Testosterone and men's health: An in-depth exploration of their relationship

Aksam Yassin , Raed M. Al-Zoubi , Raidh Talib Alzubaidi , Hatem Kamkoum , Ayman A. Zarour , Khalil Garada , Mai Elaarag , Ahmad R. Al-Qudimat , Zainab E. Fares , Abdulla A. Al-Ansari

UroPrecision ›› 2025, Vol. 3 ›› Issue (1) : 36 -46.

PDF (231KB)
UroPrecision ›› 2025, Vol. 3 ›› Issue (1) : 36 -46. DOI: 10.1002/uro2.115
REVIEW ARTICLE

Testosterone and men's health: An in-depth exploration of their relationship

Author information +
History +
PDF (231KB)

Abstract

Testosterone plays a pivotal role in male health throughout the lifespan. Men generally exhibit higher serum testosterone levels than women, influencing critical aspects of male physiology. It drives normal sexual differentiation during fetal development, promotes the acquisition of pubertal traits, and induces the development of secondary male sex characteristics. While testosterone levels naturally decline with age, this decrease varies greatly between individuals, indicating that aging alone does not account for any specific testosterone level. The interindividual variability highlights the influence of both genetic and environmental factors on testosterone production. Abnormal changes in testosterone levels, whether excessive or deficient, can have significant implications for men's health, contributing to conditions such as hypogonadism, cardiovascular disease, sexual disorders, and metabolic disorders. Precision medicine provides personalized testosterone treatment options for hypogonadism, taking into account genetic, hormonal, and lifestyle aspects to improve outcomes. This tailored approach is also relevant in dealing with broader reproductive and sexual health issues, ensuring effective and individualized care. This review focuses on testosterone's varied involvement in men's health, using biomarkers and precision medicine breakthroughs to inform tailored therapy and future research.

Keywords

aging / androgen receptor / cardiovascular disease / hypogonadism / men's health / metabolic disorders / testosterone

Cite this article

Download citation ▾
Aksam Yassin, Raed M. Al-Zoubi, Raidh Talib Alzubaidi, Hatem Kamkoum, Ayman A. Zarour, Khalil Garada, Mai Elaarag, Ahmad R. Al-Qudimat, Zainab E. Fares, Abdulla A. Al-Ansari. Testosterone and men's health: An in-depth exploration of their relationship. UroPrecision, 2025, 3(1): 36-46 DOI:10.1002/uro2.115

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Nassar GN , Leslie SW . Physiology, testosterone. Treasure Island, FL: StatPearls Publishing; 2023.

[2]

Zitzmann M , Nieschlag E . Testosterone levels in healthy men and the relation to behavioural and physical characteristics: facts and constructs. Eur J Endocrinol. 2001; 144 (3): 183- 97.

[3]

Livingston M , Kalansooriya A , Hartland AJ , Ramachandran S , Heald A . Serum testosterone levels in male hypogonadism: why and when to check—A review. Int J Clin Pract. 2017; 71 (11): e12995.

[4]

Guzelce EC , Galbiati F , Goldman AL , Gattu AK , Basaria S , Bhasin S . Accurate measurement of total and free testosterone levels for the diagnosis of androgen disorders. Best Pract Res Clin Endocrinol Metab. 2022; 36 (4): 101683.

[5]

Traish AM , Miner MM , Morgentaler A , Zitzmann M . Testosterone deficiency. Am J Med. 2011; 124 (7): 578- 87.

[6]

Rastrelli G , Corona G , Maggi M . Testosterone and sexual function in men. Maturitas. 2018; 112: 46- 52.

[7]

Morales A . Androgens are fundamental in the maintenance of male sexual health. Curr Urol Rep. 2011; 12 (6): 453- 60.

[8]

Wespes E . Current approaches to erectile dysfunction and testosterone deficiency. Minerva Urologica e Nefrologica. 2010; 62 (4): 431- 5.

