New Horizons in Testosterone and the Ageing Male

Tomás Ahern; Frederick C. W. Wu


Age Ageing. 2015;44(2):188-195. 

In This Article

Hormone Regulation of Renal Gluconeogenesis

Sexual Function

A meta-analysis of 17 randomised clinical trials (RCTs) involving 656 men (mean age 57.5 years) found that testosterone therapy moderately improved sexual symptoms and sexual function in men with a total testosterone concentration <12 nmol/l.[36] Of note, testosterone therapy had no such effect in eugonadal men. Subsequent studies have shown inconsistent effects of testosterone therapy on sexual symptoms and sexual function.[37,38]

Quality of Life

Similarly, some studies of men with age-related low testosterone levels have found that testosterone therapy improved quality of life (QOL) questionnaire scores,[38] whereas others have not.[37] A recent meta-analysis found a positive effect of testosterone therapy in hypogonadal men with depression.[39]


A recent double-blind RCT of 274 frail older men showed that testosterone therapy led to an increase in physical function in men aged 75 or greater and in men with two or more Fried frailty criteria (Figure 3).[38] Other RCTs have not found improvements in physical function with testosterone therapy,[40] suggesting that treatment may benefit only frail men with clearly low testosterone levels.

Figure 3.

(a) Change in isometric knee extension peak torque (IME-PT), isometric knee flexion peak torque (IMF-PT), isokinetic knee extension peak torque (IKE-PT) and isokinetic knee flexion peak torque (IKF-PT) in the placebo and T groups at 6 months; (b) change in lean body mass (LBM) and fat mass (FM) at 6 months compared with baseline in the placebo and T groups; (c) change in Aging Males' Symptom scale (AMS) subscale scores at 6 months compared with baseline in the placebo and T groups [38]. **Significant difference between groups (ANCOVA, comparing adjusted mean difference between placebo and T groups).

The Testosterone in Older Men with Mobility Limitations trial, a double-blind, RCT of 209 men aged 65 or older with a total testosterone of 12.0 nmol/l or less, showed that testosterone therapy (10 mg/day, double the standard replacement dose) improved muscle strength. In this trial, the group of participants allocated to testosterone therapy, at a supra-physiological dose, experienced a greater incidence of cardiovascular-related events.[41]

Bone and Metabolic Health

Meta-analyses show that intramuscular testosterone therapy improves lumbar BMD by 8% and that no trials to date have determined the effect of testosterone on fracture incidence.[42]

Although testosterone levels are lower in people with T2DM, the majority of double-blind, RCTs involving testosterone therapy for men with T2DM and/or metabolic syndrome have found no improvement in insulin resistance (as assessed by HOMA2-IR) or in glycaemic control (as assessed by HbA1c).[43]