Animal studies suggest GLP-1 receptor agonists may negatively impact ovarian function, hormone levels, and uterine health, but no human fertility data exist for women without PCOS.
0 human studiesNo clinical trials have examined GLP-1 receptor agonist effects on fertility in women without PCOS, despite millions of prescriptions.
What the researchers found
In animal models, GLP-1 receptor agonists caused lower ovarian weights, increased follicular atresia (egg cell death), and reduced serum steroid levels. They also downregulated kiss-1 and kiss-1r expression in the hypothalamus, leading to lower luteinizing hormone levels and delayed puberty. In the uterus, these drugs negatively affected the epithelial lining, though they reduced fibrosis in an intrauterine adhesion model. No human studies on fertility outcomes in non-PCOS women have been published to date.
Why it matters
Millions of reproductive-aged women without PCOS are now using GLP-1 receptor agonists for weight loss. The absence of human fertility data for this population represents a significant knowledge gap, and the concerning animal findings highlight the urgent need for clinical research before widespread long-term use.
How the study worked
This was a narrative review that critically analyzed existing animal studies using different GLP-1 receptor agonists (liraglutide, exendin-4, dulaglutide) in rats and mice, administered via subcutaneous or intracerebral routes at varying doses and durations.
What this study cannot tell us
All reproductive findings come from animal models, which may not directly translate to humans. The animal studies used heterogeneous methods — different species, drug types, routes, and dosing protocols — making direct comparisons difficult. There are no prospective human clinical trials examining fertility endpoints in non-PCOS women taking GLP-1 RAs.
How to read the evidence
This is a narrative review of animal studies with no human clinical data. While it provides important mechanistic insights, the lack of human evidence limits the strength of any conclusions about real-world fertility risks.
When this study was published
Published in 2025, this review is highly current and addresses one of the most pressing questions in reproductive medicine given the rapid adoption of GLP-1 RA medications.
The bigger picture
As GLP-1 receptor agonists become some of the most prescribed medications globally, understanding their reproductive safety profile is critical. This review highlights that the fertility implications of these drugs are being studied mostly in PCOS populations, leaving a blind spot for the much larger group of healthy women using them purely for weight management.
Questions still open
- Do GLP-1 receptor agonists affect egg quality or ovarian reserve in women without PCOS?
- Are the reproductive effects reversible once the medication is discontinued?
- Could short-term use before conception carry different risks than long-term use?
Common questions
Can GLP-1 weight-loss drugs like semaglutide affect fertility?
Should women trying to conceive stop taking GLP-1 receptor agonists?
Read the original research
Impact of the injectable weight-loss medications, glucagon-like peptide-1 receptor agonists, on reproductive health in non-polycystic ovary syndrome state.
Current opinion in obstetrics & gynecology, 37(4), 175-181
Citation
Merhi, Zaher. (2025). Impact of the injectable weight-loss medications, glucagon-like peptide-1 receptor agonists, on reproductive health in non-polycystic ovary syndrome state.. Current opinion in obstetrics & gynecology, 37(4), 175-181. https://doi.org/10.1097/GCO.0000000000001044