Podcast Summary: ENP105 – Tirzepatide and Menopause

Endocrine News Podcast — October 29, 2025
Host: Aaron Lohr
Guests: Dr. Daniela Hurtado Andrade and Dr. Regina Castaneda (Mayo Clinic)

Episode Overview

This episode examines the intersection of menopause, weight gain, hormone therapy, and the use of tirzepatide—a medication initially for type 2 diabetes, now recognized for its weight loss benefits. Host Aaron Lohr interviews Dr. Hurtado Andrade and Dr. Castaneda about their recent research on how menopause hormone therapy may impact tirzepatide-induced weight loss in postmenopausal women.

Key Discussion Points & Insights

Understanding Menopause, Weight Gain, and Hormone Therapy

• Why Does Weight Gain Happen During Menopause?

  • Declining estrogen causes redistribution of fat, increased visceral fat, muscle loss, and reduced resting energy expenditure (01:16).
  • Menopause symptoms also contribute indirectly by affecting sleep and physical activity, leading to further weight gain.
    • “During menopause, women experience a decline in estrogen levels and this can lead to changes in body composition.” (B, 01:21)

• Prevalence of Hormone Therapy Use

  • Vasomotor symptoms affect over 80% of women, but only a minority receive hormone therapy (02:06).
  • Usage has dropped significantly over the past two decades due to safety controversies and changing perceptions.
    • “The prevalence of hormone therapy sharply started to decline in the 2000s and... we never recovered.” (C, 03:16)
  • Currently, fewer than 10% of women with an indication are using hormone therapy (C, 03:56).

Previous Research Linking Hormone Therapy and Weight Loss Medication

• Prior study (semaglutide): Women on hormone therapy lost more weight than those not using it (04:40).

• Real-world evidence on tirzepatide in this context was lacking, prompting the current research.

  “Our previous study with semaglutide suggested that postmenopausal women using hormone therapy experience greater weight loss compared with those that were not using hormone therapy. However, no data existed on... tirzepatide.”
  — Dr. Castaneda (B, 04:40)

• Clinical observations: Breast cancer survivors on aromatase inhibitors (blocking estrogen) saw less effect from weight loss medications, reinforcing the suspected role of estrogen (C, 05:23).

Mechanisms of Tirzepatide and GLP-1 Medications

• Semaglutide: GLP-1 receptor agonist.
• Tirzepatide: Dual GIP/GLP-1 receptor agonist, leading to more robust weight loss and metabolic improvements (B, 07:35).

Study Details & Methods

• Design: Retrospective real-world analysis.
• Participants: Out of 15,000 tirzepatide users, researchers identified 400 postmenopausal women on the drug for ≥12 months.
• Groups: Compared 40 women using hormone therapy concurrently with tirzepatide and 80 matched controls not using hormone therapy (B, 08:04).
• Matching Factors: Age, BMI, type 2 diabetes history, prior obesity drugs, age/type of menopause.
• Endpoints: Primary—total body weight loss at 18 months; Secondary—proportion reaching key categorical weight loss thresholds.

Findings & Surprises

• Weight Loss Outcomes

  • Women on hormone therapy lost 19% of body weight at 18 months versus 14% in the non-hormone group—a 35% greater reduction (B, 09:46).

  • Hormone therapy users were twice as likely to lose more than 20% body weight.

  • Suggests a potential synergistic effect between estrogen and tirzepatide.

    “The hormone therapy group experienced a 35% greater weight loss following 18 months of treatment.”
    — Dr. Castaneda (B, 09:49)

• Cautions

  • Findings are associations, not causation—both this and prior semaglutide study are retrospective.
  • Need for prospective studies and mechanistic exploration (B, 10:52).

Unanswered Questions & Future Research

• Potential Mechanisms

  1. Healthy user bias: Hormone therapy users may generally engage in more healthy behaviors.
  2. Symptom mitigation: Alleviation of vasomotor symptoms could improve adherence to lifestyle and medication regimens.
  3. Pharmacological synergy: Preclinical data suggest estrogen may enhance GLP-1 signaling’s weight and appetite effects (B, 10:52).

  “It will be very interesting to see what can be the underlying mechanism.”
  — Dr. Castaneda (B, 11:45)

Clinical Implications & Practical Takeaways

• Individualized Approach Is Essential

  • Hormone therapy should not be used solely for weight loss.

  • Candidates for hormone therapy should be carefully evaluated for contraindications and clinical indication (vasomotor symptoms) (B, 12:41).

    “Hormone therapy is not recommended for weight loss. ...We’re not promoting the use of hormone therapy for weight loss.”
    — Dr. Castaneda (B, 12:41)

  • When both therapies are indicated, their combination may potentially improve outcomes, but decisions must be shared and personalized.

• Quality of Life Impacts

  • Managing vasomotor symptoms may make weight loss and lifestyle changes more achievable, as women feel better, sleep better, and are more able to exercise (B, 13:10).

  • Dr. Hurtado underlines real-world patient queries about combining therapies and reiterates:

    • Only suggest hormone therapy if clinically indicated.
    • Benefits extend beyond possible weight effects—it’s about global quality of life and symptom control (C, 14:32).

    “The benefits of treating vasomotor symptoms are beyond just improving the weight loss response to these medications.”
    — Dr. Hurtado (C, 14:50)

  • Comprehensive care: Assess for sleep apnea, address comorbidities (C, 16:02).

Notable Quotes & Memorable Moments

• On Decline of Hormone Therapy Use:

  • “The prevalence of hormone therapy sharply started to decline in the 2000s and... we never recovered.” (Dr. Hurtado Andrade, 03:16)

• On Study Results:

  • “The hormone therapy group experienced a 35% greater weight loss following 18 months of treatment.” (Dr. Castaneda, 09:49)
  • “They were twice as likely to achieve more than 20% total body weight loss compared to those that have never been exposed to hormone therapy.” (Dr. Castaneda, 09:51)

• On Clinical Caution:

  • “Hormone therapy is not recommended for weight loss. ...We’re not promoting the use of hormone therapy for weight loss.” (Dr. Castaneda, 12:41)

• On Quality of Life:

  • “I have no doubt that these interventions will be more feasible when a patient is feeling better, sleeping better, just enjoying a better quality of life.” (Dr. Castaneda, 13:29)

• On Real-World Application:

  • “We have had patients... asking if they should be prescribed hormone therapy... they haven’t seen the anticipated weight loss response and they are wondering if by adding hormone therapy they can achieve better weight loss outcomes.” (Dr. Hurtado, 14:32)

Timestamps for Key Segments

• Menopause & Weight Gain Overview: 01:11–02:00
• Hormone Therapy Trends & Usage: 02:00–04:33
• Previous Semaglutide Findings: 04:40–05:20
• Clinical Observations & Study Rationale: 05:20–07:26
• Medications Compared (Semaglutide vs. Tirzepatide): 07:26–07:57
• Methods & Study Design: 08:04–09:41
• Main Results & Surprising Findings: 09:41–10:46
• Mechanism Questions & Research Needs: 10:46–12:33
• Clinical Guidance for Providers: 12:33–14:32
• Quality of Life and Individualization: 14:32–17:22

Conclusion

This episode underscores a significant, evolving link between menopause hormone therapy and improved weight loss outcomes with tirzepatide among postmenopausal women. However, robust evidence is still needed, and clinical decisions must always prioritize individualized care and overall patient well-being—not just weight metrics.

For endocrinologists and other providers, the key takeaway is to assess menopausal symptoms comprehensively, consider the full clinical picture, and ensure that interventions are evidence-based and patient-centered.