Starting a GLP-1 in Perimenopause: What Actually Changed

The number on the scale was the least interesting part

I turned forty-four the year I started, and the thing I kept trying to explain to people was that my body had changed shape without changing much weight. Same jeans size on paper. Completely different jeans.

I assumed I was imagining it, or being vain, or both. Then I read the thing that reorganized how I thought about the whole project.

What the transition actually does, and it is not what I assumed

The Study of Women's Health Across the Nation followed women through the menopause transition with DXA scans rather than bathroom scales, and the finding is genuinely counterintuitive: weight climbed in a straight line through premenopause and did not accelerate at the transition. What changed was the composition underneath it — the rate of fat gain doubled, and lean mass started to fall, with both continuing until about two years after the final period¹.

So the scale is not lying to you. It is answering a question you did not ask. Two women can gain the same four pounds a year and be having completely different decades.

That reframed what I wanted from a GLP-1. I had come in thinking about a number going down. What I actually cared about, once I understood the shape of it, was which tissue was leaving.

The part that changed what I do on Tuesdays

Here is the tension nobody handed me: perimenopause is already taking lean mass, and weight loss of any kind takes some too.

A 2026 observational study followed adults on semaglutide for twelve months alongside a lifestyle-only group. The semaglutide group lost substantially more weight — about eleven kilos more — and yes, their skeletal muscle mass fell, from 29.9 to 28.7 kg, with fat-free mass down from 53.8 to 52.7 kg. But the same study measured grip strength, and absolute strength was preserved in both groups; relative strength actually improved on semaglutide².

I want to be careful with that, because it is a small single-center retrospective study using bioimpedance, not a trial. It is a reason to pay attention, not a reason to panic, and not a reason to skip the medication.

What it did was make me stop treating resistance training as the thing I would get to eventually. I lift twice a week now, badly, in my kitchen, while something roasts. It is not a fitness journey. It is trying to keep the tissue I still have.

If you are on HRT, this is the bit I would want flagged

I take estradiol. Nobody mentioned this to me, and it is the most practical thing in this article.

There is a published case report of a fifty-one-year-old woman on oral estrogen whose hot flashes and mood changes got noticeably worse during her semaglutide dose increases. The proposed explanation is that GLP-1s slow gastric emptying, which can temporarily reduce how much of an oral dose gets absorbed — and when her titration was slowed, the symptoms resolved³.

One patient. One report. A hypothesis, not a finding, and the author says so plainly.

But it is a cheap thing to know, because it points somewhere useful: the effect is tied to the titration, and it is specific to estrogen that goes through your stomach. A patch or a gel does not take that route at all. If your hot flashes get worse the same week you step up a dose, that timing is worth saying out loud to whoever prescribes your HRT rather than assuming your menopause simply got worse on its own.

Midlife women are also, finally, starting to be studied as their own group rather than a subgroup — there is now work looking specifically at GLP-1s and midlife women's outcomes beyond weight⁴. Which tells you how new all of this still is.

What I actually ask about now

Three questions, and they are not the ones I asked at thirty-four:

• What is happening to my lean mass, and how would we know — is anyone measuring, or are we both watching a scale?
• If I am on oral HRT, does the titration schedule need to be slower?
• What does maintenance look like for someone whose body is changing underneath the medication anyway?

Where this left me

Still on it. Still lifting badly in the kitchen. The difference is that I stopped grading myself on the number and started asking what the number was made of — which is, I think, the only question that was ever specific to being forty-four instead of thirty-four.

None of this is medical advice, and I am a mom with a spreadsheet, not your clinician. GLP-1 medicines are not established as safe in pregnancy or while breastfeeding, and perimenopause does not mean you cannot get pregnant.