正常プロラクチン血性排卵障害婦人に対するmetergOlineの排卵誘発効果とその機序について

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Metergoline, a potent serotonin antagonist, has proved to be effective in the treatment of hyperprolactinemic anovulation. On the other hand, some investigators have reported that bromocriptine, a potent dopamine agonist, is effective in the treatment of normoprolactinemic anovulation as well as hyperprolactinemic anovulation. But there are very few reports as to whether metergoline is effective or not in the treatment of normoprolactinemic anovulation. This study was designed to investigate the ovulation-inducing effect and the underlying mechanism of metergoline in women with normoprolactinemic anovulation. Metergoline was administered 8-12 mg daily for 8-2 weeks to 28 patients without galactorrhea (7 cases with anovulatory cycle, 17 cases with 1st grade amenorrhea defined by responding to progestin with bleeding, and 4 cases with 2nd grade amenorrhea defined by responding to estrogen and progestin with bleeding), whose serum prolactin levels were under 25 ng/ml. The serum levels of LH, FSH and prolactin, and also the pituitary responsiveness to 100 μg of LH-RH and 500 μg of TRH were examined before and during metergoline administration in 13 amenorrheic patients. In patients whose ovulation or withdrawal bleeding was induced and in patients whose menstruation was not induced, these stimulation tests during metergoline administration were performed at 5-7 days from the onset of menstruation and between 6 and 8 weeks from the beginning of treatment, respectively. In 6 other amenorrheic patients, the positive feedback effect of estrogen (Premarin 20 mg iv) on LH release was examined before and during treatment. In addition, a 12 mg dose of metergoline was administered daily for one menstrual cycle to 5 normal cycling women, and the Premarin stimulation tests were performed before and after metergoline treatment. Ovulation was induced in 14 out of 24 patients except those with 2nd grade amenorrhea (58.3%), i.e. anovulatory cycle, 85.7% (6/7); 1st grade amenorrhea, 47.1% (8/17), and in 29 out of 49 menstrual cycles (59.2%). Of a total of 38 menstrual cycles in 14 ovulationinduced patients, 29 were ovulatory (76.3%), indicating a high rate of repeated success. No ovulation was observed in 2nd grade amenorrhea, but slight increases in basal levels of LH and/or FSH and obvious elevations of serum estradiol-17β levels were observed during metergoline treatment, followed by the progesterone withdrawal bleeding in 2 out of 4 patients. The mean basal levels of LH and FSH showed no significant change. The serum LH and FSH responses to LH-RH were improved in some administration patients who responded poorly before metergoline treatment. Serum prolactin levels and the prolactin response to TRH were significantly lowered during metergoline treatment. The long-term administration of metergoline improved or restored the impaired positive feedback effect of estrogen on LH release in patients with anovulation and resulted in more prompt and further LH release by estrogen in normal cycling women. With these results we conclude that metergoline is effective in the treatment of relatively mild ovulatory disturbances and suggest that the induction of ovulation by metergoline may be mainly ascribed to the improvement or restoration of the impaired positive feedback mechanism of estrogen and pituitary gonadotropin secretion. However, it is unclear whether or not lowering normal levels of prolactin, per se, participates directly or indirectly in the mechanism of the induction of ovulation. Further investigation is needed to elucidate why the positive feedback release of LH and pituitary gonadotropin secretion were improved or restored by the long-term administration of metergoline in women with normoprolactinemic anovulation.
日本内分泌学会の論文

正常プロラクチン血性排卵障害婦人に対するmetergOlineの排卵誘発効果とその機序について

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