A model of ovulatory regulation examining the effects of insulin-mediated testosterone production on ovulatory function

Polycystic ovary syndrome (PCOS), a common cause of infertility in women, is often accompanied by abnormal reproductive and metabolic hormone levels. Specifically, androgens such as testosterone are elevated in many PCOS women, and the syndrome itself is frequently associated with insulin resistance, which leads to hyperinsulinemia, i.e., elevated insulin. Although the precise role of insulin in ovulatory function is unclear, its role in ovulatory dysfunction is often linked to the effects of increased ovarian androgen production. We present a mathematical model of the menstrual cycle that incorporates regulation by the pituitary-ovarian axis and mechanisms of ovarian testosterone production. We determine a physiological role for testosterone in the normal ovulatory cycle and study the role of hyperinsulinemia in pathological regulation of the cycle. Model results indicate increased ovulatory disruption with elevated insulin-mediated testosterone production and suggest that variations in the response of ovarian follicles to essential signals can alter the degree to which hyperinsulinemia disrupts the ovulatory cycle. The model also provides insight into the various PCOS phenotypes and the severity of ovulatory dysfunction.