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

作者：Borst Stephen E^*; Yarrow Joshua F; Conover Christine F; Nseyo Unyime; Meuleman John R; Lipinska Judyta A; Braith Randy W; Beck Darren T; Martin Jeffrey S; Morrow Matthew; Roessner Shirley; Beggs Luke A; McCoy Sean C; Cannady Darryl F II; Shuster Jonathan J

来源：American Journal of Physiology - Endocrinology And Metabolism, 2014, 306(4): E433-E442.

DOI：10.1152/ajpendo.00592.2013

• testosterone
• hypogonadal
• prostate enlargement

Testosterone acts directly at androgen receptors and also exerts potent actions following 5 alpha-reduction to dihydrotestosterone (DHT). Finasteride (type II 5 alpha-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 %26gt;= 60 yr with a serum testosterone concentration of %26lt;= 300 ng/dl or bioavailable testosterone %26lt;= 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 x 2 factorial design. Over the course of 12 mo, TE increased upper and lower body muscle strength by 8-14% (P = 0.015 to %26lt;0.001), fat-free mass 4.04 kg (P = 0.032), lumbar spine bone mineral density (BMD) 4.19% (P %26lt; 0.001), and total hip BMD 1.96% (P = 0.024) while reducing total body fat -3.87 kg (P %26lt; 0.001) and trunk fat -1.88 kg (P = 0.0051). In the first 3 mo, testosterone increased hematocrit 4.13% (P %26lt; 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.

• 出版日期2014-2