Mayo Clinic Researcher on How Hormone Therapy May Influence Weight Loss Outcomes With Tirzepatide

Postmenopausal women using hormone therapy alongside tirzepatide achieved significantly greater weight loss—nearly 20% of total body weight after 18 months—compared to 14%-15% among those not using hormone therapy, according to new research presented at The Menopause Society's Annual Meeting. In this interview, Regina Castaneda, MD, a postdoctoral research fellow at the Mayo Clinic College of Medicine and Science in Jacksonville, Florida, discusses her team's findings on how menopausal stage and hormone therapy influence weight loss outcomes with tirzepatide. Dr Castaneda emphasizes that while the results are promising, these retrospective observational studies have limitations, and hormone therapy should not be prescribed solely for weight loss. Instead, the findings underscore the importance of personalized medicine—considering the whole patient, including vasomotor symptoms, when developing treatment plans for postmenopausal women struggling with weight management.

Patient Care: What prompted you and your colleagues to explore how menopausal stage and hormone therapy might influence weight loss outcomes with tirzepatide?

Regina Castaneda, MD: We know that weight gain during midlife is a common concern among women and that it’s mainly related to aging. However, menopause itself also contributes, because estrogen has diverse effects beyond reproduction. During menopause, women experience a change in body composition that favors visceral fat accumulation. We also see changes in resting energy expenditure and a decrease in muscle mass. In addition, menopausal symptoms can contribute to sleep disturbances and reduced physical activity.
All of these factors may have a negative effect on body weight, so it’s important to explore the role of reproductive stage in obesity pharmacotherapy. In this study, we evaluated tirzepatide, the newest and most effective weight loss medication available—a dual GLP-1/GIP receptor agonist showing great outcomes.

Patient Care: What were the results, and did any of them surprise you?

Castaneda: Our previous study explored this question with semaglutide, so we wanted to see if the findings would be similar with tirzepatide. The results closely resembled those with semaglutide. Postmenopausal women using hormone therapy showed superior weight loss outcomes. Of course, our studies are retrospective and observational, so we emphasize that further research is needed to confirm these findings. But we did see that women on hormone therapy lost nearly 20% of total body weight after 18 months of treatment compared with 14% to 15% among those who had never been exposed to hormone therapy. At The Menopause Society meeting, we presented new data comparing women in the perimenopausal and premenopausal stages. Those using hormone therapy had results that closely resembled the premenopausal group. So, there’s definitely something there that deserves further exploration.

Patient Care: Why are menopause and reproductive stage important variables to consider in metabolic and weight management research?

Castaneda: This is a great question. Menopause comes with an increase in cardiovascular disease risk, and obesity further exacerbates that. Identifying effective weight loss strategies for postmenopausal women is critical. Many women wonder, “Will I have different weight loss outcomes now that I’m postmenopausal?” Our goal is to begin answering that question for the millions of women asking it.

Patient Care: For a primary care physician with a 55-year-old postmenopausal patient struggling with weight, how does this study inform the treatment conversation?

Castaneda: It’s too early to draw clinical conclusions, and we are not promoting the use of hormone therapy for weight loss. What our findings highlight is the importance of personalized medicine.
If a patient has bothersome vasomotor symptoms and is also struggling with weight gain, and there’s a clinical indication for both obesity pharmacotherapy and hormone therapy, then that combination may be appropriate. Of course, not all patients are candidates for hormone therapy, but when they are, and when both issues coexist, this could be part of a broader, individualized approach.
That said, hormone therapy should never be prescribed solely for weight loss. But imagine recommending 150 minutes of exercise to a woman dealing with severe hot flashes—it’s a difficult ask. So, listening to patients, recognizing symptoms, and individualizing therapy while following indications and contraindications is key.
We’ll need future studies to confirm our findings and explore the mechanisms behind them, but I’m sure we’ll learn a lot more in the future.

Patient Care: You mentioned the need for larger, controlled studies. What specific questions would you like to see addressed next?

Castaneda: We always emphasize the need for controlled studies, particularly with hormone therapy, because there’s always the question of whether we’re seeing a “healthy user” bias. We don’t know if women using hormone therapy are simply leading healthier lifestyles overall or if there’s a direct biological effect of estrogen.
Interestingly, preclinical studies in rodents suggest a synergistic interaction between estrogen and GLP-1 signaling, where estrogen amplifies the appetite-suppressing effects of GLP-1. But that’s animal data—we need human studies to see if this applies.
Future research should explore whether the observed effects are due to biology, behavior, or both. I’d also like to see studies on changes in body composition—given estrogen’s effects, it would be fascinating to see whether hormone therapy plus GLP-1 therapy provides additional benefits beyond weight loss.