GLP-1 Medication + Bioidentical Hormone Replacement Therapy

GLP-1 Medication + Bioidentical Hormone Replacement Therapy

By Suzanne Fenske, MD, FACOG, ABOIM, MSCP

We live in an obesogenic environment. The ultra-processed food supply, office work, commuting, technological access, and environmental toxins all promote excess body fat. In other words, human genetics aren’t compatible with the modern world, and obesity rates are rising.

To top it off, weight management becomes more challenging for women through perimenopause and in the postmenopausal years. Declining hormones make it easier to gain weight and harder to lose it.

For women with metabolic dysfunction that won’t budge, even when they’ve dialed in all the nutrition and lifestyle pieces, GLP-1 medications offer much-needed support. Although GLP-1s can be an effective tool, they don’t work in a silo. You’ll have better results when combining GLP-1s with the right lifestyle, mindset, and hormone support.

Today’s article will dive into GLP-1 medications, how they work, and the connections with hormones. If you desire midlife weight loss, this article is a must-read. We will discuss:

• What are GLP-1s?
• The research on combining GLP-1s and hormone replacement therapy (HRT)
• An integrative approach to GLP-1s and how we use them in practice

What are GLP-1s?

GLP-1 (glucagon-like peptide-1) is a natural hormone in the human body. The gut releases it in response to food intake. This hormone has several effects, including:

• Insulin regulation
• Decreased glucagon secretion (glucagon is a hormone that increases blood glucose between meals)
• Slowing the release of food from the stomach
• Reducing food intake

Greater GLP-1 secretion is associated with higher meal satisfaction and fewer thoughts about food.

GLP-1 receptor agonist medications, which we’ll call GLP-1s or GLP-1 medications in this article, mimic the natural GLP-1 hormone and bind to GLP-1 receptors in the brain. The medications have a longer-lasting effect than your body’s natural hormone, and promote decreased hunger, blood sugar control, and weight loss. First approved for type 2 diabetes treatment, GLP-1s are also FDA-approved for obesity. Additional benefits may include reduced inflammation and protection of the heart and brain.

Examples of GLP-1 medications include:

• Semaglutide (Ozempic and Wegovy)
• Tirzepatide (Mounjaro and Zepbound)
• Liraglutide (Victoza and Saxenda)
• Exenatide (Byetta)

GLP-1 medications are at the forefront of the medical weight loss landscape, yet they are not without risks. The most common side effects are digestive upset, including nausea constipation. Low hunger and food intake can also put you at risk for nutrient deficiencies.

Additionally, a recent analysis suggests that up to 40% of the weight loss achieved with GLP-1 medications is due to muscle loss. Women, older adults, and those who aren’t consuming enough protein are more at risk for muscle loss. The muscle piece is important because muscle is a metabolic currency as we age. We want to promote fat loss but preserve muscle.

Finally, weight loss, even with the aid of GLP-1 medications, can be more challenging in a hormone-deficient state, including late perimenopause, menopause, and the postmenopausal years.

GLP-1s in Midlife – the Hormone Therapy Connection

Animal research suggests that GLP-1 hormones have different effects in males and females, with females being more sensitive to GLP-1 receptor activation. Interestingly, estrogen signaling may be necessary for GLP-1 action.

In humans, we know that estradiol, the primary estrogen during the reproductive years, plays a central role in weight regulation. Estradiol helps determine food intake and metabolic rate, both of which change during the menstrual cycle in response to hormone fluctuations. In menopause, without estradiol’s protective effects, women may experience increased hunger, insulin resistance, and visceral (belly) fat accumulation.

GLP-1 hormones and estrogen work together, and new research supports the link.

A 2024 study looked at postmenopausal women on semaglutide who were overweight or obese (the median BMI was 36). The study compared the women who were using hormone therapy concurrently to those who were not. The women on hormone therapy – at every checkpoint from 3 to 12 months – achieved more weight loss. While both groups showed improved cardiometabolic health, women using estradiol with the GLP-1 were more likely to lose more than 5% or more than 10% of their total body weight.

A 2026 study published in The Lancet shows similar results. This retrospective study looked at overweight and obese postmenopausal women taking tirzepatide for weight loss and compared the results of women also using hormone therapy to those who didn’t use any hormones over 15 months. Again, both groups had positive improvements in cardiometabolic factors, including blood sugar and blood pressure, but the women on hormone therapy lost more weight. At the end of the study, the hormone therapy group lost around 19% of their body weight compared to 14% for the no HRT group.

In these studies, the weight loss medication remained the same, but the hormonal status was different. Having hormones on board improved the effectiveness of the GLP-1 medications.

GLP-1 Mindset, Lifestyle, and Hormones

In integrative medicine, we want to use conventional medical tools as appropriate and combine them with a healthy lifestyle. The goal is to address the root causes and prevent disease, not only manage current symptoms. When it comes to weight loss, body composition and metabolic health markers are more important than the number on the scale.

GLP-1 medications offer an exciting tool to help women lose fat and improve metabolic health, and they’ll achieve more impactful results when combined with bioidentical hormone replacement therapy (BHRT), which includes estradiol and progesterone support.

We also combine lifestyle support with the goals of promoting fat loss, maintaining muscle, meeting nutrient needs, and supporting a healthy relationship with food and body.

Here are some lifestyle considerations to combine with GLP-1s and BHRT:

• Monitor changes in body composition with DEXA scans or an at-home body composition scale.

• Work with your TārāMD nutritionist to ensure you’re meeting your daily nutrient needs, including protein for muscle maintenance and fiber for gut health.

• Incorporate strength training into your exercise routine to support muscle maintenance.

• Include at least 150 minutes per week of moderate cardiovascular exercise, like walking.

• Work on building a healthy mindset around the process of habit building. Focus on progress over perfection and long-term success over short-term results.

There’s no doubt that GLP-1 medications are changing the conversation about weight loss and healing from metabolic dysfunction, but understanding how GLP-1s work in harmony with other hormones and how to use the medications safely and effectively is key. Integrative medicine offers a nuanced and personalized approach to help you reach your weight and metabolic goals.

References

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