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Diagnosis and Treatment of Primary, Secondary, and Functional Male Hypogonadism: A Narrative Review

Year 2025, Volume: 78 Issue: 4, 295 - 306, 31.12.2025

Elifnaz Mutlu , Esra Eraslan Aydemir , Rifat Emral

https://doi.org/10.65092/autfm.1762927

Abstract

Male hypogonadism refers to a condition characterized by reduced testosterone production or impaired sperm production. Traditionally, it was classified into two categories: congenital and acquired hypogonadism. However, with the emergence of the concept of functional hypogonadism, which develops as a result of chronic diseases, medications, or aging, male hypogonadism is now considered under three subtypes.
The clinical manifestations and treatment strategies vary depending on the underlying cause of hypogonadism. Additionally, the desire for fertility significantly influences the treatment protocol.
This systematic review examines the diagnostic and therapeutic approaches to primary, secondary, and functional male hypogonadism.

Keywords

Testosterone Functional Hypogonadism Fertility Androgen Deficiency aging Late-Onset Hypogonadism

References

  • 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 Endocr Metab. 2018;103(5):1715-44.
  • Tajar A, Huhtaniemi IT, O'Neill TW, Finn JD, Pye SR, Lee DM, et al. Characteristics of androgen deficiency in late-onset hypogonadism: results from the European Male Aging Study (EMAS). J Clin Endocrinol Metab. 2012;97(5):1508-16.
  • Al-Sharefi A, Quinton R. Current National and International Guidelines for the Management of Male Hypogonadism: Helping Clinicians to Navigate Variation in Diagnostic Criteria and Treatment Recommendations. Endocrinol Metab (Seoul). 2020;35(3):526-40.
  • Young J, Xu C, Papadakis GE, Acierno JS, Maione L, Hietamaki J, et al. Clinical Management of Congenital Hypogonadotropic Hypogonadism. Endocr Rev. 2019;40(2):669-710.
  • Paulsen CA, Gordon DL, Carpenter RW, Gandy HM, Drucker WD. Klinefelter's syndrome and its variants: a hormonal and chromosomal study. Recent Prog Horm Res. 1968;24:321-63.
  • Gravholt CH, Chang S, Wallentin M, Fedder J, Moore P, Skakkebaek A. Klinefelter Syndrome: Integrating Genetics, Neuropsychology, and Endocrinology. Endocr Rev. 2018;39(4):389-423.
  • Gül S, Vloeberghs V, Gies I, Goossens E. Testicular mosaicism in non-mosaic postpubertal Klinefelter patients with focal spermatogenesis and in non-mosaic prepubertal Klinefelter boys. Hum Reprod. 2024;39(10):2210-20.
  • Fruhmesser A, Kotzot D. Chromosomal variants in klinefelter syndrome. Sex Dev. 2011;5(3):109-23.
  • Swerdlow AJ, Schoemaker MJ, Higgins CD, Wright AF, Jacobs PA. Cancer incidence and mortality in men with Klinefelter syndrome: a cohort study. J Natl Cancer Inst. 2005;97(16):1204-10.
  • Chang S, Skakkebaek A, Davis SM, Gravholt CH. Morbidity in Klinefelter syndrome and the effect of testosterone treatment. Am J Med Genet C Semin Med Genet. 2020;184(2):344-55.
  • Alowaysi M, Fiacco E, Astro V, Adamo A. Establishment of iPSC lines from a high-grade Klinefelter Syndrome patient (49-XXXXY) and two genetically matched healthy relatives (KAUSTi003-A, KAUSTi004-A, KAUSTi004-B, KAUSTi005-A, KAUSTi005-B, KAUSTi005-C). Stem Cell Res. 2020;49:102008.
  • Huhtaniemi I. Late-onset hypogonadism: current concepts and controversies of pathogenesis, diagnosis and treatment. Asian J Androl. 2014;16(2):192-202.
  • El Houate B, Rouba H, Sibai H, Barakat A, Chafik A, Chadli el B, et al. Novel mutations involving the INSL3 gene associated with cryptorchidism. J Urol. 2007;177(5):1947-51.
  • Foresta C, Moro E, Garolla A, Onisto M, Ferlin A. Y chromosome microdeletions in cryptorchidism and idiopathic infertility. J Clin Endocrinol Metab. 1999;84(10):3660-5.
