Metabolic and hormonal effects
Reproductive health
Bone and cardiovascular health
Neuropsychiatric considerations
Future research and clinical implications
Conclusion
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) were initially developed to regulate blood glucose levels in patients with type 2 diabetes mellitus (T2DM). However, their therapeutic effects extend beyond glycemic control, particularly in weight management and metabolic disorders. Recently, GLP-1 RAs have gained prominence for their role in weight loss, leading to their approval for obesity treatment.1
Beyond diabetes and obesity, GLP-1 RAs exhibit a broad spectrum of physiological effects that significantly impact women's health. These include cardiovascular protection, neuroprotection, and metabolic regulation, which can influence conditions such as polycystic ovary syndrome (PCOS), non-alcoholic fatty liver disease (NAFLD), and osteoporosis.
Emerging evidence suggests that GLP-1 RAs modulate hormonal balance, lipid metabolism, and inflammatory pathways, offering potential therapeutic benefits in reproductive health and menopause-related metabolic changes. Furthermore, GLP-1 RAs have shown promise in reducing cancer risk, particularly in hormone-related malignancies such as breast and ovarian cancer.1
This article explores the unexpected effects of GLP-1 RAs on women’s health, highlighting their impact on metabolic, reproductive, cardiovascular, and neuropsychiatric health while identifying gaps in research and future clinical implications.
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Metabolic and hormonal effects
GLP-1 RAs have emerged as promising therapeutic agents in managing metabolic and hormonal disturbances in PCOS. Originally developed for T2D, these agents enhance insulin sensitivity by reducing insulin resistance, as demonstrated by significant declines in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) scores.
Improved insulin sensitivity is closely linked to favorable changes in body composition, such as decreased BMI and waist circumference, which are critical for PCOS patients who often present with obesity.2
Furthermore, GLP-1 RAs have been shown to modulate the hormonal milieu in PCOS. They contribute to a mild reduction in androgen levels, evidenced by decreases in total testosterone and dehydroepiandrosterone sulfate (DHEAS), while simultaneously increasing sex hormone binding globulin (SHBG) levels. These shifts help to restore a more balanced hormonal profile, potentially mitigating the hyperandrogenism that underlies many PCOS symptoms.2
In addition to metabolic and androgen improvements, GLP-1 RAs appear to influence menstrual cyclicity positively. Enhanced insulin sensitivity and direct effects on the hypothalamus-pituitary-ovarian axis may promote more regular ovulatory cycles and improved fertility outcomes.2
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Reproductive health
GLP-1RAs have demonstrated benefits in restoring ovulation, particularly in women with PCOS, by improving insulin sensitivity and reducing androgen levels. However, their impact on endometrial receptivity and implantation remains unclear.2,3
GLP-1RAs influence the hypothalamic-pituitary-ovarian axis, enhancing gonadotropin secretion and improving ovarian function. While this supports fertility, concerns persist about their effects on early pregnancy.
Limited data suggest GLP-1RAs may alter endometrial receptivity, potentially affecting implantation success rates. Animal studies indicate GLP-1RA treatment improves ovarian morphology in PCOS models, but human data are sparse.2,3
During pregnancy, GLP-1RAs may impact fetal development due to their metabolic effects. Current guidelines advise discontinuation before conception due to unknown teratogenic risks. Furthermore, their influence on placental function and fetal growth requires further investigation.3
Overall, GLP-1RAs offer promise in reproductive medicine, particularly for obesity-related infertility. However, their safety and efficacy in pregnancy require more research to determine optimal use in fertility treatments and assisted reproduction technologies (ART).3
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Bone and cardiovascular health
GLP-1RAs influence bone metabolism by promoting bone formation and reducing resorption, potentially mitigating osteoporosis risk. However, some studies indicate an increased risk of fractures, possibly due to weight loss-associated reductions in bone mineral density (BMD).4
Postmenopausal women, already at heightened risk for osteoporosis, may benefit from GLP-1RAs’ anabolic effects on bone, yet data on long-term fracture risk remain inconclusive.
The cardiovascular benefits of GLP-1RAs are well-established, with clinical trials demonstrating reductions in major adverse cardiovascular events (MACE), improved endothelial function, and lower blood pressure. These benefits are particularly relevant for women who often present with atypical cardiovascular symptoms and higher heart failure risk.4,5
Despite these advantages, concerns about potential adverse effects, including gastrointestinal intolerance and possible cardiovascular adaptations that may influence bone health, warrant further investigation.
A personalized approach considering individual bone and cardiovascular risk profiles is essential when prescribing GLP-1RAs to women, particularly those with osteoporosis or high cardiovascular risk.4,5
Role of GLP-1 Receptor Agonists for Weight Loss
Neuropsychiatric considerations
Emerging reports indicate potential neuropsychiatric effects of GLP-1RAs, including mood changes, appetite suppression, and cognitive function implications. Patients have reported both positive and negative mood alterations.
