Personalized treatment of hypogonadism in obese male individuals: An algorithm for the combined use of incretin mimetics and testosterone medications
Abstract. In the context of global obesity pandemic, the clinical significance of male secondary (obesogenic) hypogonadism is steadily increasing. This requires the use of treatment strategies that, on the one hand, eliminate obesity as the underlying cause of the disease, and, on the other, effectively correct androgen deficiency. This article provides a comprehensive analysis of the current evidence base on the pathogenetic mechanisms of obesogenic hypogonadism and its relationship with sarcopenia, as well as the results of metabolic and hormonal therapy. A clinical model that classifies patients into four key phenotypes is proposed. A stratified clinical algorithm for personalized selection of initial and maintenance therapy for functional hypogonadism in obese male individuals is presented, allowing for the optimization of the use of incretin mimetics (glucose-dependent insulinotropic polypeptide and/or glucagon-like peptide-1 receptor agonists) and testosterone medications. The proposed algorithm ensures systemic restoration of endocrine status, body composition, and reproductive potential, taking into account individual phenotype of the patient suffering from obesogenic hypogonadism.V.V. Salukhov, E.A. Troshina, R.V. Rozhivanov, G.A. Melnichenko
Keywords
obesity
hypogonadism
weight loss
glucagon-like peptide-1 receptor agonists
dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonists
testosterone
References
1. Shenoy MT, Mondal S, Fernandez CJ, Pappachan JM. Management of male obesity-related secondary hypogonadism: A clinical update. World J Exp Med. 2024;14(2):93689.
PMID: 38948417. https://doi.org/10.5493/wjem.v14.i2.93689
2. Fernandez CJ, Chacko EC, Pappachan JM. Male obesity-related secondary hypogonadism – pathophysiology, clinical implications and management. Eur Endocrinol. 2019;15(2):83–90.
PMID: 31616498. PMCID: PMC6785957. https://doi.org/10.17925/EE.2019.15.2.83
3. Armeni E. Male hypogonadism in overweight and obesity. Metab Target Organ Damage. 2023;3:9.
https://doi.org/10.20517/mtod.2023.05
4. Роживанов Р.В., Морозова Е.В., Иоутси В.А., Анцупова М.А., Савельева Л.В., Роживанова Е.Р. с соавт. Частота встречаемости и особенности синдрома гипогонадизма у мужчин с ожирением. Ожирение и метаболизм. 2025;22(1):19–25. (Rozhivanov RV, Morozova EV, Ioutsi VA, Antsupova MA, Savelyeva LV, Rozhivanova ER et al. The frequency and peculiarities of hypogonadism in men with obesity. Ozhirenie i metabolism = Obesity and metabolism. 2025;22(1):19–25 (In Russ.)).
EDN: DJPUHM. https://doi.org/10.14341/omet13145
5. Antonic KG, Zitzmann M. The male hormone reset: How GLP-1RAs, lifestyle and testosterone transform obesity-linked problems. Aging Male. 2025;28(1):2601423.
PMID: 41399135. https://doi.org/10.1080/13685538.2025.2601423
6. Hackett G, Kirby M, Rees RW, Jones TH, Muneer A, Livingston M et al. The British Society for Sexual Medicine guidelines on male adult testosterone deficiency, with statements for practice. World J Mens Health. 2023;41(3):508–37.
PMID: 36876744. PMCID: PMC1030764. https://doi.org/10.5534/wjmh.221027
7. Салухов В.В., Айсаева С.В. Функциональный гипогонадизм у мужчин: основные причины и нейроэндокринные механизмы его развития. Медицинский совет. 2024;18(6):112–123. (Salukhov VV, Aisaeva SV. Functional hypogonadism in men: Key causes and neuroendocrine mechanisms of its development. Meditsinskiy sovet = Medical Council. 2024;18(6):112–123 (In Russ.)).
EDN: KAIDYD. https://doi.org/10.21518/ms2024-210
8. Winters SJ, Huhtaniemi IT, editors. Male hypogonadism: Basic, clinical and therapeutic principles. 2nd ed. Humana Press (Springer International Publishing AG). 2017; 436 pp.
