Male Hypogonadism (According to the Materials of the European Association of Urology)


Ihor Gorpynchenko
Yurii Gurzhenko
Volodymyr Spyrydonenko


Male hypogonadism is a clinical syndrome which is the result of insufficient production of the sex hormone testosterone by the testicles and the number of spermatozoa.

The article reveals modern views on the physiology and pathophysiology of testosteroneogenesis in the male organism, provides information on the etiology, pathogenesis, classification, diagnosis and modern treatment of hypogonadism in men. Literature on the results of global and European researches in recent years, as well as materials of the Guideline of the European Association of Urology for 2022, were used in the article.

An individual therapeutic approach to each patient with hypogonadism was demonstrated. The importance of diagnosis of chronic and systemic comorbid diseases that cause the risk of hypogonadism, the need to determine the body mass index and the measurement of waist circumference, the size of the testicles, the penis and the presence of secondary sexual characteristic was established.

The article includes necessary biochemical and instrumental studies for the diagnosis of hypogonadism.

Specific contraindications for hormone replacement therapy are identified. Absolute contraindications for testosterone therapy are indicated: topically widespread or metastatic prostate cancer (PC), breast cancer of men; men who desire to have children; hematocrit level >54%; uncontrolled or poorly controlled stagnant heart failure. Relative contraindications include IPSS>19, initial hematocrit of 48-50 %, venous thromboembolism in a family history.

The article also provides recommendations for testosterone therapy. It has been proven that testosterone therapy improves mild forms of erectile dysfunction (ED) and libido in men with hypogonade states; improves the frequency of sexual intercourses, orgasm and general pleasure; increases low-fat mass, reduces fat and improves insulin resistance; normalizes body weight, waist circumference and lipid profile; relieves the symptoms of depression in men with hypogonadism; improves bone mineral density. It has been demonstrated that the use of testosterone therapy in eugonadal men is not indicated. Testosterone therapy should be used as first-line treatment in patients with symptomatic hypogonadism and moderate ED. In addition, it is necessary to use a combination of type 5 phosphodiesterase inhibitors and testosterone treatment in more severe ED forms. It is also necessary to use standard medical treatments for severe symptoms of depression and osteoporosis.

The therapy of hypogonadism, non-medication and medication, the necessary medicines and the peculiarities of their use are widely described. The article shows that weight loss due to low calorie diet and regular physical activity leads to a slight improvement in testosterone levels, testosterone gels and prolonged injection drugs are testosterone drugs have the best safety profile, and gonadotropin treatment can be used in men with secondary hypogonadism.

It is noted that before the treatment with testosterone, it is necessary to treat organic causes of hypogonadism (for example, pituitary tumors, hyperprolactinemia, etc.), improve lifestyle and reduce body weight in persons with obesity; cancel drugs that can impair testosterone production.

Much attention is paid to the risk factors by the treatment with testosterone. Testosterone therapy is contraindicated for men with secondary hypogonadism who wish fertility, men with active PC or breast cancer.

Restoration of testosterone concentration in serum relieves the symptoms and signs of hypogonadism in men after 3 months of treatment. Therefore, testosterone therapy leads to improvement of the quality of patient’s life.


How to Cite
Gorpynchenko, I., Gurzhenko, Y., & Spyrydonenko, V. (2022). Male Hypogonadism (According to the Materials of the European Association of Urology). Health of Man, (4), 5–23.
Topical issues
Author Biographies

Ihor Gorpynchenko, Acad. O. F. Vozianov Institute of Urology NAMS of Ukraine

Ihor I. Gorpynchenko,

MD, PhD, DSc, Professor, Head of Department of Sexopathology and Andrology

Yurii Gurzhenko, Acad. O. F. Vozianov Institute of Urology NAMS of Ukraine

Yurii M. Gurzhenko,

MD, PhD, DSc, Professor, Chief Reseacher at the Department of Sexopathology and Andrology

Volodymyr Spyrydonenko, Acad. O. F. Vozianov Institute of Urology NAMS of Ukraine

Volodymyr V. Spyrydonenko,

MD, PhD, Associate Professor, Senior Researcher at the Department of Sexopathology and Andrology


Salonia, A, Rastrelli G, Hackett G, Seminara SB, Huhtaniemi IT, Rey RA et al. Paediatric and adult-onset male hypogonadism. Nat Rev Dis Primers. 2019;5(1):38. doi: 10.1038/s41572-019-0087-y.

Nieschlag E, et al. Andrology: male reproductive health and dysfunction: 3rd edn [Internet]. Heidelberg: 2010. Available from:

Khera M, Adaikan G, Buvat J, Carrier S, El-Meliegy A, Hatzimouratidis K, et al. Diagnosis and Treatment of Testosterone Deficiency: Recommendations From the Fourth International Consultation for Sexual Medicine (ICSM 2015). J Sex Med. 2016;13(12):1787–804. doi: 10.1016/j.jsxm.2016.10.009.

