What Every Woman in Midlife Needs to Know About GLP-1 Medications and Hormone Therapy
I want to begin with something I wish every woman over 40 had been told clearly and early: menopause is not just a reproductive transition. It is a whole-body metabolic event.
When estrogen declines, your body’s fat distribution strategy changes. The fat that once settled on hips and thighs begins relocating to the abdomen — not the soft, subcutaneous fat you can pinch, but the deep visceral fat wrapped around your organs. Visceral fat is metabolically active in the worst possible way. It releases inflammatory compounds, disrupts insulin signaling, and dramatically raises the risk of cardiovascular disease, type 2 diabetes, and fatty liver disease.
This shift affects the majority of women moving through midlife. It is biological, not behavioral. And for too long, medicine responded to it with a shrug and a handout that said “eat less, move more.” We can — and must — do better.
Menopause is a whole-body metabolic event
GLP-1 Medications: What They Are and How They Work
GLP-1 receptor agonists are medications that mimic a hormone your gut naturally produces after eating. They work by signaling fullness to the brain, slowing the movement of food through the digestive tract, and improving how the body processes insulin and blood sugar.
Medications like semaglutide (sold as Ozempic for diabetes and Wegovy for weight) and tirzepatide (Mounjaro, Zepbound) belong to this class. Tirzepatide is technically a dual agonist — it activates both the GLP-1 and GIP receptors, making it particularly effective for metabolic outcomes.
These are not simply appetite suppressants. Their effects include meaningful reductions in visceral fat, improved lipid panels, lower inflammatory markers, and reduced risk of major cardiovascular events. For women in midlife, that profile aligns directly with the risks that menopause introduces.
Does Combining GLP-1s With Hormone Therapy Improve Outcomes?
In my clinical experience, combining hormone therapy with a GLP-1 medication produces results that neither approach delivers on its own. The science is beginning to reflect what we’re seeing in practice.
A 2024 study in the journal Menopause followed postmenopausal women on semaglutide, comparing those who were also on hormone therapy to those who were not. The women on combination therapy lost significantly more weight at every time point measured — at 3, 6, 9, and 12 months — and were more likely to reach clinically meaningful thresholds of 5%, 10%, and even 15% weight loss.
Why might this be? Hormone therapy supports sleep quality, improves mood and energy, and helps maintain muscle mass, while estrogen specifically reduces insulin resistance and inflammation— all of which create the conditions that make a GLP-1 medication more effective over time. Better sleep means better hunger hormone regulation. More energy means a greater capacity to move. These are not small factors.
This is why, for eligible patients, I consider combination therapy a frontline strategy — not a last resort.
A Critical Point About Hormone Therapy Routes
Here is something that deserves far more attention in clinical practice than it currently receives: GLP-1 medications slow gastric emptying. That is part of their mechanism of action. But slowed gastric emptying can also reduce the absorption of oral medications — including oral estradiol, oral progestogens, and oral contraceptives.
What this means practically:
If you are on a GLP-1 and taking oral estradiol, your absorption may be impaired. Transdermal options — patches, gels, sprays — bypass the gut entirely and are worth discussing with your provider.
If you are perimenopausal and using an oral contraceptive for birth control, consider backup contraception while you are on a GLP-1 medication.
Oral micronized progesterone is the most common form of progestogen used alongside systemic estrogen. The data on absorption interference is limited but warrants a conversation with your clinician.
This is not a reason to avoid GLP-1 medications. It is a reason to have a thorough discussion about the route of administration of your hormones. If your current provider has not raised this with you, bring it to them directly.
What About Retatrutide — The Next Generation?
Retatrutide is a triple agonist in development, activating the GLP-1, GIP, and glucagon receptors simultaneously. Phase 2 trial results published in the New England Journal of Medicine in 2023 showed average weight loss approaching 25% at 48 weeks at higher doses — outcomes that exceed what any currently approved medication achieves. A separate 2024 Phase 2 trial in Nature Medicine showed dramatic reductions in liver fat in patients with metabolic-associated liver disease.
These are genuinely exciting results. Phase 3 trials under the TRIUMPH program are ongoing across multiple indications — obesity, type 2 diabetes, sleep apnea, and more.
I want to be direct here: retatrutide is not FDA approved. There is no legal prescription pathway. Any platform or telehealth provider selling compounded retatrutide is operating outside federal compounding rules, which require a drug to be either FDA approved or on the official shortage list. Sourced outside of a clinical trial, its purity, sterility, and dosing cannot be verified. The science is real. The Phase 2 data is promising. But your health is not a beta test. Wait for Phase 3 results and regulatory approval.
Managing Side Effects and Protecting Muscle
GLP-1 medications are well-tolerated for most women, but side effects — particularly nausea, constipation, and reduced appetite — are common in early weeks. Slow titration and mindful eating habits help significantly. Stay well hydrated; these medications can blunt thirst signals.
