GLP-1 Receptor Agonists and Female Reproductive Health: Mechanisms Underlying Endocrine, Ovarian, and Oocyte-Related Modifications

Panayiotis Michael Zavos, Carmen Teresa Navarro, Pedro Torrecillas Cabrera, Cesare Aragona, Maria Salomé Bezerra-Espínola, Ritu Santwani, Shady Abdelsattar Saleem, Denisa Protopopescu.

Abstract

Background and Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used by women of reproductive age, given the close relationship between energy balance, insulin sensitivity, ovarian steroidogenesis, and fertility. This narrative review synthesizes human, mechanistic, and regulatory evidence on how GLP-1 signaling and GLP-1RA treatment may influence the female reproductive axis, focusing on obesity, polycystic ovary syndrome (PCOS), menstrual function, follicular biology, assisted reproduction, and reproductive safety, and clarifies which claims are supported by direct human endpoints versus mechanistic plausibility alone.

Materials and Methods: A structured, non-systematic search of PubMed/MEDLINE, Embase, and the Cochrane Library was conducted for records published between January 2014 and September 2026, supplemented by reference-list screening and current prescribing information. Studies were stratified by evidence level using GRADE certainty principles for pooled endpoints and Oxford Centre for Evidence-Based Medicine (OCEBM) levels for individual study designs.

Results: The strongest human evidence concerns women with PCOS and/or obesity, in whom liraglutide and exenatide have been associated with weight reduction and improvements in menstrual frequency and short-term spontaneous pregnancy rates. However, later follow-up and a 2026 meta-analysis rated as low-certainty evidence show heterogeneous reproductive effects, and evidence for live birth, ovarian reserve, and direct oocyte benefit remains inadequate. Experimental studies suggest GLP-1 signaling may modify granulosa-cell inflammation and follicular development, but this does not prove that GLP-1RAs improve human oocyte competence. Current labeling recommends discontinuing semaglutide before planned pregnancy and tirzepatide once pregnancy is recognized; emerging pregnancy safety data are reassuring but still insufficient to establish routine safety.

Conclusions: GLP-1RAs should presently be viewed as metabolic and preconception tools for selected women with obesity-related reproductive dysfunction, especially PCOS, rather than as established fertility or oocyte-quality therapies, and metabolic optimization before conception must be clearly distinguished from pharmacological treatment during pregnancy.