Metoclopramide-Induced Hyperprolactinemia Impairs Ovarian Follicle Maturation and Corpus Luteum Function in Women*

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Abstract
Seven healthy women, aged 21–36 yr, were treated with metoclopramide (MC; 10 mg 3 times daily orally) from the 2nd to the 22nd cycle day over 2 consecutive menstrual cycles in order to investigate the effects of hyperprolactinemia on female gonads. Morphology of the ovarian follicles was followed by ultrasonography, and endocrine evaluation included serum LH, FSH, PRL, estradiol (E2), progesterone (P), pregnenolone, 17-hydroxyprogesterone (17-OHP), testosterone, androstenedione, and 5α-dihydrotestosterone determinations. Follicular morphological maturation appeared abnormal in 9 of 14 treated cycles with hyperprolactinemia (mean serum PRL concentrations, 60.1-85.3 jug/liter). This was seen as the appearance of multiple (2-6) follicles, with retarded growth, and lack of selection of the dominant follicle. The peak diameter of the largest follicle (mean, 11.7 mm for the first and 11.4 mm for the second treated cycle) during hyperprolactinemia was significantly smaller than the respective diameter (18.1 mm) during the control cycle before MC administration. During the early follicular phase (cycle days 5–6), hyperprolactinemia was associated with a significantly elevated ratio of P to E2. At midcycle (cycle days 13–14), serum concentrations of 17-OHP and androstenedione were significantly decreased, and LH and the ratio of LH to FSH tended to be decreased during the treated cycles. During the luteal phase of the cycle (cycle days 22–23), serum concentrations of P, 17-OHP, and 5α-dihydrotestosterone, as well as the ratio of P to E2, were significantly depressed when MC was administered. The combined data of ultrasonography and P and E2 determinations showed that deviations from normal follicular development and corpus luteum formation were recorded ultrasonographically alone in four cases, endocrinologically alone in one case, and by both methods in five cases. Four treatment cycles appeared to be normal in these examinations. The present results show that MC-induced hyperprolactinemia interferes with the gonadal reproductive processes, this action beginning during early follicular development and extending over the whole cycle. (J Clin Endocrinol Metab54: 955, 1982)