Wu FC, Tajar A, Pye SR, Silman AJ, Finn JD, O’Neill TW, et al. Hypothalamicpituitary-testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: the European Male Aging Study. J Clin Endocrinol Metab. 2008;93(7):2737–45. doi: 10.1210/jc.2007-1972.

Araujo AB, Dixon JM, Suarez EA, Murad MH, Guey LT, Wittert GA. Clinical review: Endogenous testosterone and mortality in men: a systematic review and meta-analysis. J Clin Endocrinol Metab, 2011;96(10):3007–19. doi: 10.1210/jc.2011-1137.

Wu FC, Tajar A, Beynon JM, Pye SR, Silman AJ, Finn JD, O’Neill TW et al. Identification of late-onset hypogonadism in middle-aged and elderly men. N Engl J Med. 2010;363(2):123–35. doi: 10.1056/NEJMoa0911101.

Zarotsky V, Huang M-Y, Carman W, Morgentaler A, Singhal P K, Coffin D, Jones TH, et al. Systematic literature review of the risk factors, comorbidities, and consequences of hypogonadism in men. Andrology. 2014;2(6):819–34. doi: 10.1111/andr.274.

Bonomi M, Rochira V, Pasquali D, Balercia G, Jannini EA, Ferlin A, et al. Klinefelter syndrome (KS): genetics, clinical phenotype and hypogonadism. J Endocrinol Invest. 2017. 40: 123. 2017;40(2):123–34. doi: 10.1007/s40618-016-0541-6.

Kanakis GA, Nieschlag E. Klinefelter syndrome: more than hypogonadism. Metabolism. 2018;86:135–44. doi: 10.1016/j.metabol.2017.09.017.

Aksglaede L, Link K, Giwercman A, Jorgensen N, Skakkebaek NE, Juul A. 47,XXY Klinefelter syndrome: clinical characteristics and age-specific recommendations for medical management. Am J Med Genet C Semin Med Genet. 2013;163C(1):55–63. doi: 10.1002/ajmg.c.31349.

Kelly DM, Jones TH. Testosterone and obesity. Obes Rev. 2015;16(7):581–606. doi: 10.1111/obr.12282.

Corona G, Isidori AM, Aversa A, Burnett AL, Maggi M. Endocrinologic Control of Men’s Sexual Desire and Arousal/Erection. J Sex Med. 2016;13(3):317–37. doi: 10.1016/j.jsxm.2016.01.007.

Muller M, Grobbee DE, den Tonkelaar I, Lamberts SW, van der Schouw YT. Endogenous sex hormones and metabolic syndrome in aging men. J Clin Endocrinol Metab. 2005;90(5):2618–23. doi: 10.1210/jc.2004-1158.

Dhindsa S, Prabhakar S, Sethi M, Bandyopadhyay A, Chaudhuri A, Dandona P. Frequent occurrence of hypogonadotropic hypogonadism in type 2 diabetes. J Clin Endocrinol Metab. 2004;89(11):5462–8. doi: 10.1210/jc.2004-0804.

Jones TH, Arver S, Behre HM, Buvat J, Meuleman E, Moncada I, et al. Testosterone replacement in hypogonadal men with type 2 diabetes and/or metabolic syndrome (the TIMES2 study). Diabetes Care. 2011;34(4):828–37. doi: 10.2337/dc10-1233.

Kalinchenko SY, Tishova YA, Mskhalaya GJ, Gooren LJ, Giltay EJ, Saad F. Effects of testosterone supplementation on markers of the metabolic syndrome and inflammation in hypogonadal men with the metabolic syndrome: the double-blinded placebo-controlled Moscow study. Clin Endocrinol (Oxf). 2010;73(5):602–12. doi: 10.1111/j.1365-2265.2010.03845.x.

Groti K, Žuran I, Antonič B, Foršnarič L, Pfeifer M. The impact of testosterone replacement therapy on glycemic control, vascular function, and components of the metabolic syndrome in obese hypogonadal men with type 2 diabetes. Aging Male. 2018;21(3):158–69. doi: 10.1080/13685538.2018.1468429.

Hackett G, Cole N, Bhartia M, Kennedy D, Raju J, Wilkinson P; BLAST Study Group. Testosterone replacement therapy improves metabolic parameters in hypogonadal men with type 2 diabetes but not in men with coexisting depression: the BLAST study. J Sex Med. 2014;11(3):840–56. doi: 10.1111/jsm.12404.

Yassin A, Haider A, Haider KS, Caliber M, Doros G, Saad F, Garvey WT. Testosterone Therapy in Men With Hypogonadism Prevents Progression From Prediabetes to Type 2 Diabetes: Eight-Year Data From a Registry Study. Diabetes Care. 2019;42(6):1104–11. doi: 10.2337/dc18-2388.

