Endogenous inhibitors of 11 beta-hydroxysteroid dehydrogenase type 1 do not explain abnormal cortisol metabolism in polycystic ovary syndrome

OBJECTIVE The aetiology of enhanced adrenal androgen secretion in polycysti c ovary syndrome is poorly understood. Previous reports suggest that enhanc ed peripheral metabolism of cortisol results in decreased negative feedback suppression of ACTH secretion, either by enhanced inactivation of cortisol by 5 alpha-reductase or impaired reactivation of cortisol by 11 beta-hydro xysteroid dehydrogenase type 1 (11 beta-HSD1). Endogenous inhibitors of hep atic 11 beta-HSD1 can be extracted from urine. We have tested the hypothesi s that these are increased in patients with polycystic ovary syndrome. DESIGN A case-control study. PATIENTS 57 patients with polycystic ovary syndrome and 27 healthy control women. MEASUREMENTS Aliquots from 24 h urine samples were extracted with Sep-Paks and incubated with rat liver microsomes in which 11 beta-HSD1 activity was quantified by conversion of H-3-corticosterone to H-3-11-dehydrocorticoster one. RESULTS Inhibition of 11 beta-HSD1 activity was not different in extracts f rom patients compared with controls (40.8 +/- 18.9 arbitrary units in patie nts vs. 42.7 +/- 16.6 in controls, mean (+/- SEM, P > 0.60) and did not cor relate with ratios of cortisol metabolites in urine or with body mass index . CONCLUSIONS The altered cortisol metabolism in polycystic ovarian syndrome, which is consistent with impaired 11 beta-HSD1 activity, cannot be account ed for by increased production of measurable endogenous inhibitors of this enzyme.