Extremes of Endogenous Testosterone Are Associated with Increased Risk of Incident Coronary Events in Older Women

Context: Few studies have examined whether endogenous testosterone is associated with the development of coronary heart disease (CHD) in women. Objective: This study tested the association of total testosterone (total T) and bioavailable T (BioT) levels with risk of incident coronary events among older community-dwelling women. Design, Setting, and Participants: This was a prospective, population-based study of 639 postmenopausal women, aged 50-91 (mean, 73.8) yr who had serum testosterone measurements at baseline (1984-87) and who were followed for incident CHD events through 2004. Main Outcome Measures: A total of 134 incident CHD events occurred during follow-up [45 non-fatal myocardial infarctions, 79 fatal myocardial infarctions, and 10 coronary revascularizations]. Results: The median follow-up was 12.3 yr. Age-adjusted CHD risk estimates were similar for the four highest total T quintiles relative to the lowest, suggesting a low threshold. In age-adjusted analyses, the lowest total T quintile (<= 80 pg/ml) was associated with a 1.62-fold increased risk of incident CHD [95% confidence interval (CI), 1.10-2.39] compared to higher levels. BioT showed a U-shaped association with incident CHD. Age-adjusted risk for the lowest and highest BioT quintiles relative to the third were 1.79 (95% CI, 1.03-3.16) and 1.96 (95% CI, 1.13-3.41), respectively. Additional adjustment for lifestyle, adiposity, estradiol, and ovarian status, or for CHD risk factor covariates, had minimal influence on results. Conclusions: An optimal range of testosterone may exist for cardiovascular health in women, with increased risk of CHD events at low levels of testosterone overall and at high levels of the bioavailable fraction of testosterone. (J Clin Endocrinol Metab 95: 740-747, 2010)