Phenotypic spectrum of polycystic ovary syndrome: Clinical and biochemical characterization of the three major clinical subgroups

Objective: We tested the hypothesis that the three clinical phenotypes of polycystic ovary syndrome (PCOS) represent forms of the same metabolic disorder. Design: Prospective cohort analysis. Setting: University-based tertiary care. Patient(s): Three-hundred sixteen untreated consecutive women diagnosed as having PCOS. Intervention(s): None. Main Outcome Measure(s): Each subject underwent an evaluation of ovulatory function, body habitus, acne, and hirsutism; serum free and total testosterone (T), 17-hydroxyprogesterone (17-HP), and DHEAS; and fasting plasma glucose and insulin levels. Insulin resistance and β-cell function were assessed using the homeostatic assessment model equation (HOMA-IR and HOMA-β-cell, respectively). Result(s): The Oligo+HA+Hirsutism phenotype was present in 48% of subjects, Oligo+HA in 29%, and Oligo+Hirsutism in 23%. The three phenotypes did not differ in mean body mass index, waist-to-hip ratio, racial composition, degree of oligo-ovulation, prevalence of acne, or family history of hyperandrogenic symptomatology. However, subjects demonstrating the Oligo+HA+Hirsutism phenotype were the youngest and had the greatest degrees of hyperandrogenemia, hyperinsulinemia, and β-cell function; patients with the Oligo+Hirsutism phenotype where the oldest and had the mildest degrees of hyperandrogenemia, hyperinsulinemia, and β-cell function. Subjects with the Oligo+HA phenotype demonstrated intermediate degrees of hyperandrogenemia and metabolic dysfunction. Conclusion(s): We conclude that the three clinical phenotypes of PCOS do not represent forms of the same metabolic disorder and may be the result of varying degrees of metabolic dysfunction; greater degrees of β-cell function and circulating insulin levels favored the development of hirsutism and frank hyperandrogenemia.