Scientific Statement on the Diagnostic Criteria, Epidemiology, Pathophysiology, and Molecular Genetics of Polycystic Ovary Syndrome

Abstract

Polycystic ovary syndrome (PCOS) is a heterogeneous and complex disorder that has both adverse reproductive and metabolic implications for affected women. However, there is generally poor understanding of its etiology. Varying expert-based diagnostic criteria utilize some combination of oligo-ovulation, hyperandrogenism, and the presence of polycystic ovaries. Criteria that require hyperandrogenism tend to identify a more severe reproductive and metabolic phenotype. The phenotype can vary by race and ethnicity, is difficult to define in the perimenarchal and perimenopausal period, and is exacerbated by obesity. The pathophysiology involves abnormal gonadotropin secretion from a reduced hypothalamic feedback response to circulating sex steroids, altered ovarian morphology and functional changes, and disordered insulin action in a variety of target tissues. PCOS clusters in families and both female and male relatives can show stigmata of the syndrome, including metabolic abnormalities. Genome-wide association studies have identified a number of candidate regions, although their role in contributing to PCOS is still largely unknown.

Reproductive alterations in hyperinsulinemic but normoandrogenic MSG obese female rats

“…Indeed, 50-80% of PCOS women are obese, whereas 44-70% are resistant to insulin (Dumesic et al 2015). Obesity has been associated with more severe PCOS symptoms, whereas treatments directed to weight loss, such as exercise and anorexic drugs, significantly improve reproductive parameters.…”

“…Numerous mechanisms correlating obesity and PCOS have been proposed, one of which consists in elevated insulinemia due to increased fat deposition, hypertriglyceridemia, and insulin resistance. It is important to notice that hyperinsulinemia has been proposed as a culprit for PCOS, and the concurrence of hyperinsulinemia/insulin resistance has higher prevalence in PCOS women, independent of body weight (Wu et al 2014a, Dumesic et al 2015.…”

Polycystic ovary syndrome: a common reproductive syndrome with long-term metabolic consequences

“…Recent hypothesis-free genome-wide association studies using high-density genotyping arrays that systematically investigate common variants across the genome have identified several genetic loci to be significantly associated with PCOS (Table 2). 56 These have shed light on the important role of the gonadotropin axis in the pathogenesis of PCOS, as well as several other novel pathways, including epidermal growth factor signalling. Interestingly, genetic studies have revealed a significant overlap of findings when different diagnostic criteria of PCOS have been applied, highlighting greater homogeneity than previously appreciated.…”

“…Interestingly, genetic studies have revealed a significant overlap of findings when different diagnostic criteria of PCOS have been applied, highlighting greater homogeneity than previously appreciated. 16,56,57 Clinical features and co-morbidities…”

Neuronal androgen receptor: Molecular gateway to polycystic ovary syndrome?

“…Polycystic ovary syndrome (PCOS) afflicts ∼15% of women in their reproductive years (1). PCOS women exhibit high circulating levels of testosterone (T), intermittent or absent menstrual cycles, and polycystic ovaries on ultrasound, or at least two of these three diagnostic criteria (2).…”