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Have the Testosterone Trials demonstrated the effectiveness of testosterone therapy in older men without classical hypogonadism?

Lookup NU author(s): Dr Earn Gan, Dr Richard Quinton

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Abstract

© 2016 Royal College of Physicians of Edinburgh. The ‘Testosterone Trials’ (TTT) are an interlinked and coordinated series of seven US National Institutes of Health (NIH)-sponsored, double-blinded, placebo controlled studies examining the potential benefits of testosterone therapy in a hyper-selected cohort of older men.1 TTT aimed to evaluate the impact of testosterone therapy on symptoms commonly associated with male ageing and also postulated to relate to testosterone deficiency, but were not powered to detect adverse outcomes. Findings from the three lead studies, focusing on vitality, sexual and physical function, were recently published.1 These three lead studies comprised 790 men (having screened 51,085 applicants) aged 65 years and older, with an average serum total testosterone concentration less than 275 ng/dl (9.5 nmol/l), from morning venepuncture on two separate days. Participants received either testosterone or placebo gel for 1 year. Each man could participate in one or more of the three trials, depending on their reported symptoms in relation to impairment of sexual function, physical function and/or vitality. In order to evaluate efficacy, assessments were made every three months from baseline to end-of-study at 12 months. Testogel (Androgel® 1%) was initiated at 5 g daily and the dose titrated so as to achieve serum total testosterone concentrations in what would be the mid normal range for men aged between 19 and 40. A statistically significant improvement in sexual activity from baseline was observed in the treatment arm, as ascertained by the Psychosexual Daily Questionnaire score; this emerged from the Sexual Function Trial itself and also when data from all three trials were combined: OR 0.58 (p < 0.001) and 0.62 (p < 0.001), respectively. A better response was associated with a greater increase in testosterone level. Sexual desire and erectile function also improved with a treatment effect of 2.93 (p < 0.001) and 2.64 (p < 0.001), respectively. However, the magnitude of these responses began to decline in a linear manner from 9 months until observations ceased at the study end-point of 12 months. The Physical Function Trial examined the percentage of men whose 6-min walking distance increased by at least 50 m over the course of the study, and failed to identify any benefit from testosterone therapy, although a small but significant improvement was noted when data from all three studies were pooled (20.5% in T arm vs 12.6% receiving placebo: OR 1.75; p = 0.003). The Vitality Trial likewise failed to identify any significant improvements in this domain for the testosterone arm, although there was a statistically significant difference in PANAS (positive and negative affect schedule) scores compared with the placebo arm when data from all three studies were pooled, suggesting slightly better mood and lower severity of depressive symptoms with testosterone treatment. Overall, testosterone therapy increased levels of free testosterone, estradiol and dihydrotestosterone, but unsurprisingly did not increase levels of sex hormone binding globulin. No significant adverse effects were observed in the treatment arms and no significant between-group differences were observed in cardiac adverse events in the 12-month study period. However, the study was a priori underpowered for evaluation of safety.


Publication metadata

Author(s): Gan EH, Quinton R

Publication type: Article

Publication status: Published

Journal: Journal of the Royal College of Physicians of Edinburgh

Year: 2016

Volume: 46

Issue: 3

Pages: 168-171

Acceptance date: 01/01/1900

ISSN (print): 1478-2715

Publisher: Royal College of Physicians of Edinburgh

URL: http://doi.org/10.4997/JRCPE.2016.307

DOI: 10.4997/JRCPE.2016.307


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