Effect of metoclopramide induced hyperprolactinaemia on the gonadotrophic response to oestradiol and LRH

Abstract. The effect of oral metoclopramide 10 mg three times daily during the follicular and periovulatory period on Prl, LH, FSH, oestradiol and progesterone was determined in 6 regularly menstruating women. During a control cycle and a treatment cycle the gonadotrophic response was measured after 1 mg oestradiol benzoate given im on the 8th day and after LRH 25 μg iv on the 8th and 11th day of the menstrual cycle. Prl, LH and FSH were also measured in 7 post-menopausal women either during short-term or long-term treatment with metoclopramide. Compared to a control cycle metoclopramide significantly ( P < 0.01) increased serum Prl, but a sustained hyperprolactinaemia was not obtained in 2 women. Treatment significantly ( P < 0.02) increased the LH and FSH responses to LRH and augmented the negative feedback of oestradiol on both LH and FSH ( P < 0.05). A major gonadotrophin surge occurred in those 2 women where a sustained hyperprolactinaemia was not achieved. Oestradiol benzoate caused a significant increase of the LH ( P < 0.01) and FSH ( P < 0.05) responses to LRH after 72 h during the control cycle, but failed to increase either LH or FSH responses significantly during treatment. Short-term hyperprolactinaemia in post-menopausal women was not associated with any consistent alteration in either LH or FSH levels or pulsatility, but chronic treatment resulted in a significant reduction in serum FSH ( P < 0.02), without any alteration in LH levels or pulsatility. LH and FSH responses to LRH increased in all. There was no effect on serum DHAs, urinary androgens or follicular phase serum progesterone levels. These data show that moderate drug induced moderate hyperprolactinaemia is associated with an increased responsiveness of both LH and FSH to LRH, and has a more pronounced effect on the negative feedback compared to the positive feedback of oestradiol on gonadotrophin secretion. It is suggested that hypersecretion of Prl impairs periodic LH release, mainly through an altered feedback mechanism, but also has a direct inhibitory effect on FSH secretion.