Gemfibrozil treatment is associated with elevated adrenal androgen, androstanediol glucuronide and cortisol levels in dyslipidemic men.

We have investigated the role of steroid hormones as coronary risk factors in the Helsinki Heart Study population of dyslipidemic middle-aged men. We compare here the effects of gemfibrozil and placebo on the serum levels of dehydroepiandrosterone (DHEA), its sulfate (DHEAS), their metabolite androstanediol glucuronide (3 alpha-AdiolG), androstenedione, cortisol, testosterone, and sex-hormone binding globulin (SHBG) in non-smokers. We also examined the associations between steroid and lipoprotein levels in both treatment groups. Compared with placebo gemfibrozil treatment was associated with significant elevations of the mean levels of DHEA 10.2 vs 8.0 nmol/l; P < 0.005, of DHEAS 8.0 vs 5.8 mumol/l; P < 0.001, of 3 alpha AdiolG 18.3 vs 8.4 nmol/l; P < 0.001, of androstenedione 5.7 vs 5.1 nmol/l; P < 0.02, and of cortisol 426 vs 358 nmol/l; P < 0.001. The mean SHBG levels decreased from 46.4 to 41.7 nmol/l; P = 0.03 with gemfibrozil treatment. No difference was found in testosterone levels 17.7 vs 18.8 nmol/l; P = 0.11, or the ratio of testosterone/SHBG 0.45 vs 0.43; P = 0.23. Positive correlations were found between high density lipoprotein-cholesterol and DHEAS (r = 0.267; P < 0.01) and DHEA (r = 0.282; P < 0.01) levels and negative correlations between low density lipoprotein-cholesterol and 3 alpha-AdiolG (r = -0.400; P < 0.001) and cortisol (r = -0.281; P < 0.01) levels in the gemfibrozil group. Our results indicate that gemfibrozil treatment increases the production and turnover of adrenal androgens and cortisol, and suggest that activation of the adrenocortical function and increased metabolism of androgens are related to the improved lipoprotein pattern during gemfibrozil treatment.