The Journal of Practical Medicine >

2026 , Vol. 42 >Issue 7: 1272 - 1279

DOI: https://doi.org/10.3969/j.issn.1006-5725.2026.07.021

Chronic Disease Control

Differential effects of semaglutide on gonadal function in male obesity-associated secondary hypogonadism versus simple obesity

  • Yunchong GUO ,
  • Fangping LI ,
  • Xinwei HUANG ,
  • Lijun SHEN ,
  • Yaqing WEN ,
  • Zhen ZHANG
Expand
  • Department of Endocrinology，The Seventh Affiliated Hospital，Sun Yat-sen University，Shenzhen 518107，Guangdong，China

Received date: 2026-03-11

  Revised date: 2026-03-20

  Accepted date: 2026-03-20

  Online published: 2026-04-13

Fold

Abstract

Objective To investigate the differential effects of semaglutide on gonadal function between men with male obesity-associated secondary hypogonadism （MOSH） and those with simple obesity. Methods A total of 37 obese male patients， with a body mass index （BMI） of 28 kg/m2 or higher and a waist circumference exceeding 90 cm， were recruited and divided into the MOSH group and the simple obesity group based on their baseline total testosterone levels. All patients underwent a 24-week intervention with semaglutide. The changes in the International Index of Erectile Function-5 （IIEF-5） score， sex hormone levels， and semen parameters were compared between the two groups both before and after treatment. Results After treatment， the BMI， waist circumference， and visceral fat area in both groups were significantly reduced compared to the baseline values. In the MOSH group， the IIEF-5 score， total testosterone level， and progressive sperm motility all showed significant increases （all P < 0.05）. Meanwhile， no significant alterations were detected in the follicle-stimulating hormone （FSH） or luteinizing hormone （LH） levels （both P > 0.05）. Correlation analysis indicated that in the MOSH group， the increase in total testosterone was significantly and positively correlated with the reduction in visceral fat area （r = 0.406， P = 0.013）. In the simple obesity group， only the LH level decreased significantly after treatment （P < 0.05）， and there were no significant changes in other gonadal function indicators or semen parameters （all P > 0.05）. Multiple linear regression analysis demonstrated that the baseline total testosterone level was an influencing factor for the change in total testosterone after treatment. Conclusions Semaglutide effectively enhances gonadal function and sperm quality in patients with MOSH. However， it has limited impacts on the hypothalamic-pituitary-gonadal axis in men with simple obesity without hypogonadism. Semaglutide can potentially be a therapeutic option for patients with MOSH.

Key words： hypogonadism; obesity; semaglutide; testosterone; sperm motility

Cite this article

Yunchong GUO , Fangping LI , Xinwei HUANG , Lijun SHEN , Yaqing WEN , Zhen ZHANG . Differential effects of semaglutide on gonadal function in male obesity-associated secondary hypogonadism versus simple obesity[J]. The Journal of Practical Medicine, 2026 , 42(7) : 1272 -1279 . DOI: 10.3969/j.issn.1006-5725.2026.07.021