[9]

Narinx N , David K , Walravens J , Vermeersch P , Claessens F , Fiers T , et al. Role of sex hormone-binding globulin in the free hormone hypothesis and the relevance of free testosterone in androgen physiology. Cell Mol Life Sci. 2022; 79 (11): 543.

[10]

Nassar GN , Leslie SW . Physiology, testosterone. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan 2.

[11]

Shalet SM . Normal testicular function and spermatogenesis. Pediatr Blood Cancer. 2009; 53 (2): 285- 8.

[12]

Klein CE . The hypothalamic-pituitary-gonadal axis. In: Kufe DW, Pollock RE, Weichselbaum RR, Bast RC, Gansler TS, Holland JF, et al. editors. Holland-Frei cancer medicine. 6th ed. Hamilton, ON: BC Decker; 2003.

[13]

De Klerk DP , Lombard CJ . Stromal and epithelial growth of the prostate during puberty. Prostate. 1986; 9 (2): 191- 8.

[14]

Rey RA . The role of androgen signaling in male sexual development at puberty. Endocrinology. 2021; 162 (2): bqaa215.

[15]

Clark BJ , Prough RA , Klinge CM . Chapter 2—Mechanisms of action of dehydroepiandrosterone. In: Litwack G, editor. Vitamins and hormones. Toluca Lake, North Hollywood, California, USA: Academic Press; Eur Urol. 2018. p. 29- 73.

[16]

Yassin A , Diede H . Combination therapy: alpha1-adrenceptor blockade and tadalafil in BPH population. Int J Impot Res. 2003; 15 (Suppl 6): S4- 5.

[17]

Kandeel FR , Koussa VKT , Swerdloff RS . Male sexual function and its disorders: physiology, pathophysiology, clinical investigation, and treatment. Endocr Rev. 2001; 22 (3): 342- 88.

[18]

Dean RC , Lue TF . Physiology of penile erection and pathophysiology of erectile dysfunction. Urol Clin North Am. 2005; 32 (4): 379- 95.

[19]

Traish AM , Saad F , Feeley RJ , Guay A . The dark side of testosterone deficiency: III. cardiovascular disease. J Androl. 2009; 30 (5): 477- 94.

[20]

Yassin AA , Saad F . Testosterone and erectile dysfunction. J Androl. 2008; 29 (6): 593- 604.

[21]

Shabsigh R , Rajfer J , Aversa A , Traish AM , Yassin A , Kalinchenko SY , et al. The evolving role of testosterone in the treatment of erectile dysfunction. Int J Clin Pract. 2006 Sep; 60 (9): 1087- 92.

[22]

Mykoniatis I , Pyrgidis N , Sokolakis I , Ouranidis A , Sountoulides P , Haidich AB , et al. Assessment of combination therapies vs monotherapy for erectile dysfunction: a systematic review and meta-analysis. JAMA Netw open. 2021; 4 (2): e2036337.

[23]

Alwani M , Yassin A , Talib R , Al-Qudimat A , Aboumarzouk O , Al-Zoubi RM , et al. Cardiovascular disease, hypogonadism and erectile dysfunction: early detection, prevention and the positive effects of long-term testosterone treatment: prospective observational, real-life data. Vasc Health Risk Manag. 2021; 17: 497- 508.

[24]

Seftel AD . Male hypogonadism. Part I: Epidemiology of hypogonadism. Int J Impotence Res. 2006; 18 (2): 115- 20.

[25]

Wu FCW , Tajar A , Beynon JM , Pye SR , Silman AJ , Finn JD , et al. Identification of late-onset hypogonadism in middle-aged and elderly men. N Engl J Med. 2010; 363 (2): 123- 35.

[26]

Sizar O , Leslie SW , Schwartz J . Male hypogonadism. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; J Natl Cancer Inst. 2024.

[27]

Thirumalai A , Anawalt BD . Epidemiology of male hypogonadism. Endocrinol Metab Clin North Am. 2022; 51 (1): 1- 27.

