title: Acute sex steroid withdrawal increases cholesterol efflux capacity and HDL-associated clusterin in men.
abstract: Exogenous androgens can lower HDL-cholesterol (HDL-C) concentrations, yet men with low serum testosterone have elevated rates of cardiovascular disease (CVD). HDL function may better predict CVD risk than absolute HDL-C quantity. We evaluated the acute effects of medical castration in men on HDL-C, cholesterol efflux capacity and HDL protein composition. Twenty-one healthy men, ages 18-55, received the GnRH antagonist acyline and one of the following for 28days: Group 1: placebo, Group 2: transdermal testosterone gel and placebo, Group 3: transdermal testosterone gel and an aromatase inhibitor. Sex steroids, fasting lipids, and cholesterol efflux to apoB-depleted serum were measured in all subjects. The HDL proteome was assessed in Group 1 subjects only. In Group 1, serum testosterone concentrations were reduced by >95%, and HDL-C and cholesterol efflux capacity increased (p=0.02 and p=0.03 vs. baseline, respectively). HDL-associated clusterin increased significantly with sex steroid withdrawal (p=0.007 vs. baseline). Testosterone withdrawal in young, healthy men increases HDL-C and cholesterol efflux capacity. Moreover, sex steroid deprivation changes HDL protein composition. Further investigation of the effects of sex steroids on HDL composition and function may help resolve the apparently conflicting data regarding testosterone, HDL-C, and CVD risk.
authors.affiliation: Center for Research in Reproduction and Contraception, Division of Metabolism, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98109, United States. rubinow@uw.edu
authors.forename: Katya B
authors.initials: KB
authors.lastname: Rubinow
authors.forename: Chongren
authors.initials: C
authors.lastname: Tang
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Hoofnagle
authors.forename: Christin N
authors.initials: CN
authors.lastname: Snyder
authors.forename: John K
authors.initials: JK
authors.lastname: Amory
authors.forename: Jay W
authors.initials: JW
authors.lastname: Heinecke
authors.forename: Stephanie T
authors.initials: ST
authors.lastname: Page
mesh_terms: D000293:Adolescent; D000328:Adult; D000077384:Anastrozole; D000728:Androgens / Q000008:administration & dosage / Q000097:blood; D001055:Apolipoproteins B / Q000097:blood; D047072:Aromatase Inhibitors / Q000008:administration & dosage; D002784:Cholesterol / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood; D051152:Clusterin / Q000097:blood*; D004334:Drug Administration Schedule; D005215:Fasting / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage; D006801:Humans; D008055:Lipids / Q000097:blood; D008075:Lipoproteins, HDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage*; D009842:Oligopeptides / Q000008:administration & dosage*; D013739:Testosterone / Q000008:administration & dosage* / Q000097:blood; D013997:Time Factors; D014230:Triazoles / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D000728:Androgens; D001055:Apolipoproteins B; D047072:Aromatase Inhibitors; D008076:Cholesterol, HDL; D051152:Clusterin; D008055:Lipids; D008075:Lipoproteins, HDL; D009570:Nitriles; D009842:Oligopeptides; D014230:Triazoles; D000077384:Anastrozole; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D002784:Cholesterol; C109238:acyline