ABSTRACT
Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism and
chronic anovulation. Although the etiology of PCOS is unknown, perturbations of gonadotropin
secretion are one of the hallmarks of this disorder. In normal menstrual physiology,
the monotropic rise of plasma follicle-stimulating hormone (FSH) during the luteal-follicular
transition is critical for follicular development and subsequent ovulation. One of
the mechanisms by which FSH is differentially synthesized involves the luteal slowing
of gonadotropin-releasing hormone (GnRH) pulse frequency by ovarian steroids. In PCOS,
plasma leutinizing hormone (LH) is commonly increased, FSH is typically in the lower
follicular range, and LH (and by inference GnRH) pulse frequency is persistently rapid
at approximately one LH pulse per hour. The etiology of the neuroendocrine abnormalities
in PCOS remain unclear; however, recent studies have revealed decreased sensitivity
of the GnRH pulse generator to inhibition by ovarian steroids, particularly progesterone.
This abnormality is reversed by the androgen receptor antagonist flutamide, suggesting
that elevated androgen levels may alter the sensitivity of the hypothalamic GnRH pulse
generator to steroid inhibition and lead to enhanced LH secretion. As such, women
with PCOS require higher levels of progesterone to slow the frequency of GnRH pulse
secretion, resulting in inadequate FSH synthesis and persistent LH stimulation of
ovarian androgens. The decreased sensitivity of the GnRH pulse generator may help
to explain the genesis of PCOS during puberty. In normal early puberty, sleep-entrained
increases in LH stimulate ovarian steroids, which subsequently suppress LH frequency
and amplitude during the subsequent day. In hyperandrogenemic girls destined to develop
PCOS, this nocturnal increase in ovarian steroids may not be adequate to suppress
the GnRH pulse generator, leading to a persistently rapid LH pulse frequency, impaired
FSH production, and inadequate follicular development.
KEYWORD
Gonadotropins - LH - polycystic ovary syndrome - menstrual cycle - flutamide