[28]

Dandona P , Rosenberg MT . A practical guide to male hypogonadism in the primary care setting. Int J Clin Pract. 2010; 64 (6): 682- 96.

[29]

Howell SJ . Spermatogenesis after cancer treatment: damage and recovery. J Natl Cancer Inst Monogr. 2005; 2005 (34): 12- 7.

[30]

Kumar P , Kumar N , Thakur D , Patidar A . Male hypogonadism: symptoms and treatment. J Adv Pharm Technol Res. 2010; 1 (3): 297- 301.

[31]

Daniell HW . Hypogonadism in men consuming sustained-action oral opioids. J Pain. 2002; 3 (5): 377- 84.

[32]

Al-Qudimat A , Al-Zoubi RM , Yassin AA , Alwani M , Aboumarzouk OM , AlRumaihi K , et al. Testosterone treatment improves liver function and reduces cardiovascular risk: a long-term prospective study. Arab J Urol. 2021; 19 (3): 376- 86.

[33]

Petak SM , Nankin HR , Spark RF , Swerdloff RS , Rodriguez-Rigau LJ . American Association of Clinical Endocrinologists Medical Guidelines for clinical practice for the evaluation and treatment of hypogonadism in adult male patients--2002 update. Endocr Pract. 2002; 8 (6): 440- 56.

[34]

Thirumalai A , Berkseth KE , Amory JK . Treatment of hypogonadism: current and future therapies. F1000Research. 2017; 6: 68.

[35]

Fankhauser CD , Grogg JB , Hayoz S , Wettstein MS , Dieckmann KP , Sulser T , et al. Risk factors and treatment outcomes of 1,375 patients with testicular leydig cell tumors: analysis of published case series data. J Urol. 2020; 203 (5): 949- 56.

[36]

Rajpert-De Meyts E , Aksglaede L , Bandak M , Toppari J , Jørgensen N . Testicular cancer: pathogenesis, diagnosis and management with focus on endocrine aspects. In: Feingold KR, Anawalt B, Blackman MR et al. editors. Endotext. MDText.com, Inc; 2000.

[37]

Filatova VA , Rozhivanov RV . Features of hyperandrogenism in men. Probl Endocrinol. 2021; 67: 111- 5.

[38]

Baillargeon J , Kuo Y-F , Westra JR , Urban RJ , Goodwin JS . Testosterone prescribing in the United States, 2002-2016. JAMA. 2018; 320 (2): 200- 2.

[39]

Hirschberg AL . Approach to investigation of hyperandrogenism in a postmenopausal woman. J Clin Endocrinol Metab. 2023; 108 (5): 1243- 53.

[40]

Niskanen L , Laaksonen DE , Punnonen K , Mustajoki P , Kaukua J , Rissanen A . Changes in sex hormone-binding globulin and testosterone during weight loss and weight maintenance in abdominally obese men with the metabolic syndrome. Diabetes, Obes Metab. 2004; 6 (3): 208- 15.

[41]

Corona G , Rastrelli G , Forti G , Maggi M . Update in testosterone therapy for men. J Sex Med. 2011 Mar; 8 (3): 639- 54.

[42]

Feneley MR , Carruthers M . Is testosterone treatment good for the prostate? Study of safety during long-term treatment. J Sex Med. 2012; 9 (8): 2138- 49.

[43]

Al-Zoubi RM , Yassin AA , Alwani M , Al-Qudimat A , Aboumarzouk OM , Zarour A , et al. A systematic review on the latest developments in testosterone therapy: Innovations, advances, and paradigm shifts. Arab J Urol. 2021; 19 (3): 370- 5.

[44]

Bhasin S , Cunningham GR , Hayes FJ , Matsumoto AM , Snyder PJ , Swerdloff RS , et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010; 95 (6): 2536- 59.