Kapoor D, Goodwin E, Channer KS, Jones TH. Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes. Eur J Endocrinol. 2006;154(6):899–906. doi: 10.1530/eje.1.02166.

Hackett G, Cole N, Mulay A, Strange RC, Ramachandran S. Long-term testosterone therapy in type 2 diabetes is associated with reduced mortality without improvement in conventional cardiovascular risk factors. BJU Int. 2019;123(3):519–29. doi: 10.1111/bju.14536.

Muraleedharan V, Marsh H, Kapoor D, Channer KS, Jones TH. Testosterone deficiency is associated with increased risk of mortality and testosterone replacement improves survival in men with type 2 diabetes. Eur J Endocrinol. 2013;169(6):725–33. doi: 10.1530/EJE-13-0321.

Hackett G, Cole N, Saghir A, Jones P, Strange RC, Ramachandran S. Testosterone undecanoate improves sexual function in men with type 2 diabetes and severe hypogonadism: results from a 30-week randomized placebo-controlled study. BJU Int. 2016;118(5):804–13. doi: 10.1111/bju.13516.

Miller WL, Auchus RJ. The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders. Endocr Rev. 2011;32(1):81–151. doi: 10.1210/er.2010-0013.

Santi D. Primary and Secondary Hypogonadism. In: Endocrinology of the Testis and Male Reproduction, M. Simoni & I.T. Huhtaniemi, editors. Springer International Publishing: Cham; 2017. 67 p.

Morelli A, Corona G, Filippi S, Ambrosini S, Forti G, Vignozzi L, Maggi M. Which patients with sexual dysfunction are suitable for testosterone replacement therapy? J Endocrinol Invest. 2007;30(10):880–8. doi: 10.1007/BF03349232.

Rosner W, Vesper H; Endocrine Society; American Association for Clinical Chemistry; American Association of Clinical Endocrinologists; Androgen Excess/PCOS Society; et al. Toward excellence in testosterone testing: a consensus statement. J Clin Endocrinol Metab. 2010;95(10):4542–8. doi: 10.1210/jc.2010-1314.

Stanworth RD, Kapoor D, Channer KS, Jones TH. Statin therapy is associated with lower total but not bioavailable or free testosterone in men with type 2 diabetes. Diabetes Care. 2009;32(4):541–6. doi: 10.2337/dc08-1183.

Skowron KJ, Booker K, Cheng C, Creed S, David BP, Lazzara PR, Lian A, Siddiqui Z, Speltz TE, Moore TW. Steroid receptor/coactivator binding inhibitors: An update. Mol Cell Endocrinol. 2019;493:110471. doi: 10.1016/j.mce.2019.110471

Francomano D, Greco EA, Lenzi A, Aversa A. CAG repeat testing of androgen receptor polymorphism: is this necessary for the best clinical management of hypogonadism? J Sex Med. 2013;10(10):2373–81. doi: 10.1111/jsm.12268.

Zitzmann M. Pharmacogenetics of testosterone replacement therapy. Pharmacogenomics. 2009;10(8):1341–9. doi: 10.2217/pgs.09.58.

Stanworth RD, Akhtar S, Channer KS, Jones TH. The role of androgen receptor CAG repeat polymorphism and other factors which affect the clinical response to testosterone replacement in metabolic syndrome and type 2 diabetes: TIMES2 sub-study. Eur J Endocrinol. 2013;170(2):193–200. doi: 10.1530/EJE-13-0703.

She ZY, Yang WX. Sry and SoxE genes: How they participate in mammalian sex determination and gonadal development? Semin Cell Dev Biol. 2017;63:13–22. doi: 10.1016/j.semcdb.2016.07.032.

Birnbaum W, Bertelloni S. Sex hormone replacement in disorders of sex development. Endocr Dev. 2014;27:149–59. doi: 10.1159/000363640

Richmond EJ, Rogol AD. Male pubertal development and the role of androgen therapy. Nat Clin Pract Endocrinol Metab. 2007;3(4):338–44. doi: 10.1038/ncpendmet0450.

Rochira V, Kara E, Carani C. The endocrine role of estrogens on human male skeleton. Int J Endocrinol. 2015;2015:165215. doi: 10.1155/2015/165215.

Rastrelli G, Corona G, Tarocchi M, Mannucci E, Maggi M. How to define hypogonadism? Results from a population of men consulting for sexual dysfunction. J Endocrinol Invest. 2016;39(4):473–84. doi: 10.1007/s40618-015-0425-1.

Tobiansky DJ, Wallin-Miller KG, Floresco SB, Wood RI, Soma KK. Androgen Regulation of the Mesocorticolimbic System and Executive Function. Front Endocrinol (Lausanne). 2018;9:279. doi: 10.3389/fendo.2018.00279.

