title: Effects of transdermal testosterone gel or an aromatase inhibitor on serum concentration and pulsatility of growth hormone in older men with age-related low testosterone.
abstract: Growth hormone is the major regulator of growth and body composition. Pulsatile GH secretion declines exponentially with age. Testosterone replacement is being increasingly offered to older men with age-related low testosterone. Testosterone administration has been shown to stimulate GH secretion. However, little is known about the effect of testosterone aromatization to estradiol on GH pulsatility and its impact on IGF-1 in older men.
  
  
  OBJECTIVE
  This randomized controlled proof-of-concept trial investigated the relative effects of testosterone and estradiol on GH pulsatility and IGF-1 in older men with low testosterone.
  
  
  METHODS
  Thirty-seven men, ≥65years with total testosterone <350ng/dL were randomized to 5g transdermal testosterone gel (TT), 1mg oral aromatase inhibitor (AI) or placebo daily for 12months. Primary outcome was deconvolution and approximate entropy analyses of pulsatile including basal and entropic modes of secretion performed at baseline and 3months. Secondary outcomes included IGF-1 evaluated at baseline, 3 and 6months.
  
  
  RESULTS
  At 3months, mean GH and in IGF-1 were similar between the three groups. At 6months, IGF-1 significantly increased by Δ 15.3±10.3ng/ml in the TT-group compared to placebo (P=0.03). Both intervention groups significantly increased GH pulse frequency (TT-group, P=0.04; AI-group, P=0.05) compared to placebo. The GH secretory-burst mode (duration) significantly decreased in the TT-group (P=0.0018) compared to placebo while it remained unchanged in the AI-group (P=0.059).
  
  
  CONCLUSIONS
  In older men, testosterone increases GH pulse frequency while the aromatization to estradiol is involved in the rise of IGF-1 levels.
authors.affiliation: Laboratory of Clinical Investigation, National Institute on Aging, Baltimore, MD, United States, 21225.
authors.forename: Jenny Pena
authors.initials: JP
authors.lastname: Dias
authors.affiliation: Division of Endocrinology and Metabolism, Mayo Clinic, Rochester, MN, United States.
authors.forename: Johannes D
authors.initials: JD
authors.lastname: Veldhuis
authors.affiliation: Laboratory of Clinical Investigation, National Institute on Aging, Baltimore, MD, United States, 21225.
authors.forename: Olga
authors.initials: O
authors.lastname: Carlson
authors.affiliation: Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, United States, 21225.
authors.forename: Michelle
authors.initials: M
authors.lastname: Shardell
authors.affiliation: Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, United States, 21225.
authors.forename: Chee W
authors.initials: CW
authors.lastname: Chia
authors.affiliation: Laboratory of Clinical Investigation, National Institute on Aging, Baltimore, MD, United States, 21225.
authors.forename: Denise
authors.initials: D
authors.lastname: Melvin
authors.affiliation: Laboratory of Clinical Investigation, National Institute on Aging, Baltimore, MD, United States, 21225.
authors.forename: Josephine M
authors.initials: JM
authors.lastname: Egan
authors.affiliation: Section on Men's Health, Aging and Metabolism, Brigham and Women's Hospital Harvard Medical School, Boston, MA, United States, 02115. Electronic address: sbasaria@partners.org.
authors.forename: Shehzad
authors.initials: S
authors.lastname: Basaria
mesh_terms: D000279:Administration, Cutaneous; D000368:Aged; D047072:Aromatase Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology*; D001823:Body Composition / Q000187:drug effects; D004311:Double-Blind Method; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology; D005782:Gels; D012739:Gonadal Steroid Hormones / Q000097:blood; D019382:Human Growth Hormone / Q000097:blood*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D013739:Testosterone / Q000008:administration & dosage / Q000172:deficiency* / Q000494:pharmacology*
chemical_list: D047072:Aromatase Inhibitors; D005782:Gels; D012739:Gonadal Steroid Hormones; D019382:Human Growth Hormone; D013739:Testosterone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I
keywords: Aromatase inhibitor; Growth hormone; Insulin-like growth factor-1; Testosterone replacement