Polycystic ovary syndrome (PCOS) is the most common female endocrine disorder and has important evolutionary implications for female reproduction and health. PCOS presents an interesting paradox, as it results in significant anovulation and potential sub-fecundity in industrialized populations, yet it has a surprisingly high prevalence and has a high heritability. In this review, we discuss an overview of PCOS, current diagnostic criteria, associated hormonal pathways and a review of proposed evolutionary hypotheses for the disorder. With a multifactorial etiology that includes ovarian function, metabolism, insulin signaling and multiple genetic risk alleles, PCOS is a complex disorder. We propose that PCOS is a mismatch between previously neutral genetic variants that evolved in physically active subsistence settings that have the potential to become harmful in sedentary industrialized environments. Sedentary obesogenic environments did not exist in ancestral times and exacerbate many of these pathways, resulting in the high prevalence and severity of PCOS today. Overall, the negative impacts of PCOS on reproductive success would likely have been minimal during most of human evolution and unlikely to generate strong selection. Future research and preventative measures should focus on these gene-environment interactions as a form of evolutionary mismatch, particularly in populations that are disproportionately affected by obesity and metabolic disorders.
Lay summary: The most severe form of polycystic ovary syndrome (PCOS) is likely a result of interactions between genetic predispositions for PCOS and modern obesogenic environments. PCOS would likely have been less severe ancestrally and the fitness reducing effects of PCOS seen today are likely a novel product of sedentary, urban environments.
Keywords: evolutionary medicine; infertility; mismatch; natural selection; polycystic ovary syndrome; reproduction.