Isidori AM, Buvat J, Corona G, Goldstein I, Jannini EA, Lenzi A, Porst H, Salonia A, Traish AM, Maggi M. A critical analysis of the role of testosterone in erectile function: from pathophysiology to treatment-a systematic review. Eur Urol. 2014;65(1):99–112. doi: 10.1016/j.eururo.2013.08.048.

Vignozzi L, Filippi S, Comeglio P, Cellai I, Morelli A, Marchetta M, Maggi M. Estrogen mediates metabolic syndrome-induced erectile dysfunction: a study in the rabbit. J Sex Med. 2014;11(12):2890–902. doi: 10.1111/jsm.12695.

Corona G, Jannini EA, Vignozzi L, Rastrelli G, Maggi M. The hormonal control of ejaculation. Nat Rev Urol. 2012;9(9):508–19. doi: 10.1038/nrurol.2012.147.

Giannetta E, Gianfrilli D, Barbagallo F, Isidori AM, Lenzi A. Subclinical male hypogonadism. Best Pract Res Clin Endocrinol Metab. 2012;26(4):539–50. doi: 10.1016/j.beem.2011.12.005.

Tajar A, Forti G, O’Neill TW, Lee DM, Silman AJ, Finn JD, Bartfai G, Boonen S, Casanueva FF, Giwercman A, Han TS, Kula K, Labrie F, Lean ME, Pendleton N, Punab M, Vanderschueren D, Huhtaniemi IT, Wu FC; EMAS Group. Characteristics of secondary, primary, and compensated hypogonadism in aging men: evidence from the European Male Ageing Study. J Clin Endocrinol Metab. 2010;95(4):1810–8. doi: 10.1210/jc.2009-1796.

Corona G, Rastrelli G, Dicuio M, Concetti S, Minnetti M, Pivonello R, Isidori A, Sforza A, Maggi M. Subclinical male hypogonadism. Minerva Endocrinol (Torino). 2021;46(3):252–61. doi: 10.23736/S2724-6507.20.03208-3.

Corona G, Pizzocaro A, Vena W, Rastrelli G, Semeraro F, Isidori AM, Pivonello R, Salonia A, Sforza A, Maggi M. Diabetes is most important cause for mortality in COVID-19 hospitalized patients: Systematic review and meta-analysis. Rev Endocr Metab Disord. 2021;22(2):275–96. doi: 10.1007/s11154-021-09630-8.

Salonia A, Corona G, Giwercman A, Maggi M, Minhas S, Nappi RE, Sofikitis N, Vignozzi L. SARS-CoV-2, testosterone and frailty in males (PROTEGGIMI): A multidimensional research project. Andrology. 2021;9(1):19–22. doi: 10.1111/andr.12811.

Pivonello R, Auriemma RS, Pivonello C, Isidori AM, Corona G, Colao A, Millar RP. Sex Disparities in COVID-19 Severity and Outcome: Are Men Weaker or Women Stronger? Neuroendocrinol. 2021;111(11):1066–85. doi: 10.1159/000513346.

Rastrelli G, Di Stasi V, Inglese F, Beccaria M, Garuti M, Di Costanzo D, et al. Low testosterone levels predict clinical adverse outcomes in SARS-CoV-2 pneumonia patients. Andrology. 2021;9(1):88–98. doi: 10.1111/andr.12821.

Salciccia S, Del Giudice F, Gentile V, Mastroianni CM, Pasculli P, Di Lascio G, et al. Interplay between male testosterone levels and the risk for subsequent invasive respiratory assistance among COVID-19 patients at hospital admission. Endocrine. 2020;70(2):206–10. doi: 10.1007/s12020-020-02515-x.

Cinislioglu AE, Cinislioglu N, Demirdogen SO, Sam E, Akkas F, Altay MS, et al. The relationship of serum testosterone levels with the clinical course and prognosis of COVID-19 disease in male patients: A prospective study. Andrology. 2022;10(1):24–33. doi: 10.1111/andr.13081.

Kadihasanoglu M, Aktas S, Yardimci E, Aral H, Kadioglu A. SARS-CoV-2 Pneumonia Affects Male Reproductive Hormone Levels: A Prospective, Cohort Study. J Sex Med. 2021;18(2):256–64. doi: 10.1016/j.jsxm.2020.11.007.

Salonia A, Pontillo M, Capogrosso P, Gregori S, Tassara M, Boeri L, et al. Severely low testosterone in males with COVID-19: A case-control study. Androl. 2021;9(4):1043–52. doi: 10.1111/andr.12993.

Dhindsa S, Zhang N, McPhaul MJ, Wu Z, Ghoshal AK, Erlich EC, et al. Association of Circulating Sex Hormones With Inflammation and Disease Severity in Patients With COVID-19. JAMA Netw Open. 2021;4(5):e2111398. doi: 10.1001/jamanetworkopen.2021.11398.

