The Impact of GLP-1 Receptor Agonists on Semen Parameters and the Hypothalamic–Pituitary–Gonadal Axis in Men with Obesity — A Literature Review
DOI:
https://doi.org/10.12775/QS.2026.71.75106Keywords
GLP-1, semaglutide, liraglutide, tirzepatide, semen quality, male infertility, obesity, functional hypogonadism, weight loss, physical activityAbstract
Background. Rising global obesity prevalence has coincided with a debated decline in semen quality. GLP-1 receptor agonists (GLP-1 RAs) are now widely used for weight reduction in men of reproductive age, raising questions about their effect on fertility, particularly relative to testosterone replacement therapy (TRT), which suppresses spermatogenesis.
Aim. To review evidence on GLP-1 RAs and the male reproductive system, focusing on semen parameters and the hypothalamic-pituitary-gonadal axis, and whether effects are drug-specific or mediated by weight loss.
Material and methods. Narrative review of PubMed, Scopus and Web of Science on GLP-1 RAs, semen quality, male fertility, testosterone, functional hypogonadism, obesity and weight loss, with reference-list screening and ClinicalTrials.gov. English-language studies only; no time restriction.
Results. GLP-1 receptors are expressed in human testis and spermatozoa. Obesity impairs semen quality via endocrine, inflammatory and thermal mechanisms. GLP-1 RAs raise testosterone while preserving gonadotropic function, unlike TRT; a randomized trial showed semaglutide improved sperm morphology while testosterone worsened sperm count. Weight loss, not the drug itself, appears the principal mediator, as exercise gave comparable benefit to liraglutide. Bariatric surgery did not reliably improve semen quality. Sexual-function data remain conflicting. Evidence is limited by small samples and short follow-up.
Conclusions. GLP-1 RAs appear reproductively safe and may improve semen parameters in men with obesity-related functional hypogonadism, offering a fertility-sparing alternative to TRT. Benefit is largely attributable to weight loss; lifestyle intervention remains reasonable first-line. Larger, longer trials, including tirzepatide, are needed.
References
1. Carlsen E, Giwercman A, Keiding N, Skakkebaek NE. Evidence for decreasing quality of semen during past 50 years. BMJ. 1992;305:609–13. https://doi:10.1136/bmj.305.6854.609
2. Levine H, Jørgensen N, Martino-Andrade A, Mendiola J, Weksler-Derri D, Mindlis I, et al. Temporal trends in sperm count: a systematic review and meta-regression analysis. Hum Reprod Update. 2017;23:646–59. https://doi:10.1093/humupd/dmx022
3. Abarca-Gómez L, Abdeen ZA, Hamid ZA, Abu-Rmeileh NM, Acosta-Cazares B, Acuin C, et al. Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128·9 million children, adolescents, and adults. Lancet. 2017;390:2627–42. https://doi:10.1016/S0140-6736(17)32129-3
4. Sermondade N, Faure C, Fezeu L, Shayeb AG, Bonde JP, Jensen TK, et al. BMI in relation to sperm count: an updated systematic review and collaborative meta-analysis. Hum Reprod Update. 2013;19:221–31. https://doi:10.1093/humupd/dms050
5. Salas-Huetos A, Maghsoumi-Norouzabad L, James ER, Carrell DT, Aston KI, Jenkins TG, et al. Male adiposity, sperm parameters and reproductive hormones: An updated systematic review and collaborative meta-analysis. Obes Rev. 2021;22:e13082. https://doi:10.1111/obr.13082
6. Andersen JM, Herning H, Aschim EL, Hjelmesæth J, Mala T, Hanevik HI, et al. Body Mass Index Is Associated with Impaired Semen Characteristics and Reduced Levels of Anti-Müllerian Hormone across a Wide Weight Range. PLOS ONE. 2015;10:e0130210. https://doi:10.1371/journal.pone.0130210
