Increased 5 alpha-reductase and normal 11 beta-hydroxysteroid dehydrogenase metabolism of C19 and C21 steroids in a young population with polycystic ovarian syndrome

Objective: To test the hypothesis that 5 alpha-reductase (5 alpha R) and 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) activity are increased in adolescent and young-adult women with PCOS and that an altered regulation o f the hypothalamic-pituitary-adrenal (HPA) axis occurred in these subjects, Design: Prospective non-randomized study in an academic research environmen t. Patients: Eleven women, aged 14 to 25 years, were studied who were at least one year post-menarche and who had a diagnosis of PCOS based on a history of oligomenorrhea and elevated total and or free serum testosterone. Intervention: 24-Hour urinary metabolites were assessed in nine subjects an d five underwent stimulation with ovine corticotropin releasing factor (oCR F). Outcome measures: C19 and C21 steroid urinary metabolite 5-alpha/5-beta pai rs, 11-oxo/11-hydroxy products and the ratio of the total 5-alpha/5-beta re duced and 11-oxo/11-hydroxy products were compared to values in control wom en, Urinary cortisol (F) (sum of conjugated and free, and free F) and total F metabolites (the sum of THE, THF, 5 alpha-THF, cortolones, and cortols) were determined, A 1 mu g/kg oCRF stimulation test was performed with timed samples determined for plasma ACTH and serum F levels. Results: The 24-hour total and free urinary F were not different from contr ol, However, the total F metabolites were markedly elevated (7922+/-2666 vs 5418+/-1549 mu g/24 h, p<0.01). A marked increase in the total 5-alpha red uced C19 and C21 metabolites was observed in the PCOS population vs control (5084+/-1977 vs 2681+/-1188 mu g/24 h, p<0.01). The total urinary 11-oxo/1 1-hydroxy metabolite ratio was not different, p=0.23. The basal values and response of both ACTH and F to oCRF stimulation were not different from tho se of controls, Conclusion: There is a marked increase in 5 alpha R metabolism of both C19 and C21 steroids in younger women with PCOS.