Postmenopausal Women on Hormone Therapy Achieve Greater Weight Loss with GLP-1 Medications: What the Research Shows

If you're a woman going through menopause and struggling with unwanted weight gain despite your best efforts, new research offers encouraging news. Recent research presented at The Menopause Society's 2025 Annual Meeting reveals that postmenopausal women taking hormone therapy alongside GLP-1 medications experience significantly better weight loss outcomes than those using GLP-1s alone.

The findings add another compelling reason to consider hormone replacement therapy (HRT) during menopause—and they align with what healthcare providers have observed for years: addressing the hormonal changes of menopause can make a real difference in how your body responds to weight management treatments.

The Study: How Hormone Therapy Enhanced Weight Loss Results

Researchers at the Mayo Clinic examined 160 women taking tirzepatide, a GLP-1/GIP dual-receptor agonist medication, to understand how reproductive stage and hormone therapy affected weight loss outcomes. The women were matched based on diabetes status, prior weight loss medication use, and baseline BMI, then divided into four groups: premenopausal women, perimenopausal women, postmenopausal women not on hormone therapy, and postmenopausal women taking hormone therapy.

Over an average treatment period of 18 months, all groups experienced significant weight loss. But here's what stood out: postmenopausal women taking hormone therapy lost 19.9% of their total body fat—comparable to the premenopausal and perimenopausal groups. In contrast, postmenopausal women not taking hormone therapy lost only 15.6% of their total body fat, a statistically significant difference.

"These results are very encouraging, and also not surprising," remarks Dr. Michael Koehler, Affinity Whole Health's medical director. "We've known that women going through menopause gain unwanted fat mainly due to the loss of their hormone production. It's great to see medical data showing that women on HRT can achieve even better fat loss results when combined with GLP1s."

Why Menopause Changes Everything About Weight Management

Understanding why hormone therapy makes such a difference requires looking at what happens to a woman's body during menopause. As estrogen, testosterone, and progesterone production declines, women typically experience changes in body composition that go beyond simple aging.

Research consistently shows that estrogen plays a crucial role in regulating where and how the body stores fat. When estrogen levels drop during menopause, women tend to shift from storing fat in the hips and thighs to accumulating it around the abdomen. This visceral fat isn't just cosmetically concerning—it's metabolically active tissue that increases the risk of cardiovascular disease, type 2 diabetes, and other health conditions.

Midlife weight gain has been directly associated with increased cardiovascular risk, making effective weight management during and after menopause a crucial component of long-term health. The hormonal changes of menopause also affect metabolism, making it harder to lose weight and easier to gain it, even when diet and exercise habits remain unchanged.

How GLP-1 Medications Work for Weight Loss

GLP-1 (glucagon-like peptide-1) medications like semaglutide and tirzepatide have emerged as the most effective weight management medications currently available. These medications work by mimicking natural hormones that regulate appetite and blood sugar levels.

When you take a GLP-1 medication, it helps you feel fuller for longer periods, reduces hunger signals, and slows stomach emptying. The result is a natural reduction in calorie intake without the constant battle against hunger that makes traditional dieting so difficult. Tirzepatide, the medication studied in this research, also activates GIP (glucose-dependent insulinotropic polypeptide) receptors, which may enhance weight loss beyond GLP-1 action alone.

For many women, GLP-1 medications represent a breakthrough in weight management. But as this new research shows, the hormonal environment matters significantly when it comes to how well these medications work.

Why Hormone Therapy and GLP-1s Work Better Together

The Mayo Clinic researchers proposed several explanations for why postmenopausal women on hormone therapy achieved better weight loss results with tirzepatide.

The Healthy User Effect

One possibility involves what researchers call "healthy user bias." Women who are taking hormone therapy may already be more engaged in healthy lifestyle behaviors. If hormone therapy is helping manage symptoms like hot flashes, night sweats, and sleep disturbances, these women may find it easier to maintain regular exercise routines and make healthier food choices. Better sleep quality and stable energy levels can significantly impact the motivation and ability to stay active.

Synergistic Hormonal Effects

Perhaps more intriguing is the potential for direct biological synergy between estrogen and GLP-1 signaling. Regina Castaneda, MD, the lead researcher, noted that preclinical evidence in mice suggests estrogen may provide an additive effect to GLP-1's impact on appetite suppression. While this research is preliminary, it suggests that maintaining adequate estrogen levels might actually enhance how the body responds to GLP-1 medications.

Estrogen receptors exist throughout the body, including in areas of the brain that regulate appetite and metabolism. When estrogen levels are restored through hormone therapy, these systems may function more optimally, potentially making the body more responsive to the metabolic effects of GLP-1 medications.

Recent FDA Action on Hormone Therapy

The timing of this research coincides with a significant shift in how the medical community views hormone replacement therapy. Just days ago, the FDA announced the removal of "black box" warnings from hormone therapy products for menopause, marking a historic moment for women's health.