ISBN: 978-3-319-53296-7. https://doi.org/10.1007/978-3-319-53298-1
9. Muir CA, Wittert GA, Handelsman DJ. Approach to the patient: Low testosterone concentrations in men with obesity. J Clin Endocrinol Metab. 2025;110(9):e3125–e3130.
PMID: 40052430. PMCID: PMC12342380. https://doi.org/10.1210/clinem/dgaf137
10. Liu Y, Ding Z. Obesity, a serious etiologic factor for male subfertility in modern society. Reproduction. 2017;154(4):R123–R131.
PMID: 28747541. https://doi.org/10.1530/REP-17-0161
11. Kang Y, Li P, Yuan S, Fu S, Zhang X, Zhang J et al. Progress in investigating the impact of obesity on male reproductive function. Biomedicines. 2025; 13(9):2054.
PMID: 41007618. PMCID: PMC12467420. https://doi.org/10.3390/biomedicines13092054
12. Contessa M, Ambrosio MR, Fabris B, SBernardi S. Obesity and fertility. Obes Endocrinol. 2026;2(1):wjag003.
https://doi.org/10.1093/obendo/wjag003
13. Spaziani M, Carlomagno F, Tarantino C, Angelini F, Vincenzi L, Gianfrilli D. New perspectives in functional hypogonadotropic hypogonadism: Beyond late onset hypogonadism. Front Endocrinol (Lausanne). 2023;14:1184530.
PMID: 37455902. PMCID: PMC10344362. https://doi.org/10.3389/fendo.2023.1184530
14. Rabijewski M. Male-specific consequences of obesity – functional hypogonadism and fertility disorders. Endokrynol Pol. 2023;74(5):480–89.
PMID: 37779374. https://doi.org/10.5603/ep.95626
15. Santi D, Greco C, Barbonetti A, Simoni M, Maggi M, Corona G. Weight loss as therapeutic option to restore fertility in obese men: A meta-analytic study. World J Mens Health. 2025;43(2):333–43.
PMID: 39344112. PMCID: PMC11937353. https://doi.org/10.5534/wjmh.240091
16. Gonzalez-Gil AM, Barnouin Y, Celli A, Viola V, Villarreal MD, Duremdes Nava ML et al. Metabolic effects of testosterone added to intensive lifestyle intervention in older men with obesity and hypogonadism. J Clin Endocrinol Metab. 2025;110(3):e814–e826.
PMID: 38606934. PMCID: PMC11470114. https://doi.org/10.1210/clinem/dgae249
17. 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.
PMID: 30707677. PMCID: PMC6391904. https://doi.org/10.1530/EC-18-0514
18. Corona G, Rastrelli G, Morelli A, Sarchielli E, Cipriani S, Vignozzi L, Maggi M. Treatment of functional hypogonadism besides pharmacological substitution. World J Mens Health. 2020;38(3):256–70.
PMID: 31496147. PMCID: PMC7308235. https://doi.org/10.5534/wjmh.190061
19. Camacho EM, Huhtaniemi IT, O’Neill TW, Finn JD, Pye SR, Lee DM et al.; EMAS Group. 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):445–55.
PMID: 23425925. https://doi.org/10.1530/EJE-12-0890
20. Corona G, Rastrelli G, Monami M, Saad F, Luconi M, Lucchese M et al. Body weight loss reverts obesity-associated hypogonadotropic hypogonadism: A systematic review and meta-analysis. Eur J Endocrinol. 2013;168(6):829–43.
PMID: 23482592. https://doi.org/10.1530/EJE-12-0955
21. EAU Guidelines. Edn. presented at the EAU Annual Congress Madrid, Spain 2025. ISBN: 978-94-92671-29-5.
22. Borst SE, Shuster JJ, Zou B, Ye F, Jia H, Wokhlu A, Yarrow JF. Cardiovascular risks and elevation of serum DHT vary by route of testosterone administration: A systematic review and meta-analysis. BMC Med. 2014;12:211.