[45]

Haider A , Gooren LJ , Padungtod P , Saad F . Concurrent improvement of the metabolic syndrome and lower urinary tract symptoms upon normalisation of plasma testosterone levels in hypogonadal elderly men. Andrologia. 2009; 41 (1): 7- 13.

[46]

Zacharin MR , Pua J , Kanumakala S . Bone mineral density outcomes following long-term treatment with subcutaneous testosterone pellet implants in male hypogonadism. Clin Endocrinol. 2003; 58 (6): 691- 5.

[47]

Wang C , Nieschlag E , Swerdloff R , Behre HM , Hellstrom WJ , Gooren LJ , et al. Investigation, treatment, and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA, and ASA recommendations. J Androl. 2009; 30 (1): 1- 9.

[48]

McGill JJ , Shoskes DA , Sabanegh ES . Androgen deficiency in older men: indications, advantages, and pitfalls of testosterone replacement therapy. Cleve Clin J Med. 2012; 79 (11): 797- 806.

[49]

Hellstrom WJG , Paduch D , Donatucci CF . Importance of hypogonadism and testosterone replacement therapy in current urologic practice: a review. Int Urol Nephrol. 2012; 44 (1): 61- 70.

[50]

Sleumer B , Zwerwer J , van Faassen M , Vos MJ , Bischoff R , Kema IP , et al. An antibody-free LC-MS/MS method for the quantification of sex hormone binding globulin in human serum and plasma. Clin Chem Lab Med. 2023; 61 (7): 1266- 74.

[51]

Olesen IA , Joensen UN , Petersen JH , Almstrup K , Rajpert-De Meyts E , Carlsen E , et al. Decrease in semen quality and Leydig cell function in infertile men: a longitudinal study. Hum Reprod. 2018; 33 (11): 1963- 74.

[52]

Snead MC , Black CM , Kourtis AP . The use of biomarkers of semen exposure in sexual and reproductive health studies. J Women's Health. 2014; 23 (10): 787- 91.

[53]

Kapoor D , Clarke S , Stanworth R , Channer KS , Jones TH . The effect of testosterone replacement therapy on adipocytokines and C-reactive protein in hypogonadal men with type 2 diabetes. Eur J Endocrinol. 2007; 156 (5): 595- 602.

[54]

Panizzon MS , Bree K , Hsieh TC , Hauger R , Xian H , Jacobson K , et al. Genetic variation in the androgen receptor modifies the association between testosterone and vitality in middle-aged men. J Sex Med. 2020; 17 (12): 2351- 61.

[55]

Yassin DJ , Doros G , Hammerer PG , Yassin AA . Long-term testosterone treatment in elderly men with hypogonadism and erectile dysfunction reduces obesity parameters and improves metabolic syndrome and health-related quality of life. J Sex Med. 2014; 11 (6): 1567- 76.

[56]

Anawalt BD , Matsumoto AM . Aging and androgens: Physiology and clinical implications. Rev Endocr Metab Disord. 2022; 23 (6): 1123- 37.

[57]

Basaria S , Harman SM , Travison TG , Hodis H , Tsitouras P , Budoff M , et al. Effects of testosterone administration for 3 years on subclinical atherosclerosis progression in older men with low or low-normal testosterone levels: a randomized clinical trial. JAMA. 2015; 314 (6): 570- 81.

[58]

Wu FCW , Tajar A , Pye SR , Silman AJ , Finn JD , O'Neill TW , et al. Hypothalamic-pituitary-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.

[59]

Goldman AL , Bhasin S , Wu FCW , Krishna M , Matsumoto AM , Jasuja R . A reappraisal of testosterone's binding in circulation: physiological and clinical implications. Endocr Rev. 2017; 38 (4): 302- 24.

[60]

Handelsman DJ , Yeap BB , Flicker L , Martin S , Wittert GA , Ly LP . Age-specific population centiles for androgen status in men. Eur J Endocrinol. 2015; 173 (6): 809- 17.

[61]

Park HJ . The future role of precision medicine in male sexual dysfunction. Investig Clin Urol. 2023; 64 (3): 200- 1.