  • Mendonca BB, Inacio M, Arnhold IJ, Costa EM, Bloise W, Martin RM, et al. Male pseudohermaphroditism due to 17 beta-hydroxysteroid dehydrogenase 3 deficiency. Diagnosis, psychological evaluation, and management. Medicine (Baltimore). 2000;79(5):299-309.
  • Batista RL, Costa EMF, Rodrigues AS, Gomes NL, Faria JA, Jr., Nishi MY, et al. Androgen insensitivity syndrome: a review. Arch Endocrinol Metab. 2018;62(2):227-35.
  • Ramos L. Novel non-synonymous and synonymous gene variants of SRD5A2 in patients with 46,XY-DSD and DSD-free subjects. PLoS One. 2025;20(3):e0316497.
  • Harper P, Penny R, Foley TP, Jr., Migeon CJ, Blizzard RM. Gonadal function in males with myotonic dystrophy. J Clin Endocrinol Metab. 1972;35(6):852-6.
  • Beard CM, Benson RC, Jr., Kelalis PP, Elveback LR, Kurland LT. The incidence and outcome of mumps orchitis in Rochester, Minnesota, 1935 to 1974. Mayo Clin Proc. 1977;52(1):3-7.
  • Brauner R, Czernichow P, Cramer P, Schaison G, Rappaport R. Leydig-cell function in children after direct testicular irradiation for acute lymphoblastic leukemia. N Engl J Med. 1983;309(1):25-8.
  • Handelsman DJ, Turtle JR. Testicular damage after radioactive iodine (I-131) therapy for thyroid cancer. Clin Endocrinol (Oxf). 1983;18(5):465-72.
  • Sharma A, Mollier J, Brocklesby RWK, Caves C, Jayasena CN, Minhas S. Endocrine-disrupting chemicals and male reproductive health. Reprod Med Biol. 2020;19(3):243-53.
  • Whorton D, Krauss RM, Marshall S, Milby TH. Infertility in male pesticide workers. Lancet. 1977;2(8051):1259-61.
  • Laitinen EM, Vaaralahti K, Tommiska J, Eklund E, Tervaniemi M, Valanne L, et al. Incidence, phenotypic features and molecular genetics of Kallmann syndrome in Finland. Orphanet J Rare Dis. 2011;6:41.
  • Boehm U, Bouloux PM, Dattani MT, de Roux N, Dodé C, Dunkel L, et al. Expert consensus document: European Consensus Statement on congenital hypogonadotropic hypogonadism--pathogenesis, diagnosis and treatment. Nat Rev Endocrinol. 2015;11(9):547-64.
  • Millar AC, Faghfoury H, Bieniek JM. Genetics of hypogonadotropic hypogonadism. Transl Androl Urol. 2021;10(3):1401-9.
  • Balasubramanian R. Isolated gonadotropin-releasing hormone deficiency UpToDate2025 [Available from: https://www.uptodate.com/contents/isolated-gonadotropin-releasing-hormone-deficiency-idiopathic-hypogonadotropic-hypogonadism?search=ısolated%20gonadotropin%20releasing&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1.
  • Dwyer AA, McDonald IR, Cangiano B, Giovanelli L, Maione L, Silveira LFG, et al. Classes and predictors of reversal in male patients with congenital hypogonadotropic hypogonadism: a cross-sectional study of six international referral centres. Lancet Diabetes Endocrinol. 2024;12(4):257-66.
  • Shalender Bhasin JLJ. Disorders of the testes and male reproductive system. In: Joseph Loscalzo DLK, Dan L. Longo, Anthony S. Fauci, Stephen L. Hauser, J. Larry Jameson, editor. Harrison’s Princeples of Internal Medicine. 21st ed2022.
  • Lofrano-Porto A, Barra GB, Giacomini LA, Nascimento PP, Latronico AC, Casulari LA, et al. Luteinizing hormone beta mutation and hypogonadism in men and women. N Engl J Med. 2007;357(9):897-904.
  • Basciani S, Watanabe M, Mariani S, Passeri M, Persichetti A, Fiore D, et al. Hypogonadism in a patient with two novel mutations of the luteinizing hormone β-subunit gene expressed in a compound heterozygous form. J Clin Endocrinol Metab. 2012;97(9):3031-8.
  • Phillip M, Arbelle JE, Segev Y, Parvari R. Male hypogonadism due to a mutation in the gene for the beta-subunit of follicle-stimulating hormone. N Engl J Med. 1998;338(24):1729-32.
  • Salenave S, Trabado S, Maione L, Brailly-Tabard S, Young J. Male acquired hypogonadotropic hypogonadism: diagnosis and treatment. Ann Endocrinol (Paris). 2012;73(2):141-6.
  • Esquivel-Zuniga R, Rogol AD. Functional hypogonadism in adolescence: an overlooked cause of secondary hypogonadism. Endocr Connect. 2023;12(11).
