Musculoskeletal and prostate effects of combined testosterone and finasteride administration in older hypogonadal men: a randomized, controlled trial

Abstract

Testosterone acts directly at androgen receptors and also exerts potent actions following 5α-reduction to dihydrotestosterone (DHT). Finasteride (type II 5α-reductase inhibitor) lowers DHT and is used to treat benign prostatic hyperplasia. However, it is unknown whether elevated DHT mediates either beneficial musculoskeletal effects or prostate enlargement resulting from higher-than-replacement doses of testosterone. Our purpose was to determine whether administration of testosterone plus finasteride to older hypogonadal men could produce musculoskeletal benefits without prostate enlargement. Sixty men aged ≥60 yr with a serum testosterone concentration of ≤300 ng/dl or bioavailable testosterone ≤70 ng/dl received 52 wk of treatment with testosterone enanthate (TE; 125 mg/wk) vs. vehicle, paired with finasteride (5 mg/day) vs. placebo using a 2 × 2 factorial design. Over the course of 12 mo, TE increased upper and lower body muscle strength by 8-14% (P = 0.015 to <0.001), fat-free mass 4.04 kg (P = 0.032), lumbar spine bone mineral density (BMD) 4.19% (P < 0.001), and total hip BMD 1.96% (P = 0.024) while reducing total body fat -3.87 kg (P < 0.001) and trunk fat -1.88 kg (P = 0.0051). In the first 3 mo, testosterone increased hematocrit 4.13% (P < 0.001). Coadministration of finasteride did not alter any of these effects. Over 12 mo, testosterone also increased prostate volume 11.4 cm(3) (P = 0.0051), an effect that was completely prevented by finasteride (P = 0.0027). We conclude that a higher-than-replacement TE combined with finasteride significantly increases muscle strength and BMD and reduces body fat without causing prostate enlargement. These results demonstrate that elevated DHT mediates testosterone-induced prostate enlargement but is not required for benefits in musculoskeletal or adipose tissue.

Keywords: hypogonadal; prostate enlargement; testosterone.

Fig. 1.

Flow of participants through the trial.

Fig. 2.

Changes occurring from baseline to 12 mo in testosterone, dihydrotestosterone (DHT), hematocrit, prostate volume, lumbar spine bone miberal density (BMD), total body fat, fat-free mass and one-repetition maximum (1-RM) leg press strength in participants receiving vehicle (veh)-placebo(plac), veh-finasteride(finast), testosterone enanthate (test)-plac or test-finast. A: significant increase shown in nadir serum testosterone levels following testosterone-enanthate (TE) administration. B: significant increase shown in serum DHT following TE administration and a significant decrease in DHT following finasteride administration. C: significant increase shown in hematocrit following TE administration. D: significant increase shown in prostate volume following TE administration and a significant decrease in prostate volume following finasteride administration. E: significant increase shown in lumbar spine BMD following TE administration. F: significant decrease shown in fat mass following TE administration. G: significant increase shown in fat-free mass following TE administration. H: significant increase shown in 1-RM leg press strength following TE administration. Values are means ± SE; n = 7–13 per group. Effect and interaction columns are derived from repeated-measures analysis for effects of T, F, and Interaction. These effects/interactions are indicative of the mean change occurring over each individual 3-, 6-, 9-, and 12-mo time point, as applicable, with Main Effects representing the average of testosterone under placebo and finasteride (weighted 50–50) or finasteride under vehicle and testosterone (weighted 50–50) and Interaction addressing whether or not the difference between the means for the first treatment factor (e.g., testosterone vs. vehicle) differ quantitatively based on the level of the second treatment factor (e.g., finasteride vs. placebo).