Syndrome (PCOS) – Discussion of the Three Diagnostic Criteria.
PCOS was considered to be a poorly understood reproductive disorder characterized by hyperandrogenism, anovulatory infertility, and polycystic ovarian morphology (PCO) until the 1980s when it was discovered that the syndrome was also associated with insulin resistance and an increased risk for type 2 diabetes mellitus. It became apparent that the effective study of PCOS required standardized diagnostic criteria, an issue of that was addressed in 1990 at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Conference on PCOS. This conference was a meeting of experts who discussed various features of the syndrome. Participants were asked to vote on potential diagnostic features, including androgen excess, menstrual dysfunction, disordered gonadotropin secretion, and insulin resistance. Those features receiving the most votes, hyperandrogenism and chronic anovulation, with the exclusion of secondary causes, became what are known as the NICHD or NIH criteria and are inaccurately referred to as consensus criteria.
The NICHD criteria did not include PCO because 20%–30% of women with regular menses and no androgenic symptoms had PCO on ovarian ultrasound examination, making this finding nonspecific. Many of these women did have elevated testosterone or luteinizing hormone (LH) levels, although some were endocrinologically normal. Further, recent studies indicate that the prevalence of PCO is age related and decreases in frequency with increasing age, further confounding the diagnostic utility of this finding. In addition, a subset of women with the endocrine features of PCOS has normal ovarian morphology. An increased LH to follicle-stimulating hormone ratio was not included in the NICHD diagnostic criteria, since this finding could escape detection on a random blood sample because of the pulsatile nature of LH release. It also was recognized at this time that women with ovulatory cycles and hyperandrogenemia and/or PCO were metabolically normal.
The 2003 Rotterdam PCOS Conference, where recommendations were again based on expert opinion rather than any formal consensus process, added PCO on ultrasound as a diagnostic criterion to the NICHD criteria. No other diagnostic criteria were added. The result of adding PCO as a criterion was the inclusion of two additional phenotypes in the diagnosis of PCOS: (1) women with hyperandrogenism and PCO but normal ovulation, and (2) women with anovulation and PCO but no hyperandrogenism. The 2006 Androgen Excess Society criteria, also based on expert opinion, deemed hyperandrogenism essential for the diagnosis of PCOS, thereby excluding one of the additional Rotterdam phenotypes.
Family studies have supported hyperandrogenemia as a central feature of the syndrome. Elevated androgen levels are present in male as well as female first-degree relatives, including girls indicating the early onset of abnormalities in steroidogenesis. Recent genetic analyses have found PCOS risk alleles associated with testosterone levels. These analyses also have found that PCOS diagnosed by the NICHD but not the Rotterdam criteria is associated with risk alleles for the syndrome. Insulin resistance also clusters within a PCOS family but varies in severity according to phenotype. Further, evidence for pancreatic β-cell dysfunction is present in first-degree relative girls in association with elevated testosterone levels, so it is not possible to determine whether metabolic defects precede reproductive ones or vice versa. Cross-sectional studies suggest that only women fulfilling the NICHD criteria for PCOS are at high risk for associated metabolic abnormalities.
