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Hypogonadotropic Disorders in Men and Women: Diagnosis and Therapy with Pulsatile Gonadotropin-Releasing Hormone

NANETTE SANTORO, MARCO FILICORI^* and WILLIAM F. CROWLEY, JR.

Reproductive Endocrine Unit of the Departments of Medicine and Gynecology, Vincent Memorial Research Laboratories, Massachusetts General Hospital Boston, Massachusetts 02114

Abstract

HYPOGONADOTROPIC hypogonadism (HH) is a clinical syndrome occurring in both sexes which has long puzzled clinicians due to the apparent paradox of nonfunctioning gonads in the face of normal or only slightly lowered levels of circulating gonadotropins. Using frequent sampling of gonadotropin levels as an index of hypothalamic GnRH secretion, we have examined the hypothesis that this group of disorders represents a spectrum of abnormal patterns of the pulsatile release of endogenous GnRH. After a broad, normative data base was established in both men and women for purposes of comparison, it appears that quantifiable abnormalities of GnRH secretion are discernible in both males and females with HH. These abnormalities include a total absence of GnRH secretion, defects of the amplitude and frequency of its secretion, and altered bioactivity of the gonadotropins released. In addition, physiological regimens of hypothalamic replacement therapy with exogenous GnRH, which are fashioned to mimic the normal frequency of endogenous GnRH secretion, result in complete normalization of reproductive function and fertility in hypogonadotropic subjects of both sexes.

Footnotes

^* Current address: Department of Reproductive Medicine, University of Bologna, via Masserenti 13, Bologna, Italy.

To whom reprint requests should be addressed.

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