title: 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.
authors: Geriatric Research, Education and Clinical Center, Malcom Randall Veterans Affairs Medical Center, Gainesville, Florida;
authors: Stephen E
authors: SE
authors: Borst
authors: Joshua F
authors: JF
authors: Yarrow
authors: Christine F
authors: CF
authors: Conover
authors: Unyime
authors: U
authors: Nseyo
authors: John R
authors: JR
authors: Meuleman
authors: Judyta A
authors: JA
authors: Lipinska
authors: Randy W
authors: RW
authors: Braith
authors: Darren T
authors: DT
authors: Beck
authors: Jeffrey S
authors: JS
authors: Martin
authors: Matthew
authors: M
authors: Morrow
authors: Shirley
authors: S
authors: Roessner
authors: Luke A
authors: LA
authors: Beggs
authors: Sean C
authors: SC
authors: McCoy
authors: Darryl F
authors: DF
authors: Cannady
authors: Jonathan J
authors: JJ
authors: Shuster
mesh_terms: D000368:Aged; D001823:Body Composition / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects*; D004359:Drug Therapy, Combination; D018120:Finasteride / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007006:Hypogonadism / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D053580:Muscle Strength / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects*; D011467:Prostate / Q000187:drug effects*; D013739:Testosterone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D013739:Testosterone; D018120:Finasteride; C004648:testosterone enanthate
keywords: hypogonadal; prostate enlargement; testosterone