For this study, researchers analyzed health data from the Mayo Clinic Health System that included 120 postmenopausal women with an average age of about 56, who had overweight or obesity, and received treament with tirzepatide for 12 months or more.

Of this number, 40 were also using menopausal hormone therapy and 80 were not.

“Our decision to specifically investigate tirzepatide’s interaction with menopausal hormone therapy stems from both significant clinical observations and compelling scientific rationale,” Regina Castaneda, MD, a postdoctoral research fellow at Mayo Clinic and first author of the study, told Medical News Today.

“Studies in animal models have suggested a potential synergy, with estrogen shown to enhance the appetite-suppressing effects of GLP-1,” said Castaneda.

“This, coupled with prior observations that semaglutide — a medication with a similar mechanism of action — also suggested a potential synergy, motivated our investigation into whether a similar pattern exists with tirzepatide. We focused on tirzepatide because it is among the most effective current pharmacotherapies for weight loss, underscoring the clinical importance of understanding factors that may modify its response.”

– Regina Castaneda, MD

At the study’s conclusion, researchers found that postmenopausal women taking menopausal hormone therapy lost about 35% more weight on tirzepatide, when compared to those taking tirzepatide alone.

“This finding is meaningful because postmenopausal women face a high burden of obesity and a corresponding rise in cardiometabolic risk, making effective weight-loss strategies especially important in this group,” Maria Daniela Hurtado Andrade, MD, PhD, an endocrinologist at Mayo Clinic and senior author of this study, explained to MNT.

“The greater weight loss we observed suggests that menopausal hormone therapy may be an important modifier of response to tirzepatide, pointing toward a more personalized approach, where menopausal status and menopausal hormone therapy use is considered when counseling midlife women and designing treatment plans,” Hurtado Andrade detailed.

“While this observational study cannot prove causality, it underscores the need for prospective trials to determine whether and how menopausal hormone therapy modifies response to obesity pharmacotherapy,” Castaneda went on to say.

“We plan to conduct a prospective, randomized controlled trial to confirm these findings and explore the underlying mechanisms,” she told us.

“We also aim to determine whether the benefits of combining menopausal hormone therapy with obesity treatments extend beyond weight loss to encompass improvements in metabolic and cardiovascular parameters, thereby informing more comprehensive therapeutic strategies,” added Castaneda.

“This approach will advance precision medicine for obesity-centric cardiometabolic risk management, ensuring that therapeutic strategies reflect midlife women’s unique needs,” she explained.

MNT had the opportunity to speak with Mir Ali, MD, a bariatric surgeon and medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, CA, about this study, which he called “significant.”

“The results are consistent with what we observe in bariatric practice — specifically, that postmenopausal hormonal changes can significantly impact a woman’s weight,” Ali, who was not involved in this research, explained.

MNT also spoke with Prudence Hall, MD, an OB/GYN in private practice in Santa Monica, CA, who was likewise not involved in this research.

Hall commented that the conclusion that both menopausal hormone therapy and tirzepatide are more successful with weight loss than as a single treatment is a reasonable result that she would anticipate.

“In early menopause, women gain an average of 30 pounds, and once estradiol, progesterone, thyroid, and stress hormones are corrected back to healthy, youthful levels, the weight starts to regain its youthful, healthy levels also,” she explained. “If you add tirzepatide, the body’s sugar damage falls, which helps decrease sugar and carb cravings. Both of these therapies approach weight loss in different ways, which works well.”

“As a gynecologist managing women’s hormones for over 4 decades, one of the major sources of concern I hear from women is their dismay over weight gain,” Hall continued. “As they age, excess weight not only causes women to feel less confident, more exhausted, more marginalized and invisible but also tends to cause them to isolate themselves more.“

“Women are now very aware that with increased body fat, breast cancer, heart disease, inflammatory conditions, high blood pressure, and neurodegenerative disease all can increase. These conditions can cause considerable suffering as well as shorten our health span for an active life,” she added.

“As for next steps in research that I would love to see, it would be the role that testosterone plays in weight reduction in menopausal women,” said Hall.