Cardiovascular risk factors in men: The role of gonadal steroids and sex hormone-binding globulin

Males have higher risk of cardiovascular disease (CVD) than premenopausal f emales. Gonadal steroids are probably involved in the gender difference in CVD, but previous results have been conflicting. We investigated the associ ations between CVD risk factors and sex hormones in a cross-sectional desig ned study of 508 healthy mates, aged 41 to 72 years. We determined total te stosterone (T), sex hormone-binding globulin (SHBG), free androgen index (F AI), and estradiol (E2) and studied their relationship to body fat mass (BF ), blood pressure (BP), aortic compliance, left ventricular mass (LVM), and plasma lipids (total cholesterol, high-density lipoprotein [HDL], low-dens ity lipoprotein [LDL], very-low-density lipoprotein [VLDL], and triglycerid es). In quartile analyses after adjustment for confounders (age, body mass index [BMI], alcohol consumption, and smoking), SHBG and E2 were positively associated with HDL, while FAI was negatively associated with HDL. T and S HBG were negatively associated with VLDL and triglycerides, while FAI was p ositively associated with VLDL and triglycerides. T and SHBG were negativel y associated with BMI and BF, while FAI and E2 were positively associated w ith BMI and BF. E2 was negatively associated with LVM. No hormone varied wi th total cholesterol, LDL, BP, and aortic compliance in the adjusted analys es. In multiple regression analyses, SHBG was the main predictive variable of HDL, VLDL, and triglycerides explaining 12%, 17%,,and 17% of the variati on, respectively. No other hormones were selected as predictive variables f or VLDL and triglycerides, but E2, T, and FAI were selected in the HDL regr ession, explaining 3%, 2%, and less than 1%, respectively. Our regression a nalyses illustrate the diverging results when investigating associations be tween gonadal steroids and lipids with and without SHBG adjustment. Atherog enic lipid profile in males is associated with low SHBG, low T levels, and a high FAI Males with high E2 levels may have a less atherogenic lipid prof ile and lower LVM. SHBG is a key hormone in the association between sex hor mones and plasma lipids. We suggest that conflicting results of cross-secti onal and intervention studies of sex hormones and lipids, in part, may be e xplained by interindividual differences or changes in SHBG. Thus, further s tudies on the potential role of SHBG in the development of ischemic heart d isease (IHD) should be performed. Copyright (C) 2001 by W.B. Saunders Compa ny.