The acute and long term effect of the H2-receptor antagonists cimetidine and ranitidine on the pituitary-gonadal axis in men.

We have investigated the effect on the human pituitary-gonadal axis of the H2-receptor antagonists cimetidine 300 mg and ranitidine 50, 100, and 200 mg by i.v. bolus, or treatment for 6 months with either cimetidine (1000 mg/day for 1.5 months followed by 400 mg/day for 4.5 months) or ranitidine (200-400 mg/day for 1.5 months followed by 100-200 mg/day for 4.5 months). Administration of the H2-antagonists (i.v.) to normal men did not cause any release of LH, FSH, or testosterone. Long-term treatment with cimetidine of duodenal ulcer patients caused a significant rise in basal LH (6 weeks) and FSH secretion (11 weeks). Following reduction of the cimetidine dose LH and later FSH returned to pre-treatment values. However, despite reduction of the cimetidine dose, the LH and FSH responses to LHRH stimulation were still significantly higher after 6 months of treatment compared with pre-treatment responses. No changes were found in basal or in LHRH stimulated testosterone or dihydrotestosterone secretion. Treatment with the more potent H2-antagonist ranitidine did not cause any change in basal or in LHRH stimulated LH and FSH secretion. The effects on LH and FSH secretion observed during cimetidine treatment might therefore be caused by other mechanisms than blockade of H2-receptors. It is possible that cimetidine, having anti-androgen properties, blocks pituitary or hypothalamic androgen receptors.