Relationships in men of sex hormones, insulin, adiposity, and risk factors for myocardial infarction.

That sex hormones, insulin, and obesity all correlate with the constellation of risk factors for myocardial infarction (MI) that has come to be known as "syndrome X," the "insulin-resistance syndrome," or the "metabolic syndrome" suggests that any one or more of them could underlie and link the risk factors to form the constellation. That sex hormones, insulin, and obesity also correlate with each other complicates their identification as an underlying link. To compare the likelihood of each being a link, we measured and determined the interrelationships of sex hormones, insulin, adiposity variables, and risk factors for MI in 80 apparently healthy men. Of the adiposity variables, visceral adipose tissue (VAT) correlated more strongly with the risk factors for MI than did body mass index (BMI), total adipose tissue (TAT), subcutaneous adipose tissue (SCAT), waist-to-hip ratio (WHR), and waist circumference (W). Controlling for VAT eliminated all of the other adiposity correlations that had been significant. VAT, therefore, was used as the measure of adiposity for further data analysis. VAT correlated more strongly with risk factors for MI than did sex hormones and insulin, and most of the correlations of sex hormones and insulin with risk factors for MI lost statistical significance after controlling for VAT. Testosterone and the ratio of estradiol-to-testosterone (E/T) correlated with insulin; on controlling for VAT, only the E/T-insulin correlation remained significant (r =.38, P <.001) and on multiple linear regression analysis, insulin was associated with estradiol (P =.01) and testosterone (P =.04) independently of VAT and age. In conclusion, (1) VAT in men may largely explain the correlations of sex hormones, insulin, and obesity with the risk factors for MI measured, (2) VAT may be the principal factor in men, independently of other measures of adiposity, that links risk factors for MI to form the constellation, and (3) estradiol may play a more important role in the sex hormone-insulin relationship in men than has generally been considered.