PMID: 25428524. PMCID: PMC4245724. https://doi.org/10.1186/s12916-014-0211-5
23. Camacho EM, Huhtaniemi IT, O’Neill TW, Finn JD, Pye SR, Lee DM et al.; EMAS Group. 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):445–55.
PMID: 23425925. https://doi.org/10.1530/EJE-12-0890
24. Ken-Dror G, Fluck D, Fry CH, Han TS. Meta-analysis and construction of simple-to-use nomograms for approximating testosterone levels gained from weight loss in obese men. Andrology. 2024;12(2):297–315.
PMID: 37345263. https://doi.org/10.1111/andr.13484
25. Дедов И.И., Мокрышева Н.Г., Мельниченко Г.А., Трошина Е.А., Мазурина Н.В., Ершова Е.В. с соавт. Клинические рекомендации «Ожирение» Минздрава России. Версия 2024 года. Вестник репродуктивного здоровья. 2025;4(2):14–30. (Dedov II, Mokrysheva NG, Melnichenko GA, Troshina EA, Mazurina NV, Ershova EV et al. Clinical recommendations “Obesity” of the Ministry of Healthcare of Russia. Version of the year 2024. Vestnik reproduktivnogo zdorov’ya = Bulletin of Reproductive Health. 2025;4(2):14–30 (In Russ.)).
EDN: QRGXVP. https://doi.org/10.14341/brh12763
26. Трошина Е.А., Терехов П.А. Гипогонадизм и висцеральное ожирение у мужчин — полноправные компоненты метаболического синдрома. Ожирение и метаболизм. 2023;20(1):84–91. (Troshina EA, Terekhov PA. Hypogonadism and visceral obesity in men are full-fledged components of the metabolic syndrome. Ozhirenie i metabolizm = Obesity and Metabolism. 2023;20(1):84–91 (In Russ.)).
EDN: QSZMAZ. https://doi.org/10.14341/omet12980
27. Дедов И.И., Мокрышева Н.Г., Мельниченко Г.А., Роживанов Р.В., Камалов А.А., Мкртумян А.М. с соавт. Проект клинических рекомендаций «Синдром гипогонадизма у мужчин». Ожирение и метаболизм. 2021;18(4):496–507. (Dedov II, Mokrysheva NG, Melnichenko GA, Rozhivanov RV, Kamalov AA, Mkrtumyan AM et al. Draft of Russian clinical practice guidelines «Male hypogonadism». Ozhirenie i metabolizm = Obesity and Metabolism. 2021;18(4):496–507 (In Russ.)).
EDN: FUWRTV. https://doi.org/10.14341/omet12817
28. Isidori AM, Aversa A, Calogero A, Ferlin A, Francavilla S, Lanfranco F et al. Adult- and late-onset male hypogonadism: The clinical practice guidelines of the Italian Society of Andrology and Sexual Medicine (SIAMS) and the Italian Society of Endocrinology (SIE). J Endocrinol Invest. 2022;45(12):2385–403.
PMID: 36018454. PMCID: PMC9415259. https://doi.org/10.1007/s40618-022-01859-7
29. Corona G, Morgado LA, Boeri L, Capogrosso P, Cocci A, Dinkelman-Smit M et al. EAU guidelines on sexual and reproductive health: A summary of the 2026 recommendations for measurement and biochemical confirmation of hypogonadism. Eur Urol Focus. 2026:S2405-4569(26)00064-7. Online ahead of print.
PMID: 42177105. https://doi.org/10.1016/j.euf.2026.04.015
30. Роживанов Р.В., Роживанова Е.Р., Андреева Е.Н., Мельниченко Г.А., Мокрышева Н.Г. Синдром гипогонадизма у мужчин. Учебное пособие. М.: ФГБУ «НМИЦ эндокринологии» Минздрава России. 2025; с 31. (Rozhivanov RV, Rozhivanova ER, Andreeva EN, Melnichenko GA, Mokrysheva NG. Hypogonadism syndrome in men. Study guide. Moscow: Endocrinology Research Centre. 2025; p. 31 (In Russ.)).