Lanser L, Burkert FR, Thommes L, Egger A, Hoermann G, Kaser S, et al. Testosterone Deficiency Is a Risk Factor for Severe COVID-19. Front Endocrinol (Lausanne). 2021;12:694083. doi: 10.3389/fendo.2021.694083.

Nie X, Qian L, Sun R, Huang B, Dong X, Xiao Q, et al. Multi-organ proteomic landscape of COVID-19 autopsies. Cell. 2021;184(3):775–791.e14. doi: 10.1016/j.cell.2021.01.004.

Gianzo M, Munoa-Hoyos I, Urizar-Arenaza I, Larreategui Z, Quintana F, Garrido N, et al. Angiotensin II type 2 receptor is expressed in human sperm cells and is involved in sperm motility. Fertil Steril. 2016;105(3):608–16. doi: 10.1016/j.fertnstert.2015.11.004.

Aitken RJ. COVID-19 and human spermatozoa-Potential risks for infertility and sexual transmission? Andrology. 2021;9(1):48–52. doi: 10.1111/andr.12859.

Turner HE, Wass JA. Gonadal function in men with chronic illness. Clin Endocrinol (Oxf). 1997;47(4):379–403. doi: 10.1046/j.1365-2265.1997.2611108.x.

Corona G, Maseroli E, Rastrelli G, Francomano D, Aversa A, Hackett GI, et al. Is late-onset hypogonadotropic hypogonadism a specific age-dependent disease, or merely an epiphenomenon caused by accumulating disease-burden? Minerva Endocrinol. 2016;41(2):196–210.

Guay A, Miller MG, McWhirter CL. Does early morning versus late morning draw time influence apparent testosterone concentration in men aged > or =45 years? Data from the Hypogonadism In Males study. Int J Impot Res. 2008;20(2):162–7. doi: 10.1038/sj.ijir.3901580.

Travison TG, Vesper HW, Orwoll E, Wu F, Kaufman JM, Wang Y, et al. Harmonized Reference Ranges for Circulating Testosterone Levels in Men of Four Cohort Studies in the United States and Europe. J Clin Endocrinol Metab. 2017;102(4):1161–73. doi: 10.1210/jc.2016-2935.

Gagliano-Juca T, Li Z, Pencina KM, Beleva YM, Carlson OD, Egan JM, et al. Oral glucose load and mixed meal feeding lowers testosterone levels in healthy eugonadal men. Endocrine. 2019;63(1):149–56. doi: 10.1007/s12020-018-1741-y.

Huhtaniemi IT, Tajar A, Lee DM, O’Neill TW, Finn JD, Bartfai G, et al. Comparison of serum testosterone and estradiol measurements in 3174 European men using platform immunoassay and mass spectrometry; relevance for the diagnostics in aging men. Eur J Endocrinol. 2012;166(6):983–91. doi: 10.1530/EJE-11-1051.

Corona G, Giagulli VA, Maseroli E, Vignozzi L, Aversa A, Zitzmann M, et al. THERAPY OF ENDOCRINE DISEASE: Testosterone supplementation and body composition: results from a meta-analysis study. Eur J Endocrinol. 2016;174(3):R99–116. doi: 10.1530/EJE-15-0262.

Corona G, Rastrelli G, Morgentaler A, Sforza A, Mannucci E, Maggi M. Meta-analysis of Results of Testosterone Therapy on Sexual Function Based on International Index of Erectile Function Scores. Eur Urol. 2017;72(6):1000–11. doi: 10.1016/j.eururo.2017.03.032.

Bhasin S, Brito JP, Cunningham GR, Hayes FJ, Hodis HN, Matsumoto AM, et al. Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2018;103(5):1715–44. doi: 10.1210/jc.2018-00229.

Isidori AM, Balercia G, Calogero AE, Corona G, Ferlin A, Francavilla S, et al. Outcomes of androgen replacement therapy in adult male hypogonadism: recommendations from the Italian society of endocrinology. J Endocrinol Invest. 2015;38(1):103–12. doi: 10.1007/s40618-014-0155-9.

Dalvi M, Walker BR, Strachan MW, Zammitt NN, Gibb FW. The prevalence of structural pituitary abnormalities by MRI scanning in men presenting with isolated hypogonadotrophic hypogonadism. Clin Endocrinol (Oxf). 2016;84(6):858–61. doi: 10.1111/cen.13015.

Molitch ME. Diagnosis and Treatment of Pituitary Adenomas: A Review. JAMA. 2017;317(5):516–24. doi: 10.1001/jama.2016.19699.

Cayan S, Uğuz M, Saylam B, Akbay E. Effect of serum total testosterone and its relationship with other laboratory parameters on the prognosis of coronavirus disease 2019 (COVID-19) in SARS-CoV-2 infected male patients: a cohort study. Aging Male. 2020;23(5):1493–503. doi: 10.1080/13685538.2020.1807930.