Introduce fiber gradually to minimize GI discomfort. Avoid carbonation in the early weeks. And if you are losing more than about two pounds per week, speak with your clinician — too-rapid loss increases the risk of gallstones, muscle wasting, and hair shedding.
The muscle piece deserves its own emphasis. Because GLP-1 medications reduce appetite, they can unintentionally reduce protein intake — and that puts muscle mass at risk. Studies consistently show that approximately 25–39% of total weight lost with GLP-1 medication is muscle. Muscle is not vanity. Muscle determines your resting metabolic rate, your risk of falls and fractures, your blood sugar control, and your long-term vitality. On or off a GLP-1, I recommend aiming for 1.3 to 1.6 grams of protein per kilogram of ideal body weight daily, and incorporating resistance training at least two to three times per week.
This Is Biology, Not a Moral Failing
I need to say this plainly, because too many women have internalized the opposite message: weight gain during menopause is not a failure of discipline. It is a physiological response to hormonal changes — the same hormonal changes that affect your sleep, your bones, your brain, and your cardiovascular system.
The tools we now have — evidence-based, grounded in real clinical data — mean that suffering through this transition is no longer inevitable. What is required is accurate information, a provider who understands your biology, and a willingness to advocate for yourself.
If you suspect you are a candidate for GLP-1 therapy, hormone therapy, or a combination approach, bring that conversation to your next appointment. You deserve a clinician who can meet you there.
Defy Menopause - Own the Change
Many women tell me: "One day I feel amazing. The next, I can barely get out of bed. Is this normal?"
Yes, it is. And no, you don’t have to suffer through it alone.
Hormonal fluctuations during perimenopause can make you feel like you’ve lost control of your body. But knowledge is powerful. And there are clear, science-backed ways to support your hormones, ease symptoms, and reclaim your energy.
That’s exactly why I created Defy Menopause: Own the Change — a 30-day program designed to give you the tools, knowledge, and support you need to move through these changes with clarity and confidence.
Inside, you’ll find:
Access to Dr. Tracy Verrico at one (1) live, group session
Clear action steps for managing symptoms naturally
Because you deserve more than just "putting up with it."
You deserve to thrive.
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Medical Disclaimer: The information provided in this blog is for general educational and informational purposes only and is not intended as, nor should it be considered, medical advice. This content does not establish a physician-patient relationship and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified healthcare provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay seeking it because of something you have read in this newsletter. If you think you may have a medical emergency, call your doctor or emergency services immediately.
References
1. Hurtado MD, Tama E, Fansa S, et al. Weight loss response to semaglutide in postmenopausal women with and without hormone therapy use. Menopause. 2024;31(4):266–274. https://pubmed.ncbi.nlm.nih.gov/38446869/
2. Ushanova F, Demidova T. Menopause, obesity, and incretin therapy: new horizons in the fight for women's metabolic health. Women's Health and Reproduction. 2025. https://doi.org/10.31550/2712-8598-2025-4-8-zhzir
3. Jastreboff AM, Kaplan LM, Frías JP, et al. Triple-hormone-receptor agonist retatrutide for obesity: a Phase 2 trial. New England Journal of Medicine. 2023;389(6):514–526. https://www.nejm.org/doi/full/10.1056/NEJMoa2301972
4. Sanyal AJ, Kaplan LM, Frias JP, et al. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized Phase 2a trial. Nature Medicine. 2024;30:2037–2048. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11271400/
5. Giblin K, Kaplan L, Somers V, et al. Retatrutide for the treatment of obesity, obstructive sleep apnea and knee osteoarthritis: rationale and design of the TRIUMPH registrational clinical trials. Diabetes, Obesity and Metabolism. 2025;28:83–93. https://doi.org/10.1111/dom.70209
6. Rosenstock J, Frias JP, Jastreboff AM, et al. Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo- and active-controlled, parallel-group, Phase 2 trial conducted in the USA. The Lancet. 2023. https://doi.org/10.1016/S0140-6736(23)01053-X
7. Liu Q. Mechanisms of action and therapeutic applications of GLP-1 and dual GIP/GLP-1 receptor agonists. Frontiers in Endocrinology. 2024;15. https://doi.org/10.3389/fendo.2024.1431292
8. Fisman EZ, Tenenbaum A. The dual GIP and GLP-1 receptor agonist tirzepatide: a novel cardiometabolic therapeutic prospect. Cardiovascular Diabetology. 2021;20. https://doi.org/10.1186/s12933-021-01412-5
9. Coskun T, Urva S, Roell WC, et al. LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: from discovery to clinical proof of concept. Cell Metabolism. 2022. https://doi.org/10.1016/j.cmet.2022.07.013
10. Tewari J, Qidwai K, Tewari A, et al. Efficacy and safety of triple hormone receptor agonist retatrutide for the management of obesity: a systematic review and meta-analysis. Expert Review of Clinical Pharmacology. 2025;18:51–66. https://doi.org/10.1080/17512433.2025.2450254
