Pulsatile Administration of Gn-RH in Hypothalamic Amenorrhea

Abstract

Gonadotropin releasing-hormone (Gn-RH) was the second of the neurohumoral agents postulated by Harris more than three decades ago to mediate hypothalamic control of anterior pituitary function that has been isolated, identified in its structure and synthesized. Since this was achieved by the groups of Schally and Guillemin in 1971 and the synthetic hormone became available, Gn-RH has been used extensively as a tool in neuroendocine research. Early attempts to use this decapeptide clinically for the treatment of reproductive disorders supposed to be due to an inadequate secretion of endogenous Gn-RH, however, were of only limited sucess. Effective therapeutic use had to await further progress in the understanding of the physiologic significance of pulsatile gonadotropin secretion and gonadal function. The demonstration that the pattern of the hypophysiotropic stimulation is of critical importance in this respect and the elucidation of the physiologic significance of pulsatile Gn-RH-secretion have provided the rational basis for the efficient use of synthetic Gn-RH in the treatment of Gn-RH deficiency. These findings have also furthered the understanding of the seemingly paradoxical antifertility effects of long acting Gn-RH analogues initially designed to compensate for the short action of the parent decapeptide and thus to simplify treatment of infertility. In this communication, following a short review on physiologic and pathophysiologic aspects of hypothalamic control of gonadotropin secretion in the human female, clinical data obtained with chronic-intermittent (pulsatile) administration of Gn-RH in hypothalamic amenorrhea (HA) will be presented.