Sex‐specific Difference in the Interconversion of Cortisol and Cortisone in Men and Women

OBJECTIVE: Our objective was to demonstrate that the smaller oxoreductase activity of 11beta-HSD1 in women would shift the interconversion of cortisol and cortisone toward cortisone, resulting in a larger amount of generated labeled cortisone in healthy women than in healthy men. RESEARCH METHODS AND PROCEDURES: Using mass spectrometry, the amount of cortisone generated from a continuous infusion (8 am to 6 pm) of stable-labeled cortisol (1alpha,2alpha-d-cortisol) was determined in non-obese and in obese (BMI>35 kg/m2) men and women during steady-state conditions (from 2 pm to 6 pm). In this setting, the amount of generated labeled cortisone (expressed as % of the achieved steady-state concentrations of labeled cortisol) reflects the sum of the bi-directional conversion of cortisol into cortisone (and vice versa) by 11beta-hydroxysteroid dehydrogenase. RESULTS: The amount of generated labeled cortisone was higher in men than in women (p<0.0001). This sex difference was higher in obese than in non-obese patients (p=0.0062). CONCLUSIONS: The interconversion of cortisol and cortisone during steady-state conditions is shifted toward cortisol in men as compared with women. This suggests a higher overall oxoreductase activity of 11beta-hydroxysteroid dehydrogenase type 1 in men than in women. This sex-specific difference is maintained in obesity.