Neuroendocrine dysfunction in polycystic ovary syndrome

Polycystic ovarian syndrome (PCOS) is a common disorder characterized by ovulatory dysfunction and hyperandrogenemia (HA). Neuroendocrine abnormalities including increased gonadotropin-releasing hormone (GnRH) pulse frequency, increased luteinizing hormone (LH) pulsatility, and relatively decreased follicle stimulating hormone contribute to its pathogenesis. HA reduces inhibition of GnRH pulse frequency by progesterone, causing rapid LH pulse secretion and increasing ovarian androgen production. The origins of persistently rapid GnRH secretion are unknown but appear to evolve during puberty. Obese girls are at risk for HA and develop increased LH pulse frequency with elevated mean LH by late puberty. However, even early pubertal girls with HA have increased LH pulsatility and enhanced daytime LH pulse secretion, indicating the abnormalities may begin early in puberty. Decreasing sensitivity to progesterone may regulate normal maturation of LH secretion, potentially related to normally increasing levels of testosterone during puberty. This change in sensitivity may become exaggerated in girls with HA. Many girls with HA—especially those with hyperinsulinemia—do not exhibit normal LH pulse sensitivity to progesterone inhibition. Thus, HA may adversely affect LH pulse regulation during pubertal maturation leading to persistent HA and the development of PCOS.

► Excess androgens impair progesterone inhibition of GnRH pulse frequency in PCOS.
► Rapid pulses favor LH secretion, promoting androgens over follicle maturation.
► Early pubertal obese girls with excess androgens already have rapid GnRH pulses.
► Excess androgens may impair progesterone sensitivity more in overweight girls.
► Decreased sensitivity to progesterone may enhance LH secretion in normal puberty.