Features of hypogonadism in men with obesity
E. V. Morozova,
R. V. Rozhivanov,
E. R. Rozhivanova,
K. E. Gaidaichuk,
E. N. Andreeva,
G. A. Mel’nichenko,
N. G. Mokrysheva https://doi.org/10.14341/brh12762
Abstract
The relationship between testosterone production and obesity has been found in numerous epidemiological studies. The main feature of obesity in males lies in the fact that it is abdominal obesity, i.e. deposition of adipose tissue mainly in the abdominal area, which has the consequence of affecting sex hormones metabolism. Androgen aromatization, leptin resistance, testosterone deposition, and the influence of other comorbid factors all contribute to the formation of bidirectional relationship between obesity and low testosterone levels. The increased interest in this problem has been observed in recent years, and there is data confirming the link between excess body weight and decreased testosterone levels in males. This latter data is presented in this published review. Meanwhile, reduction of body fat mass can be considered as a proposed approach to correcting hypogonadism associated with metabolic disorders, since hypogonadism in males with metabolic disorders is potentially reversible.
About the Authors
E. V. Morozova
Endocrinology Research Centre
Russian Federation
Russian Federation
Elena V. Morozova, MD
11 Dm. Ulyanova street, 117036 Moscow
R. V. Rozhivanov
Endocrinology Research Centre
Roman V. Rozhivanov, MD, PhD
Moscow
E. R. Rozhivanova
Endocrinology Research Centre
Ekaterina R. Rozhivanova, MD
Moscow
K. E. Gaidaichuk
Endocrinology Research Centre
Konstantin E. Gaidaichuk, MD
Moscow
E. N. Andreeva
Endocrinology Research Centre; Russian University of Medicine
Elena N. Andreeva, MD, PhD, Professor
Moscow
G. A. Mel’nichenko
Endocrinology Research Centre
Galina A. Mel’nichenko, MD, PhD, Professor
Moscow
N. G. Mokrysheva
Endocrinology Research Centre
Natalya G. Mokrysheva, MD, PhD, Professor
Moscow
References
1. Mayoral LP, Andrade GM, Mayoral EP, et al. Obesity subtypes, related biomarkers & heterogeneity. Indian J Med Res. 2020;151(1):11-21. doi: https://doi.org/10.4103/ijmr.IJMR_1768_17
2. WHO – World Health organization Retrieved from https://www.who.int/ru/news-room/fact-sheets/detail/obesity-and-overweight [Internet]. Retrieved from http://www.who.int/ mediacentre/factsheets/fs311/en/
3. NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults. Lancet. 2024;403(10431):1027-1050. doi: https://doi.org/10.1016/S0140-6736(23)02750-2
4. Alferova VI, Mustafina SV. The prevalence of obesity in the adult population of the Russian Federation (literature review). Obesity and metabolism. 2022;19(1):96-105. (In Russ.). doi: https://doi.org/10.14341/omet12809
5. Marin P, Arver S. Androgens and abdominal obesity. Baillieres Clin Endocrinol Metab. 1998;12(3):441-451. doi: https://doi:10.1016/s0950-351x(98)80191-2
6. Rebuffé-Scrive M, Mårin P, Björntorp P. Effect of testosterone on abdominal adipose tissue in men. Int J Obes. 1991;15(11):791-795
7. Schoettl T, Fischer IP, Ussar S. Heterogeneity of adipose tissue in development and metabolic function. J Exp Biol. 2018;221(Pt Suppl 1):jeb162958. doi: https://doi.org/10.1242/jeb.162958
8. Moon KH, Park SY, Kim YW. Obesity and Erectile Dysfunction: From Bench to Clinical Implication. World J Mens Health. 2019;37(2):138. doi: https://doi.org/10.5534/wjmh.180026
9. Grossmann M, Matsumoto AM. A Perspective on Middle-Aged and Older Men With Functional Hypogonadism: Focus on Holistic Management. J Clin Endocrinol Metab. 2017;102(3):1067-1075. doi: https://doi.org/10.1210/jc.2016-3580