  • Lee CP, Chiu YW, Chu CL, Chen Y, Jiang KH, Chen JL, et al. A reliability generalization meta-analysis of coefficient alpha and test-retest coefficient for the aging males' symptoms (AMS) scale. Aging Male. 2016;19(4):244-53.
  • Purifoy FE, Koopmans LH, Mayes DM. Age differences in serum androgen levels in normal adult males. Hum Biol. 1981;53(4):499-511.
  • Ly LP, Sartorius G, Hull L, Leung A, Swerdloff RS, Wang C, et al. Accuracy of calculated free testosterone formulae in men. Clin Endocrinol (Oxf). 2010;73(3):382-8.
  • Mingrone G, Greco AV, Giancaterini A, Scarfone A, Castagneto M, Pugeat M. Sex hormone-binding globulin levels and cardiovascular risk factors in morbidly obese subjects before and after weight reduction induced by diet or malabsorptive surgery. Atherosclerosis. 2002;161(2):455-62.
  • Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab. 1999;84(10):3666-72.
  • Campbell MJ, Lotti F, Baldi E, Schlatt S, Festin MPR, Björndahl L, et al. Distribution of semen examination results 2020 - A follow up of data collated for the WHO semen analysis manual 2010. Andrology. 2021;9(3):817-22.
  • Matsumoto AM. Diagnosis and Evaluation of Hypogonadism. Endocrinol Metab Clin North Am. 2022;51(1):47-62.
  • A. Salonia (Chair) LB, P. Capogrosso, G. Corona. EAU Guidelines on Sexual and Reproductive Health. 2025.
  • Bassil N, Alkaade S, Morley JE. The benefits and risks of testosterone replacement therapy: a review. Ther Clin Risk Manag. 2009;5(3):427-48.
  • 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.
  • Zitzmann M, Nieschlag E. Hormone substitution in male hypogonadism. Mol Cell Endocrinol. 2000;161(1-2):73-88.
  • Lincoff AM, Bhasin S, Flevaris P, Mitchell LM, Basaria S, Boden WE, et al. Cardiovascular Safety of Testosterone-Replacement Therapy. New England Journal of Medicine. 2023;389(2):107-17.
  • Pencina KM, Travison TG, Cunningham GR, Lincoff AM, Nissen SE, Khera M, et al. Effect of Testosterone Replacement Therapy on Sexual Function and Hypogonadal Symptoms in Men with Hypogonadism. J Clin Endocrinol Metab. 2024;109(2):569-80.
  • Behre HM, Kliesch S, Leifke E, Link TM, Nieschlag E. Long-term effect of testosterone therapy on bone mineral density in hypogonadal men. J Clin Endocrinol Metab. 1997;82(8):2386-90.
  • Kanakis GA, Nieschlag E. Klinefelter syndrome: more than hypogonadism. Metabolism. 2018;86:135-44.
  • Esteves SC, Achermann APP, Simoni M, Santi D, Casarini L. Male infertility and gonadotropin treatment: What can we learn from real-world data? Best Pract Res Clin Obstet Gynaecol. 2023;86:102310.
  • Corona G, Rastrelli G, Sparano C, Vignozzi L, Sforza A, Maggi M. Pharmacological management of testosterone deficiency in men current advances and future directions. Expert Rev Clin Pharmacol. 2024;17(8):665-81.
  • 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.
  • Jaschke N, Wang A, Hofbauer LC, Rauner M, Rachner TD. Late-onset hypogonadism: Clinical evidence, biological aspects and evolutionary considerations. Ageing Res Rev. 2021;67:101301.
  • Snyder PJ, Bhasin S, Cunningham GR, Matsumoto AM, Stephens-Shields AJ, Cauley JA, et al. Effects of Testosterone Treatment in Older Men. N Engl J Med. 2016;374(7):611-24.
  • Anderson RA, Martin CW, Kung AW, Everington D, Pun TC, Tan KC, et al. 7Alpha-methyl-19-nortestosterone maintains sexual behavior and mood in hypogonadal men. J Clin Endocrinol Metab. 1999;84(10):3556-62.
  • Nieschlag E, Kumar N, Sitruk-Ware R. 7α-methyl-19-nortestosterone (MENTR): the population council's contribution to research on male contraception and treatment of hypogonadism. Contraception. 2013;87(3):288-95.
  • Solomon ZJ, Mirabal JR, Mazur DJ, Kohn TP, Lipshultz LI, Pastuszak AW. Selective Androgen Receptor Modulators: Current Knowledge and Clinical Applications. Sex Med Rev. 2019;7(1):84-94.