For more than two decades, many women avoided hormone therapy due to concerns about cardiovascular disease, breast cancer, and dementia—concerns that stemmed from a flawed 2002 study that examined older women taking hormone formulations no longer commonly used. The FDA's comprehensive review of scientific literature now shows that when initiated within 10 years of menopause onset (generally before age 60), hormone therapy may reduce the risk of cardiovascular disease by up to 50%, Alzheimer's disease by 35%, and bone fractures by 50-60%.

This policy change reflects what many women's health specialists have advocated for years: that the benefits of properly prescribed hormone therapy often outweigh the risks for women experiencing menopausal symptoms. The new weight loss research adds yet another data point supporting comprehensive hormone management during menopause.

What This Means for Women Considering Weight Loss Treatment

If you're a postmenopausal woman struggling with weight management, these findings suggest that addressing your hormone levels may improve your results with weight loss medications. However, it's crucial to understand that hormone therapy isn't indicated solely for weight loss—it's prescribed to manage menopausal symptoms and, in some cases, to prevent osteoporosis.

Dr. Castaneda emphasized in her presentation that the study shows association, not causation, and that "improved response to GLP-1s is not a reason to start women on hormones in the absence of other indications." Hormone therapy decisions should be individualized based on your symptoms, health history, and personal goals.

That said, if you're already experiencing menopausal symptoms like hot flashes, night sweats, brain fog, or sleep disturbances—or if you're considering hormone therapy for these symptoms—this research suggests you may experience enhanced benefits if you're also using GLP-1 medications for weight management.

A Comprehensive Approach to Midlife Health

The most encouraging aspect of this research is that it reinforces the importance of comprehensive care during menopause. Rather than treating symptoms in isolation, addressing the underlying hormonal changes can have cascading positive effects across multiple areas of health.

Women who address their menopausal hormone deficiency often report improvements not just in classic symptoms like hot flashes, but also in energy levels, libido, mood, cognitive function, sleep quality, and now, as this research suggests, weight management outcomes. When combined with evidence-based treatments like GLP-1 medications for weight loss, the results can be even more significant.

At Affinity Whole Health, we've seen firsthand how personalized hormone optimization can transform quality of life for women in midlife. Our approach involves comprehensive hormone testing to establish your unique baseline, followed by customized treatment plans that address your specific symptoms and health goals. Every woman's hormone journey is different, which is why having a dedicated Patient Care Coordinator to guide you through the process makes such a difference. We have treated patients with hormone deficiencies since 2012, and also have experience with GLP-1 medications for weight loss since they were approved in 2021.

Looking Ahead: What Future Research May Reveal

While this study provides valuable insights, researchers acknowledge there's more to learn. Future studies will likely examine whether different types of hormone therapy—such as oral versus transdermal estrogen, or different progestin formulations—affect weight loss outcomes differently. Understanding the biological mechanisms behind the estrogen-GLP-1 interaction could also lead to even more effective treatment protocols.

For now, though, the message is clear: hormone therapy may enhance the already impressive weight loss results that many women achieve with GLP-1 medications. For postmenopausal women struggling with weight gain, this research offers hope that addressing hormonal health alongside weight management efforts may lead to better, more sustainable results.

Frequently Asked Questions

Can I start hormone therapy just to improve my weight loss results with GLP-1 medications?

No, hormone therapy isn't indicated for weight loss alone. However, if you're experiencing menopausal symptoms like hot flashes, night sweats, brain fog, or sleep disturbances, hormone therapy may be appropriate for you—and this research suggests you may see enhanced weight loss results if you're also using GLP-1 medications.

What types of hormone therapy were used in this study?

The study included postmenopausal women taking estrogen with or without progesterone.

How long does it take to see weight loss results with GLP-1 medications?

Most people begin noticing weight loss within the first few weeks of starting GLP-1 therapy, with more significant results developing over several months. The study tracked outcomes over an average of 18 months, showing sustained weight loss throughout the treatment period.

Are there risks to combining hormone therapy with GLP-1 medications?

Both hormone therapy and GLP-1 medications have their own safety profiles that should be discussed with your healthcare provider. There's no evidence suggesting that combining these treatments creates additional risks, but individual factors like your age, health history, and other medications need to be considered.

What if I'm already taking a GLP-1 medication but not on hormone therapy?

If you're experiencing menopausal symptoms, talk to your healthcare provider about whether hormone therapy might be appropriate for you. The decision should be based on your symptoms and health profile, not solely on weight loss considerations.

Do I need to be on hormone therapy before starting a GLP-1 medication?

No, the timing doesn't matter. The research showed that postmenopausal women who were already on hormone therapy experienced better results, but you can start either treatment first depending on your individual needs and health priorities.