Rastrelli G, Vignozzi L, Corona G, Maggi M. Testosterone and Benign Prostatic Hyperplasia. Sex Med Rev. 2019;7(2):259–71. doi: 10.1016/j.sxmr.2018.10.006.

Colpi GM, Francavilla S, Haidl G, Link K, Behre HM, Goulis DG, et al. European Academy of Andrology guideline Management of oligo-astheno-teratozoospermia. Androl. 2018;6(4):513–24. doi: 10.1111/andr.12502.

Corona G, Rastrelli G, Maggi M. The pharmacotherapy of male hypogonadism besides androgens. Expert Opin Pharmacother. 2015;16(3):369–87. doi: 10.1517/14656566.2015.993607.

Mirone V, Debruyne F, Dohle G, Salonia A, Sofikitis N, Verze P, et al. European Association of Urology Position Statement on the Role of the Urologist in the Management of Male Hypogonadism and Testosterone Therapy. Eur Urol. 2017;72(2):164–7. doi: 10.1016/j.eururo.2017.02.022.

Nieschlag E. Late-onset hypogonadism: a concept comes of age. Androl. 2020;8(6):1506–11. doi: 10.1111/andr.12719.

Huo S, Scialli AR, McGarvey S, Hill E, Tugertimur B, Hogenmiller A, et al. Treatment of Men for «Low Testosterone»: A Systematic Review. PLoS One. 2016;11(9):e0162480. doi: 10.1371/journal.pone.0162480.

Rastrelli G, Guaraldi F, Reismann Y, Sforza A, Isidori AM, Maggi M, et al. Testosterone Replacement Therapy for Sexual Symptoms. Sex Med Rev. 2019;7(3):464–75. doi: 10.1016/j.sxmr.2018.11.005.

Snyder PJ, Bhasin S, Cunningham GR, Matsumoto AM, Stephens-Shields AJ, Cauley JA, et al. Lessons From the Testosterone Trials. Endocr Rev. 2018;39(3):369–86. doi: 10.1210/er.2017-00234.

Corona G, Giagulli VA, Maseroli E, Vignozzi L, Aversa A, Zitzmann M, et al. Testosterone supplementation and body composition: results from a meta-analysis of observational studies. J Endocrinol Invest. 2016;39(9):967–81. doi: 10.1007/s40618-016-0480-2.

Traish AM. Testosterone and weight loss: the evidence. Curr Opin Endocrinol Diabetes Obes. 2014;21(5):313–22. doi: 10.1097/MED.0000000000000086.

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):162–70. doi: 10.1038/ijo.2015.139.

Rosen RC, Wu F, Behre HM, Porst H, Meuleman EJH, Maggi M, et al. Quality of Life and Sexual Function Benefits of Long-Term Testosterone Treatment: Longitudinal Results From the Registry of Hypogonadism in Men (RHYME). J Sex Med. 2017;14(9):1104–15. doi: 10.1016/j.jsxm.2017.07.004.

Smith JB, Rosen J, Colbert A. Low Serum Testosterone in Outpatient Psychiatry Clinics: Addressing Challenges to the Screening and Treatment of Hypogonadism. Sex Med Rev. 2018;6(1):69–76. doi: 10.1016/j.sxmr.2017.08.007.

Walther A, Breidenstein J, Miller R. Association of Testosterone Treatment With Alleviation of Depressive Symptoms in Men: A Systematic Review and Meta-analysis. JAMA Psychiatry. 2019;76(1):31–40. doi: 10.1001/jamapsychiatry.2018.2734.

Rochira V, Antonio L, Vanderschueren D. EAA clinical guideline on management of bone health in the andrological out patient clinic. Androl. 2018;6(2):272–85. doi: 10.1111/andr.12470.

Isidori AM, Giannetta E, Greco EA, Gianfrilli D, Bonifacio V, Isidori A, et al. Effects of testosterone on body composition, bone metabolism and serum lipid profile in middle-aged men: a meta-analysis. Clin Endocrinol (Oxf). 2005;63(3):280–93. doi: 10.1111/j.1365-2265.2005.02339.x.

Tracz MJ, Sideras K, Bolona ER, Haddad RM, Kennedy CC, Uraga MV, et al. Testosterone use in men and its effects on bone health. A systematic review and meta-analysis of randomized placebo-controlled trials. J Clin Endocrinol Metab. 2006;91(6):2011–6. doi: 10.1210/jc.2006-0036.

Nieschlag E, Vorona E. MECHANISMS IN ENDOCRINOLOGY: Medical consequences of doping with anabolic androgenic steroids: effects on reproductive functions. Eur J Endocrinol. 2015;173(2):R47–58. doi: 10.1530/EJE-15-0080.