Some individuals experience improved well-being, reduced anxiety, and better emotional stability, potentially linked to weight loss and metabolic improvements. Conversely, others report increased depression, anxiety, and, in some cases, suicidal thoughts. The European Medicines Agency (EMA) has begun monitoring these concerns.6
GLP-1RAs significantly reduce appetite, which may help control compulsive eating behaviors. Notably, some users report a reduction in cravings for not just food but also substances like alcohol and nicotine, suggesting a potential role in managing addictive behaviors.6
Preliminary evidence indicates that GLP-1RAs may influence cognitive function by modulating neurotransmitters and inflammation. Some users report clearer thinking and improved focus, while others experience brain fog or fatigue, potentially linked to hypoglycemia.
While GLP-1RAs offer substantial benefits, their psychological impact requires further investigation to ensure long-term safety.6
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Future research and clinical implications
Current studies focus on short-term efficacy, but gaps persist regarding the impact on reproductive health, hormonal balance, and bone density over prolonged use. Ongoing research aims to assess GLP-1 RAs’ influence on menstrual irregularities, fertility, and pregnancy outcomes.
Given their appetite-suppressing properties, concerns arise about potential nutritional deficiencies and their consequences on maternal and fetal health. Additionally, their effects on postmenopausal women, especially regarding osteoporosis risk, warrant further investigation.7
The metabolic and cardiovascular benefits of GLP-1 RAs are evident, yet sex-specific responses remain unclear. Women’s hormonal fluctuations may alter drug efficacy and side effect profiles, necessitating gender-stratified trials. Furthermore, the psychosocial impact, particularly in those with eating disorders, requires careful evaluation.7
Future research should prioritize longitudinal studies to determine safety and effectiveness in diverse female populations.
Tailored dosing and monitoring guidelines must be developed to mitigate risks while maximizing benefits. Addressing these gaps is critical to ensuring that GLP-1 RAs serve as a safe and effective intervention for women’s metabolic health.7
Conclusion
Current evidence supports the efficacy of GLP-1 RAs in managing T2DM and obesity, with additional benefits for cardiovascular and renal health. However, specific considerations are necessary for women, including reproductive health, pregnancy, and long-term metabolic outcomes.
While GLP-1 medications show promising weight loss effects and glycemic control, their safety in pregnancy remains uncertain, necessitating alternative therapeutic approaches for women of childbearing age.
Emerging research focuses on optimizing GLP-1 therapies through combination treatments, novel oral formulations, and personalized medicine approaches. Investigations into sex-specific metabolic responses, hormonal influences, and potential long-term adverse effects are crucial for refining treatment guidelines. Moreover, research into GLP-1’s impact on PCOS, menopausal metabolic shifts, and osteoporosis risk is gaining attention.
Clinicians should adopt an individualized approach, considering patient-specific factors such as age, reproductive plans, comorbidities, and tolerance. Ongoing trials and real-world data will further shape best practices, ensuring the safe and effective use of GLP-1 medications in women.
Collaborative, interprofessional care remains essential in maximizing benefits while mitigating risks associated with this drug class.
References
- Zhao, X., Wang, M., Wen, Z., Lu, Z., Cui, L., Fu, C., Xue, H., Liu, Y. and Zhang, Y. (2021). GLP-1 receptor agonists: beyond their pancreatic effects. Frontiers in endocrinology, 12, 721135.
- Zhou, L., Qu, H., Yang, L., & Shou, L. (2023). Effects of GLP1RAs on pregnancy rate and menstrual cyclicity in women with polycystic ovary syndrome: a meta-analysis and systematic review. BMC Endocrine Disorders, 23(1), 245.
- Sola‐Leyva, A., Pathare, A. D., Apostolov, A., Aleksejeva, E., Kask, K., Tammiste, T., ... & Salumets, A. (2025). The hidden impact of GLP‐1 receptor agonists on endometrial receptivity and implantation. Acta Obstetricia et Gynecologica Scandinavica, 104(2), 258-266.
- Xie, B., Chen, S., Xu, Y., Han, W., Hu, R., Chen, M., Zhang, Y. and Ding, S. (2021). The impact of glucagon-like peptide 1 receptor agonists on bone metabolism and its possible mechanisms in osteoporosis treatment. Frontiers in Pharmacology, 12, 697442.
- Ferhatbegović, L., Mršić, D., & Macić-Džanković, A. (2023). The benefits of GLP1 receptors in cardiovascular diseases. Frontiers in clinical diabetes and healthcare, 4, 1293926.
- Arillotta, D., Floresta, G., Guirguis, A., Corkery, J.M., Catalani, V., Martinotti, G., Sensi, S.L. and Schifano, F. (2023). GLP-1 receptor agonists and related mental health issues; insights from a range of social media platforms using a mixed-methods approach. Brain sciences, 13(11), 1503.
- Cooper, D. M., Rothstein, M. A., Amin, A., Hirsch, J. D., & Cooper, E. (2023). Unintended consequences of glucagon-like peptide-1 receptor agonists medications in children and adolescents: a call to action. Journal of Clinical and Translational Science, 7(1), e184.https://doi.org/10.1017/cts.2023.612
Further Reading