References

[1] CARRAGETA D F， OLIVEIRA P F， ALVES M G， et al. Obesity and male hypogonadism： Tales of a vicious cycle［J］. Obes Rev， 2019， 20（8）： 1148-1158. doi： 10.1111/obr.12863 .
[2] WANG L， ZHOU B， ZHAO Z， et al. Body-mass index and obesity in urban and rural China： Findings from consecutive nationally representative surveys during 2004-18［J］. Lancet， 2021， 398（10294）： 53-63. doi： 10.1016/S0140-6736（21）00798-4 .
[3] FERNANDEZ C J， CHACKO E C， PAPPACHAN J M. Male Obesity-related Secondary Hypogonadism - Pathophysiology， Clinical Implications and Management［J］. Eur Endocrinol， 2019， 15（2）： 83-90. doi： 10.17925/EE.2019.15.2.83 .
[4] GENCHI V A， ROSSI E， LAURIOLA C， et al. Adipose Tissue Dysfunction and Obesity-Related Male Hypogonadism［J］. Int J Mol Sci， 2022， 23（15）： 8194. doi： 10.3390/ijms23158194 .
[5] CHOSICH J， BRADFORD A P， ALLSHOUSE A A， et al. Acute recapitulation of the hyperinsulinemia and hyperlipidemia characteristic of metabolic syndrome suppresses gonadotropins［J］. Obesity （Silver Spring）， 2017， 25（3）： 553-560. doi： 10.1002/oby.21754 .
[6] YANG Y， HE L， HAN S， et al. Sex Differences in the Efficacy of Glucagon-Like Peptide-1 Receptor Agonists for Weight Reduction： A Systematic Review and Meta-Analysis［J］. J Diabetes， 2025， 17（3）： e70063. doi： 10.1111/1753-0407.70063 .
[7] KIM K S， PARK J S， HWANG E， et al. GLP-1 increases preingestive satiation via hypothalamic circuits in mice and humans［J］. Science， 2024， 385（6707）： 438-446. doi： 10.1126/science.adj2537 .
[8] RAGO V， DE ROSE D， SANTORO M， et al. Human Sperm Express the Receptor for Glucagon-like Peptide-1 （GLP-1）， Which Affects Sperm Function and Metabolism［J］. Endocrinology， 2020， 161（4）：bqaa031. doi： 10.1210/endocr/bqaa031 .
[9] DEAMEH M G， RAMEZ M， ROWAIEE R， et al. Effects of glucagon-like peptide-1 receptor agonists on male reproductive hormones， semen parameters， and metabolic outcomes： A systematic review［J］. J Sex Med， 2026， 23（2）：qdaf381. doi： 10.1093/jsxmed/qdaf381 .
[10] ANDERSEN E， JUHL C R， KJ?LLER E T， et al. Sperm count is increased by diet-induced weight loss and maintained by exercise or GLP-1 analogue treatment： A randomized controlled trial［J］. Hum Reprod， 2022， 37（7）： 1414-1422. doi： 10.1093/humrep/deac096 .
[11] JENSTERLE M， PODBREGAR A， GORICAR K， et al. Effects of liraglutide on obesity-associated functional hypogonadism in men［J］. Endocr Connect， 2019， 8（3）： 195-202. doi： 10.1530/EC-18-0514 .
[12] GREGORI? N， ?IKONJA J， JANE? A， et al. Semaglutide improved sperm morphology in obese men with type 2 diabetes mellitus and functional hypogonadism［J］. Diabetes Obes Metab， 2025， 27（2）： 519-528. doi： 10.1111/dom.16042 .
[13] LENGSFELD S， PROBST L， EMARA Y， 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［J］. EBioMedicine， 2024， 107： 105284. doi： 10.1016/j.ebiom .
[14] LA VIGNERA S， CONDORELLI R A， CALOGERO A E， et al. Sexual and Reproductive Outcomes in Obese Fertile Men with Functional Hypogonadism after Treatment with Liraglutide： Preliminary Results［J］. J Clin Med， 2023， 12（2）：672. doi： 10.3390/jcm12020672 .
[15] 林丹红， 全会标， 欧倩滢， 等. 利拉鲁肽对超重或肥胖男性2型糖尿病患者睾酮及性功能的影响［J］.实用医学杂志， 2023， 39（7）： 894-898. doi： 10.3969/j.issn.1006-5725.2023.07.018 .
[16] BARBOUNI K， JOTAUTIS V， METALLINOU D， et al. When Weight Matters： How Obesity Impacts Reproductive Health and Pregnancy-A Systematic Review［J］. Curr Obes Rep， 2025， 14（1）： 37. doi： 10.1007/s13679-025-00629-9 .