Grossmann M. Hypogonadism and male obesity: Focus on unresolved questions. Clin Endocrinol (Oxf). 2018;89(1):11–21. doi: 10.1111/cen.13723.

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. doi: 10.1530/EJE-12-0955.

Corona G, Rastrelli G, Morelli A, Sarchielli E, Cipriani S, Vignozzi L, et al. Treatment of Functional Hypogonadism Besides Pharmacological Substitution. World J Mens Health. 2020;38(3):256–70. doi: 10.5534/wjmh.190061.

Pasquali R, Casanueva F, Haluzik M, van Hulsteijn L, Ledoux S, Monteiro MP, et al. European Society of Endocrinology Clinical Practice Guideline: Endocrine work-up in obesity. Eur J Endocrinol. 2020;182(1):G1–G32. doi: 10.1530/EJE-19-0893.

Wittert G, Bracken K, Robledo KP, Grossmann M, Yeap BB, Handelsman DJ, et al. Testosterone treatment to prevent or revert type 2 diabetes in men enrolled in a lifestyle programme (T4DM): a randomised, double-blind, placebo-controlled, 2-year, phase 3b trial. Lancet Diabetes Endocrinol. 2021;9(1):32–45. doi: 10.1016/S2213-8587(20)30367-3.

Rastrelli G, Maggi M, Corona G. Pharmacological management of late-onset hypogonadism. Expert Rev Clin Pharmacol. 2018;11(4):439–58. doi: 10.1080/17512433.2018.1445969.

Ohlander SJ, Varghese B, Pastuszak AW. Erythrocytosis Following Testosterone Therapy. Sex Med Rev. 2018;6(1):77–85. doi: 10.1016/j.sxmr.2017.04.001.

Rastrelli G, Corona G, Mannucci E, Maggi M. Factors affecting spermatogenesis upon gonadotropin-replacement therapy: a meta-analytic study. Andrology. 2014;2(6):794–808. doi: 10.1111/andr.262.

Fentiman IS. The endocrinology of male breast cancer. Endocr Relat Cancer. 2018;25(6):365–73. doi: 10.1530/ERC-18-0117.

Traish AM, Johansen V. Impact of Testosterone Deficiency and Testosterone Therapy on Lower Urinary Tract Symptoms in Men with Metabolic Syndrome. World J Mens Health. 2018;36(3):199–222. doi: 10.5534/wjmh.180032.

Okada K, Miyake H, Ishida T, Sumii K, Enatsu N, Chiba K, et al. Improved Lower Urinary Tract Symptoms Associated With Testosterone Replacement Therapy in Japanese Men With Late-Onset Hypogonadism. Am J Mens Health. 2018;12(5):1403–08. doi: 10.1177/1557988316652843.

Lopez DS, Advani S, Tsilidis KK, Wang R, Canfield S. Endogenous and exogenous testosterone and prostate cancer: decreased-, increased- or null-risk? Transl Androl Urol. 2017;6(3):566–79. doi: 10.21037/tau.2017.05.35.

Gray H, Seltzer J, Talbert RL. Recurrence of prostate cancer in patients receiving testosterone supplementation for hypogonadism. Am J Health Syst Pharm. 2015;72(7):536–41. doi: 10.2146/ajhp140128.

Kardoust PM, Abufaraj M, Fajkovic H, Kimura S, Iwata T, D’Andrea D, Karakiewicz PI, et al. Oncological safety of testosterone replacement therapy in prostate cancer survivors after definitive local therapy: A systematic literature review and meta-analysis. Urol Oncol. 2019;37(10):637–46. doi: 10.1016/j.urolonc.2019.06.007.

Corona G, Rastrelli G, Di Pasquale G, Sforza A, Mannucci E, Maggi M. Endogenous Testosterone Levels and Cardiovascular Risk: Meta-Analysis of Observational Studies. J Sex Med. 2018;15(9):1260–71. doi: 10.1016/j.jsxm.2018.06.012.

Malkin CJ, Pugh PJ, Morris PD, Asif S, Jones TH, Channer KS. Low serum testosterone and increased mortality in men with coronary heart disease. Heart. 2010;96(22):1821–5. doi: 10.1136/hrt.2010.195412.

Haring R, Völzke H, Steveling A, Krebs A, Felix SB, Schöfl C, et al. Low serum testosterone levels are associated with increased risk of mortality in a population-based cohort of men aged 20-79. Eur Heart J. 2010;31(12):1494–501. doi: 10.1093/eurheartj/ehq009.

Khaw KT, Dowsett M, Folkerd E, Bingham S, Wareham N, Luben R, et al. Endogenous testosterone and mortality due to all causes, cardiovascular disease, and cancer in men: European prospective investigation into cancer in Norfolk (EPIC-Norfolk) Prospective Population Study. Circulation. 2007;116(23):2694–701. doi: 10.1161/CIRCULATIONAHA.107.719005.