10. EAU Guidelines. Edn. presented at the EAU Annual Congress Milan 2023. ISBN 978-94-92671-19-6
11. Dedov I.I., Melnichenko G.A., Rozhivanov R.V., Kurbatov D.G. Guidelines for the Diagnosis and Treatment of testosterone deficiency (hypogonadism) in male patients. Problems of Endocrinology. 2016;62(6):78-80. (In Russ.) doi: https://doi.org/10.14341/probl201662678-80
12. Rozhivanov R.V., Morozova E.V., Ioutsi V.A., Antsupova M.A., Savelyeva L.V., Rozhivanova E.R., Andreeva E.N., Mel’nichenko G.A., Mokrysheva N.G. The frequency and peculiarities of hypogonadism in men with obesity. Obesity and metabolism. 2025;22(1):19-25. (In Russ.) ] doi: https://doi.org/10.14341/omet13145
13. Veldhuis JD, Zwart A, Mulligan T, Iranmanesh A. Muting of androgen negative feedback unveils impoverished gonadotropin-releasing hormone/luteinizing hormone secretory reactivity in healthy older men. J Clin Endocrinol Metab. 2001;86(2):529-535. doi: https://doi.org/10.1210/jcem.86.2.7200
14. Spratt DI, Finkelstein JS, Butler JP, Badger TM, Crowley WF Jr. Effects of increasing the frequency of low doses of gonadotropin-releasing hormone (GnRH) on gonadotropin secretion in GnRH-deficient men. J Clin Endocrinol Metab. 1987;64(6):1179-1186. doi: https://doi.org/10.1210/jcem-64-6-117915
15. Dandona P, Dhindsa S, Ghanim H, Saad F. Mechanisms underlying the metabolic actions of testosterone in humans: A narrative review. Diabetes Obes Metab. 2021;23(1):18-28. doi: https://doi.org/10.1111/dom.14206
16. Karpova T, de Oliveira AA, Naas H, Priviero F, Nunes KP. Blockade of Toll-like receptor 4 (TLR4) reduces oxidative stress and restores phospho-ERK1/2 levels in Leydig cells exposed to high glucose. Life Sci. 2020;245:117365. doi: https://doi.org/10.1016/j.lfs.2020.11736517
17. Kim SD, Cho KS. Obstructive Sleep Apnea and Testosterone Deficiency. World J Mens Health. 2019;37(1):12-18. doi: https://doi.org/10.5534/wjmh.180017
18. Savel’eva LV, Rozhivanov RV, Shurdumova BO, Fadeev VV. Normogonadotropic hypogonadism in men with obesity. Obesity and metabolism. 2009;6(3):39-42. (In Russ.) doi: https://doi.org/10.14341/2071-8713-5243
19. Bélanger C, Luu-The V, Dupont P, Tchernof A. Adipose tissue intracrinology: potential importance of local androgen/estrogen metabolism in the regulation of adiposity. Horm Metab Res. 2002;34(11-12):737-745. doi: https://doi.org/10.1055/s-2002-38265
20. Bélanger C, Hould FS, Lebel S, Biron S, Brochu G, Tchernof A. Omental and subcutaneous adipose tissue steroid levels in obese men. Steroids. 2006;71(8):674-682. doi: https://doi.org/10.1016/j.steroids.2006.04.008
21. Di Nisio A, Sabovic I, De Toni L, et al. Testosterone is sequestered in dysfunctional adipose tissue, modifying androgen-responsive genes. Int J Obes (Lond). 2020;44(7):1617-1625. doi: https://doi.org/10.1038/s41366-020-0568-9
22. Antonio L, Wu FC, O’Neill TW, et al. Associations between sex steroids and the development of metabolic syndrome: a longitudinal study in European men. J Clin Endocrinol Metab. 2015;100(4):1396-1404. doi: https://doi.org/10.1210/jc.2014-4184 23
23. Dhindsa S, Miller MG, Mcwhirter CL, et al. Testosterone concentrations in diabetic and nondiabetic obese men. Diabetes Care. 2010. doi: https://doi.org/10.2337/dc09-1649
24. Xu X, Sun M, Ye J, et al. The Effect of Aromatase on the Reproductive Function of Obese Males. Horm Metab Res. 2017;49(8):572-579. doi: https://doi.org/10.1055/s-0043-107835
