Testosterone, dihydrotestosterone and estradiol are differentially associated with carotid intima-media thickness and the presence of carotid plaque in men with and without coronary artery disease

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Clarifying the relationship of sex hormones to preclinical atherosclerosis could illuminate pathways by which androgens are associated with cardiovascular events and mortality. Our aim was to determine hormone profiles associated with carotid intima-media thickness (CIMT) and carotid atheroma, in men with and without known coronary artery disease (CAD). We included 492 community-based men aged 20-70 years (Group A) and 426 men with angiographically proven CAD aged <60 years (Group B). Fasting early morning sera were assayed for testosterone (T), dihydrotestosterone (DHT) and estradiol (E2) using mass spectrometry. CIMT and carotid plaque were assessed ultrasonographically. Mean (±SD) age was Group A: 53.8±12.6 and Group B: 49.6±5.1 years. Higher T was associated with reduced CIMT (-0.011 mm per 1-SD increase, p=0.042) and lower prevalence of carotid plaque (odds ratio [OR] per 1-SD increase, 0.68, p=0.012) in Group A, but not B. E2 was associated with increased CIMT in Group A (0.013 mm, p=0.011) but not B. Higher DHT and E2 were associated with reduced carotid plaque in Group B (DHT: OR=0.77, p=0.024; E2: OR=0.75, p=0.008), but not A. In community-dwelling men, higher T is associated with favourable CIMT and lower prevalence of carotid plaque, while higher E2 is associated with worse CIMT. In men with CAD, higher DHT or E2 are associated with less carotid plaque. T, DHT and E2 are differentially associated with preclinical carotid atherosclerosis in a cardiovascular phenotype-specific manner. Interventional studies are needed to examine effects of exogenous T and its metabolites DHT and E2, on atherogenesis.