title: Testosterone administration to older men improves muscle function: molecular and physiological mechanisms.
abstract: We investigated the effects of 6 mo of near-physiological testosterone administration to older men on skeletal muscle function and muscle protein metabolism. Twelve older men (> or =60 yr) with serum total testosterone concentrations <17 nmol/l (480 ng/dl) were randomly assigned in double-blind manner to receive either placebo (n = 5) or testosterone enanthate (TE; n = 7) injections. Weekly intramuscular injections were given for the 1st mo to establish increased blood testosterone concentrations at 1 mo and then changed to biweekly injections until the 6-mo time point. TE doses were adjusted to maintain nadir serum testosterone concentrations between 17 and 28 nmol/l. Lean body mass (LBM), muscle volume, prostate size, and urinary flow were measured at baseline and at 6 mo. Protein expression of androgen receptor (AR) and insulin-like growth factor I, along with muscle strength and muscle protein metabolism, were measured at baseline and at 1 and 6 mo of treatment. Hematological parameters were followed monthly throughout the study. Older men receiving testosterone increased total and leg LBM, muscle volume, and leg and arm muscle strength after 6 mo. LBM accretion resulted from an increase in muscle protein net balance, due to a decrease in muscle protein breakdown. TE treatment increased expression of AR protein at 1 mo, but expression returned to pre-TE treatment levels by 6 mo. IGF-I protein expression increased at 1 mo and remained increased throughout TE administration. We conclude that physiological and near-physiological increases of testosterone in older men will increase muscle protein anabolism and muscle strength.
authors.affiliation: Department of Surgery, The University of Texas Medical Branch, Galveston, Texas 77550, USA. aferrand@utmb.edu
authors.forename: Arny A
authors.initials: AA
authors.lastname: Ferrando
authors.forename: Melinda
authors.initials: M
authors.lastname: Sheffield-Moore
authors.forename: Catherine W
authors.initials: CW
authors.lastname: Yeckel
authors.forename: Charles
authors.initials: C
authors.lastname: Gilkison
authors.forename: Jie
authors.initials: J
authors.lastname: Jiang
authors.forename: Alison
authors.initials: A
authors.lastname: Achacosa
authors.forename: Steven A
authors.initials: SA
authors.lastname: Lieberman
authors.forename: Kevin
authors.initials: K
authors.lastname: Tipton
authors.forename: Robert R
authors.initials: RR
authors.lastname: Wolfe
authors.forename: Randall J
authors.initials: RJ
authors.lastname: Urban
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D001823:Body Composition; D004231:Diuresis; D004311:Double-Blind Method; D006801:Humans; D007273:Injections, Intramuscular; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology*; D010919:Placebos; D011467:Prostate / Q000033:anatomy & histology; D011944:Receptors, Androgen / Q000032:analysis; D013739:Testosterone / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D010919:Placebos; D011944:Receptors, Androgen; D013739:Testosterone; D007334:Insulin-Like Growth Factor I