25. Porro S, Genchi VA, Cignarelli A, et al. Dysmetabolic adipose tissue in obesity: morphological and functional characteristics of adipose stem cells and mature adipocytes in healthy and unhealthy obese subjects. J Endocrinol Invest. 2021;44(5):921-941. doi: https://doi.org/10.1007/s40618-020-01446-826
26. Genchi VA, D’Oria R, Palma G, et al. Impaired Leptin Signalling in Obesity: Is Leptin a New Thermolipokine?. Int J Mol Sci. 2021;22(12):6445. doi: https://doi.org/10.3390/ijms22126445
27. Leisegang K, Bouic PJ, Menkveld R, Henkel RR. Obesity is associated with increased seminal insulin and leptin alongside reduced fertility parameters in a controlled male cohort. Reprod Biol Endocrinol. 2014;12:34. doi: https://doi.org/10.1186/1477-7827-12-34
28. Lima TFN, Nackeeran S, Rakitina E, et al. Association of Leptin with Total and Free Testosterone: Results from the National Health and Nutrition Examination Surveys. Androg Clin Res Ther. 2020;1(1):94-100. doi: https://doi.org/10.1089/andro.2020.0007
29. True C, Kirigiti M, Ciofi P, Grove KL, Smith MS. Characterisation of arcuate nucleus kisspeptin/neurokinin B neuronal projections and regulation during lactation in the rat. J Neuroendocrinol. 2011;23(1):52-64. doi: https://doi.org/10.1111/j.1365-2826.2010.02076.x
30. Genchi VA, Rossi E, Lauriola C, et al. Adipose Tissue Dysfunction and Obesity-Related Male Hypogonadism. Int J Mol Sci. 2022;23(15):8194. doi: https://doi.org/10.3390/ijms23158194
31. Landry D, Paré A, Jean S, Martin LJ. Adiponectin influences progesterone production from MA-10 Leydig cells in a dose-dependent manner. Endocrine. 2015;48(3):957-967. doi: https://doi.org/10.1007/s12020-014-0456-y
32. Cignarelli A, Genchi VA, Perrini S, Natalicchio A, Laviola L, Giorgino F. Insulin and Insulin Receptors in Adipose Tissue Development. Int J Mol Sci. 2019;20(3):759. doi: https://doi.org/10.3390/ijms20030759 33
33. Neeland IJ, Ayers CR, Rohatgi AK, et al. Associations of visceral and abdominal subcutaneous adipose tissue with markers of cardiac and metabolic risk in obese adults. Obesity (Silver Spring). 2013;21(9):E439-E447. doi: https://doi.org/10.1002/oby.20135 34
34. Caminos JE, Nogueiras R, Gaytán F, et al. Novel expression and direct effects of adiponectin in the rat testis. Endocrinology. 2008;149(7):3390-3402. doi: https://doi.org/10.1210/en.2007-1582
35. Choubey M, Ranjan A, Bora PS, Baltazar F, Krishna A. Direct actions of adiponectin on changes in reproductive, metabolic, and anti-oxidative enzymes status in the testis of adult mice. Gen Comp Endocrinol. 2019;279:1-11. doi: https://doi.org/10.1016/j.ygcen.2018.06.002
36. Kawai T, Autieri MV, Scalia R. Adipose tissue inflammation and metabolic dysfunction in obesity. Am J Physiol Cell Physiol. 2021;320(3):C375-C391. doi: https://doi.org/10.1152/ajpcell.00379.2020
37. Tsilidis KK, Rohrmann S, McGlynn KA, et al. Association between endogenous sex steroid hormones and inflammatory biomarkers in US men. Andrology. 2013;1(6):919-928. doi: https://doi.org/10.1111/j.2047-2927.2013.00129.x
38. Bobjer J, Katrinaki M, Tsatsanis C, Lundberg Giwercman Y, Giwercman A. Negative association between testosterone concentration and inflammatory markers in young men: a nested cross-sectional study. PLoS One. 2013;8(4):e61466. doi: https://doi.org/10.1371/journal.pone.0061466
39. Dhillo WS, Chaudhri OB, Patterson M, et al. Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males. J Clin Endocrinol Metab. 2005;90(12):6609-6615. doi: https://doi.org/10.1210/jc.2005-1468
40. Engin A. Adipose Tissue Hypoxia in Obesity and Its Impact on Preadipocytes and Macrophages: Hypoxia Hypothesis. Adv Exp Med Biol. 2017;960:305-326. doi: https://doi.org/10.1007/978-3-319-48382-5_13
