New Drug Combo May Enhance Weight Loss for Older Women

Recent research suggests a potential drug combination that could boost popular weight-loss treatments for older women. In a limited retrospective study, women using tirzepatide—a weight loss medication—alongside menopausal hormone therapy experienced a 35 percent greater total body weight loss over 15 months compared to those who did not use hormone therapy.

This research, conducted by scientists at the Mayo Clinic and Wayne State University, analyzed health data from 120 women, primarily White and in their 50s. Out of these, 80 relied solely on tirzepatide for weight loss, while 40 also took some form of menopausal hormone therapy, with their health tracked for an average of 18 months.

On average, women utilizing both tirzepatide (a GLP-1 drug marketed as Zepbound or Mounjaro) and hormone therapy shed 19.2 percent of their original body weight, in contrast to a 14 percent average loss for those on tirzepatide alone. That notable 5.2 percentage-point disparity is statistically significant.

A higher percentage of women undergoing hormone therapy achieved a total body weight loss of 30 percent or more.

The study’s authors are now looking forward to controlled, randomized trials to validate whether this apparent drug synergy genuinely causes enhanced weight loss.

This initial finding on tirzepatide coincides with previous research from 2024 by some of the same Mayo Clinic team, which showed a higher rate of 10 percent or more total body weight loss in postmenopausal women using semaglutide alongside hormone therapy, compared to those on the GLP-1 drug alone.

Lead author Regina Castaneda noted, “The magnitude of this difference warrants future studies to clarify how GLP-1-based obesity medications and menopausal hormone therapy may interact.”

Menopause marks a significant life transition, often accompanied by widespread physical and hormonal changes. Symptoms such as fatigue, hot flashes, poor sleep, and low libido can emerge during this period. Hormone therapy aims to alleviate these challenges and may provide protection against menopause-related issues like osteoporosis and potentially heart disease. It typically replaces lost hormones in various forms, including pills, patches, or topical treatments.

While there are some indications that menopause replacement therapy might prevent weight gain, its role in promoting weight loss remains unclear. There’s a considerable gap in menopause-related research, and GLP-1 drugs are still a relatively new area of study.

Commonly, both pre- and post-menopausal women experience weight gain, which can also affect those with reproductive issues impacting their ovaries and uterus. For example, women with polycystic ovary syndrome often face insulin-related problems that heighten their risk of type 2 diabetes and subsequent weight gain.

Interestingly, the current study did not differentiate between hormone therapy types or doses; they were analyzed collectively.

Castaneda previously addressed the Menopause Society Annual Meeting in October 2025, emphasizing the need for further investigation: “Millions of women struggle with midlife weight gain, and the reality is we still lack clear answers.”

She voiced uncertainty regarding the superior weight loss outcomes seen in women using tirzepatide with hormone therapy, mentioning initial rodent studies that suggest estrogen treatments might enhance the body’s GLP-1 signaling system. However, results have been inconsistent, prompting further questions. Senior author Maria Daniela Hurtado Andrade noted, “It’s also possible that women on hormone therapy were already adopting healthier lifestyle changes, or that alleviating menopause symptoms improved their quality of life, aiding in dietary and exercise adherence.”

Ultimately, rigorous clinical trials are necessary to fully understand the effectiveness of this drug combination. Looking ahead, Hurtado Andrade indicated plans for a randomized controlled trial to investigate whether the advantages of hormone therapy extend beyond weight loss, specifically concerning its effects on cardiometabolic health.

“If confirmed,” she argued, “this could hasten the introduction of new, evidence-based strategies to help millions of postmenopausal women manage this stage of life.”

The study has been published in The Lancet Obstetrics, Gynaecology, & Women’s Health.