Tirzepatide and Menopausal Hormone Therapy May Boost Weight Loss in Older Women

Scientists have identified a possible drug combination that could boost the effects of widely used weight-loss treatments in older women.

Tirzepatide and menopausal hormone therapy

A small retrospective study examined women using different doses of tirzepatide for weight loss. After 15 months of treatment, those also receiving menopausal hormone therapy had achieved 35 percent more total bodyweight loss than women who were not using hormone therapy.

Researchers from the Mayo Clinic and Wayne State University in the US collected health data from 120 women, most of whom were White and in their 50s.

Of the participants, 80 used tirzepatide alone for weight loss, while 40 took tirzepatide alongside some form of menopausal hormone therapy. Their health records were followed for an average of 18 months.

Women using both tirzepatide - a GLP-1-based medicine marketed as Zepbound or Mounjaro - and hormone therapy lost an average of 19.2 percent of their initial body weight. By comparison, those taking tirzepatide alone lost 14 percent on average. The 5.2 percentage-point gap was statistically significant.

A greater share of women receiving hormone therapy also reached total bodyweight loss of 30 percent or more.

The study authors now want to run controlled, randomised trials of the combination to determine whether the apparent drug synergy holds up to closer examination and is genuinely causing the additional weight loss.

These early results involving tirzepatide follow a 2024 study, written by several of the same Mayo Clinic researchers. That research found that, after 12 months, a larger proportion of postmenopausal women taking semaglutide with hormone therapy achieved total body weight loss of at least 10 percent than those using the GLP-1 drug alone.

"The magnitude of this difference warrants future studies that could help clarify how GLP-1-based obesity medications and menopausal hormone therapy may interact," says lead author and women's health researcher Regina Castaneda at the Mayo Clinic Center.

Menopause, weight gain and hormone treatment

Menopause begins when menstruation stops, marking a major transition accompanied by extensive hormonal changes in the body and brain. Both the transition itself and its lasting effects can bring numerous difficult physical symptoms, including tiredness, hot flushes, night sweats, disrupted sleep and reduced libido.

Menopausal hormone therapy may help manage these issues and could provide some protection against conditions associated with menopause, including osteoporosis and possibly heart disease. Usually available as tablets, patches or topical treatments, the medication is intended to replace some of the hormones lost by the body, such as oestrogen or progesterone.

Although some research indicates that menopause replacement therapy may help prevent weight gain later in life, it remains uncertain whether, or how, it could encourage weight loss.

Menopause has historically been under-researched and underfunded. GLP-1 medicines are also a relatively new class of drugs that researchers are still working to understand.

However, weight gain is known to be common among women before and after menopause, as well as among people with reproductive conditions affecting the ovaries and uterus.

For example, people with polycystic ovary syndrome are more likely to have insulin problems, which may raise the risk of type 2 diabetes and contribute to weight gain.

The present research did not separate participants according to the type or dosage of hormone therapy they received, instead assessing all hormone therapies as one group.

Why further trials are needed

In October 2025, Castaneda discussed her team's latest findings at the Menopause Society Annual Meeting, highlighting how much remains unknown.

"Millions of women struggle with weight gain during midlife, and the reality is that we don't know what the answer is," she said.

"We don't know why we're observing these superior weight loss outcomes in women using tirzepatide in addition to hormone therapy."

Castaneda cites early rodent research suggesting that oestrogen treatment may strengthen the body's natural GLP-1 signalling system. Yet the findings have been inconsistent, and other explanations may account for the result, according to endocrinologist and senior author Maria Daniela Hurtado Andrade.

"It is possible that women using hormone therapy were already engaged in healthier behaviors," Hurtado Andrade says, "or that menopause symptom relief improved sleep and quality of life, making it easier to stay engaged with dietary and physical activity changes."

Only rigorous clinical trials of the drug combination can establish the answer with confidence.

Hurtado Andrade says that she and her team will conduct a randomised controlled trial to find out whether the advantages of menopausal hormone therapy "extend beyond weight loss – specifically, whether hormone therapy also enhances the effects of these medications on cardiometabolic measures."

"If confirmed," she argues, "this work could speed the development and adoption of new, evidence-based strategies to reduce this risk for millions of postmenopausal women navigating this life stage."

The study was published in The Lancet Obstetrics, Gynaecology, & Women's Health.