Testosterone administration to older men improves muscle function: molecular and physiological mechanisms

Abstract

. Testosterone administration to older men improves muscle function: molecular and physiological mechanisms. Am J Physiol Endocrinol Metab 282: E601-E607, 2002. First published November 13; 10.1152/ajpendo.00362.2001.-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 (Ն60 yr) with serum total testosterone concentrations Ͻ17 nmol/l (480 ng/dl) were randomly assigned in double-blind manner to receive either placebo (n ϭ 5) or testosterone enanthate (TE; n ϭ 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. aging; muscle strength; lean body mass; insulin-like growth factor I MOST AGING MEN SHOW A REDUCTION in circulating serum testosterone concentrations (16,22). This reduction in serum testosterone concentration is a core physiological event in what is termed andropause. Andropause can be clinically characterized by decreased potency and libido, increased fatigability, and decreased muscle strength (13,24). A significant decrease in serum total testosterone occurs as early as ages 50-59 (16). This decrease in testosterone production is associated with the loss of lean body mass (LBM) and muscle strength. When men are made hypogonadal with a gonadotropin-releasing hormone analog (14), LBM and muscle strength are lost. Once weakened, older individuals are prone to falls that prevent an independent living status and diminish the quality of life. As the population of older Americans grows, the need to develop therapies to counteract the aging-induced loss in skeletal muscle mass and function becomes critically important.Previously we demonstrated that testosterone administration primes skeletal muscle for growth by increasing net protein synthesis in the fasted state (10, 18). The logic...

Physiological elevation of endogenous hormones results in superior strength training adaptation

“…Furthermore, administration of testosterone (without strength training) increases the content of androgen receptors in animal muscles (Carson et al 2002;Lee et al 2003) and humans (Ferrando et al 2002). This is in line with the suggestion that androgens increase their receptor expression (Bhasin et al 2001;Esposito et al 2002;Gobinet et al 2002).…”

Overload-induced androgen receptor expression in the aged rat hindlimb receiving nandrolone decanoate

“…This change in androgen receptor concentration coincides with a dramatic reduction in circulating testosterone levels in Fischer 344 ϫ Brown Norway rats between 4 and 28 mo of age (15). Skeletal muscle androgen receptor protein expression increases in aged men administered a physiological dose of testosterone for 1 mo (18). Rat Sol and Plan androgen receptor concentrations are induced by anabolic steroid administration in both young and old rats (12).…”

Relationship between testosterone supplementation and insulin-like growth factor-I levels and cognition in healthy older men

“…T enanthate 300-600 mg weekly) or treatment continued for a longer period of time than the present study (e.g. 4-6 months) (Bhasin et al, 2001;Ferrando et al, 2002;Hobbs et al, 1993).…”

“…Androgen effects on IGF-I levels and the somatropic axis have been reported in both young and old men (Ferrando et al, 2002;Hobbs et al, 1993;Veldhuis et al, 1997;Weissberger and Ho, 1993). Our results indicate a significant interaction effect of IGF-I levels between the treatment and placebo group.…”

“…Testosterone (T) administration has been reported to increase serum IGF-I levels in both young and older men (Ferrando et al, 2002;Hobbs et al, 1993;Veldhuis et al, 1997;Weissberger and Ho, 1993). Although studies examining the effects of T supplementation on cognition have been mixed, several studies have reported ben-eficial effects of T on verbal and spatial memory, and verbal fluency in healthy older and younger men (Cherrier et al, 2001;Janowsky et al, 1994Janowsky et al, , 2000O'Connor et al, 2001;Sih et al, 1997;Wolf et al, 2000).…”