As GLP-1 medications gain attention for weight management, researchers investigate whether their effects extend to menstrual health, hormone regulation, and fertility in women with PCOS.
Reproductive and Gynecologic Effects of Glucagon-Like Peptide-1 Receptor Agonists in Women With Polycystic Ovary Syndrome: A Scoping Review. Image Credit: Pixel-Shot / Shutterstock
In a recent scoping review published in Cureus, researchers at Nova Southeastern University, Davie, USA, examined evidence on gynecologic and reproductive effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in polycystic ovary syndrome (PCOS).
PCOS, now referred to as polyendocrine metabolic ovarian syndrome (PMOS), is among the most common endocrine disorders in reproductive-aged females. It is also associated with obesity, dyslipidemia, insulin resistance, and a higher risk of diabetes. Lifestyle modification and weight management are central components of care for women with PCOS who have overweight or obesity, but sustaining weight reduction is often difficult.
Pharmacological treatments are increasingly used to manage metabolic dysfunction in PCOS. GLP-1RAs can improve glycemic control and promote weight reduction. Beyond their metabolic effects, GLP-1RAs may influence gynecologic and reproductive outcomes in subjects with PCOS. However, current literature remains diverse, with heterogeneity in interventions and endpoints.
About the study
In the present study, the researchers conducted a scoping review to characterize existing evidence on gynecologic and reproductive outcomes associated with GLP-1RA therapy in females with PCOS. First, they searched the Nursing and Allied Health Premium, Web of Science, Embase, and PubMed databases for studies assessing GLP-1RA treatment in females with PCOS and gynecologic or reproductive outcomes.
Reviews, letters, systematic reviews and meta-analyses, editorials, study protocols, and conference abstracts lacking sufficient outcome data were excluded. Two independent reviewers deduplicated the search results and screened them at the title/abstract level. Studies meeting eligibility criteria underwent full-text analysis. Relevant data were extracted from studies, including study and participant characteristics, interventions, treatment durations, comparators, outcomes, and principal findings.
Results were summarized narratively because study designs, treatments, outcome measures, and follow-up periods differed considerably. Outcomes of interest were ovulation, fertility, pregnancy, menstrual function, ovarian function, reproductive hormones, and hyperandrogenism. In addition, secondary metabolic outcomes were summarized.
Findings
Database searches identified 1,416 records. After deduplication, titles/abstracts of 697 unique records were screened, followed by full-text review of 76 articles, resulting in the inclusion of 28 studies. These studies assessed a wide range of gynecologic and reproductive outcomes following GLP-1RA treatment in subjects with PCOS. The most common GLP-1RAs were liraglutide, exenatide, and semaglutide, evaluated in 15, five, and four studies, respectively.
Menstrual function was assessed in 13 studies; three studies found improvements in menstrual frequency or regularity after GLP-1RA treatment, particularly among individuals with significant weight loss. Menstrual regularity was restored in a considerable proportion of individuals receiving liraglutide, exenatide, semaglutide, and combination treatment with metformin. Two studies found improvements in bleeding patterns and decreases in amenorrhea.
Other studies found no significant differences in menstrual outcomes. Further, fertility, pregnancy, and ovulation outcomes were examined in nine studies. Improved ovulation rates were observed after treatment with GLP-1RAs, particularly in combination with metformin. A small randomized pilot trial involving 28 women reported higher pregnancy rates during subsequent in vitro fertilization (IVF) after preconception treatment with liraglutide plus metformin than after metformin alone.
Individual reports described spontaneous conception after weight loss during GLP-1RA therapy, sometimes alongside other metabolic treatments.
The review did not assess pregnancy safety; separate clinical guidance recommends stopping GLP-1RAs before planned conception because pregnancy safety data remain limited.
Hyperandrogenism, assessed in 18 studies, was the reproductive outcome with the most consistent improvement. Multiple studies found significant decreases in total and free testosterone, androstenedione, and the free androgen index, with increases in sex hormone-binding globulin; some also reported lower luteinizing hormone after GLP-1RA treatment. Some studies also reported improvements in clinical manifestations, including hirsutism and acne, but results were inconsistent.
Two studies assessed ovarian morphology and function, with some favorable changes in ovarian volume but inconsistent findings for other ovarian measures. Other exploratory research described follicular development and endometrial gene-expression changes potentially relevant to implantation, without confirming improved receptivity. Nearly all studies examined metabolic outcomes and reported reductions in body mass index, body weight, and insulin resistance, alongside improved glucose regulation. Several reports suggested that reproductive and metabolic improvements coexisted. Few studies assessed whether reproductive changes occurred independently of weight loss and improved insulin sensitivity.
Conclusions
Taken together, the results suggest that GLP-1RA treatment may confer gynecologic and reproductive benefits in PCOS subjects, in addition to its established metabolic improvements. Biochemical markers of hyperandrogenism showed the most consistent improvement, followed by menstrual function, where findings varied. Evidence of benefit in fertility, pregnancy, and ovulation outcomes was relatively limited but promising.
Reproductive improvements often accompanied weight loss and reduced insulin resistance, but the underlying mechanisms remain uncertain. The study's limitations include the lack of critical appraisal and assessment of risk of bias and certainty of evidence, the restriction to English-language publications, and the inclusion of studies involving combination therapies or dual glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide receptor agonists.
Many studies also had smaller sample sizes, shorter follow-ups, or examined reproductive outcomes as secondary endpoints. Overall, while the evidence is encouraging, these limitations, along with substantial heterogeneity among studies and the coexistence of metabolic benefit, constrain efforts to determine the extent of reproductive improvements attributable to GLP-1RAs. Larger randomized trials should directly test reproductive outcomes and distinguish treatment effects from those of weight loss.
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