Pulsatile gonadotrophin-releasing hormone therapy in patients with pituitary tumours treated by surgery and irradiation

Abstract

Objective: Pulsatile administration of GnRH for induction of ovulation is effective for women with idiopathic hypogonadotrophic hypogonadism. We were interested to assess the pituitary-ovarian response to pulsatile GnRH infusion and the therapeutic effectiveness of restoring ovulation in a group of hypogonadotrophic women previously treated with surgery and irradiation to pituitary tumours.

Patients: The group of patients comprised 15 hypogonadotrophic women, aged 29-40 years (mean 32.4 years), who had undergone transsphenoidal adenomectomy or craniotomy and irradiation with a total of 4500-5400 cGy in 25 fractional doses divided over 5-6 weeks. The time interval from irradiation to study was 6.3 +/- 2.0 years (mean +/- SD).

Treatment: A single bolus GnRH (100 micrograms) test and pulsatile infusion of GnRH were performed to assess the pituitary gonadotrophin reserve and induce ovulation. We tried to correlate the pituitary response with characteristics of intracranial lesions on computerized tomography findings. We undertook ovarian biopsy in one patient who failed to respond to gonadotrophin therapy and pulsatile infusion of GnRH.

Results: Twelve women (80%) showed evidence of ovulation in response to pulsatile GnRH treatment and five subsequently became pregnant. Four of 12 ovulators were previous non-ovulators to exogenous gonadotrophin therapy. There was no correlation between pituitary response and character of lesions based on computerized tomography findings. A patient who failed to respond to either gonadotrophin or pulsatile infusion of GnRH had premature ovarian failure on ovarian histology.

Conclusions: The functional reserve capacity of pituitary gonadotrophs may remain less impaired by tumour encroachment, pituitary surgery or irradiation than had previously been thought. This holds promise for ovulation induction in hypogonadotrophic patients who had been treated with surgery and irradiation for pituitary tumours.