Adrenal dynamic responses to physiologic and pharmacologic adrenocorticotropic hormone stimulation before and after ovarian steroid modulation in women with polycystic ovary syndrome

Objective: To test the hypothesis that in women with polycystic ovary syndr ome (PCOS), adrenal cytochrome P450c 17 alpha activity is different after p hysic,logic vs. pharmacologic ACTH stimulation and that ovarian activity pr omotes adrenal hyperactivity that is different after physiologic vs. pharma cologic ACTH stimulation. Design: Prospective controlled pilot study. Setting: Reproductive endocrinology unit of an academic medical center. Patient(s): Six women with PCOS who had adrenal hyperandrogenism were compa red with four women with normal ovulation. Intervention(s): Adrenal dynamic blood sampling was performed before and af ter 6 months of GnRH agonist administration. Main Outcome Measure(s): Comparison of physic,logic and pharmacologic ACTH- stimulated levels of progesterone, 17-hydroxyprogesterone, and androgens be fore and after ovarian steroid modulation. Result(s): In women with PCOS, exaggerated responses of androstenedione and 11 beta-hydroxyandrostenedione as well as elevated ratios of 17-hydroxypro gesterone to progesterone and of androstenedione to 17-hydroxyprogesterone after physiologic ACTH stimulation did not persist after GnRH-agonist admin istration. Three of the six women with PCOS had an increased response of an drostenedione and a ratio of androstenedione to 17-hydroxyprogesterone that were >2 SD above the mean of those in the women with normal ovulation afte r pharmacologic ACTH stimulation; this finding persisted after GnRH-agonist administration. Conclusion(s): In women with PCOS, increases in adrenal androgen sensitivit y after physiologic ACTH stimulation reflected in both arms of cytochrome P 450c 17 alpha activity may be influenced by ovarian activity. However, 17,2 0-lyase hyperactivity in a subset after pharmacologic ACTH stimulation may be an intrinsic adrenal disorder. (Fertil Steril(R) 1999;71:439-44. (C)1999 by American Society for Reproductive Medicine.).