[17] MUIR C A， WITTERT G A， HANDELSMAN D J. Approach to the Patient： Low Testosterone Concentrations in Men With Obesity［J］. J Clin Endocrinol Metab， 2025， 110（9）： e3125-e3130. doi： 10.1210/clinem/dgaf137 .
[18] XU X， SUN M， YE J， et al. The Effect of Aromatase on the Reproductive Function of Obese Males［J］. Horm Metab Res， 2017， 49（8）： 572-579. doi： 10.1055/s-0043-107835 .
[19] AHMED F， HETTY S， LATERVEER R， et al. Altered Expression of Aromatase and Estrogen Receptors in Adipose Tissue From Men With Obesity or Type 2 Diabetes［J］. J Clin Endocrinol Metab， 2025， 110（10）： e3410-e3424. doi： 10.1210/clinem/dgaf038 .
[20] PATEL B， KOYSOMBAT K， MILLS E G， et al. The Emerging Therapeutic Potential of Kisspeptin and Neurokinin B［J］. Endocr Rev. 2024 Jan 4；45（1）：30-68. DOI： 10.1210/endrev/bnad023 .
[21] ORIDE A， KANASAKI H， MIJIDDORJ T，et al. GLP-1 increases Kiss-1 mRNA expression in kisspeptin-expressing neuronal cells［J］. Biol Reprod， 2017， 97（2）： 240-248. doi： 10.1093/biolre/iox087 .
[22] MARTINS A D， MONTEIRO M P， SILVA B M， et al. Metabolic dynamics of human Sertoli cells are differentially modulated by physiological and pharmacological concentrations of GLP-1［J］. Toxicol Appl Pharmacol， 2019， 362： 1-8. doi： 10.1016/j.taap.2018.10.009 .
[23] CALTABIANO R， CONDORELLI D， PANZA S， et al. Glucagon-like peptide-1 receptor is expressed in human and rodent testis［J］. Andrology， 2020， 8（6）： 1935-1945. doi： 10.1111/andr.12871 .
[24] SUN J， SHEN X， LIU H， et al. Caloric restriction in female reproduction： Is it beneficial or detrimental？［J］. Reprod Biol Endocrinol， 2021， 19（1）： 1. doi： 10.1186/s12958-020-00681-1 .
[25] LINDBLOM J， HAITINA T， FREDRIKSSON R， et al. Differential regulation of nuclear receptors， neuropeptides and peptide hormones in the hypothalamus and pituitary of food restricted rats［J］. Brain Res Mol Brain Res， 2005， 133（1）： 37-46. doi： 10.1016/j.molbrainres.2004.09.025 .
[26] MORO T， TINSLEY G， LONGO G， et al. Time-restricted eating effects on performance， immune function， and body composition in elite cyclists： A randomized controlled trial［J］. J Int Soc Sports Nutr， 2020， 17（1）： 65. doi： 10.1186/s12970-020-00396-z .
[27] BUTT M D， ONG S C， RAFIQ A， et al. Long-Term clinical efficacy of liraglutide for type 2 diabetes： Real-world evidence and outcomes from Pakistan［J］. J Pharm Policy Pract， 2024， 17（1）： 2432462. doi： 10.1080/20523211.2024.2432462 .
[28] ALENZI S， ALZAHRANI A， ALJALOUD A， et al. The effectiveness of 0.5 mg and 1mg of semaglutide in patients with type two diabetes and predictors of response： A retrospective cohort study［J］. Front Endocrinol （Lausanne）， 2024， 15： 1395651. doi： 10.3389/fendo.2024.1395651 .
[29] HERMANSEN K， B?KDAL T A， DüRING M， et al. Liraglutide suppresses postprandial triglyceride and apolipoprotein B48 elevations after a fat-rich meal in patients with type 2 diabetes： A randomized， double-blind， placebo-controlled， cross-over trial［J］. Diabetes Obes Metab， 2013， 15（11）： 1040-1048. doi： 10.1111/dom.12133 .
[30] 马明梅， 马晓春， 马生花， 等. 司美格鲁肽注射液治疗不同体质量指数2型糖尿病对糖脂代谢和脂肪因子的影响［J］. 实用医学杂志， 2025， 41（9）： 1394-1400. doi： 10.3969/j.issn.1006-5725.2025.09.018 .
[31] LEE D S， CHOI J B， SOHN D W. Impact of Sleep Deprivation on the Hypothalamic-Pituitary-Gonadal Axis and Erectile Tissue［J］. J Sex Med， 2019， 16（1）： 5-16. doi： 10.1016/j.jsxm.2018.10.014 .
Options
Outlines

/

〈 〉