Polycystic ovary syndrome etiology as a complex trait involving two hits

Congenital predisposing "hit"

Heritable traits and gene variants affecting ovarian function
Heritable traits and gene variants predisposing to insulin resistance, obesity, and type 2 diabetes mellitus
Congenital virilization
Disturbed fetal nutrition

Postnatal provocative "hit"

Insulin-resistant hyperinsulinemia
- Metabolic syndrome
- Postnatal obesity
Puberty

Modified from: Rosenfield RL, Ehrmann DA. The pathogenesis of polycystic ovary syndrome (PCOS): The hypothesis of PCOS as functional ovarian hyperandrogenism revisited. Endocrine Reviews 2016; 37:467. By permission of Oxford University Press on behalf of The Endocrine Society. Copyright © 2016.

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Polycystic ovary syndrome etiology as a complex trait involving two hits