Pituitary-ovarian responses to leuprolide acetate testing in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

To assess whether patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency exhibit a steroidogenic response to GnRH agonist consistent with functional ovarian hyperandrogenism (FOH) and elucidate the relationship between adrenal and ovarian hyperandrogenism, the LH, FSH, estradiol, 17-hydroxyprogesterone (17-OHP), androstenedione, total testosterone, dehydroepiandrosterone, and 17-hydroxypregnenolone responses to a sc dose of leuprolide acetate (500 micrograms) were evaluated in 10 patients with classic CAH (mean age, 18.4 +/- 0.95 yr), 7 of whom had oligomenorrhea, pretreated with dexamethasone (2 mg/day for 5 days, including the day of the test). The results were compared with those obtained in 11 patients with FOH (mean age, 18.7 +/- 0.46 yr) and 17 normal women (mean age, 19.68 +/- 0.59 yr) not pretreated with dexamethasone. Leuprolide acetate stimulation caused a significant augmentation of plasma E2, 17-OHP, androstenedione, testosterone, and 17-hydroxypregnenolone concentrations in all CAH patients. However, in only 6 (60%) of them, all with oligomenorrhea, was the 17-OHP response (posttest minus pretest value) similar to that of FOH patients and significantly higher than that in controls. In this subset of CAH patients, LH plasma levels after stimulation were significantly higher than those of CAH subjects with 17-OHP responses in the normal range, controls, and FOH patients, whereas FSH levels were similar to those of controls. In this latter group, plasma FSH concentrations after stimulation were significantly higher than those in FOH. In conclusion, the results of the present study indicate that LH-dependent functional ovarian hyperandrogenism is frequent in patients with classic CAH. As ovarian hyperandrogenism might be partially responsible for the menstrual irregularities that are common complications in such patients, all classic CAH patients with oligomenorrhea should undergo short term stimulation with GnRH agonists to ascertain the presence of ovarian hyperandrogenism and receive appropriate treatment.