7. Hernáez Á, Rogne T, Skåra KH, Håberg SE, Page CM, Fraser A, et al. Body mass index and subfertility: multivariable regression and Mendelian randomization analyses in the Norwegian Mother, Father and Child Cohort Study. Hum Reprod. 2021;36:3141–51. https://doi:10.1093/humrep/deab224
8. Service CA, Puri D, Al Azzawi S, Hsieh TC, Patel DP. The impact of obesity and metabolic health on male fertility: a systematic review. Fertil Steril. 2023;120:1098–111. https://doi:10.1016/j.fertnstert.2023.10.017
9. Lincoff AM, Brown-Frandsen K, Colhoun HM, Deanfield J, Emerson SS, Esbjerg S, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. N Engl J Med. 2023;389:2221–32. https://doi:10.1056/NEJMoa2307563
10. Orra SH, Martinez JVN, Porto BC, Passerotti CC, Sardenberg RAS, Da Cruz JAS. Effect of GLP-1 agonists on testosterone levels: a systematic review and meta-analysis. BMC Urol. 2025;25:311. https://doi:10.1186/s12894-025-02005-0
11. Cohen PG. The hypogonadal–obesity cycle: role of aromatase in modulating the testosterone–estradiol shunt – a major factor in the genesis of morbid obesity. Med Hypotheses. 1999;52:49–51. https://doi:10.1054/mehy.1997.0624
12. Fernandez CJ, Chacko EC, Pappachan JM. Male Obesity-related Secondary Hypogonadism – Pathophysiology, Clinical Implications and Management. Eur Endocrinol. 2019;15:83. https://doi:10.17925/EE.2019.15.2.83
13. Cooper LA, Page ST, Amory JK, Anawalt BD, Matsumoto AM. The association of obesity with sex hormone-binding globulin is stronger than the association with ageing – implications for the interpretation of total testosterone measurements. Clin Endocrinol (Oxf). 2015;83:828–33. https://doi:10.1111/cen.12768
14. Garolla A, Torino M, Miola P, Caretta N, Pizzol D, Menegazzo M, et al. Twenty-four-hour monitoring of scrotal temperature in obese men and men with a varicocele as a mirror of spermatogenic function. Hum Reprod. 2015;30:1006–13. https://doi:10.1093/humrep/dev057
15. Garolla A, Torino M, Sartini B, Cosci I, Patassini C, Carraro U, et al. Seminal and molecular evidence that sauna exposure affects human spermatogenesis. Hum Reprod. 2013;28:877–85. https://doi:10.1093/humrep/det020
16. Oroojan AA, Etedali H, Shirani Lapari H. A systematic review on the impact of type 2 diabetes on Leydig and Sertoli cells: Molecular mechanisms and functional consequences. Diabetes Metab Syndr Clin Res Rev. 2026;20:103423. https://doi:10.1016/j.dsx.2026.103423
17. Leisegang K, Henkel R. The in vitro modulation of steroidogenesis by inflammatory cytokines and insulin in TM3 Leydig cells. Reprod Biol Endocrinol. 2018;16:26. https://doi:10.1186/s12958-018-0341-2
18. Caltabiano R, Condorelli D, Panza S, Boitani C, Musso N, Ježek D, et al. Glucagon-like peptide-1 receptor is expressed in human and rodent testis. Andrology. 2020;8:1935–45. https://doi:10.1111/andr.12871
19. Rago V, De Rose D, Santoro M, Panza S, Malivindi R, Andò S, et al. Human Sperm Express the Receptor for Glucagon-like Peptide-1 (GLP-1), Which Affects Sperm Function and Metabolism. Endocrinology. 2020;161:bqaa031. https://doi:10.1210/endocr/bqaa031
20. Izzi-Engbeaya C, Jones S, Crustna Y, Machenahalli PC, Papadopoulou D, Modi M, et al. Effects of Glucagon-like Peptide-1 on the Reproductive Axis in Healthy Men. J Clin Endocrinol Metab. 2020;105:1119–25. https://doi:10.1210/clinem/dgaa072
