Ovulation after glucocorticoid suppression of adrenal androgens in the polycystic ovary syndrome is not predicted by the basal dehydroepiandrosteronesulfate level

Adrenal androgen (AA) excess, primarily in the form of dehydroepiandrostero ne sulfate (DHEAS), affects over 50% of women with the polycystic ovary syn drome (PCOS). Nonetheless, it is unclear what role AA excess plays in the P COS-associated oligo-ovulation. We have hypothesized that AAs are important in the maintenance of the ovulatory dysfunction of women with PCOS and AA excess, which can be improved by glucocorticoid suppression. To test our hy pothesis we prospectively studied 36 unselected women, ages 18-40 yr, with PCOS; i.e. oligomenorrhea (cycles > 35 days in length), and clinical/ bioch emical evidence of hyperandrogenism (i.e. hirsutism and/or hyperandrogenemi a), after the exclusion of related disorders. After informed consent, all p atients underwent an acute ACTH-(1-24) stimulation test, measuring androste nedione, dehydroepiandrosterone (DHEA) and cortisol (F), and were then trea ted with dexamethasone 0.5 mg/day for four cycles. Ovulatory function was a ssessed before and during treatment using a basal body temperature calendar and day 22-24 progesterone (P4) levels. If patients were anovulatory (P4 < 4 ng/mL), a withdrawal bleed was induced by the administration of 100 mg P 4 in oil i.m. Before and during treatment the levels of total and free test osterone (T), sex hormone-binding globulin, androstenedione, DHEA, DHEAS, c ortisol, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) we re monitored. With therapy, all patients demonstrated a significant decreas e in all androgens (-40-60%), a 24% increase in sex hormone-binding globuli n, and no change in LH/FSH. Mean body weight increased by over 4 kg (4.4%) during treatment. Of the 138 cycles monitored, 78% remained anovulatory. Tw enty-five percent, 17%, 14%, and 20% of the first, second, third, and fourt h treatment cycles, were ovulatory, respectively (P = 0.381). Of the 36 pat ients studied, 18 (50%) did not demonstrate a single ovulatory cycle (i.e, a day 22-24 P4 level > 4 ng/mL); and of the remaining, 10 (28%) had only on e, five (14%) had two, and three (8%) had three ovulatory cycles. There wer e no significant differences either in physical features, basal hormones, a drenal response to ACTH stimulation, or hormonal levels at the end of treat ment, between those women ovulating and those not. Finally, there were no d ifferences in ovulatory response to dexamethasone therapy between women wit h (n = 14) and without (n = 22) DHEAS excess (i.e. DHEAS > 2750 ng/mL). In conclusion, the data from this prospective study do not suggest that contin uous dexamethasone suppression results in consistent ovulation in any PCOS patient, regardless of basal DHEAS levels. Furthermore, this treatment is a ssociated with significant side-effects, notably weight gain. Finally, thes e data suggest that, while AA may be an important risk factor for PCOS, onc e the syndrome is established, they play a limited role in the associated o vulatory dysfunction.