Obesity, Polycystic Ovary Syndrome, and Infertility: A New Avenue for GLP-1 Receptor Agonists

Overview

Journal J Clin Endocrinol Metab

Publisher Oxford University Press

Specialty Endocrinology

Date 2020 May 23

PMID 32442310

Citations 94

Authors

Hellas Cena

Luca Chiovato

Rossella E Nappi

Affiliations

Soon will be listed here.

Abstract

Context: Obesity is responsible for an increased risk of sub-fecundity and infertility. Obese women show poorer reproductive outcomes regardless of the mode of conception, and higher body mass index (BMI) is associated with poorer fertility prognosis. Polycystic ovary syndrome (PCOS) is one of the leading causes of infertility, and many women with PCOS are also overweight or obese.

Evidence Acquisition: The aim of the present narrative review is to describe the mechanisms responsible for the development of infertility and PCOS in women with obesity/overweight, with a focus on the emerging role of glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1 RAs) as a therapeutic option for obese women with PCOS.

Evidence Synthesis: Weight reduction represents the most significant factor affecting fertility and pregnancy outcomes. Current experimental and clinical evidence suggests the presence of an underlying pathophysiological link between obesity, GLP-1 kinetic alterations, and PCOS pathogenesis. Based on the positive results in patients affected by obesity, with or without diabetes, the administration of GLP-1 RA (mainly liraglutide) alone or in combination with metformin has been investigated in women with obesity and PCOS. Several studies demonstrated significant weight loss and testosterone reduction, with mixed results relative to improvements in insulin resistance parameters and menstrual patterns.

Conclusions: The weight loss effects of GLP-1 RA offer a unique opportunity to expand the treatment options available to PCOS patients.

Citing Articles

Unveiling Gestational Diabetes: An Overview of Pathophysiology and Management.

Mittal R, Prasad K, Lemos J, Arevalo G, Hirani K Int J Mol Sci. 2025; 26(5).

PMID: 40076938 PMC: 11900321. DOI: 10.3390/ijms26052320.

A System-Based Review on Effects of Glucagon-Like Peptide-1 Receptor Agonists: Benefits vs Risks.

Fadel L, Thao G, Chitre T, Rojas E, Nguyen Fricko M, Domingo V Cureus. 2025; 17(2):e78575.

PMID: 40062098 PMC: 11888820. DOI: 10.7759/cureus.78575.

Neuropsychiatric adverse events associated with Glucagon-like peptide-1 receptor agonists: a pharmacovigilance analysis of the FDA Adverse Event Reporting System database.

Lu W, Wang S, Tang H, Yuan T, Zuo W, Liu Y Eur Psychiatry. 2025; 68(1):e20.

PMID: 39901452 PMC: 11823005. DOI: 10.1192/j.eurpsy.2024.1803.

Cardiovascular Risk Biomarkers in Women with and Without Polycystic Ovary Syndrome.

Nandakumar M, Das P, Sathyapalan T, Butler A, Atkin S Biomolecules. 2025; 15(1).

PMID: 39858399 PMC: 11763313. DOI: 10.3390/biom15010004.

Evaluating the effects of time-restricted eating on overweight and obese women with polycystic ovary syndrome: A randomized controlled trial study protocol.

Liu H, Shangguan F, Liu F, Guo Y, Yu H, Li H PLoS One. 2025; 20(1):e0316333.

PMID: 39787136 PMC: 11717230. DOI: 10.1371/journal.pone.0316333.

References

Kahal H, Aburima A, Ungvari T, Rigby A, Coady A, Vince R . The effects of treatment with liraglutide on atherothrombotic risk in obese young women with polycystic ovary syndrome and controls. BMC Endocr Disord. 2015; 15:14. PMC: 4389314. DOI: 10.1186/s12902-015-0005-6. View

Haqq L, McFarlane J, Dieberg G, Smart N . Effect of lifestyle intervention on the reproductive endocrine profile in women with polycystic ovarian syndrome: a systematic review and meta-analysis. Endocr Connect. 2014; 3(1):36-46. PMC: 3938041. DOI: 10.1530/EC-14-0010. View

. ACOG Practice Bulletin No 156: Obesity in Pregnancy. Obstet Gynecol. 2015; 126(6):e112-e126. DOI: 10.1097/AOG.0000000000001211. View

Baggio L, Drucker D . Biology of incretins: GLP-1 and GIP. Gastroenterology. 2007; 132(6):2131-57. DOI: 10.1053/j.gastro.2007.03.054. View

