POTENTIAL FOR FERTILITY WITH REPLACEMENT OF HYPOTHALAMIC GONADOTROPIN-RELEASING-HORMONE IN LONG-TERM FEMALE SURVIVORS OF CRANIAL TUMORS

Dysfunction of the hypothalamic-pituitary axis presenting as hypogonad otropic amenorrhea is a common sequelae of treatment for cranial tumor s with surgery and/or radiation. We hypothesized that the site of the defect in this condition is hypothalamic, rather than pituitary, in th e majority of patients. Nine women with acquired hypogonadotropic hypo gonadism after treatment with transphenoidal pituitary surgery (n = 3) , transphenoidal surgery plus conventional radiotherapy (XRT; n = 1), hypothalamic surgery plus XRT (n = 2), or XRT with or without noncentr al nervous system surgery (n = 3) underwent assessment of endogenous p ulsatile LH secretion and a standard GnRH test followed by iv administ ration of a physiological replacement regimen of exogenous GnRH. A tot al of 25 cycles were completed at doses of 75 or 100 ng/kg.bolus. Ovul ation occurred in 78% of patients, with all ovulatory patients who des ired fertility becoming pregnant. The hormonal responses in these cycl es did not differ from the patterns of sex steroids and gonadotropins in normal women. The response to pulsatile GnRH was not influenced by GH deficiency or PRL abnormalities. Of the two patients who failed to ovulate, there was no evidence of folliculogenesis in one, whereas the second consistently developed follicles, but proved incapable of moun ting a LH surge despite adequate preovulatory estradiol levels. Both p atients had a history of pituitary radiation and surgery. There was no consistent relationship between the results of GnRH testing and the p attern of pulsatile LH secretion. However, the only patient who failed to achieve folliculogenesis was the only patient without a FSH respon se to GnRH testing and an apulsatile baseline study. Hypothalamic GnRH deficiency is the etiology of hypogonadism in the majority of patient s after treatment with hypothalamic or pituitary surgery or cranial ir radiation. Therefore, exogenous pulsatile GnRH represents a physiologi cal replacement therapy that completely restores normal gonadotropin d ynamics, resulting in ovulation and fertility.