Functional Ovarian Hyperandrogenism/Minority Adolescents

DESCRIPTION (provided by applicant): Functional Ovarian Hyperandrogenism (FOH), also called Polycystic Ovarian Syndrome (PCOS) consists of a spectrum of dysfunction with varying degrees of ovulatory dysfunction, hyperandrogenemia, and clinically evident hyperandrogenism. The biochemical and clinical criteria for hyperandrogenemia and hyperandrogenism have not yet been determined for a large ethnic minority female adolescent population. The specific aims of the study are: 1) to determine the relationship between the clinical presentation and the biochemical determinants of FOH/PCOS in a clinical sample of predominantly Caribbean-Hispanic and African-American female adolescents; 2) to establish norms for the biochemical determinants of hyperandrogenemia in this population; 3) to determine the clinical correlates of hyperandrogenemia in adolescent girls; and 4) to determine if adolescent females with FOH/PCOS are more likely than normal, weight-matched adolescents to be Caribbean-Hispanic, to have a family history of diabetes, high blood pressure or cardiovascular disease, or to have significantly higher glucose to insulin ratios. The hypotheses are as follows: 1) the testosterone and androstenedione levels in subjects with menstrual cycle abnormalities and/or physical evidence of hyperandrogenism will be significantly greater than in those with normal menstrual cycles and no physical evidence for hyperandrogenism; 2) a combination of clinical and historical features may be used to develop a model that can predict serum androgen levels; and 3) subjects with FOH/PCOS will be more likely than normal subjects to be of Caribbean-Hispanic descent, to have evidence of risk factors for diabetes mellitus and cardiovascular disease, and to have significantly higher glucose to insulin ratios. 250 females aged 12 to 21 will be consecutively recruited from several clinical sites; girls with chronic illnesses or on hormonally active drugs will be excluded. Subjects will complete a questionnaire to elicit features of menstrual and family history and will undergo a physical examination to evaluate for clinical signs of hyperandrogenism. Serum levels of fasting free and total testosterone, androstenedione, luteinizing hormone, follicle stimulating hormone, insulin, 17-OH progesterone, and glucose will be measured. To determine the association of serum androgen levels with clinical features of FOH/PCOS, all subjects will be clinically stratified into three different categories and androgen levels will be compared among these groups, using ANOVA. Hyperandrogenism will be defined as two standard deviations above the mean testosterone and androstenedione levels in subjects with normal menstrual cycles and no physical evidence of hyperandrogenism (category I). A clinical prediction model for hyperandrogenemia will be developed using multiple linear regression analyses for androgen measures. A case-control study will be performed to determine differences between adolescent subjects with and without FOH/PCOS. Improved understanding of the boichemical and clinical features of FOH/PCOS in minority adolescents will facilitate the development of earlier treatment modalities and prevention of later serious health problems that result from the natural progression of this disorder.