[62]

Mata DA , Katchi FM , Ramasamy R . Precision medicine and men's health. Am J Men's Health. 2017; 11 (4): 1124- 9.

[63]

Cittadini A , Isidori AM , Salzano A . Testosterone therapy and cardiovascular diseases. Cardiovasc Res. 2022; 118 (9): 2039- 57.

[64]

Sobel V , Schwartz B , Zhu Y-S , Cordero JJ , Imperato-McGinley J . Bone mineral density in the complete androgen insensitivity and 5α-reductase-2 deficiency syndromes. J Clin Endocrinol Metab. 2006; 91 (8): 3017- 23.

[65]

Turer AT , Khera A , Ayers CR , Turer CB , Grundy SM , Vega GL , et al. Adipose tissue mass and location affect circulating adiponectin levels. Diabetologia. 2011; 54 (10): 2515- 24.

[66]

Yassin A . Testosterone therapy: injectable androgens. In: Hohl A editor. Testosterone: from basic to clinical aspects. Springer International Publishing. 2023. p. 315- 30.

[67]

Haider A , Yassin A , Haider KS , Doros G , Saad F , Rosano GM . Men with testosterone deficiency and a history of cardiovascular diseases benefit from long-term testosterone therapy: observational, real-life data from a registry study. Vasc Health Risk Manag. 2016; 12: 251- 61.

[68]

Hahn AW , Koutroumpakis E , Narayan V , Aparicio A . The need for precision medicine in managing cardiovascular risk for men receiving ADT. Prostate Cancer Prostatic Dis. Epub 2024 May 25.

[69]

Malkin CJ , Pugh PJ , Jones RD , Kapoor D , Channer KS , Jones TH . The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profiles in hypogonadal men. J Clin Endocrinol Metab. 2004; 89 (7): 3313- 8.

[70]

Abriel H , Zaklyazminskaya EV . Cardiac channelopathies: genetic and molecular mechanisms. Gene. 2013; 517 (1): 1- 11.

[71]

Saad F , Doros G , Haider A , Haider K , Yassin A , Traish A . PS-08-011 77 men with pre-existing cardiovascular disease (CVD) and hypogonadism show improved erectile function on long-term treatment with testosterone undecanoate injections (TU). J Sex Med. 2016; 13 (5): S114- 5.

[72]

Lovšin N , Zupan J , Marc J . Genetic effects on bone health. Curr Opin Clin Nutr Metab Care. 2018; 21 (4): 233- 9.

[73]

Al-Zoubi RM , Alwani M , Aboumarzouk OM , Elaarag M , Al-Qudimat AR , Ojha L , et al. Updates on androgen replacement therapy and lower urinary tract symptoms: a narrative review. The Aging Male. 2022; 25 (1): 234- 41.

[74]

Zhao B , Peng Q , Zhou R , Liu H , Qi S , Wang R . Precision medicine in tissue engineering on bone. Methods Mol Biol. 2020; 2204: 207- 15.

[75]

Zitzmann M . Testosterone, mood, behaviour and quality of life. Andrology. 2020; 8 (6): 1598- 605.

[76]

Anderson DJ , Vazirnia P , Loehr C , Sternfels W , Hasoon J , Viswanath O , et al. Testosterone replacement therapy in the treatment of depression. Health Psychol Res. 2022; 10 (4): 38956.

[77]

Wainwright SR , Workman JL , Tehrani A , Hamson DK , Chow C , Lieblich SE , et al. Testosterone has antidepressant-like efficacy and facilitates imipramine-induced neuroplasticity in male rats exposed to chronic unpredictable stress. Horm Behav. 2016; 79: 58- 69.

[78]

Santos-Toscano R , Arevalo MA , Garcia-Segura LM , Grassi D , Lagunas N . Interaction of gonadal hormones, dopaminergic system, and epigenetic regulation in the generation of sex differences in substance use disorders: a systematic review. Front Neuroendocrinol. 2023; 71: 101085.