Birincil, İkincil ve Fonksiyonel Erkek Hipogonadizminin Tanı ve Tedavisi: Anlatısal Derleme

Year 2025, Volume: 78 Issue: 4, 295 - 306, 31.12.2025

Elifnaz Mutlu , Esra Eraslan Aydemir , Rifat Emral

https://doi.org/10.65092/autfm.1762927

Abstract

Erkek hipogonadizmi, testosteron üretiminin azalması veya sperm üretiminde bozulma ile karakterize bir durumdur. Geleneksel olarak konjenital ve edinsel hipogonadizm olarak iki kategoriye ayrılmaktaydı. Ancak, kronik hastalıklar, ilaçlar veya yaşlanma sonucunda gelişen fonksiyonel hipogonadizm kavramının ortaya çıkmasıyla birlikte, erkek hipogonadizmi günümüzde üç alt tip altında değerlendirilmektedir.
Hipogonadizmin klinik bulguları ve tedavi yaklaşımları, altta yatan nedene göre değişiklik göstermektedir. Ayrıca, fertilite isteği tedavi protokolünü önemli ölçüde etkilemektedir.
Bu sistematik derleme, primer, sekonder ve fonksiyonel erkek hipogonadizmine yönelik tanısal ve terapötik yaklaşımları incelemektedir.

Keywords

Testosteron Fonksiyonel Hipogonadizm Fertilite Androjen Eksikliği Yaşlanma Geç Başlangıçlı Hipogonadizm

