SEX-DIFFERENCES IN THE HUMAN METABOLISM OF CORTISOL

Sex differences in steroid metabolism have been clearly demonstrated i n animal studies, but few studies have addressed this question in the human. Our preliminary studies suggested human sex differences in both cortisol production and metabolism. We therefore looked in more detai l at indices of cortisol metabolism derived from 24 hour urinary stero id profiles in a group of 20 men and 20 women who were age-matched, dr ug-flee and had no endocrine disorder. Steroid analysis was by high re solution gas chromatography. Men excreted more total cortisol metaboli tes (7620+/-620 v 4750+/-380 mu g/24h, p<0.001), 11-oxo metabolites of cortisol (11-oxo FM, 4320+/-400 v 2890+/-250 mu g124h, p<0.001) and 1 1 beta-hydroxy metabolites of cortisol (11-OH FM, 3290+/-240 v 1860+/- 140 mu g/24h, p<0.001). These differences remained significant when co rrected for body surface area. The ratio of 11-oxo FM/11-OH FM, an ind ex of 11 beta-phydroxysteroid dehydrogenase (11-HSD) activity, was hig her in women (1.57+/-0.07 v 1.31+/-0.06, p<0.01). The ratios of 5 alph a/5 beta and 20-ore/20-OH metabolites of cortisol were both higher in men (1.07+/-0.15 v 0.58+/-0.04, p<0.01, and 2.78+/-0.06 v 2.27+/-0.11, p<0.01), while the ratio of 20 alpha 20 beta metabolites of cortisol was higher in women (1.79+/-0.13 v 1.32+/-0.06, p<0.01). We conclude t hat there are considerable sex differences in both the production and metabolism of cortisol in healthy men and women. In particular, the da ta are consistent with a sex difference in 11-HSD activity, with relat ively greater conversion of cortisol to cortisone in women.