Abstract 1023: Extremes of Endogenous Testosterone Are Associated With Increased Risk of Coronary Heart Disease Events in Older Women: The Rancho Bernardo Study
Background: Women’s favorable cardiovascular risk, compared to men, is usually attributed to endogenous estrogen levels. Few studies have tested the hypothesis that extremes of endogenous testosterone may contribute to the development of coronary heart disease (CHD) in women.
Methods: We examined the prospective association of total testosterone (T) and bioavailable testosterone (BioT) levels with incident CHD events among 639 community-dwelling, non-estrogen-using postmenopausal women, aged 50 to 91, who were followed from 1984 – 87 thru 2004. Analyses were performed using Cox proportional hazards regressions.
Results: A total of 134 incident CHD events occurred. Age-adjusted CHD risk estimates were similar for the 4 highest T quintiles relative to the lowest, suggesting a low threshold. We therefore derived risk estimates for the lowest quintile of total T (≤80 pg/ml) versus all higher. In age-adjusted analyses, low T was associated with an almost 2-fold increased risk of incident CHD (HR=1.72, 95% CI 1.16 to 2.56). BioT showed a u-shaped association with incident CHD. Age-adjusted risk estimates for the lowest and highest quintiles relative to the 3rd were 1.79 (95% CI 1.03, 3.16) and 1.96 (95% CI 1.13, 3.41), respectively. Additional adjustment for lifestyle and adiposity did not influence results. In analyses adjusted for total T, high BioT was associated with a 2.6 fold (95% CI 1.43, 4.71) increased risk of CHD; low BioT was not associated with CHD risk (HR=1.09, 95% CI 0.54, 2.21) independent of total T. Separate adjustment for SHBG or estradiol did not alter T or BioT associations. Exclusion of CHD events that occurred in the first 5 yrs of follow-up (n=44) attenuated the low T association (HR=1.48), but not that for high BioT (HR=2.04). Women with high BioT had a higher prevalence of diabetes and the metabolic syndrome; separate adjustment for these conditions reduced the strength of the high BioT association (HR=1.79 and 1.66, respectively).
Conclusions: An optimal range of testosterone may exist for cardiovascular health in women, with increased risk of CHD events at low levels of T overall and at high levels of the bioavailable fraction of T. These fraction-specific results may explain divergent reports in the female heart disease - androgen literature.
This research has received full or partial funding support from the American Heart Association, National Center.