41. Luk’yanova LD. Signal’nye mekhanizmy gipoksii. M.: RAN; 2019. (In Russ.)
42. Roychoudhury S, Chakraborty S, Choudhury AP, et al. Environmental Factors-Induced Oxidative Stress: Hormonal and Molecular Pathway Disruptions in Hypogonadism and Erectile Dysfunction. Antioxidants (Basel). 2021;10(6):837. doi: https://doi.org/10.3390/antiox10060837
43. Tsai SC, Lu CC, Lin CS, Wang PS. Antisteroidogenic actions of hydrogen peroxide on rat Leydig cells. J Cell Biochem. 2003;90(6):1276-1286. doi: https://doi.org/10.1002/jcb.10738
44. Perrini S, Cignarelli A, Quaranta VN, et al. Correction of intermittent hypoxia reduces inflammation in obese subjects with obstructive sleep apnea. JCI Insight. 2017;2(17):e94379. doi: https://doi.org/10.1172/jci.insight.94379
45. Camacho EM, Huhtaniemi IT, O’Neill TW, et al. Age-associated changes in hypothalamic-pituitary-testicular function in middle-aged and older men are modified by weight change and lifestyle factors: longitudinal results from the European Male Ageing Study. Eur J Endocrinol. 2013;168(3):445-455 doi: https://doi.org/10.1530/EJE-12-0890
46. La Vignera S, Cannarella R, Galvano F, et al. The ketogenic diet corrects metabolic hypogonadism and preserves pancreatic ß-cell function in overweight/obese men: a single-arm uncontrolled study. Endocrine. 2021;72(2):392-399. doi: https://doi.org/10.1007/s12020-020-02518-8
47. Sahebkar A, Simental-Mendía LE, Reiner Ž, et al. Effect of orlistat on plasma lipids and body weight: A systematic review and meta-analysis of 33 randomized controlled trials. Pharmacol Res. 2017;122:53-65. doi: https://doi.org/10.1016/j.phrs.2017.05.022
48. Suleiman JB, Nna VU, Othman ZA, Zakaria Z, Bakar ABA, Mohamed M. Orlistat attenuates obesity-induced decline in steroidogenesis and spermatogenesis by up-regulating steroidogenic genes. Andrology. 2020;8(5):1471-1485. doi: https://doi.org/10.1111/andr.12824
49. Cannarella R, Calogero AE, Condorelli RA, Greco EA, Aversa A, La Vignera S. Is there a role for glucagon-like peptide-1 receptor agonists in the treatment of male infertility?. Andrology. 2021;9(5):1499-1503. doi: https://doi.org/10.1111/andr.13015
50. Jensterle M, Podbregar A, Goricar K, Gregoric N, Janez A. Effects of liraglutide on obesity-associated functional hypogonadism in men. Endocr Connect. 2019;8(3):195-202. doi: https://doi.org/10.1530/EC-18-0514
51. Capoccia D, Coccia F, Guarisco G, et al. Long-term Metabolic Effects of Laparoscopic Sleeve Gastrectomy. Obes Surg. 2018;28(8):2289-2296. doi: https://doi.org/10.1007/s11695-018-3153-8
52. Escobar-Morreale HF, Santacruz E, Luque-Ramírez M, Botella Carretero JI. Prevalence of ‘obesity-associated gonadal dysfunction’ in severely obese men and women and its resolution after bariatric surgery: a systematic review and meta-analysis. Hum Reprod Update. 2017;23(4):390-408. doi: https://doi.org/10.1093/humupd/dmx012
53. Zhu C, Mei F, Gao J, Zhou D, Lu L, Qu S. Changes in inflammatory markers correlated with increased testosterone after laparoscopic sleeve gastrectomy in obese Chinese men with acanthosis nigricans. J Dermatol. 2019;46(4):338-342. doi: https://doi.org/10.1111/1346-8138.14783
54. Calderón B, Galdón A, Calañas A, et al. Effects of bariatric surgery on male obesity-associated secondary hypogonadism: comparison of laparoscopic gastric bypass with restrictive procedures. Obes Surg. 2014;24(10):1686-1692. doi: https://doi.org/10.1007/s11695-014-1233-y
55. Saad F, Haider A, Doros G, Traish A. Long-term treatment of hypogonadal men with testosterone produces substantial and sustained weight loss. Obesity (Silver Spring). 2013;21(10):1975-1981. doi: https://doi.org/10.1002/oby.20407
56. Haider A, Yassin A, Doros G, Traish AM, Saad F. Reductions of weight and waist size in 362 hypogonadal men with obesity grades I to III under longterm treatment with testosterone undecanoate. (TU): observational data from two registry studies. In: Abstract (SAT-0940) Presented at the Endocrine Society’s 96th Annual Meeting (2014)
57. Yassin A, Doros G. Testosterone therapy in hypogonadal men results in sustained and clinically meaningful weight loss. Clin Obes. 2013;3:73–83. doi: https://doi.org/10.1111/cob.12022
58. Saad F, Yassin A, Doros G, Haider A. Effects of long-term treatment with testosterone on weight and waist size in 411 hypogonadal men with obesity classes I-III: observational data from two registry studies. Int J Obes (Lond). 2016;40(1):162-170. doi: https://doi.org/10.1038/ijo.2015.139
59. Ng Tang Fui M, Prendergast LA, Dupuis P, et al. Effects of testosterone treatment on body fat and lean mass in obese men on a hypocaloric diet: a randomised controlled trial. BMC Med. 2016;14(1):153. doi: https://doi.org/10.1186/s12916-016-0700-9
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Morozova E.V., Rozhivanov R.V., Rozhivanova E.R., Gaidaichuk K.E., Andreeva E.N., Mel’nichenko G.A., Mokrysheva N.G. Features of hypogonadism in men with obesity. Bulletin of Reproductive Health. 2025;4(2):31-36. (In Russ.) https://doi.org/10.14341/brh12762
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