References

  • 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 Endocr Metab. 2018;103(5):1715-44.
  • Tajar A, Huhtaniemi IT, O'Neill TW, Finn JD, Pye SR, Lee DM, et al. Characteristics of androgen deficiency in late-onset hypogonadism: results from the European Male Aging Study (EMAS). J Clin Endocrinol Metab. 2012;97(5):1508-16.
  • Al-Sharefi A, Quinton R. Current National and International Guidelines for the Management of Male Hypogonadism: Helping Clinicians to Navigate Variation in Diagnostic Criteria and Treatment Recommendations. Endocrinol Metab (Seoul). 2020;35(3):526-40.
  • Young J, Xu C, Papadakis GE, Acierno JS, Maione L, Hietamaki J, et al. Clinical Management of Congenital Hypogonadotropic Hypogonadism. Endocr Rev. 2019;40(2):669-710.
  • Paulsen CA, Gordon DL, Carpenter RW, Gandy HM, Drucker WD. Klinefelter's syndrome and its variants: a hormonal and chromosomal study. Recent Prog Horm Res. 1968;24:321-63.
  • Gravholt CH, Chang S, Wallentin M, Fedder J, Moore P, Skakkebaek A. Klinefelter Syndrome: Integrating Genetics, Neuropsychology, and Endocrinology. Endocr Rev. 2018;39(4):389-423.
  • Gül S, Vloeberghs V, Gies I, Goossens E. Testicular mosaicism in non-mosaic postpubertal Klinefelter patients with focal spermatogenesis and in non-mosaic prepubertal Klinefelter boys. Hum Reprod. 2024;39(10):2210-20.
  • Fruhmesser A, Kotzot D. Chromosomal variants in klinefelter syndrome. Sex Dev. 2011;5(3):109-23.
  • Swerdlow AJ, Schoemaker MJ, Higgins CD, Wright AF, Jacobs PA. Cancer incidence and mortality in men with Klinefelter syndrome: a cohort study. J Natl Cancer Inst. 2005;97(16):1204-10.
  • Chang S, Skakkebaek A, Davis SM, Gravholt CH. Morbidity in Klinefelter syndrome and the effect of testosterone treatment. Am J Med Genet C Semin Med Genet. 2020;184(2):344-55.
  • Alowaysi M, Fiacco E, Astro V, Adamo A. Establishment of iPSC lines from a high-grade Klinefelter Syndrome patient (49-XXXXY) and two genetically matched healthy relatives (KAUSTi003-A, KAUSTi004-A, KAUSTi004-B, KAUSTi005-A, KAUSTi005-B, KAUSTi005-C). Stem Cell Res. 2020;49:102008.
  • Huhtaniemi I. Late-onset hypogonadism: current concepts and controversies of pathogenesis, diagnosis and treatment. Asian J Androl. 2014;16(2):192-202.
  • El Houate B, Rouba H, Sibai H, Barakat A, Chafik A, Chadli el B, et al. Novel mutations involving the INSL3 gene associated with cryptorchidism. J Urol. 2007;177(5):1947-51.
  • Foresta C, Moro E, Garolla A, Onisto M, Ferlin A. Y chromosome microdeletions in cryptorchidism and idiopathic infertility. J Clin Endocrinol Metab. 1999;84(10):3660-5.
  • Mendonca BB, Inacio M, Arnhold IJ, Costa EM, Bloise W, Martin RM, et al. Male pseudohermaphroditism due to 17 beta-hydroxysteroid dehydrogenase 3 deficiency. Diagnosis, psychological evaluation, and management. Medicine (Baltimore). 2000;79(5):299-309.
  • Batista RL, Costa EMF, Rodrigues AS, Gomes NL, Faria JA, Jr., Nishi MY, et al. Androgen insensitivity syndrome: a review. Arch Endocrinol Metab. 2018;62(2):227-35.
  • Ramos L. Novel non-synonymous and synonymous gene variants of SRD5A2 in patients with 46,XY-DSD and DSD-free subjects. PLoS One. 2025;20(3):e0316497.
  • Harper P, Penny R, Foley TP, Jr., Migeon CJ, Blizzard RM. Gonadal function in males with myotonic dystrophy. J Clin Endocrinol Metab. 1972;35(6):852-6.
  • Beard CM, Benson RC, Jr., Kelalis PP, Elveback LR, Kurland LT. The incidence and outcome of mumps orchitis in Rochester, Minnesota, 1935 to 1974. Mayo Clin Proc. 1977;52(1):3-7.