31. Роживанов Р.В., Курбатов Д.Г., Кравцова Н.С. Дифференциально-диагностическое, прогностическое и терапевтическое значение пробы с кломифеном у мужчин с гипогонадизмом. Проблемы эндокринологии. 2016;62(1):35–37. (Rozhivanov RV, Kurbatov DG, Kravtsova NS. Differential and diagnostic, predictive and therapeutic value of test with clomifene in men with a hypogonadism. Problemy endokrinologii = Problems of Endocrinology. 2016;62(1):35–37 (In Russ.)).
EDN: VMDTDL. https://doi.org/10.14341/probl201662135-37
32. Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyere O, Cederholm T et al.; Writing Group for the European Working Group on Sarcopenia in Older People 2 (EWGSOP2), and the Extended Group for EWGSOP2. Sarcopenia: Revised European consensus on definition and diagnosis. Age Ageing. 2019;48(1):16–31.
PMID: 30312372. PMCID: PMC6322506. https://doi.org/10.1093/ageing/afy169. Erratum in: Age Ageing. 2019;48(4):601. PMID: 31081853. https://doi.org/10.1093/ageing/afz046
33. Салухов В.В., Галстян Г.Р., Неймарк А.Е., Самойлов В.С., Халимов Ю.Ш., Каронова Т.Л., Сухоцкая Н.А. «Эстафетный подход» в лечении ожирения: от инкретиномиметиков до бариатрической хирургии и снова к медикаментозной терапии. Медицинский совет. 2026;20(5):158–173. (Salukhov VV, Galstyan GR, Neimark AE, Samoylov VS, Khalimov YuSh, Karonova TL, Sukhotskaya NA. The “relay approach” in obesity management: From incretin mimetics to bariatric surgery and back to pharmacotherapy. Meditsinskiy sovet = Medical Council 2026;20(5):158–173 (In Russ.)).
https://doi.org/10.21518/ms2026-155
34. Kuchakulla M, Poppas PJ, Wald G, Masterson JM, Gurayah AA, Bhambhvani HP, Kashanian JA. Impact of GLP-1 receptor agonists on male fertility: Emerging evidence and future directions. Urology. 2025:S0090-4295(25)00912-4. Online ahead of print.
PMID: 41016449. https://doi.org/10.1016/j.urology.2025.09.038
35. Salvio G, Ciarloni A, Ambo N, Bordoni M, Perrone M, Rossi S, Balercia G. Effects of glucagon-like peptide 1 receptor agonists on testicular dysfunction: A systematic review and meta-analysis. Andrology. 2025;13(8):2022-2034.
PMID: 40105090. PMCID: PMC12569732. https://doi.org/10.1111/andr.70022
36. Corona G, Sparano C, Romeo M, Rastrelli G, Vignozzi L, Maggi M. Emerging effects of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors on male sexual hormones and behaviors: Systematic review and meta-analysis. Andrology. 2026. Online ahead of print.
PMID: 42011503. https://doi.org/10.1111/andr.70238
37. Gregoric N, Sikonja J, Janez A, Jensterle M. Semaglutide improved sperm morphology in obese men with type 2 diabetes mellitus and functional hypogonadism. Diabetes Obes Metab. 2025;27(2):519–28.
PMID: 39511836. PMCID: PMC11701185. https://doi.org/10.1111/dom.16042
38. 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(2):qdaf381.
PMID: 41498523. https://doi.org/10.1093/jsxmed/qdaf381
39. Kuchakulla M, Poppas PJ, Wald G, Masterson JM, Gurayah AA, Bhambhvani HP, Kashanian JA. Impact of GLP-1 receptor agonists on male fertility: Emerging evidence and future directions. Urology. 2025:S0090-4295(25)00912-4.
