Medically Reviewed by Larry Siegel, APRN

Weight after menopause plays by different rules. Estrogen drops, belly fat climbs, muscle thins, and insulin resistance sets in. The usual strategies — eat less, move more — often don’t budge the scale.

A new study presented at the 2025 Endocrine Society annual meeting put a spotlight on a possible shift. Postmenopausal women taking tirzepatide with menopause hormone therapy (MHT) lost more weight than women taking tirzepatide alone.

The finding is early, but it is the first hint that estrogen replacement can amplify the effect of a GLP-1/GIP drug in this group.

We will walk through the ENDO 2025 data, the limits of what we know so far, and the clinical red flags that mean the combination is not for everyone.

Weight Loss Gets Harder After Menopause

Once estrogen falls, the system rewires. Muscles stop pulling in glucose the way they used to. The liver stores more fat around the waist. Hunger rises even when fuel is already available, and the signal to stop eating comes late.

That is why the same diet, the same gym routine, the same level of effort stops delivering. The operating system has shifted, and weight starts moving in one direction only.

The ENDO 2025 Data Point to Synergy

Researchers wanted to know if restoring estrogen alongside tirzepatide could help women past the weight-loss plateau that follows menopause. At ENDO 2025, they shared real-world results from an analysis of 120 postmenopausal women on tirzepatide.

Combination therapy: 40 women used tirzepatide plus menopause hormone therapy
Tirzepatide alone: 80 women used tirzepatide without hormone therapy
Duration: median follow-up of 18 months

The outcomes were striking:

Average weight loss
- 17% of total body weight in the combination group
- 14% with tirzepatide alone
Deep responders
- 45% of women on both therapies lost at least 20% of body weight
- 18% reached that mark without hormone therapy

These are early findings, but they suggest that stabilizing estrogen can amplify how strongly tirzepatide lowers weight in postmenopausal women.

Tirzepatide Alone Improves Weight and Metabolic Control

Tirzepatide targets the gut hormones GLP-1 and GIP. These hormones drive appetite, fullness after eating, and how the body handles blood sugar. Activating both reduces hunger, sharpens insulin response, and pushes metabolism toward fat loss.

Tirzepatide produces greater and more consistent weight loss than semaglutide, because it activates both GLP-1 and GIP rather than GLP-1 alone.

The SURMOUNT trials mapped the effect in detail:

Participants ate smaller portions as satiety signals fired earlier
Muscles and liver processed glucose more efficiently, lowering fasting blood sugar
The average weight loss reached 15–20% of total body weight over 72 weeks
Blood pressure, cholesterol, and waist circumference improved alongside the weight loss

Tirzepatide delivers these changes on its own. Researchers at ENDO 2025 asked what happens when hormone therapy enters the equation.

Hormone Therapy Rebuilds the Ground for Weight Loss

Estrogen is a metabolic driver. It tells your muscles how to process glucose, directs where fat is stored, and stabilizes the brain’s control over sleep and appetite. When estrogen drops, those signals fade. Hormone therapy puts them back in play.

Muscle stays anabolic: estrogen drives protein synthesis, which maintains lean mass and keeps metabolism higher
Glucose clears faster: muscle tissue pulls sugar out of the blood efficiently, lowering post-meal spikes
Fat storage shifts: estrogen prevents the liver from pushing fat into the abdomen and around organs
Sleep anchors appetite: deeper sleep from hormone stability restores the brain’s control over hunger and satiety

Hormone therapy doesn’t guarantee weight loss, but it resets the same pathways that menopause disrupted — which is why it changes the playing field for nutrition, training, and medications like tirzepatide.

Evidence Is Early and Needs Proof Over Time

The ENDO 2025 results came from an electronic medical record analysis, not a randomized trial. Researchers presented the data at a meeting, which means it hasn’t been through peer review. Safety tracking was limited, and long-term outcomes — cardiovascular, cancer, and bone — remain unanswered.

The weight-loss numbers are strong, but no one should mistake them for a final verdict.

Personalized Oversight Decides Who Benefits

Not every woman is a candidate for hormone therapy. Cardiovascular risk, breast and uterine cancer history, and the timing of menopause all matter.

Tirzepatide adds its own layer of complexity, with dosing that must be monitored and side effects that need management. The combination may work best in carefully selected women, under close supervision, with labs and follow-up built into the plan.

Tirzepatide Plus MHT Works Better, But Not for Everyone

The ENDO 2025 data show a clear pattern: postmenopausal women lost more weight with tirzepatide plus hormone therapy than with tirzepatide alone.

Estrogen restores metabolic pathways that make weight loss possible, and tirzepatide amplifies the effect.

The catch is that not everyone qualifies for hormone therapy, and not everyone tolerates tirzepatide. The combination looks powerful, but only when risks are screened and the plan is built for the individual woman in front of you — not for the average case.

Yunique Medical Builds Resilience From Evidence

We measure what most people overlook: hormone balance, nutrient stores, inflammatory load, and body composition. Those data points tell us how your system is operating right now and where it can move next. The plan doesn’t start with a therapy; it starts with evidence from your own biology.

Every client’s path looks different — some need hormonal recalibration, some need metabolic support, some need structural changes in training, nutrition, or recovery.

The common thread is precision.

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Schedule a consultation and see what your numbers reveal.

Are Tirzepatide and MHT Good for Menopause Weight Loss?