  • Brauner R, Czernichow P, Cramer P, Schaison G, Rappaport R. Leydig-cell function in children after direct testicular irradiation for acute lymphoblastic leukemia. N Engl J Med. 1983;309(1):25-8.
  • Handelsman DJ, Turtle JR. Testicular damage after radioactive iodine (I-131) therapy for thyroid cancer. Clin Endocrinol (Oxf). 1983;18(5):465-72.
  • Sharma A, Mollier J, Brocklesby RWK, Caves C, Jayasena CN, Minhas S. Endocrine-disrupting chemicals and male reproductive health. Reprod Med Biol. 2020;19(3):243-53.
  • Whorton D, Krauss RM, Marshall S, Milby TH. Infertility in male pesticide workers. Lancet. 1977;2(8051):1259-61.
  • Laitinen EM, Vaaralahti K, Tommiska J, Eklund E, Tervaniemi M, Valanne L, et al. Incidence, phenotypic features and molecular genetics of Kallmann syndrome in Finland. Orphanet J Rare Dis. 2011;6:41.
  • Boehm U, Bouloux PM, Dattani MT, de Roux N, Dodé C, Dunkel L, et al. Expert consensus document: European Consensus Statement on congenital hypogonadotropic hypogonadism--pathogenesis, diagnosis and treatment. Nat Rev Endocrinol. 2015;11(9):547-64.
  • Millar AC, Faghfoury H, Bieniek JM. Genetics of hypogonadotropic hypogonadism. Transl Androl Urol. 2021;10(3):1401-9.
  • Balasubramanian R. Isolated gonadotropin-releasing hormone deficiency UpToDate2025 [Available from: https://www.uptodate.com/contents/isolated-gonadotropin-releasing-hormone-deficiency-idiopathic-hypogonadotropic-hypogonadism?search=ısolated%20gonadotropin%20releasing&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1.
  • Dwyer AA, McDonald IR, Cangiano B, Giovanelli L, Maione L, Silveira LFG, et al. Classes and predictors of reversal in male patients with congenital hypogonadotropic hypogonadism: a cross-sectional study of six international referral centres. Lancet Diabetes Endocrinol. 2024;12(4):257-66.
  • Shalender Bhasin JLJ. Disorders of the testes and male reproductive system. In: Joseph Loscalzo DLK, Dan L. Longo, Anthony S. Fauci, Stephen L. Hauser, J. Larry Jameson, editor. Harrison’s Princeples of Internal Medicine. 21st ed2022.
  • Lofrano-Porto A, Barra GB, Giacomini LA, Nascimento PP, Latronico AC, Casulari LA, et al. Luteinizing hormone beta mutation and hypogonadism in men and women. N Engl J Med. 2007;357(9):897-904.
  • Basciani S, Watanabe M, Mariani S, Passeri M, Persichetti A, Fiore D, et al. Hypogonadism in a patient with two novel mutations of the luteinizing hormone β-subunit gene expressed in a compound heterozygous form. J Clin Endocrinol Metab. 2012;97(9):3031-8.
  • Phillip M, Arbelle JE, Segev Y, Parvari R. Male hypogonadism due to a mutation in the gene for the beta-subunit of follicle-stimulating hormone. N Engl J Med. 1998;338(24):1729-32.
  • Salenave S, Trabado S, Maione L, Brailly-Tabard S, Young J. Male acquired hypogonadotropic hypogonadism: diagnosis and treatment. Ann Endocrinol (Paris). 2012;73(2):141-6.
  • Esquivel-Zuniga R, Rogol AD. Functional hypogonadism in adolescence: an overlooked cause of secondary hypogonadism. Endocr Connect. 2023;12(11).
  • Lee CP, Chiu YW, Chu CL, Chen Y, Jiang KH, Chen JL, et al. A reliability generalization meta-analysis of coefficient alpha and test-retest coefficient for the aging males' symptoms (AMS) scale. Aging Male. 2016;19(4):244-53.
  • Purifoy FE, Koopmans LH, Mayes DM. Age differences in serum androgen levels in normal adult males. Hum Biol. 1981;53(4):499-511.