Laughlin GA, Barrett-Connor E, Bergstrom J. Low serum testosterone and mortality in older men. J Clin Endocrinol Metab. 2008;93(1):68–75. doi: 10.1210/jc.2007-1792.

Shores MM, Matsumoto AM, Sloan KL, Kivlahan DR. Low serum testosterone and mortality in male veterans. Arch Intern Med. 2006;166(15):1660–5. doi: 10.1001/archinte.166.15.1660.

Vikan T, Schirmer H, Njølstad I, Svartberg J. Endogenous sex hormones and the prospective association with cardiovascular disease and mortality in men: the Tromso Study. Eur J Endocrinol. 2009;161(3):435–42. doi: 10.1530/EJE-09-0284.

Guo C, Gu W, Liu M, Peng BO, Yao X, Yang B, Zheng J. Efficacy and safety of testosterone replacement therapy in men with hypogonadism: A meta-analysis study of placebo-controlled trials. Exp Ther Med. 2016;11(3):853–63. doi: 10.3892/etm.2015.2957.

Corona G, Rastrelli G, Monami M, Guay A, Buvat J, Sforza A, et al. Hypogonadism as a risk factor for cardiovascular mortality in men: a meta-analytic study. Eur J Endocrinol. 2011;165(5):687–701. doi: 10.1530/EJE-11-0447.

Malkin CJ, Pugh PJ, West JN, van Beek EJ, Jones TH, Channer KS. Testosterone therapy in men with moderate severity heart failure: a double-blind randomized placebo controlled trial. Eur Heart J. 2006;27(1):57–64. doi: 10.1093/eurheartj/ehi443.

Caminiti G, Volterrani M, Iellamo F, Marazzi G, Massaro R, Miceli M et al. Effect of long-acting testosterone treatment on functional exercise capacity, skeletal muscle performance, insulin resistance, and baroreflex sensitivity in elderly patients with chronic heart failure a double-blind, placebo-controlled, randomized study. J Am Coll Cardiol. 2009;54(10):919–27. doi: 10.1016/j.jacc.2009.04.078.

Pugh PJ, Jones RD, West JN, Jones TH, Channer KS. Testosterone treatment for men with chronic heart failure. Heart. 2004;90(4):446–7. doi: 10.1136/hrt.2003.014639.

Sharma R, Oni OA, Gupta K, Chen G, Sharma M, Dawn B,et al. Normalization of testosterone level is associated with reduced incidence of myocardial infarction and mortality in men. Eur Heart J. 2015;36(40):2706–15. doi: 10.1093/eurheartj/ehv346.

Gagnon DR, Zhang TJ, Brand FN, Kannel WB. Hematocrit and the risk of cardiovascular disease – the Framingham study: a 34-year follow-up. Am Heart J. 1994;127(3):674–82. doi: 10.1016/0002-8703(94)90679-3.

Brown DW, Giles WH, Croft JB. Hematocrit and the risk of coronary heart disease mortality. Am Heart J. 2001;142(4):657–63. doi: 10.1067/mhj.2001.118467.

Puddu PE, Lanti M, Menotti A, Mancini M, Zanchetti A, Cirillo M, et al. Red blood cell count in short-term prediction of cardiovascular disease incidence in the Gubbio population study. Acta Cardiol. 2002;57(3):177–85. doi: 10.2143/AC.57.3.2005387.

Boffetta P, Islami F, Vedanthan R, Pourshams A, Kamangar F, Khademi H, et al. A U-shaped relationship between haematocrit and mortality in a large prospective cohort study. Int J Epidemiol. 2013;42(2):601–15. doi: 10.1093/ije/dyt013.

Madaeva IM, Berdina ON, Semenova NV, Madaev VV, Rychkova LV, Kolesnikova LI. Sindrom obstruktivnogo apnoé sna i vozrastnoĭ gipogonadizm [Obstructive sleep apnea syndrome and age-related hypohonadism]. Zh Nevrol Psikhiatr Im S S Korsakova. 2017;117(4. Vyp.2):79–83. doi: 10.17116/jnevro20171174279-83.

Mottet N, De Santis M, Briers E, Bourke L, Gillessen S, Grummet JP, et al. Updated Guidelines for Metastatic Hormone-sensitive Prostate Cancer: Abiraterone Acetate Combined with Castration Is Another Standard. Eur Urol. 2018;73(3):316–21. doi: 10.1016/j.eururo.2017.09.029.

Corona G, Dicuio M, Rastrelli G, Maseroli E, Lotti F, Sforza A, et al. Testosterone treatment and cardiovascular and venous thromboembolism risk: what is ‘new’? J Investig Med. 2017;65(6):964–73. doi: 10.1136/jim-2017-000411.