Purpose of Review
The purpose of this review was to assess the results of the Testosterone (T) Trials with regard to their clinical and scientific implications.
The T Trials investigated 1 year of T gel versus placebo in 790 men 65 years and older with unequivocally low serum T concentrations (< 275 ng/dl). Safety monitoring was performed for an additional year. Primary results were improvement over placebo for sexual desire, sexual activity, erection quality, physical activity, and mood. Vitality improved with some instruments, but not all. Improvement was noted in bone density and anemia. Coronary CT provided mixed results—coronary calcium scores were unchanged whereas volume of non-calcified plaque increased more in the testosterone group. There were no worrisome safety concerns. Major adverse cardiovascular events over 2 years occurred in 9 testosterone-treated men and 16 placebo-treated men.
The T Trials provide high-level evidence of strong, broad benefits of T therapy, without substantive safety concerns.
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Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
•• 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. This article provides the primary results of the Testosterone Trials.
Cunningham GR, Stephens-Shields AJ, Rosen RC, Wang C, Bhasin S, Matsumoto AM, et al. Testosterone treatment and sexual function in older men with low testosterone levels. J Clin Endocrinol Metab. 2016 Aug;101(8):3096–104.
Snyder PJ, Kopperdahl DL, Stephens-Shields AJ, Ellenberg SS, Cauley JA, Ensrud KE, et al. Effect of testosterone treatment on volumetric bone density and strength in older men with low testosterone: a controlled clinical trial. JAMA Intern Med. 2017;177(4):471–9.
Roy CN, Snyder PJ, Stephens-Shields AJ, Artz AS, Bhasin S, Cohen HJ, et al. Association of testosterone levels with anemia in older men: a controlled clinical trial. JAMA Intern Med. 2017;177(4):480–90.
• Budoff MJ, Ellenberg SS, Lewis CE, Mohler ER 3rd, Wenger NK, Bhasin S, et al. Testosterone treatment and coronary artery plaque volume in older men with low testosterone. JAMA. 2017;317(7):708–16. This paper provides coronary computed tomography results from a sub-study within the Testosterone Trials.
Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA. 2002;288(3):321–33.
•• Traish AM, Vance JC, Morgentaler A. Overselling hysteria: the role of the media and medical journals in promoting questionable risks—a case study of the testosterone controversy. Embo Rep. 2017;18:11–7. This paper uses testosterone as a case example to show how the media and medical journals unwittingly collaborate to create exaggerated concerns regarding medical risks.
Aub JC. Reports on medical progress. Endocrines: the use of testosterone. N Engl J Med. 1940;222:877–81.
Wu FC, 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.
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. doi:10.1016/j.eururo.2017.03.032.
Hackett G, Cole N, Bhartia M, Kennedy D, Raju J, Wilkinson P, et al. The response to testosterone undecanoate in men with type 2 diabetes is dependent on achieving threshold serum levels (the BLAST study). Int J Clin Pract. 2014;68(2):203–15.
Morgentaler A, Crews D. Role of the anterior hypothalamus-preoptic area in the regulation of reproductive behavior in the lizard, Anolis carolinensis: implantation studies. Horm Behav. 1978;11:61.
• Morgentaler A. Controversies and advances with testosterone therapy: a 40-year perspective. Urology. 2016;89:27–32. This paper provides a broad perspective on testosterone therapy by a clinician-scientist.
Sakr WA, Grignon DJ, Crissman JD, et al. High grade prostatic intraepithelial neoplasia (HGPIN) and prostatic adenocarcinoma between the ages of 20–69: an autopsy study of 249 cases. In Vivo. 1994;8:439–43.
Shigehara K, Sugimoto K, Konaka H, Iijima M, Fukushima M, Maeda Y, et al. Androgen replacement therapy contributes to improving lower urinary tract symptoms in patients with hypogonadism and benign prostate hypertrophy: a randomised controlled study. Aging Male. 2011 Mar;14(1):53–8.
Morgentaler A, Traish A. Shifting the paradigm of testosterone and prostate cancer: the saturation model and the limits of androgen-dependent growth. Eur Urol. 2009;55:310–20.
Morgentaler A, Benesh JA, Denes BS, Kan-Dobrosky N, Harb D, Miller MG. Factors influencing prostate-specific antigen response among men treated with testosterone therapy for 6 months. J Sex Med. 2014 Nov;11(11):2818–25.
Vigen R, O’Donnell CI, Baron AE, et al. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA. 2013;310(17):1829–36.
Finkle WD, Greenland S, Ridgeway GK, et al. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. Plos One. 2014;9(1):76.
Wallis CJ, Lo K, Lee Y, Krakowsky Y, et al. Survival and cardiovascular events in men treated with replacement therapy: an intention-to-treat observational cohort study. Lancet Diabetes Endocrinol. 2016;4:498–506.
Sharma R, Oni OA, Gupta K, Barua, et al. Normalization of testosterone level is associated with reduced incidence myocardial infarction and mortality in men. Eur Heart J. 2015;36(40):2706–015.
• Morgentaler A, Miner MM, Caliber M, et al. Testosterone therapy and cardiovascular risk: advances and controversies. Mayo Clin Proc. 2015;90:224–51. Comprehensive review of evidence regarding cardiovascular risks of testosterone.
Finkelstein JS, Lee H, Burnett-Bowie SA, Pallais JC, EW Y, Borges LF, et al. Gonadal steroids and body composition, strength, and sexual function in men. N Engl J Med. 2013;369(11):1011–22.
• Nguyen CP, Hirsch MS, Moeny D, Kaul S, Mohamoud M, Joffe HV. Testosterone and “age-related hypogonadism”—FDA concerns. N Engl J Med. 2015;373(8):689–91. In this commentary, the FDA provides arguments in favor of its controversial actions to restrict the use of testosterone.
Conflict of Interest
Abraham Morgentaler reports personal fees from Aytu, Bayer, Antares, Acerus, AbbVie, Endo, Besins, Pfizer, and Repros, and personal fees from BioTE Medical, LLC outside the submitted work.
Human and Animal Rights and Informed Consent
All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).
This article is part of the Topical Collection on Medical Comorbidities
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Morgentaler, A. The Testosterone Trials: What the Results Mean for Healthcare Providers and for Science. Curr Sex Health Rep 9, 290–295 (2017). https://doi.org/10.1007/s11930-017-0135-0
- Sexual function