  • Ly LP, Sartorius G, Hull L, Leung A, Swerdloff RS, Wang C, et al. Accuracy of calculated free testosterone formulae in men. Clin Endocrinol (Oxf). 2010;73(3):382-8.
  • Mingrone G, Greco AV, Giancaterini A, Scarfone A, Castagneto M, Pugeat M. Sex hormone-binding globulin levels and cardiovascular risk factors in morbidly obese subjects before and after weight reduction induced by diet or malabsorptive surgery. Atherosclerosis. 2002;161(2):455-62.
  • Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab. 1999;84(10):3666-72.
  • Campbell MJ, Lotti F, Baldi E, Schlatt S, Festin MPR, Björndahl L, et al. Distribution of semen examination results 2020 - A follow up of data collated for the WHO semen analysis manual 2010. Andrology. 2021;9(3):817-22.
  • Matsumoto AM. Diagnosis and Evaluation of Hypogonadism. Endocrinol Metab Clin North Am. 2022;51(1):47-62.
  • A. Salonia (Chair) LB, P. Capogrosso, G. Corona. EAU Guidelines on Sexual and Reproductive Health. 2025.
  • Bassil N, Alkaade S, Morley JE. The benefits and risks of testosterone replacement therapy: a review. Ther Clin Risk Manag. 2009;5(3):427-48.
  • 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.
  • Zitzmann M, Nieschlag E. Hormone substitution in male hypogonadism. Mol Cell Endocrinol. 2000;161(1-2):73-88.
  • Lincoff AM, Bhasin S, Flevaris P, Mitchell LM, Basaria S, Boden WE, et al. Cardiovascular Safety of Testosterone-Replacement Therapy. New England Journal of Medicine. 2023;389(2):107-17.
  • Pencina KM, Travison TG, Cunningham GR, Lincoff AM, Nissen SE, Khera M, et al. Effect of Testosterone Replacement Therapy on Sexual Function and Hypogonadal Symptoms in Men with Hypogonadism. J Clin Endocrinol Metab. 2024;109(2):569-80.
  • Behre HM, Kliesch S, Leifke E, Link TM, Nieschlag E. Long-term effect of testosterone therapy on bone mineral density in hypogonadal men. J Clin Endocrinol Metab. 1997;82(8):2386-90.
  • Kanakis GA, Nieschlag E. Klinefelter syndrome: more than hypogonadism. Metabolism. 2018;86:135-44.
  • Esteves SC, Achermann APP, Simoni M, Santi D, Casarini L. Male infertility and gonadotropin treatment: What can we learn from real-world data? Best Pract Res Clin Obstet Gynaecol. 2023;86:102310.
  • Corona G, Rastrelli G, Sparano C, Vignozzi L, Sforza A, Maggi M. Pharmacological management of testosterone deficiency in men current advances and future directions. Expert Rev Clin Pharmacol. 2024;17(8):665-81.
  • 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.
  • Jaschke N, Wang A, Hofbauer LC, Rauner M, Rachner TD. Late-onset hypogonadism: Clinical evidence, biological aspects and evolutionary considerations. Ageing Res Rev. 2021;67:101301.
  • Snyder PJ, Bhasin S, Cunningham GR, Matsumoto AM, Stephens-Shields AJ, Cauley JA, et al. Effects of Testosterone Treatment in Older Men. N Engl J Med. 2016;374(7):611-24.
  • Anderson RA, Martin CW, Kung AW, Everington D, Pun TC, Tan KC, et al. 7Alpha-methyl-19-nortestosterone maintains sexual behavior and mood in hypogonadal men. J Clin Endocrinol Metab. 1999;84(10):3556-62.
  • Nieschlag E, Kumar N, Sitruk-Ware R. 7α-methyl-19-nortestosterone (MENTR): the population council's contribution to research on male contraception and treatment of hypogonadism. Contraception. 2013;87(3):288-95.
  • Solomon ZJ, Mirabal JR, Mazur DJ, Kohn TP, Lipshultz LI, Pastuszak AW. Selective Androgen Receptor Modulators: Current Knowledge and Clinical Applications. Sex Med Rev. 2019;7(1):84-94.
There are 57 citations in total.

