Characterizing Discrete Subsets of Polycystic Ovary Syndrome as Defined by the Rotterdam Criteria: The Impact of Weight on Phenotype and Metabolic Features

Abstract

A lack of standard criteria for diagnosing polycystic ovary syndrome (PCOS) has made it very difficult to compare phenotypes around the world. A workshop held recently in Rotterdam attempted to reconcile the differences by adding ultrasonography to expand the diagnostic criteria. PCOS is diagnosed if two of three findings are present: irregular menses (IM); clinical or biochemical hyperandrogenism (HA); and/or polycystic ovary morphology (PCOM) on pelvic ultrasound study, all in the absence of a disorder that can cause the same symptoms. The four possible diagnostic subgroups of PCOS are IM/HA/PCOM, IM/HA, HA/PCOM, and IM/PCOM. The phenotypic features of women in these subgroups were compared in a large population of women with PCOS residing in Boston and in Iceland. Of the 481 women evaluated, 71% met criteria for IM/HA/PCOM. Another 2% had IM/HA; 18% had HA/PCOM; and 9% had IM/PCOM. Virtually all women with IM/HA also had PCOM. Women with IM/HA and normal ovarian morphology differed from those with PCOM only by being older and having higher levels of follicle-stimulating hormone. Because follicle counts and the frequency of PCOM decline with advancing age in women with PCOS, the IM/HA/PCOM and IM/HA groups were combined and designated IM/HA. Ferriman-Gallwey scores and androgen levels were highest in the IM/HA and HA/PCOM groups. Ovarian volumes were higher in all subgroups compared to control women without PCOS. Women in the IM/HA subgroup had the highest body mass index (BMI) values and circulating insulin levels. Insulin resistance was most frequent in the IM/HA subgroup, but there were no group differences in fasting glucose or glycosylated hemoglobin levels, or in the frequency of type 2 diabetes. Women in the IM/HA and IM/PCOM subgroups had the largest ovarian volumes and the most follicles on ultrasound study. These parameters were greater in all groups of women with PCOS than in the control subjects. This study shows that women with PCOS defined by HA are most severely affected. They also have the highest BMIs, suggesting that weight gain or intrinsic insulin resistance may worsen symptoms of PCOS or lead to irregular cycles in women with HA at baseline. Further studies will be needed to learn whether phenotypic differences influence such long-term sequelae as infertility and cardiovascular disease.