Location
Suwanee, GA
Start Date
17-4-2026 12:00 PM
End Date
17-4-2026 1:00 PM
Description
Introduction
Obesity is a major modifiable risk factor for reproductive dysfunction and is associated with anovulation and polycystic ovary syndrome (PCOS) in women, as well as hypogonadism and impaired semen quality in men. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), originally developed for the management of diabetes and obesity, have demonstrated potential reproductive benefits that extend beyond weight reduction. GLP-1 receptors are distributed throughout key components of the reproductive axis, including the hypothalamus, pituitary, gonads, and endometrium, suggesting possible direct effects on reproductive tissues. This review synthesizes current evidence regarding the mechanisms and clinical outcomes through which GLP-1 RAs may enhance fertility in both sexes.
Methods
This narrative review integrates findings from systematic reviews, meta-analyses, randomized controlled trials, and preclinical studies evaluating the effects of GLP-1 receptor agonists on reproductive outcomes through 2026. Primary outcomes assessed included menstrual regularity, pregnancy rates, hormonal parameters (testosterone, luteinizing hormone [LH], follicle-stimulating hormone [FSH], androgens), and semen quality. Both weight loss-dependent and direct GLP-1 receptor-mediated mechanisms affecting the reproductive axis were evaluated.
Results
Female Fertility
In women with obesity and polycystic ovary syndrome (PCOS), meta-analyses demonstrate that liraglutide increases menstrual frequency (SMD: 1.76, 95% CI 0.28-3.24) and spontaneous pregnancy rates (RR: 1.72, 95% CI 1.22-2.43) compared with metformin or placebo. Liraglutide therapy has also been associated with significant reductions in body mass index (BMI), improved insulin resistance (HOMA-IR), decreased luteinizing hormone (LH) and free androgen index, and increased sex hormone-binding globulin (SHBG).
Preclinical studies suggest additional direct reproductive effects, including hypothalamic stimulation of LH secretion, anti-inflammatory actions within the endometrium, and reversal of polycystic ovarian morphology. Experimental models further implicate modulation of the hypothalamic RASA1/Ras/AKT/GnRH signaling pathway as a potential mechanism through which GLP-1 receptor agonists restore hypothalamic-pituitary-gonadal (HPG) axis homeostasis in PCOS.
Male Fertility
In men with obesity, diabetes, or functional hypogonadism, GLP-1 receptor agonists have been associated with consistent increases in total testosterone while preserving or increasing luteinizing hormone (LH) and follicle-stimulating hormone (FSH), in contrast to testosterone replacement therapy. Systematic reviews also report improvements in sperm motility and concentration in metabolically compromised men, although these benefits have not been consistently observed in otherwise healthy individuals.
Preclinical studies further demonstrate enhanced spermatogenesis through activation of cAMP/PKA and PI3K/Akt signaling pathways, with GLP-1 receptors highly expressed in Leydig cells, suggesting a potential direct testicular mechanism.
Discussion
GLP-1 receptor agonists may improve fertility through both metabolic improvements and direct effects on reproductive tissues. In women with PCOS, reductions in hyperinsulinemia-driven androgen production, along with direct hypothalamic effects, may help restore ovulatory cycles. In men with metabolic dysfunction, GLP-1 receptor agonists increase endogenous testosterone while maintaining gonadotropin function, thereby preserving fertility potential, unlike testosterone replacement therapy.
Important limitations include an incomplete understanding of the relative contributions of weight loss versus direct receptor-mediated mechanisms, as well as limited long-term reproductive safety data. GLP-1 receptor agonists are contraindicated during pregnancy because of potential fetal toxicity, necessitating appropriate contraception and discontinuation of therapy prior to conception.
Embargo Period
6-1-2026
Included in
GLP-1 Receptor Agonists and Fertility. Metabolic and Direct Reproductive Mechanisms in Obesity-Related Infertility
Suwanee, GA
Introduction
Obesity is a major modifiable risk factor for reproductive dysfunction and is associated with anovulation and polycystic ovary syndrome (PCOS) in women, as well as hypogonadism and impaired semen quality in men. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), originally developed for the management of diabetes and obesity, have demonstrated potential reproductive benefits that extend beyond weight reduction. GLP-1 receptors are distributed throughout key components of the reproductive axis, including the hypothalamus, pituitary, gonads, and endometrium, suggesting possible direct effects on reproductive tissues. This review synthesizes current evidence regarding the mechanisms and clinical outcomes through which GLP-1 RAs may enhance fertility in both sexes.
Methods
This narrative review integrates findings from systematic reviews, meta-analyses, randomized controlled trials, and preclinical studies evaluating the effects of GLP-1 receptor agonists on reproductive outcomes through 2026. Primary outcomes assessed included menstrual regularity, pregnancy rates, hormonal parameters (testosterone, luteinizing hormone [LH], follicle-stimulating hormone [FSH], androgens), and semen quality. Both weight loss-dependent and direct GLP-1 receptor-mediated mechanisms affecting the reproductive axis were evaluated.
Results
Female Fertility
In women with obesity and polycystic ovary syndrome (PCOS), meta-analyses demonstrate that liraglutide increases menstrual frequency (SMD: 1.76, 95% CI 0.28-3.24) and spontaneous pregnancy rates (RR: 1.72, 95% CI 1.22-2.43) compared with metformin or placebo. Liraglutide therapy has also been associated with significant reductions in body mass index (BMI), improved insulin resistance (HOMA-IR), decreased luteinizing hormone (LH) and free androgen index, and increased sex hormone-binding globulin (SHBG).
Preclinical studies suggest additional direct reproductive effects, including hypothalamic stimulation of LH secretion, anti-inflammatory actions within the endometrium, and reversal of polycystic ovarian morphology. Experimental models further implicate modulation of the hypothalamic RASA1/Ras/AKT/GnRH signaling pathway as a potential mechanism through which GLP-1 receptor agonists restore hypothalamic-pituitary-gonadal (HPG) axis homeostasis in PCOS.
Male Fertility
In men with obesity, diabetes, or functional hypogonadism, GLP-1 receptor agonists have been associated with consistent increases in total testosterone while preserving or increasing luteinizing hormone (LH) and follicle-stimulating hormone (FSH), in contrast to testosterone replacement therapy. Systematic reviews also report improvements in sperm motility and concentration in metabolically compromised men, although these benefits have not been consistently observed in otherwise healthy individuals.
Preclinical studies further demonstrate enhanced spermatogenesis through activation of cAMP/PKA and PI3K/Akt signaling pathways, with GLP-1 receptors highly expressed in Leydig cells, suggesting a potential direct testicular mechanism.
Discussion
GLP-1 receptor agonists may improve fertility through both metabolic improvements and direct effects on reproductive tissues. In women with PCOS, reductions in hyperinsulinemia-driven androgen production, along with direct hypothalamic effects, may help restore ovulatory cycles. In men with metabolic dysfunction, GLP-1 receptor agonists increase endogenous testosterone while maintaining gonadotropin function, thereby preserving fertility potential, unlike testosterone replacement therapy.
Important limitations include an incomplete understanding of the relative contributions of weight loss versus direct receptor-mediated mechanisms, as well as limited long-term reproductive safety data. GLP-1 receptor agonists are contraindicated during pregnancy because of potential fetal toxicity, necessitating appropriate contraception and discontinuation of therapy prior to conception.