THE IMPACT OF ESTROGEN ON ADRENAL ANDROGEN SENSITIVITY AND SECRETION IN POLYCYSTIC-OVARY-SYNDROME

Adrenal hyperandrogenism is a common feature of patients with polycyst ic ovary syndrome (PCO). This may be due to enhanced adrenal sensitivi ty to ACTH. Because enhanced ovarian androgen secretion does not appea r to explain this phenomenon, we explored the role of estrogen in indu cing enhanced adrenal sensitivity, in that a state of relative hyperes trogenism exists in PCO. Eight patients with PCO and seven matched con trols received ovine corticotropin-releasing hormone (oCRH; 0.1 mu g/k g) iv before and after hypoestrogenism was induced by leuprolide aceta te (LA; 1 mg, sc, each day). In patients with PCO, a third oCRH test w as repeated after transdermal estradiol (E(2); 0.1 mg) had been applie d for a week, during which time LA was continued. At baseline, patient s with PCO had increased responses of 11 beta-hydroxyandrostenedione a nd dehydroepiandrosterone (P < 0.03 and P < 0.02) and increased Delta maximal ratios of androstenedione (A4)/ACTH and dehydroepiandrosterone /ACTH (P < 0.01) after oCRH treatment. After LA administration to pati ents with PCO, these ratios were significantly suppressed (P < 0.01) a nd returned to baseline after E(2) was added. There were no changes in controls. Steroid ratio responses to oCRH suggested that 17,20-desmol ase activity (Delta maximum change in the ratio of A4/17-hydroxyproges terone) was lowered with estrogen suppression and increased again afte r transdermal E(2) administration. There was a significant positive co rrelation between changes in E(2) levels and Delta maximum change in t he ratios of A4/17-OHP after oCRH treatment, signifying 17,20-desmolas e activity (r = 0.58, P < 0.02). In conclusion, these data provide evi dence that estrogen is at least one factor that influences adrenal and rogen sensitivity in PCO and may help explain the frequent finding of adrenal hyperandrogenism in this syndrome.