title: Testosterone replacement in hypogonadal men alters the HDL proteome but not HDL cholesterol efflux capacity.
abstract: The effects of androgens on cardiovascular disease (CVD) risk in men remain unclear. To better characterize the relationship between androgens and HDL, we investigated the effects of testosterone replacement on HDL protein composition and serum HDL-mediated cholesterol efflux in hypogonadal men. Twenty-three older hypogonadal men (ages 51-83, baseline testosterone < 280 ng/dl) were administered replacement testosterone therapy (1% transdermal gel) with or without the 5α-reductase inhibitor dutasteride. At baseline and after three months of treatment, we determined fasting lipid concentrations, HDL protein composition, and the cholesterol efflux capacity of serum HDL. Testosterone replacement did not affect HDL cholesterol (HDL-C) concentrations but conferred significant increases in HDL-associated paraoxonase 1 (PON1) and fibrinogen α chain (FGA) (P = 0.022 and P = 0.023, respectively) and a decrease in apolipoprotein A-IV (apoA-IV) (P = 0.016). Exogenous testosterone did not affect the cholesterol efflux capacity of serum HDL. No differences were observed between men who received testosterone alone and those who also received dutasteride. Testosterone replacement in older hypogonadal men alters the protein composition of HDL but does not significantly change serum HDL-mediated cholesterol efflux. These effects appear independent of testosterone conversion to dihydrotestosterone. Further research is needed to determine how changes in HDL protein content affect CVD risk in men.
authors.affiliation: Center for Research in Reproduction and Contraception, Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA. rubinow@uw.edu
authors.forename: Katya B
authors.initials: KB
authors.lastname: Rubinow
authors.forename: Tomas
authors.initials: T
authors.lastname: Vaisar
authors.forename: Chongren
authors.initials: C
authors.lastname: Tang
authors.forename: Alvin M
authors.initials: AM
authors.lastname: Matsumoto
authors.forename: Jay W
authors.initials: JW
authors.lastname: Heinecke
authors.forename: Stephanie T
authors.initials: ST
authors.lastname: Page
mesh_terms: D008076:Cholesterol, HDL / Q000097:blood / Q000378:metabolism*; D005215:Fasting; D006801:Humans; D007006:Hypogonadism / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020543:Proteome / Q000187:drug effects*; D013739:Testosterone / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D008076:Cholesterol, HDL; D020543:Proteome; D013739:Testosterone