21. Kuchakulla M, Poppas PJ, Wald G, Masterson JM, Gurayah AA, Bhambhvani HP, et al. Impact of GLP-1 Receptor Agonists on Male Fertility: Emerging Evidence and Future Directions. Urology. 2026;213:9–17. https://doi:10.1016/j.urology.2025.09.038
22. Yin D, Li F, Xia L, Wei T, Shan C, Zhang Z, et al. GLP-1 receptor agonists show no detrimental effect on sperm quality in mouse models and cell lines. Endocrine. 2025;89:614–26. https://doi:10.1007/s12020-025-04245-4
23. Du Plessis SS, Omolaoye TS, Cardona Maya WD. Potential impact of GLP-1 receptor agonists on male fertility: a fable of caution. Front Physiol. 2024;15:1496416. https://doi:10.3389/fphys.2024.1496416
24. Deameh MG, Ramez M, Rowaiee R, Bani Irshid BA, Mohamed H, Abdelshafi A, et al. Effects of glucagon-like peptide-1 receptor agonists on male reproductive hormones, semen parameters, and metabolic outcomes: a systematic review. J Sex Med. 2026;23:qdaf381. https://doi:10.1093/jsxmed/qdaf381
25. Gregorič N, Šikonja J, Janež A, Jensterle M. Semaglutide improved sperm morphology in obese men with type 2 diabetes mellitus and functional hypogonadism. Diabetes Obes Metab. 2025;27:519–28. https://doi:10.1111/dom.16042
26. Lengsfeld S, Probst L, Emara Y, Werlen L, Vogt DR, Bathelt C, et al. Effects of the glucagon-like peptide-1 receptor agonist dulaglutide on sexuality in healthy men: a randomised, double-blind, placebo-controlled crossover study. eBioMedicine. 2024;107:105284. https://doi:10.1016/j.ebiom.2024.105284
27. La Vignera S, Condorelli RA, Calogero AE, Cannarella R, Aversa A. Sexual and Reproductive Outcomes in Obese Fertile Men with Functional Hypogonadism after Treatment with Liraglutide: Preliminary Results. J Clin Med. 2023;12:672. https://doi:10.3390/jcm12020672
28. Fontoura P, Cardoso MCDA, Erthal-Martins MC, Werneck C, Sartorio C, Ramos CF. The effects of liraglutide on male fertility: a case report. Reprod Biomed Online. 2014;29:644–6. https://doi:10.1016/j.rbmo.2014.07.009
29. Andersen E, Juhl CR, Kjøller ET, Lundgren JR, Janus C, Dehestani Y, et al. Sperm count is increased by diet-induced weight loss and maintained by exercise or GLP-1 analogue treatment: a randomized controlled trial. Hum Reprod. 2022;37:1414–22. https://doi:10.1093/humrep/deac096
30. Jensen SBK, Lundgren JR, Janus C, Juhl CR, Olsen LM, Rosenkilde M, et al. Protocol for a randomised controlled trial of the combined effects of the GLP-1 receptor agonist liraglutide and exercise on maintenance of weight loss and health after a very low-calorie diet. BMJ Open. 2019;9:e031431. https://doi:10.1136/bmjopen-2019-031431
31. Lundgren JR, Janus C, Jensen SBK, Juhl CR, Olsen LM, Christensen RM, et al. Healthy Weight Loss Maintenance with Exercise, Liraglutide, or Both Combined. N Engl J Med. 2021;384:1719–30. https://doi:10.1056/NEJMoa2028198
32. Håkonsen LB, Thulstrup AM, Aggerholm AS, Olsen J, Bonde JP, Andersen CY, et al. Does weight loss improve semen quality and reproductive hormones? results from a cohort of severely obese men. Reprod Health. 2011;8:24. https://doi:10.1186/1742-4755-8-24
33. Faure C, Dupont C, Baraibar MA, Ladouce R, Cedrin-Durnerin I, Wolf JP, et al. In Subfertile Couple, Abdominal Fat Loss in Men Is Associated with Improvement of Sperm Quality and Pregnancy: A Case-Series. PLOS ONE. 2014;9:e86300. https://doi:10.1371/journal.pone.0086300
34. Mir J, Franken D, Andrabi SW, Ashraf M, Rao K. Impact of weight loss on sperm DNA integrity in obese men. Andrologia. 2018;50:e12957. https://doi:10.1111/and.12957
35. Best D, Avenell A, Bhattacharya S. How effective are weight-loss interventions for improving fertility in women and men who are overweight or obese? A systematic review and meta-analysis of the evidence. Hum Reprod Update. 2017;23:681–705. https://doi:10.1093/humupd/dmx027
