title: Short-Term Estrogen Withdrawal Increases Adiposity in Healthy Men.
abstract: T deprivation increases risk of insulin resistance in men, but whether this risk is independent of changes in body composition is unknown. Further, the metabolic roles of T and its metabolite estradiol have not been clearly defined in men.
  
  
  
  This study sought to establish the effects of selective sex steroid withdrawal on insulin sensitivity in healthy men.
  
  
  
  This was a double-blinded, placebo-controlled, randomized trial at an academic medical center of 56 healthy men, 19-55 years of age.
  
  
  
  Subjects received the GnRH antagonist acyline plus one of the following: placebo gel (Castrate), 1.25 g testosterone gel (Low T/E), 5 g testosterone gel (Normal T/E), or 5 g testosterone gel with letrozole (Normal T/Low E) daily for 4 weeks. Body composition and glucose tolerance were assessed at baseline and end of treatment.
  
  
  
  Insulin sensitivity was quantified by the Matsuda index.
  
  
  
  Predicted circulating sex steroid concentrations were achieved in all treatment groups. The time-by-group interaction for Matsuda index did not achieve significance in overall repeated measures ANOVA (baseline vs week 4; P = .16). A significant time-by-group interaction was observed for fat mass (P = .003), with changes in fat mass attributable predominantly to estrogen exposure in linear regression analysis (P = .016). A time-by-group interaction also was observed for lean mass (P = .03) and influenced by androgen exposure (P = .003).
  
  
  
  Short-term sex steroid withdrawal in healthy men causes adverse changes in body composition. These findings support the role of estradiol as a determinant of adiposity in men.
authors.affiliation: Center for Research in Reproduction and Contraception (J.C., K.B.R., S.T.P., J.K.A.) and Diabetes Institute, Division of Metabolism, Endocrinology, and Nutrition (K.B.R. and S.T.P.) and Division of Gerontology & Geriatric Medicine (A.M.M.), Department of Medicine, University of Washington School of Medicine, Seattle, Washington 98195; The Fred Hutchinson Cancer Research Center (M.K.); and the Geriatric Research, Education and Clinical Center (A.M.M.), VA Puget Sound Health Care System, Seattle, Washington 98108.
authors.forename: Jing
authors.initials: J
authors.lastname: Chao
authors.affiliation: Center for Research in Reproduction and Contraception (J.C., K.B.R., S.T.P., J.K.A.) and Diabetes Institute, Division of Metabolism, Endocrinology, and Nutrition (K.B.R. and S.T.P.) and Division of Gerontology & Geriatric Medicine (A.M.M.), Department of Medicine, University of Washington School of Medicine, Seattle, Washington 98195; The Fred Hutchinson Cancer Research Center (M.K.); and the Geriatric Research, Education and Clinical Center (A.M.M.), VA Puget Sound Health Care System, Seattle, Washington 98108.
authors.forename: Katya B
authors.initials: KB
authors.lastname: Rubinow
authors.affiliation: Center for Research in Reproduction and Contraception (J.C., K.B.R., S.T.P., J.K.A.) and Diabetes Institute, Division of Metabolism, Endocrinology, and Nutrition (K.B.R. and S.T.P.) and Division of Gerontology & Geriatric Medicine (A.M.M.), Department of Medicine, University of Washington School of Medicine, Seattle, Washington 98195; The Fred Hutchinson Cancer Research Center (M.K.); and the Geriatric Research, Education and Clinical Center (A.M.M.), VA Puget Sound Health Care System, Seattle, Washington 98108.
authors.forename: Mario
authors.initials: M
authors.lastname: Kratz
authors.affiliation: Center for Research in Reproduction and Contraception (J.C., K.B.R., S.T.P., J.K.A.) and Diabetes Institute, Division of Metabolism, Endocrinology, and Nutrition (K.B.R. and S.T.P.) and Division of Gerontology & Geriatric Medicine (A.M.M.), Department of Medicine, University of Washington School of Medicine, Seattle, Washington 98195; The Fred Hutchinson Cancer Research Center (M.K.); and the Geriatric Research, Education and Clinical Center (A.M.M.), VA Puget Sound Health Care System, Seattle, Washington 98108.
authors.forename: John K
authors.initials: JK
authors.lastname: Amory
authors.affiliation: Center for Research in Reproduction and Contraception (J.C., K.B.R., S.T.P., J.K.A.) and Diabetes Institute, Division of Metabolism, Endocrinology, and Nutrition (K.B.R. and S.T.P.) and Division of Gerontology & Geriatric Medicine (A.M.M.), Department of Medicine, University of Washington School of Medicine, Seattle, Washington 98195; The Fred Hutchinson Cancer Research Center (M.K.); and the Geriatric Research, Education and Clinical Center (A.M.M.), VA Puget Sound Health Care System, Seattle, Washington 98108.
authors.forename: Alvin M
authors.initials: AM
authors.lastname: Matsumoto
authors.affiliation: Center for Research in Reproduction and Contraception (J.C., K.B.R., S.T.P., J.K.A.) and Diabetes Institute, Division of Metabolism, Endocrinology, and Nutrition (K.B.R. and S.T.P.) and Division of Gerontology & Geriatric Medicine (A.M.M.), Department of Medicine, University of Washington School of Medicine, Seattle, Washington 98195; The Fred Hutchinson Cancer Research Center (M.K.); and the Geriatric Research, Education and Clinical Center (A.M.M.), VA Puget Sound Health Care System, Seattle, Washington 98108.
authors.forename: Stephanie T
authors.initials: ST
authors.lastname: Page
mesh_terms: D050154:Adiposity; D000328:Adult; D000728:Androgens / Q000008:administration & dosage / Q000494:pharmacology*; D047072:Aromatase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism*; D004311:Double-Blind Method; D004958:Estradiol / Q000097:blood*; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D006727:Hormone Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007333:Insulin Resistance; D000077289:Letrozole; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage / Q000494:pharmacology; D013739:Testosterone / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology; D055815:Young Adult
chemical_list: D000728:Androgens; D047072:Aromatase Inhibitors; D001786:Blood Glucose; D006727:Hormone Antagonists; D009570:Nitriles; D014230:Triazoles; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D004958:Estradiol; D000077289:Letrozole