The Polycystic Ovary Syndrome (PCOS) affects 2-5 percent of women, and has significant reproductive, psychosocial and metabolic morbidity. While adrenal androgen (AA) excess is present in 40 percent-60 percent of PCOS patients, its etiology remains unclear. We have hypothesized that AA secretion is a genetically determined trait which, when present in excess, increases the risk for developing PCOS . Furthermore, since the majority of AA excess of PCOS appears to occur independent of ovarian factors, it is probable that elucidation of the mechanisms underlying the AA excess will yield clues to the underlying and fundamental cause of PCOS. The Aims of the proposal are: 1) To determine the prevalence of PCOS with AA excess, using age specific criteria. Hypothesis: Due to the decrease in AAs with age, the prevalence of PCOS w/AA excess is over-estimated in younger women, and is less than previously reported when age-adjusted criteria are used. 2) To determine the long-term variability of AAs and their response to ACTH stimulation, in patients with PCOS and normal women. Hypothesis: As for other genetic traits, the relative degree of AA secretion between subjects should remain stable over time. 3) To determine the relative prevalence of the CYP17 alleles in PCOS patients w/ and w/o AA excess, and in controls. Hypothesis: PCOS w/AA excess in a genetically distinct from PCOS w/o AA excess, and is associated with the CYP17-A1 allele. 4) To determine the heritability of AAs. Hypothesis: The basal AA levels, and their response to ACTH, are highly inherited; and PCOS w/AA excess in inherited separately from PCOS w/o AA excess. Of additional significance, the proposed studies may also serve to: i) identify a population at high risk for PCOS, i.e. females who are genetically predisposed to producing elevated AA levels; and ii) give support to the concept of PCOS as a disorder whose risk can be modeled logistically, explaining the heterogeneity of the disorder, and aiding in the development of such a logistic model.