Effects of metoclopramide-induced hyperprolactinemia during early follicular development on human ovarian function

Nine healthy women, aged 25 to 36 yr, were treated with metoclopramide (MC) (10 mg orally three times daily) from the first to the sixth day of their cycle (treatment A) for two successive cycles (n = 18) and six of these women later received MC from -3 to the fifth day of the menstrual cycle (treatment B) during one or two cycles (n = 10), to investigate the effects of hyperprolactinemia during the early phase of ovarian follicular growth. Comparisons were performed with control cycles in the same women. The treatment cycles were characterized by low serum concentrations of LH during the early follicular phase and at midcycle, low early follicular phase serum testosterone (T) levels and high luteal phase T and free T index values, with no significant differences between A and B treatment modalities. We classified the treatment cycles into two categories, seriously disturbed and normal or only slightly disturbed, on the basis of ultrasonographic findings and midcycle estradiol (E2) and luteal phase progesterone (P) concentrations. Folliculogenesis was seriously disturbed in 11 of the 28 treatment cycles (39%). During these cycles, midcycle serum LH and the LH to FSH ratio were lowered, luteal phase LH and FSH increased, midcycle E2 and luteal phase P and the P to E2 ratio decreased, luteal phase T and the free T index and androstenedione increased, and luteal phase 5 alpha-dihydrotestosterone decreased. During the early follicular phase and at midcycle the ratios of T to E2 and androstenedione to E2 were increased, and at midcycle and during the luteal phase of the cycle the ratio of T to 5 alpha-dihydrotestosterone was increased. These changes in steroid hormones were probably of ovarian origin since the serum concentrations of dehydroepiandrosterone sulfate and sex hormone-binding globulin were similar in seriously disturbed and control cycles. Four of the nine study subjects were hyperprolactinemia sensitive (disturbed folliculogenesis) and five hyperprolactinemia resistant (no disturbance in folliculogenesis). During the control cycles the hyperprolactinemia-sensitive women had significantly higher serum concentrations of T than the other women. The present observations indicate that hyperprolactinemia may impair the development of the ovarian follicles during their recruitment period, especially in women with relatively high serum T levels.