Association of serum cholesterol and cholesterol-lowering drug use with serum sex steroid hormones in men in NHANES III

Purpose: Low cholesterol levels and statin drugs may protect against prostate cancer with a worse prognosis. Their protective mechanism is unknown, but has been hypothesized to be related to cholesterol's role as a sex steroid hormone precursor. We evaluated whether serum testosterone and estradiol differ by cholesterol or cholesterol-lowering drug use. Materials and methods: Testosterone and estradiol were measured for 1,457 male participants in the Third National Health and Nutrition Examination Survey. We estimated multivariable-adjusted geometric mean hormone concentration by quintiles of cholesterol concentration and by cholesterol-lowering drugs use. Results: Across quintiles of cholesterol, testosterone level did not differ (mean, 95% confidence interval (CI); Q1: 5.25, 5.02-5.49, Q5: 5.05, 4.76-5.37 ng/ml; p-trend = 0.32), whereas estradiol levels were lower (Q1: 38.7, 36.9-40.5; Q5: 33.1, 31.8-34.5 pg/ml; p-trend < 0.0001). Neither testosterone (no: 5.12, 4.94-5.30, yes: 4.91, 4.33-5.57 ng/ml, p = 0.57) nor estradiol (no: 35.9, 34.8-37.1; yes: 33.9, 29.4-39.2 pg/ml; p = 0.39) differed by cholesterol-lowering drugs use. Conclusion: Testosterone did not differ by cholesterol or cholesterol-lowering drug use. Estradiol was lower in men with higher cholesterol, but did not differ by cholesterol-lowering drug use. Our results suggest that the lower risk of advanced prostate cancer among statin users is not readily explained by a cholesterol-mediated effect of statins on sex hormone levels.