Wang B, Zhong J, Lin H, Zhao Z, Yan Z, He H . Blood pressure-lowering effects of GLP-1 receptor agonists exenatide and liraglutide: a meta-analysis of clinical trials. Diabetes Obes Metab. 2013; 15(8):737-49. DOI: 10.1111/dom.12085. View

Apridonidze T, Essah P, Iuorno M, Nestler J . Prevalence and characteristics of the metabolic syndrome in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2004; 90(4):1929-35. DOI: 10.1210/jc.2004-1045. View

Wise L, Rothman K, Mikkelsen E, Sorensen H, Riis A, Hatch E . An internet-based prospective study of body size and time-to-pregnancy. Hum Reprod. 2009; 25(1):253-64. PMC: 2794667. DOI: 10.1093/humrep/dep360. View

Jensterle Sever M, Kocjan T, Pfeifer M, Kravos N, Janez A . Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin. Eur J Endocrinol. 2013; 170(3):451-9. PMC: 3922503. DOI: 10.1530/EJE-13-0797. View

Broughton D, Moley K . Obesity and female infertility: potential mediators of obesity's impact. Fertil Steril. 2017; 107(4):840-847. DOI: 10.1016/j.fertnstert.2017.01.017. View

10.

Nylander M, Frossing S, Clausen H, Kistorp C, Faber J, Skouby S . Effects of liraglutide on ovarian dysfunction in polycystic ovary syndrome: a randomized clinical trial. Reprod Biomed Online. 2017; 35(1):121-127. DOI: 10.1016/j.rbmo.2017.03.023. View

11.

Elkind-Hirsch K, Marrioneaux O, Bhushan M, Vernor D, Bhushan R . Comparison of single and combined treatment with exenatide and metformin on menstrual cyclicity in overweight women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2008; 93(7):2670-8. DOI: 10.1210/jc.2008-0115. View

12.

Legro R, Dodson W, Kris-Etherton P, Kunselman A, Stetter C, Williams N . Randomized Controlled Trial of Preconception Interventions in Infertile Women With Polycystic Ovary Syndrome. J Clin Endocrinol Metab. 2015; 100(11):4048-58. PMC: 4702450. DOI: 10.1210/jc.2015-2778. View

13.

Jonasson J, Brismar K, Sparen P, Lambe M, Nyren O, Ostenson C . Fertility in women with type 1 diabetes: a population-based cohort study in Sweden. Diabetes Care. 2007; 30(9):2271-6. DOI: 10.2337/dc06-2574. View

14.

Wadden T, Hollander P, Klein S, Niswender K, Woo V, Hale P . Weight maintenance and additional weight loss with liraglutide after low-calorie-diet-induced weight loss: the SCALE Maintenance randomized study. Int J Obes (Lond). 2013; 37(11):1443-51. DOI: 10.1038/ijo.2013.120. View

15.

Galindo Munoz J, Jimenez Rodriguez D, Hernandez Morante J . Diurnal rhythms of plasma GLP-1 levels in normal and overweight/obese subjects: lack of effect of weight loss. J Physiol Biochem. 2014; 71(1):17-28. DOI: 10.1007/s13105-014-0375-7. View

16.

Escobar-Morreale H . Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment. Nat Rev Endocrinol. 2018; 14(5):270-284. DOI: 10.1038/nrendo.2018.24. View

17.

Clark A, Thornley B, Tomlinson L, Galletley C, Norman R . Weight loss in obese infertile women results in improvement in reproductive outcome for all forms of fertility treatment. Hum Reprod. 1998; 13(6):1502-5. DOI: 10.1093/humrep/13.6.1502. View

18.

Grundy S, Cleeman J, Daniels S, Donato K, Eckel R, Franklin B . Diagnosis and management of the metabolic syndrome. An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Executive summary. Cardiol Rev. 2006; 13(6):322-7. View

19.

Moran L, Noakes M, Clifton P, Wittert G, le Roux C, Ghatei M . Postprandial ghrelin, cholecystokinin, peptide YY, and appetite before and after weight loss in overweight women with and without polycystic ovary syndrome. Am J Clin Nutr. 2007; 86(6):1603-10. DOI: 10.1093/ajcn/86.5.1603. View

20.

Arusoglu G, Koksal G, Cinar N, Tapan S, Yazgan Aksoy D, Yildiz B . Basal and meal-stimulated ghrelin, PYY, CCK levels and satiety in lean women with polycystic ovary syndrome: effect of low-dose oral contraceptive. J Clin Endocrinol Metab. 2013; 98(11):4475-82. DOI: 10.1210/jc.2013-1526. View