PMID: 41016449. https://doi.org/10.1016/j.urology.2025.09.038
40. La Vignera S, Cannarella R, Garofalo V, Crafa A, Barbagallo F, Condorelli RA, Calogero AE. Short-term impact of tirzepatide on metabolic hypogonadism and body composition in patients with obesity: A controlled pilot study. Reprod Biol Endocrinol. 2025;23(1):92.
PMID: 40604795. PMCID: PMC12220628. https://doi.org/10.1186/s12958-025-01425-9
41. Клинические рекомендации. Мужское бесплодие. Общероссийская общественная организация «Российское общество урологов». Рубрикатор клинических рекомендаций Минздрава России. 2025. ID: 5_3. Доступ: https://cr.minzdrav.gov.ru/view-cr/5_3 (дата обращения – 18.03.2026). (Clinical guidelines. Male infertility. Russian Society of Urologists. Rubricator of clinical guidelines of the Ministry of Healthcare of Russia. 2025. ID: 5_3. URL: https://cr.minzdrav.gov.ru/view-cr/5_3 (date of access – 18.03.2026) (In Russ.)).
42. Alissou M, Demangeat T, Folope V, Van Elslande H, Lelandais H, Blanchemaison J et.al. Impact of semaglutide on fat mass, lean mass and muscle function in patients with obesity: The SEMALEAN study Diabetes Obes Metab. 2026;28(1):112–21.
PMID: 41068996. PMCID: PMC12673431. https://doi.org/10.1111/dom.70141
43. Hackett GI. long term cardiovascular safety of testosterone therapy: A review of the TRAVERSE study. World J Mens Health. 2025;43(2):282–90.
PMID: 39344109. PMCID: PMC11937349. https://doi.org/10.5534/wjmh.240081
44. Seminara G, Leuzzi M, Meduri L, Greco EA, Aversa A. Effects of testosterone undecanoate as add-on therapy in obese hypogonadal men that are late responders to tirzepatide: A pilot study. Minerva Endocrinol (Torino). 2026;51(2):104–17.
PMID: 41801155. https://doi.org/10.23736/S2724-6507.26.04541-0
45. Салухов В.В., Шустов С.Б., Петранков К.В. Влияние семаглутида и тирзепатида на скелетную мускулатуру: существенная польза или значительный риск? Медицинский совет. 2025;19(16):301–312. (Salukhov VV, Shustov SB, Petrankov KV. The impact of semaglutide and tirzepatide on skeletal muscle: Significant benefit or substantial risk? Meditsinskiy sovet = Medical Council. 2025;19(16):301–312 (In Russ.)).
EDN: BLBQXA. https://doi.org/10.21518/ms2025-467
About the Authors
Vladimir V. Salukhov, MD, Dr. Sci. (Medicine), professor, head of the first Department and clinic (continuing medical education, therapy) named after Academician N.S. Molchanov, S.M. Kirov Military Medical Academy, Saint Petersburg, Russian Federation.E-mail: vlasaluk@yandex.ru
ORCID: https://orcid.org/0000-0003-1851-0941
Ekaterina A. Troshina, MD, Dr. Sci. (Medicine), corresponding member of RAS, professor, director of the Institute of clinical endocrinology, Endocrinology Research Centre, Moscow, Russian Federation.
E-mail: troshina@inbox.ru
ORCID: https://orcid.org/0000-0002-8520-8702
Roman V. Rozhivanov, MD, Dr. Sci. (Medicine), professor, chief researcher at Endocrinology Research Centre, Moscow, Russian Federation.
E-mail: rrozhivanov@mail.ru
ORCID: https://orcid.org/0000-0002-5386-4289. eLibrary SPIN: 8052-3310
Galina A. Melnichenko, MD, Dr. Sci. (Medicine), professor, academician of RAS, head of the Department of clinical endocrinology of the Institute of higher and continuing professional education, deputy director for research, Endocrinology Research Centre, Moscow, Russian Federation.
E-mail: teofrast2000@mail.ru
ORCID: https://orcid.org/0000-0002-5634-7877. eLibrary SPIN: 8615-0038
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