Details

Primary Language English
Subjects Endocrinology
Journal Section Review
Authors

Elifnaz Mutlu 0009-0004-0794-2356

Esra Eraslan Aydemir 0000-0003-2718-3081

Rifat Emral 0000-0002-5732-2284

Submission Date August 11, 2025
Acceptance Date December 12, 2025
Publication Date December 31, 2025
Published in Issue Year 2025 Volume: 78 Issue: 4

Cite

APA Mutlu, E., Eraslan Aydemir, E., & Emral, R. (2025). Diagnosis and Treatment of Primary, Secondary, and Functional Male Hypogonadism: A Narrative Review. Ankara Üniversitesi Tıp Fakültesi Mecmuası, 78(4), 295-306. https://doi.org/10.65092/autfm.1762927
AMA Mutlu E, Eraslan Aydemir E, Emral R. Diagnosis and Treatment of Primary, Secondary, and Functional Male Hypogonadism: A Narrative Review. Ankara Üniversitesi Tıp Fakültesi Mecmuası. December 2025;78(4):295-306. doi:10.65092/autfm.1762927
Chicago Mutlu, Elifnaz, Esra Eraslan Aydemir, and Rifat Emral. “Diagnosis and Treatment of Primary, Secondary, and Functional Male Hypogonadism: A Narrative Review”. Ankara Üniversitesi Tıp Fakültesi Mecmuası 78, no. 4 (December 2025): 295-306. https://doi.org/10.65092/autfm.1762927.
EndNote Mutlu E, Eraslan Aydemir E, Emral R (December 1, 2025) Diagnosis and Treatment of Primary, Secondary, and Functional Male Hypogonadism: A Narrative Review. Ankara Üniversitesi Tıp Fakültesi Mecmuası 78 4 295–306.
IEEE E. Mutlu, E. Eraslan Aydemir, and R. Emral, “Diagnosis and Treatment of Primary, Secondary, and Functional Male Hypogonadism: A Narrative Review”, Ankara Üniversitesi Tıp Fakültesi Mecmuası, vol. 78, no. 4, pp. 295–306, 2025, doi: 10.65092/autfm.1762927.
ISNAD Mutlu, Elifnaz et al. “Diagnosis and Treatment of Primary, Secondary, and Functional Male Hypogonadism: A Narrative Review”. Ankara Üniversitesi Tıp Fakültesi Mecmuası 78/4 (December2025), 295-306. https://doi.org/10.65092/autfm.1762927.
JAMA Mutlu E, Eraslan Aydemir E, Emral R. Diagnosis and Treatment of Primary, Secondary, and Functional Male Hypogonadism: A Narrative Review. Ankara Üniversitesi Tıp Fakültesi Mecmuası. 2025;78:295–306.
MLA Mutlu, Elifnaz et al. “Diagnosis and Treatment of Primary, Secondary, and Functional Male Hypogonadism: A Narrative Review”. Ankara Üniversitesi Tıp Fakültesi Mecmuası, vol. 78, no. 4, 2025, pp. 295-06, doi:10.65092/autfm.1762927.
Vancouver Mutlu E, Eraslan Aydemir E, Emral R. Diagnosis and Treatment of Primary, Secondary, and Functional Male Hypogonadism: A Narrative Review. Ankara Üniversitesi Tıp Fakültesi Mecmuası. 2025;78(4):295-306.