[79]

Zhang Z , Kang D , Li H . Testosterone and cognitive impairment or dementia in middle-aged or aging males: causation and intervention, a systematic review and meta-analysis. J Geriatr Psychiatry Neurol. 2021; 34 (5): 405- 17.

[80]

Bianchi VE . Impact of testosterone on Alzheimer's disease. World J Men's Health. 2022; 40 (2): 243.

[81]

Peterson BS . Editorial: Biomarkers in precision medicine for mental illnesses. J Child Psychol Psychiatr. 2020; 61 (12): 1279- 81.

[82]

Yassin A , Alwani M , Al-Zoubi RM , Aboumarzouk OM , Talib R , Nettleship J , et al. Voiding function improves under long-term testosterone treatment (TTh) in hypogonadal men, independent of prostate size. Int Urol Nephrol. 2023; 55 (7): 1649- 58.

[83]

Watts EL , Perez-Cornago A , Fensom GK , Smith-Byrne K , Noor U , Andrews CD , et al. Circulating free testosterone and risk of aggressive prostate cancer: prospective and Mendelian randomisation analyses in international consortia. Int J Cancer. 2022; 151 (7): 1033- 46.

[84]

Kim JW . Questioning the evidence behind the Saturation Model for testosterone replacement therapy in prostate cancer. Investig Clin Urol. 2020; 61 (3): 242.

[85]

Yassin A , Alrumaihi K , Talib R , Alkadhi S , Al Ansari A . Voiding function improves under long-term treatment with testosterone undecanoate injections (TU) in hypogonadal men for up to 14 years independent of prostate size. Eur Urol Suppl. 2019; 18 (1): e253.

[86]

Alwani M , Al-Zoubi RM , Al-Qudimat A , Yassin A , Aboumarzouk O , Al-Rumaihi K , et al. The impact of long-term Testosterone Therapy (TTh) in renal function (RF) among hypogonadal men: An observational cohort study. Ann Med Surg. 2021; 69: 102748.

[87]

Kohli M , Qin R , Jimenez R , Dehm SM . Biomarker-based targeting of the androgen-androgen receptor axis in advanced prostate cancer. Adv Urol. 2012; 2012: 781459.

[88]

Pandey AV , Miller WL . Regulation of 17,20 lyase activity by cytochrome b5 and by serine phosphorylation of P450c17. J Biol Chem. 2005; 280 (14): 13265- 71.

[89]

Grande G , Barrachina F , Soler-Ventura A , Jodar M , Mancini F , Marana R , et al. The role of testosterone in spermatogenesis: lessons from proteome profiling of human spermatozoa in testosterone deficiency. Front Endocrinol. 2022; 13: 852661.

[90]

Thirumalai A , Page ST . Male hormonal contraception. Annu Rev Med. 2020; 71: 17- 31.

[91]

Thirumalai A , Page ST . Testosterone and male contraception. Curr Opin Endocrinol Diabetes Obes. 2024; 31 (6): 236- 42.

[92]

Giorgini F , Di Dalmazi G , Diciotti S . Artificial intelligence in endocrinology: a comprehensive review. J Endocrinol Invest. 2024; 47 (5): 1067- 82.

[93]

Naik N , Roth B , Lundy SD . Artificial intelligence for clinical management of male infertility, a scoping review. Curr Urol Rep. 2024; 26 (1): 17.

[94]

Spratt DE , Tang S , Sun Y , Huang HC , Chen E , Mohamad O , et al. Artificial intelligence predictive model for hormone therapy use in prostate cancer. NEJM Evid. 2023; 2 (8): EVIDoa2300023.

RIGHTS & PERMISSIONS

The Author(s). UroPrecision published by John Wiley & Sons Australia, Ltd on behalf of Higher Education Press.

AI Summary AI Mindmap
PDF (231KB)

1042

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/