title: Relation between sex hormone concentrations, peripheral arterial disease, and change in ankle-brachial index: findings from the Framingham Heart Study.
abstract: OBJECTIVE
  Our objective was to investigate cross-sectional and longitudinal associations of sex hormone concentrations with ankle-brachial index (ABI) and peripheral arterial disease (PAD).
  
  
  RESULTS
  We used data from 3034 (1612 women) participants of the Framingham Heart Study. ABI was measured and PAD defined as ABI below 0.90, intermittent claudication, or lower extremity revascularization. Sex hormone concentrations were measured by liquid chromatography-tandem mass spectrometry [total testosterone (T), total estradiol, and estrone], immunofluorometric assay (SHBG), or calculated (free T). Sex-specific multivariable linear and logistic regression models were conducted for each sex hormone separately. Cross-sectional multivariable analyses revealed that men with lower free T and higher estrone (E1) concentrations had a significantly lower ABI [for free T, lowest vs. higher quartiles, β = -0.02, with 95% confidence interval (CI) = -0.04 to -0.001; and for E1, highest vs. lower quartiles, β = -0.02, with 95% CI = -0.04 to -0.002, respectively). Lower total T and SHBG concentrations were also associated with prevalent PAD in age-adjusted [odds ratio (OR) = 2.24, 95% CI = 1.17-4.32; and OR = 2.06; 95% CI = 1.07-3.96, lowest vs. highest quartile, respectively), but not in multivariable logistic regression models. Longitudinal multivariable analyses showed an association of lower SHBG with ABI change (decline ≥ 0.15; n = 69) in men [OR for SHBG quartiles 1, 2, and 3 as compared with quartile 4 were 2.56 (95% CI = 1.01-6.45), 2.28 (95% CI = 0.98-5.32), and 2.93 (95% CI = 1.31-6.52), respectively]. In women, none of the investigated associations yielded statistically significant estimates.
  
  
  CONCLUSIONS
  Our investigation of a middle-aged community-based sample suggests that sex hormone concentrations in men but not in women may be associated with PAD and ABI change.
authors.affiliation: Preventive Medicine and Epidemiology Section, Boston University School of Public Health, Boston, Massachusetts 02118, USA. robin.haring@uni-greifswald.de
authors.forename: Robin
authors.initials: R
authors.lastname: Haring
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Travison
authors.forename: Shalender
authors.initials: S
authors.lastname: Bhasin
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
authors.forename: Henri
authors.initials: H
authors.lastname: Wallaschofski
authors.forename: Maithili N
authors.initials: MN
authors.lastname: Davda
authors.forename: Andrea
authors.initials: A
authors.lastname: Coviello
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Murabito
mesh_terms: D000328:Adult; D000368:Aged; D055109:Ankle Brachial Index; D004958:Estradiol / Q000097:blood*; D004970:Estrone / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D058729:Peripheral Arterial Disease / Q000097:blood* / Q000503:physiopathology; D012737:Sex Factors; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism*; D013739:Testosterone / Q000097:blood*
chemical_list: D012738:Sex Hormone-Binding Globulin; D004970:Estrone; D013739:Testosterone; D004958:Estradiol