Impact of the injectable weight-loss medications, glucagon-like peptide-1 receptor agonists, on reproductive health in non-polycystic ovary syndrome state.

Purpose of review: The use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) is on the rise and their impact on reproductive health in healthy women without polycystic ovary syndrome (PCOS) remains unclear. This review provides a critical analysis of existing data about their impact on reproduction in non-PCOS state.

Recent findings: To date, studies in animal models have been very heterogeneous using different models (rats versus mice) and different types of GLP-1 RAs (liraglutide versus exendin-4 versus dulaglutide), with variable modes of administration (subcutaneous versus intracerebral) and variable duration/dose of administration. In the ovaries, GLP-1 RA caused lower ovarian weights, more follicular atresia, and a drop in serum steroid levels. In the hypothalamus, GLP-1 RA caused downregulation in kiss-1 and kiss-1r expression leading to lower serum luteinizing hormone levels and delay in puberty. In the uterus, GLP-1 RAs caused a negative impact on the epithelium, however, in the intrauterine adhesion mouse model, they lowered uterine fibrosis. No human studies to examine the effect of GLP-1 RAs on fertility in women without PCOS have been published.

Summary: Further research is essential to understand the impact of GLP-1 RA in non-PCOS women, especially because many reproductive-aged women without PCOS are using these medications for weight loss.