POLYCYSTIC OVARY SYNDROME: ORIGINS AND IMPLICATIONS: Gestational anti-Müllerian hormone and testosterone excess combined with maternal adiposity program for polycystic ovary syndrome

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

In brief A 'two hit' developmental origin involving testosterone and anti-Müllerian hormone is proposed to initiate PCOS pathogenesis during gestation. Epigenetic mechanisms amplify genetically heritable traits, while accompanying metabolic perturbations, including gestational hyperglycemia, hypertension and maternal obesity, exaggerate PCOS expression. Abstract Pre- or perinatal excess of anti-Müllerian hormone (AMH) or testosterone faithfully reproduce many polycystic ovary syndrome (PCOS)-like reproductive and metabolic traits in animal models. Epigenetic transgenerational transmission of such developmental programming has been repeatedly demonstrated in mice and is likely to exist in nonhuman primates. In humans, hyperandrogenic PCOS is reliably heritable and repeatedly associated with >20 PCOS risk genes and altered epigenetic signatures. Infant daughters of women with PCOS exhibit traits consistent with a hyperandrogenic fetal environment that is accompanied by precocious onset of AMH hypersecretion. Elevated AMH levels, likely of ovarian origin, persist from birth through adolescence in daughters of women with PCOS, and in adult women with PCOS, and associate with extending the reproductive years and delaying peri-menopause. Evidence is accumulating for fetal extra-ovarian production and action of AMH in various tissues: the brain, for survival of GnRH neurons migrating

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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