Gonadotropin-Releasing Hormone Pulsatile Administration Restores Luteinizing Hormone Pulsatility and Normal Testosterone Levels in Males with Hyperprolactinemia∗

Abstract

Hyperprolactinemia in men is frequently associated with hypogonadism. Normalization of serum PRL [prolactin] levels is generally associated with an increase in serum testosterone (T) to normal. To determine the mechanism of the inhibitory effect of hyperprolactinemia on the hypothalamic-pituitary gonadal axis, the effect of intermittent pulsatile GnRH [gonadotropin-releasing hormone] administration on LH [luteinizing hormone] pulsatility and T levels in 4 men with prolactinomas was studied. All patients had high PRL values (100-3000 ng/ml, low LH (mean .+-. SEM [standard error of the mean]), 2.2 .+-. 0.1 mIU/ml and low T values (2.3 .+-. 0.3 ng/ml), with no other apparent abnormality of pituitary function. GnRH was administered i.v. using a pump delivering a bolus dose of 10 .mu.g every 90 min for 12 days. No LH pulses were detected before treatment. Pulsatile GnRH administration resulted in a significant increase in basal LH levels (6.7 .+-. 0.6 mIU/ml; P < 0.001) and restored LH pulsatility. T levels significantly increased to normal values in all patients (7.8 .+-. 0.4 ng/nl; P < 0.001) and were normal or supranormal as long as the pump was in use, although PRL levels remained elevated. Apparently, hyperprolactinemia produces hypogonadism primarily by interferring with pulsatile GnRH release.