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 11β‐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 (1α,2α‐d‐cortisol) was determined in non‐obese and in obese (BMI >35 kg/m 2 ) 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 11β‐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 11β‐hydroxysteroid dehydrogenase type 1 in men than in women. This sex‐specific difference is maintained in obesity.