Characterization of the inappropriate gonadotropin secretion in polycystic ovary syndrome.

Abstract

A B S T R A C r To evaluate gonadotropin release in polycystic ovary syndrome (PCO), one or more of the following hypothalamic-pituitary function tests were performed on 24 patients with the syndrome. These tests included (a) the pulsatile pattern and day-to-day fluctuation of gonadotropin release; (b) effects of exogenous estrogen and antiestrogen (clomiphene) administration on gonadotropin release; and (c) pituitary responsiveness to maximal (150 i'g) and submaximal (10 Ag) luteinizing hormone-releasing factor (LRF) injections. In 10 of the 14 patients sampled frequently (15 min) for 6 h, luteinizing hormone (LH) levels were elevated above the concentration seen in normal cycling women (except the LH surge). These high LH concentrations appeared to be maintained by and temporally related to the presence of exaggerated pulsatile LH release, either in the form of enhanced amplitude or increased frequency. In all subjects, levels of folliclestimulating hormone (FSH) were low or low normal, and a pulsatile pattern was not discernible. In four patients, daily sampling revealed marked day-to-day fluctuation of LH but not FSH. That the elevated LH levels were not related to a defect in the negative-feedback effect of estrogen was suggested by the appropriate fall of LH in four patients given an acute intravenous infusion of 17fi-estradiol. This infusion had no effect on FSH levels. In addition, clomiphene elicited rises of both LH and FSH that were comparable to the ones observed in normal women given the same treatment. The clomiphene study also suggested that the positive-feedback mechanism of estrogen on LH release was intact when the preovulatory rises of 179-estradiol induced appropriate LH surges. The elevated LH levels appeared to be related to a heightened pituitary responsiveness to the LRF. This was found in the 11 and 2 patients given maximal (150 sg) and submaximal (10 /Ag) doses of LRF, respectively. The augmented pituitary sensitivity for LH release correlated with the basal levels of both estrone (P <0.025) and 17j8-estradiol (P < 0.02). The net increase in FSH was significantly greater (P < 0.001) in the PCO patients than the normal women with maximal doses of LRF. With the smaller dose study, none of the injections had a discernible effect on FSH concentrations in either subject. The disparity between LH and FSH secretion could be explained by the preferential inhibitory action of estrogen on FSH release, coupled with a relative insensitivity of FSH release.These data indicate that in these PCO patients the abnormalities of the hypothalamic-pituitary regulation of gonadotropin secretion was not an inherent defect but represented a functional derangement consequent to inappropriate estrogen feedback, which led to a vicious cycle of chronic anovulation and inappropriate gonadotropin secretion.

Serum Immunoreactive Inhibin Levels in Polycystic Ovarian Disease (PCOD) and Hypogonadotropic Amenorrhea.

“…One of the characteristic features of PCOD is high LH with low or normal FSH [13,14]. This discordant gonadotropin secretion in PCOD women has long been speculated to be produced by selective inhibition of FSH release presumably by increased inhibin [15,16].…”

Diagnosis of Polycystic Ovary Syndrome

“…(8) Typically, endocrinological features are overproduction of ovarian androgens and excessive secretion of luteinizing hormone (LH), but with normal or low serum levels of follicle-stimulating hormone (FSH). (9)(10) Notably, ultrasonography has not been considered an essential requirement for the diagnosis of the PCOS (11) though the early descriptions of polycystic ovary are based on ovarian morphology ultrasonographically (Fig. 1).…”

Influence of hormonal control on LH pulsatility and secretion in women with classical congenital adrenal hyperplasia

“…This study showed that PCOS and NC CAH women had increased LH pulse amplitude compared with control women, but only PCOS women had decreased LH interpulse interval compared with controls. Data suggesting abnormalities of LH pulsatility in PCOS women are related to a relative insensitivity to progesterone-induced LH inhibition (6,7,8,9), an abnormality that can be reversed by blockade of androgen action (10). Gonadotropin abnormalities of NC CAH women therefore appear to be intermediate between those of controls and PCOS patients (5).…”