacement therapy has been associated with a 50% reduction in heart attack risk, 64% reduction in cognitive decline, 34% lower risk of Alzheimer’s." – Dr. Gabrielle Lyon [00:00]
• "Will women grow a beard? That's what my wife would want to know... No. Not at clinical doses." – Dr. Gabrielle Lyon [04:24]
• "If estrogen is too high in men... they don't like the way they feel... low estrogen seems to kill sex drive in men." – Dr. Gabrielle Lyon [05:56]
• "Who should not go on hormone replacement therapy? Active breast cancer or active cancers. Undiagnosed vaginal bleeding. And stroke." – Dr. Gabrielle Lyon [17:10]
• "A black box warning is a major problem, major risk. But because of the reevaluated data, those fears have largely been reduced." – Dr. Gabrielle Lyon [18:00]
• "You can improve your type 2 muscle fibers by getting on a great resistance training program... three days a week of doing resistance training... it doesn't have to be barbell squats." – Dr. Gabrielle Lyon [35:31]
• "Testosterone is not FDA approved for muscle mass, but sarcopenia is really dangerous." – Dr. Gabrielle Lyon [54:00]
• "Women aren't even thinking about that. Similarly, just how men aren't even thinking about estrogen, which is equally important for men and women." – Dr. Gabrielle Lyon [57:31]

Timestamps for Important Segments

• FDA Black Box Warning removal, context: [03:06–04:49]
• Risks/contraindications clarified: [17:10]
• Testosterone dosing, clinical ranges: [07:28–10:04]
• Discussion of estrogen in men: [05:37–07:06]
• Virilization/myth-busting: [13:08]
• Testosterone study in women: [24:56–29:01]
• Lab testing best practices: [52:19–53:20]
• Case study patient transformation: [53:38–57:01]
• DHEA as an alternative: [59:13–61:33]

Final Thoughts and Takeaways

• The landscape for hormone replacement—especially for women—has shifted based on new evidence, offering significant benefits for appropriate patients.
• Testosterone, often misunderstood and stigmatized in women, is safe and effective in physiological doses for selected candidates.
• Optimizing hormone health is nuanced and requires attention to lab monitoring, delivery methods, and individual goals.
• Both men and women benefit from balanced hormone regulation—sex hormones matter to all.
• Clinical oversight and holistic testing remain paramount for safety and efficacy.

This episode is a must-listen for anyone seeking clarity on HRT, testosterone in women, or nuanced, evidence-based hormone management.