Cardiovascular and prostate cancer risk associated to testosterone replacement therapy – a systematic review and meta-analysis of 41 randomized controlled trials

Giagulli VA, Castellana M, Lisco G, Triggiani V. Critical evaluation of different available guidelines for late-onset hypogonadism. Andrology. 2020;8:1628–41.

Article  PubMed  Google Scholar 

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

Article  PubMed  PubMed Central  Google Scholar 

Klotz L. Testosterone therapy and prostate cancer-safety concerns are well founded. Nat Rev Urol. 2015;12:48–54.

Article  CAS  PubMed  Google Scholar 

Ho CCK, Tong SF, Low WY, Ng CJ, Khoo EM, Lee VKM, et al. A randomized, double-blind, placebo-controlled trial on the effect of long-acting testosterone treatment as assessed by the Aging Male Symptoms scale. BJU Int. 2012;110:260–5.

Article  CAS  PubMed  Google Scholar 

Basaria S, Coviello Andrea D, Travison Thomas G, Storer Thomas W, Farwell Wildon R, Jette Alan M, et al. Adverse events associated with testosterone administration. N Engl J Med. 363:109–22.

Lincoff AM, Bhasin S, Flevaris P, Mitchell LM, Basaria S, Boden WE, et al. Cardiovascular safety of testosterone-replacement therapy. N Engl J Med. 2023;389:107–17.

Article  CAS  PubMed  Google Scholar 

Bhasin S, Travison TG, Pencina KM, O’Leary M, Cunningham GR, Lincoff AM, et al. Prostate safety events during testosterone replacement therapy in men with hypogonadism: a randomized clinical trial. JAMA Netw Open. 2023;6:e2348692.

Article  PubMed  PubMed Central  Google Scholar 

Huggins C, Stevens RE, Hodges CV. Studies on prostatic cancer: II. the effects of castration on advanced carcinoma of the prostate gland. Arch Surg. 1941;43:209–23.

Article  CAS  Google Scholar 

Morgentaler A, Traish AM. Shifting the paradigm of testosterone and prostate cancer: the saturation model and the limits of androgen-dependent growth. Eur Urol. 2009;55:310–20.

Article  PubMed  Google Scholar 

Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71.

Article  PubMed  PubMed Central  Google Scholar 

Epstein JI, Egevad L, Amin MB, Delahunt B, Srigley JR, Humphrey PA, et al. The 2014 international society of urological pathology (isup) consensus conference on gleason grading of prostatic carcinoma: definition of grading patterns and proposal for a new grading system. Am J Surg Pathol. 2016;40:244–52.

Article  PubMed  Google Scholar 

Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol. 2005;5:13.

Article  PubMed  PubMed Central  Google Scholar 

Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898.

Article  PubMed  Google Scholar 

Rao G, Lopez-Jimenez F, Boyd J, D’Amico F, Durant NH, Hlatky MA, et al. Methodological standards for meta-analyses and qualitative systematic reviews of cardiac prevention and treatment studies: a scientific statement from the american heart association. Circulation. 2017;136:e172–94.

Article  PubMed  Google Scholar 

Viechtbauer W. Bias and efficiency of meta-analytic variance estimators in the random-effects model. J Educ Behav Stat. 2005;30:261–93.

Article  Google Scholar 

Cheng J, Pullenayegum E, Marshall JK, Iorio A, Thabane L. Impact of including or excluding both-armed zero-event studies on using standard meta-analysis methods for rare event outcome: a simulation study. BMJ Open. 2016;6:e010983.

Article  PubMed  PubMed Central  Google Scholar 

Marks LS, Mazer NA, Mostaghel E, Hess DL, Dorey FJ, Epstein JI, et al. Effect of testosterone replacement therapy on prostate tissue in men with late-onset hypogonadism: a randomized controlled trial. JAMA. 2006;296:2351–61.

Article  CAS  PubMed  Google Scholar 

Magnussen LV. Testosterone therapy of men with type 2 diabetes mellitus - a randomized, double-blinded, placebo-controlled study. Dan Med J. 2017;64:B5396.

PubMed  Google Scholar 

Snyder Peter J, Bhasin S, Cunningham Glenn R, Matsumoto Alvin M, Stephens-Shields Alisa J, Cauley Jane A, et al. Effects of testosterone treatment in older men. N Engl J Med. 374:611–24.

