CHRONIC ANOVULATORY HYPERANDROGENISM: SORTING GENOTYPES

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Chronic anovulatory hyperandrogenism is a common heterogeneous disorder of unknown etiology characterized by hirsutism, oligo/amenorrhea, anovulation, infertility, acne, hyperandrogenism, increased LH/FSH ratio, and insulin resistance. Because insulin resistance is often accompanied by known risk factors for coronary artery disease, it has been speculated that chronic anovulatory hyperandrogenism indicates a greater propensity for coronary artery disease. Recently, it has been suggested that premature pubic hair is a harbinger of chronic anovulatory hyperandrogenism. If this proves to be true, it may he possible to identify and intervene earlier in the subset of patients at risk for chronic anovulatory hyperandrogenism and its associated complications. Preliminary data supports genotype analysis of steroidogenic enzymes especially 21- hydroxylase (CYP21). The hypotheses of this proposal are: 1) pre- mature pubic hair precedes chronic anovulatory hyperandrogenism in some patients; 2) the abnormal gonadal and/or adrenal steroid production limits FSH secretion to below the threshold concentrations needed for ovulation and 3) there are useful genetic and/or hormonal markers associated with an increased risk for chronic anovulatory hyperandrogenism. Genotype analysis of candidate genes in conjunction with sequential evaluation of patients with premature/excessive virilization, serial determinations of gonadotropin excretion and repeated assessments of insulin sensitivity will be used to test these hypotheses. Correlation of clinical features with results of hormonal and genetic evaluations may help unravel the sequence of events leading to chronic anovulatory hyperandrogenism.