The frequency and peculiarities of hypogonadism in men with obesity

BACKGROUND: Male hypogonadism is associated with obesity, therefore, it is of interest to study its frequency. The clinical symptoms of hypogonadism are not specific, and laboratory diagnostics is the basis for its detection. The optimal method for this diagnostics is isotope dilution liquid chromatography/tandem mass spectrometry, which was used in our study.

AIM: To assess of the incidence and features of hypogonadism in men with obesity.

MATERIALS AND METHODS: A full-design, cross-sectional, screening, single-center, non-interventional study of hypogonadal men with obesity, who were treated in Endocrinology Research Centre, Moscow. The study was conducted from January 2023 to May 2024. Medical history assessment, physical examination with determination of body mass index (BMI), measurement estimation of total testosterone by isotope dilution liquid chromatography/tandem mass spectrometry, lipid profiles and uric acid were performed. The groups were compared using the Mann-Whitney U-test for quantitative indicators and χ² with Yates’ correction for qualitative ones. Differences were considered statistically significant with p <0,05.

RESULTS: Hypogonadism was detected in 230 (76,7 (95% CI 71,9–81,5)%) men with obesity. The prevalence of male hypogonadism in overweight was 63,7 (95% CI 53,2–74,3)% of cases, in 1^st degree obesity — 74,8 (95% CI 66,8–82,7)%, in 2^nd degree obesity — 88,2 (95% CI 76,1–95,6)% and in 3^rd degree obesity — 88,9 (95% CI 77,4–95,8)%. Patients with hypogonadism had statistically significantly higher levels of cholesterol, uric acid and triglycerides compared to eugonadal men.

CONCLUSION: The prevalence of male hypogonadism in obesity was 76,7 (95% CI 71,9–81,5)%. It was associated with dyslipidemia and hyperuricemia.

1. WHO – World Health organization (2022). Fact sheet: Obesity and overweight. Updated March 2024 Retrieved from Obesity and overweight (who.int)

2. Dedov II, Melnichenko GA, Rozhivanov RV, Kurbatov DG. 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

3. 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

4. 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

5. Finkelstein JS, Lee H, Burnett-Bowie SA, et al. Gonadal steroids and body composition, strength, and sexual function in men. N Engl J Med. 2013;369(11):1011-1022. doi: https://doi.org/10.1056/NEJMoa1206168

6. 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/s40618-020-01446-8

7. Genchi VA, D’Oria R, Palma G, et al. Impaired leptin signalling in obesity: is leptin a new thermolipokine? Int. J. Mol. Sci. 2021;22:6445. doi: https://doi.org/10.3390/IJMS22126445

8. 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

9. Bai J, Liu Y, Niu GF, et al. Relationship between adiponectin and testosterone in patients with type 2 diabetes. Biochem Med (Zagreb). 2011;21(1):65-70. doi: https://doi.org/10.11613/bm.2011.013

10. Yeap BB, Knuiman MW, Divitini ML, et al. Differential associations of testosterone, dihydrotestosterone and oestradiol with physical, metabolic and health-related factors in community dwelling men aged 17-97 years from the Busselton Health Survey. Clin Endocrinol (Oxf). 2014;81(1):100-108. doi: https://doi.org/10.1111/cen.12407

11. Niederberger C. Re: determinants of testosterone recovery after bariatric surgery: is it only a matter of reduction of body mass index?. J Urol. 2014;191(3):753-754. doi: https://doi.org/10.1016/j.juro.2013.11.073

12. Malysheva NM, Kolesnikova GS, Ioutsi VA, Il`in AV, Golovkina NA, Tyul`pakov AN. The comparative analysis of the results of detection of testosterone in blood serum applying analyzers Architect and Vitros and tandem mass-spectrometry, a highly efficient fluid chromatography technique. Klinicheskaya Laboratornaya Diagnostika (Russian Clinical Laboratory Diagnostics). 2017;62(10):592-599. (in Russ.) doi: https://dx.doi.org/10.18821/0869-2084-2017-62-10-592-599

13. Goncharov NP, Katsiya GV, Kolesnikova GS. Key hormones in endocrinology and methods for their determination. Moscow: Adamant; 2014. — 230 p. (In Russ.)