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;314:570–81.

Article  CAS  PubMed  Google Scholar 

Basaria S, Travison TG, Alford D, Knapp PE, Teeter K, Cahalan C, et al. Effects of testosterone replacement in men with opioid-induced androgen deficiency: a randomized controlled trial. Pain. 2015;156:280–8.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Barnouin Y, Armamento-Villareal R, Celli A, Jiang B, Paudyal A, Nambi V, et al. Testosterone replacement therapy added to intensive lifestyle intervention in older men with obesity and hypogonadism. J Clin Endocrinol Metab. 2021;106:e1096–110.

Article  PubMed  Google Scholar 

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 Off J Int Soc Study. Aging Male. 2018;21:158–69.

Article  CAS  PubMed  Google Scholar 

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;34:828–37.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Malkin CJ, Pugh PJ, Morris PD, Kerry KE, Jones RD, Jones TH, et al. Testosterone replacement in hypogonadal men with angina improves ischaemic threshold and quality of life. Heart Br Card Soc. 2004;90:871–6.

CAS  Google Scholar 

Hackett G, Cole N, Bhartia M, Kennedy D, Raju J, Wilkinson P. Testosterone replacement therapy with long-acting testosterone undecanoate improves sexual function and quality-of-life parameters vs. placebo in a population of men with type 2 diabetes. J Sex Med. 2013;10:1612–27.

Article  CAS  PubMed  Google Scholar 

Legros JJ, Meuleman EJH, Elbers JMH, Geurts TBP. Kaspers MJGH, Bouloux PMG. Oral testosterone replacement in symptomatic late-onset hypogonadism: effects on rating scales and general safety in a randomized, placebo-controlled study. Eur J Endocrinol. 2009;160:821–31.

Article  CAS  PubMed  Google Scholar 

Gianatti EJ, Dupuis P, Hoermann R, Zajac JD, Grossmann M. Effect of testosterone treatment on constitutional and sexual symptoms in men with type 2 diabetes in a randomized, placebo-controlled clinical trial. J Clin Endocrinol Metab. 2014;99:3821–8.

Article  CAS  PubMed  Google Scholar 

Gopal RA, Bothra N, Acharya SV, Ganesh HK, Bandgar TR, Menon PS, et al. Treatment of hypogonadism with testosterone in patients with type 2 diabetes mellitus. Endocr Pract Off J Am Coll Endocrinol Am Assoc Clin Endocrinol. 2010;16:570–6.

Google Scholar 

Paduch DA, Polzer PK, Ni X, Basaria S. Testosterone replacement in androgen-deficient men with ejaculatory dysfunction: a randomized controlled trial. J Clin Endocrinol Metab. 2015;100:2956–62.

Article  CAS  PubMed  Google Scholar 

Ng Tang Fui M, Hoermann R, Prendergast LA, Zajac JD, Grossmann M. Symptomatic response to testosterone treatment in dieting obese men with low testosterone levels in a randomized, placebo-controlled clinical trial. Int J Obes. 2017;41:420–6.

Article  CAS  Google Scholar 

Aversa A, Bruzziches R, Francomano D, Rosano G, Isidori AM, Lenzi A, et al. Effects of testosterone undecanoate on cardiovascular risk factors and atherosclerosis in middle-aged men with late-onset hypogonadism and metabolic syndrome: results from a 24-month, randomized, double-blind, placebo-controlled study. J Sex Med. 2010;7:3495–503.

Article  CAS  PubMed  Google Scholar 

Kaufman JM, Miller MG, Fitzpatrick S, McWhirter C, Brennan JJ. One-year efficacy and safety study of a 1.62% testosterone gel in hypogonadal men: results of a 182-day open-label extension of a 6-month double-blind study. J Sex Med. 2012;9:1149–61.

Article  CAS  PubMed  Google Scholar 

Inoue Y, Nakamura K, Kuwahara Y, Lu Y, Masuda N, Horie S, et al. Efficacy of testosterone treatment in hemodialysis patients as assessed by aging males’ symptoms scores: a pilot study. Am J Mens Health. 2018;12:1541–7.

Article 

Comments (0)

No login
gif