title: Relationship between serum levels of sex hormones and progression of subclinical atherosclerosis in postmenopausal women.
abstract: BACKGROUND
  Postmenopausal hormone therapy has been examined extensively in relation to cardiovascular disease. However, research relating serum levels of sex hormones to cardiovascular disease is sparse, and the results are inconclusive.
  
  
  METHODS
  We measured sex hormones in longitudinally collected samples of 180 postmenopausal women, 91 randomized to 17beta-estradiol and 89 to placebo, in the Estrogen in the Prevention of Atherosclerosis Trial. Repeated measures of sex hormone levels were tested for an association with carotid artery intima-media thickness (CIMT), which was also assessed longitudinally over 2 yr.
  
  
  RESULTS
  In all women, changes in serum estrone (P = 0.02), total estradiol (P = 0.01), free estradiol (P = 0.02), and SHBG (P = 0.005) were significantly inversely associated with CIMT progression, controlling for age and body mass index. All the estrogen compounds and SHBG were significantly inversely related with low-density lipoprotein cholesterol and positively associated with high-density lipoprotein cholesterol (all P < 0.0001), whereas free testosterone was positively related with low-density lipoprotein cholesterol and inversely associated with high-density lipoprotein cholesterol (P < 0.003). Despite an increase in serum-free estradiol with estradiol therapy, women with unchanged SHBG and free testosterone levels had an average (se) progression in CIMT of 8.53 (4.72) microm/yr, whereas women with increased free estradiol and SHBG and decreased free testosterone had the largest reduction in CIMT progression [-5.45 (2.77) microm/yr; trend P = 0.03].
  
  
  CONCLUSIONS
  Estrogen and SHBG are associated with reduced subclinical atherosclerosis progression in healthy postmenopausal women. These associations are partially mediated by their beneficial effects on lipids. Among women taking estradiol, the most beneficial hormone profile for CIMT progression was increased free estradiol and SHBG with concomitant decreased free testosterone.
authors.affiliation: Department of Pediatrics, Keck School of Medicine, University of Southern California, 1540 Alcazar Street, CHP Suite 222R, Los Angeles, California 90033, USA. rkarim@usc.edu
authors.forename: Roksana
authors.initials: R
authors.lastname: Karim
authors.forename: Howard N
authors.initials: HN
authors.lastname: Hodis
authors.forename: Frank Z
authors.initials: FZ
authors.lastname: Stanczyk
authors.forename: Rogerio A
authors.initials: RA
authors.lastname: Lobo
authors.forename: Wendy J
authors.initials: WJ
authors.lastname: Mack
mesh_terms: D050197:Atherosclerosis / Q000097:blood*; D001786:Blood Glucose / Q000378:metabolism; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000473:pathology; D002784:Cholesterol / Q000097:blood; D018450:Disease Progression; D004311:Double-Blind Method; D004958:Estradiol / Q000008:administration & dosage* / Q000097:blood*; D015914:Estrogen Replacement Therapy / Q000379:methods*; D004970:Estrone / Q000097:blood*; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D008137:Longitudinal Studies; D008875:Middle Aged; D012738:Sex Hormone-Binding Globulin / Q000819:agonists; D013739:Testosterone / Q000097:blood; D014280:Triglycerides / Q000097:blood; D014463:Ultrasonography
chemical_list: D001786:Blood Glucose; D007328:Insulin; D012738:Sex Hormone-Binding Globulin; D014280:Triglycerides; D004970:Estrone; D013739:Testosterone; D004958:Estradiol; D002784:Cholesterol