QUANTITATIVE AND QUALITATIVE CHANGES IN LH SECRETION FOLLOWING PULSATILE GnRH THERAPY IN A MAN WITH IDIOPATHIC HYPOGONADOTROPHIC HYPOGONADISM

Abstract
The pattern of bioactive and immunoreactive LH secretion before and during pulsatile GnRH therapy (18 .mu.g/90 min) in a hypogonadotrophic hypogonadal male has been studied. Before treatment the patient was azoospermic and had low testosterone (1.2 nmol/l) with low and apulsatile immunoreactive LH (1.9 .+-. 0.2 IU/l) and FSH (1.4 .+-. 1.9 IU/l) levels. There was no detectable LH bioactivity. During the first 24 h of GnRH therapy there was a small increase in immunoreactive (5.4 .+-. 0.8 IU/l) and bioactive (6.7 .+-. 1.3 IU/l) LH, with an irregular pattern and little effect on testosterone production (2.2 nmol/l). Within 1 week of treatment both bioactive (30.5 .+-. 6.4 IU/l) and immunoreactive (13.6 .+-. 1.5 IU/l) LH levels were above the normal range and the pattern of secretion was pulsatile. The bioactive to immunoreactive (B:I) LH ratios within the pulses (2.6 .+-. 0.3) were higher (P < 0.01) than between pulses (1.97 .+-. 0.1) and the testosterone concentration (17.8 .+-. 2.1 nmol/l) was now normal. At one month LH secretion was similar and testosterone pulses of high amplitude were evident corresponding to high-amplitude bioactive LH pulses. By 3 months mature spermatozoa (1.3 .times. 106.ml) were seen in the patient''s semen. The pattern of LH secretion was pulsatile but the levels of bioactive (13.1 .+-. 3.6 IU/l) and immunoreactive (9.5 .+-. 1.3 IU/l) LH decreased towards the normal range reflecting maturation of the testicular feedback control at the pituitary level. This effect was more pronounced on bioactive rather than immunoreactive LH secretion(57% vs 32% relative decrease). At 6 months LH levels were similar and the sperm count was normal (34 .times. 106/ml). We conclude that episodic GnRH stimulates the secretion of LH pulses enriched in biological activity and that the negative testicular feedback effect at the pituitary level modulates both the quantity and quality of LH secretion.