Women with polycystic ovary syndrome (PCOS): Likelihood of cooccurring neuropsychiatric conditions and the dual hit hypothesis

Abstract

Polycystic Ovary Syndrome (PCOS) is the most common endocrine-metabolic disorder in women of reproductive age. Hyperandrogenism has been proposed as its main pathophysiological feature. PCOS is associated with co-occurring conditions, including psychiatric disorders such as anxiety, depression, and neurodevelopmental conditions such as autism. Exposure to hyperandrogenism during prenatal life and adolescence may explain this association. PCOS women exhibit hyperandrogenism during pregnancy, and up to 70% of their daughters will present a similar phenotype from puberty onwards. The ’dual hit hypothesis’ proposes that stressors during prenatal life and adolescence can synergistically lead to co-occurring conditions in adulthood. PCOS has been recently proposed as an independent likelihood factor for the development of neuropsychiatric conditions. However, the specific mechanisms require further research to develop effective interventions. This review discusses how hyperandrogenism can affect neurodevelopment during two key periods of brain development, which may explain the long-term impact of PCOS on mental health.