This classic neuroendocrine feedback mechanism between the ovaries and the hypothalamus is impaired in women with PCOS (7, 113), resulting in hyperactivity of GnRH neurons, which in turn results in elevated LH pulse frequency and amplitude, elevated serum concentrations of LH, and an increased LH : FSH ratio (113–115). The gene discussed is PLOD1; the disease is polycystic ovary syndrome.