14. Botelho JC, Shacklady C, Cooper HC, et al. Isotope-dilution liquid chromatography-tandem mass spectrometry candidate reference method for total testosterone in human serum. Clin Chem. 2013;59(2):372-380. doi: https://doi.org/10.1373/clinchem.2012.190934

15. Antonio L, Wu FCW, 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

16. Bobkov DN. Testikulyarnaya antioksidantnaya aktivnost` u muzhchin s visceral`ny`m ozhireniem: dis. kand.med.nauk: 3.1.19. — NMICz endokrinologii. — Moskva, 2022:104. (In Russ.)

17. Svartberg J, von Mühlen D, Sundsfjord J, et al. Waist Circumference and Testosterone Levels in Community Dwelling Men. The Tromsø Study. Eur J Epidemiol 2004;19:657–663. doi: https://doi.org/10.1023/B:EJEP.0000036809.30558.8f

18. Dhindsa S, Miller MG, McWhirter CL, et al. Testosterone concentrations in diabetic and nondiabetic obese men. Diabetes Care. 2010;33(6):1186-1192. doi: https://doi.org/10.2337/dc09-1649

19. Tai, SSC, Xu B, Welch MJ, et al. Development and evaluation of a candidate reference measurement procedure for the determination of testosterone in human serum using isotope dilution liquid chromatography/tandem mass spectrometry. Anal Bioanal Chem. 2007;388:1087–1094. doi: https://doi.org/10.1007/s00216-007-1355-3

20. Botelho JC, Shacklady C, Cooper HC, et al. Isotope-dilution liquid chromatography-tandem mass spectrometry candidate reference method for total testosterone in human serum. Clin Chem. 2013;59(2):372-380. doi: https://doi.org/10.1373/clinchem.2012.190934

21. Akinloye O, Blessing Popoola B, Bolanle Ajadi M, et al. Hypogonadism and metabolic syndrome in nigerian male patients with both type 2 diabetes and hypertension. Int J Endocrinol Metab. 2014;12(1):e10749. doi: https://doi.org/10.5812/ijem.10749

22. Blaya R, Thomaz LD, Guilhermano F, et al. Total testosterone levels are correlated to metabolic syndrome components. Aging Male. 2016;19(2):85-89. doi: https://doi.org/10.3109/13685538.2016.1154523

23. Mäkinen JI, Perheentupa A, Irjala K, et al. Endogenous testosterone and serum lipids in middle-aged men. Atherosclerosis. 2008;197(2):688-693. doi: https://doi.org/10.1016/j.atherosclerosis.2007.05.009

24. Van Pottelbergh I, Braeckman L, De Bacquer D, et al. Differential contribution of testosterone and estradiol in the determination of cholesterol and lipoprotein profile in healthy middle-aged men. Atherosclerosis. 2003;166(1):95-102. doi: https://doi.org/10.1016/S0021-9150(02)00308-8

25. Veldhuis JD, Zwart A, Mulligan T, et al. 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

26. Zhang Q, Chen W, Yun C, et al. The application value of serum 25(OH)D3, uric acid, triglyceride, and homeostasis model assessment of insulin resistance in male patients with hyperuricemia combined with hypogonadism. BMC Endocr Disord. 2021;21:102. doi: https://doi.org/10.1186/s12902-021-00765-y

27. Lim J.H, Kim YK, Kim YS, et al. Relationship between serum uric Acid levels, metabolic syndrome, and arterial stiffness in korean. Korean Circ J. 2010;40(7):314–20. doi: https://doi.org/10.4070/kcj.2010.40.7.314