GLP-1 peptides for endometriosis: hype vs. actual evidence

What did @the_endolls actually say?

The creator, who identifies as someone living with endometriosis and adenomyosis, made a case for a specific peptide "stack" including tirzepatide, KPV, and SS-31. The core argument was nuanced: tirzepatide may help some women with endometriosis, but only those with overlapping metabolic dysfunction. More provocatively, she warned that "GLP-1 receptor signaling is not universally anti-growth" and that in certain disease contexts, GLP-1 activation could theoretically push growth-promoting pathways, specifically PI3K, AKT, and mTOR, in endometriosis lesions that share "cancer-like behavior." She was careful to say she is not claiming GLP-1 drugs definitely fuel endometriosis, but that assuming they are neutral in every phenotype would be "lazy."

Does the science back this up?

On the metabolic overlap between PCOS and endometriosis, yes, largely. On the GLP-1 growth signaling concern in endometriosis tissue specifically, the evidence is thin, speculative, and extrapolated from unrelated disease models. That does not automatically make her wrong, but it does mean she is presenting hypothesis as near-established risk.

The PCOS-insulin-GLP-1 connection is well documented. A 2022 meta-analysis by Elkind-Hirsch et al. in Fertility and Sterility confirmed GLP-1 receptor agonists improve ovulation rates and metabolic markers in women with PCOS and insulin resistance. That part of her argument is solid ground.

Her claim that endometriosis is not "primarily an insulin resistance disease" is accurate. A 2021 review by Falconer et al. in Human Reproduction Update describes endometriosis as driven by local estrogen synthesis, progesterone resistance, immune dysregulation, and neuroangiogenesis, not primarily glucose metabolism.

The GLP-1 growth signaling concern is where the evidence gets murky. Studies showing GLP-1 receptor activation stimulating PI3K-AKT pathways come mostly from pancreatic beta-cell and certain cancer cell line research, not endometriosis tissue. Applying that logic to endo lesions is an extrapolation, a reasonable one to flag, but an extrapolation nonetheless.

What did they get wrong (or right)?

She got a lot right, and deserves credit for it. Most peptide content on TikTok skips phenotype entirely. The fact that she separated PCOS-dominant endometriosis from lean, non-insulin-resistant endometriosis is clinically meaningful and reflects real heterogeneity in the literature.

Where she overcooks it: the framing of GLP-1 drugs potentially "feeding endometriosis" is stated with a confidence level that outpaces the evidence. There is currently no published clinical data showing tirzepatide or semaglutide promotes endometriosis lesion growth in humans. The mechanistic concern she raises, GLP-1 receptor expression in endometrial stromal cells activating proliferative signaling, has not been specifically studied in endometriosis tissue in peer-reviewed literature as of early 2025.

She also promotes KPV and SS-31 as part of a "stack" without acknowledging that neither peptide has any published clinical trial evidence in endometriosis or adenomyosis. SS-31 (elamipretide) has early-stage mitochondrial research, mostly in cardiac and renal tissue. KPV has preclinical anti-inflammatory data in gut models. Presenting these alongside tirzepatide as a coherent treatment strategy for endo is not supported by evidence.

What should you actually know?

GLP-1 drugs are not endometriosis treatments. They are metabolic drugs with documented benefits in insulin resistance, PCOS, and obesity-related inflammation. If you have endometriosis and also have insulin resistance, PCOS, or significant metabolic dysfunction, a GLP-1 agonist might reduce systemic inflammatory burden. That is a plausible, indirect benefit, not a disease-modifying treatment for endometriosis itself.

The phenotype argument she makes is genuinely useful. A lean woman with no metabolic dysfunction, high estrogen-driven lesion activity, and no PCOS overlap is not the same patient as someone with endo, PCOS, and insulin resistance. Treating them identically is bad medicine. On that point, she is ahead of most TikTok health creators.

What is missing entirely: there is no mention of consulting a reproductive endocrinologist or endometriosis specialist before adding any of these compounds. Tirzepatide is a prescription medication. KPV and SS-31 are unregulated research peptides not approved by the FDA for any indication. None of these should be self-prescribed based on a social media video, regardless of how medically literate that video sounds.