36. Rosety MÁ, Díaz AJ, Rosety JM, Pery MT, Brenes-Martín F, Bernardi M, et al. Exercise improved semen quality and reproductive hormone levels in sedentary obese adults. Nutr Hosp. 2017;34:603. https://doi:10.20960/nh.549
37. Sun B, Messerlian C, Sun ZH, Duan P, Chen HG, Chen YJ, et al. Physical activity and sedentary time in relation to semen quality in healthy men screened as potential sperm donors. Hum Reprod. 2019;34:2330–9. https://doi:10.1093/humrep/dez226
38. Pärn T, Grau Ruiz R, Kunovac Kallak T, Ruiz JR, Davey E, Hreinsson J, et al. Physical activity, fatness, educational level and snuff consumption as determinants of semen quality: findings of the ActiART study. Reprod Biomed Online. 2015;31:108–19. https://doi:10.1016/j.rbmo.2015.03.004
39. Lazaros L, Hatzi E, Markoula S, Takenaka A, Sofikitis N, Zikopoulos K, et al. Dramatic reduction in sperm parameters following bariatric surgery: report of two cases. Andrologia. 2012;44:428–32. https://doi:10.1111/j.1439-0272.2012.01300.x
40. Samavat J, Cantini G, Lotti F, Di Franco A, Tamburrino L, Degl’Innocenti S, et al. Massive Weight Loss Obtained by Bariatric Surgery Affects Semen Quality in Morbid Male Obesity: a Preliminary Prospective Double-Armed Study. Obes Surg. 2018;28:69–76. https://doi:10.1007/s11695-017-2802-7
41. Wei Y, Chen Q, Qian W. Effect of Bariatric Surgery on Semen Parameters: A Systematic Review and Meta-Analysis. Med Sci Monit Basic Res. 2018;24:188–97. https://doi:10.12659/MSMBR.910862
42. Lee Y, Dang JT, Switzer N, Yu J, Tian C, Birch DW, et al. Impact of Bariatric Surgery on Male Sex Hormones and Sperm Quality: a Systematic Review and Meta-Analysis. Obes Surg. 2019;29:334–46. https://doi:10.1007/s11695-018-3557-5
43. Peel A, Lyons H, Tully CA, Vincent AD, Jesudason D, Wittert G, et al. The effect of obesity interventions on male fertility: a systematic review and meta-analysis. Hum Reprod Update. 2026;32:154–80. https://doi:10.1093/humupd/dmaf025
44. Lisco G, Bartolomeo N, De Tullio A, De Pergola G, Guastamacchia E, Jirillo E, et al. Long-acting glucagon-like peptide 1 receptor agonists boost erectile function in men with type 2 diabetes mellitus complaining of erectile dysfunction: A retrospective cohort study. Andrology. 2024;12:633–42. https://doi:10.1111/andr.13519
45. Bajaj HS, Gerstein HC, Rao-Melacini P, Basile J, Colhoun H, Conget I, et al. Erectile function in men with type 2 diabetes treated with dulaglutide: an exploratory analysis of the REWIND placebo-controlled randomised trial. Lancet Diabetes Endocrinol. 2021;9:484–90. https://doi:10.1016/S2213-8587(21)00115-7
46. Able C, Liao B, Saffati G, Maremanda A, Applewhite J, Nasrallah AA, et al. Prescribing semaglutide for weight loss in non-diabetic, obese patients is associated with an increased risk of erectile dysfunction: a TriNetX database study. Int J Impot Res. 2025;37:315–9. https://doi:10.1038/s41443-024-00895-6
47. Pourabhari Langroudi A, Chen AL, Basran S, Sommer ER, Stinson J, Cheng YS, et al. Male sexual dysfunction associated with GLP-1 receptor agonists: a cross-sectional analysis of FAERS data. Int J Impot Res. 2025;37:661–7. https://doi:10.1038/s41443-025-01061-2
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Aleksandra Mliczek, Brajan Roczyński, Izabela Polok, Julia Obersztyn, Adrianna Szczecińska

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Stats
Number of views and downloads: 22
Number of citations: 0