Early Origins of Polycystic Ovary Syndrome: Hypotheses May Change without Notice

Abstract

Polycystic ovary syndrome (PCOS) is an evolving concept, as illustrated by its consecutive definitions. In 2004, the definition of PCOS in women changed from the classic National Institutes of Health (NIH) definition (clinical and/or biochemical androgen excess plus oligoovulation, with exclusion of specific etiologies such as hyperprolactinemia and 21-hydroxylase deficiency) (1) to the more inclusive Rotterdam definition (any two of the following three criteria, after similar exclusions: clinical and/or biochemical androgen excess, oligoor anovulation, and polycystic morphology on ultrasound) (2). In 2009, the Androgen Excess Society launched a new definition that considers PCOS primarily as a disorder of clinical and/or biochemical androgen excess, plus either chronic oligoovulation and/or polycystic ovaries, still with exclusion of specific etiologies (3). The core of the consecutive PCOS populations, however, changed little over the past decades because it continues to consist of women with hyperinsulinemic androgen excess (4–6). This core still constitutes the majority of PCOS women diagnosed by the latest definition, which, just as the earlier definitions, remains to be validated in adolescent girls (3). A better insight into the (epi-)genetics, early origins, and natural history of hyperinsulinemic androgen excess may sharpen the perspective of PCOS prevention and is therefore a priority in the current research agenda for PCOS.