無月経婦人におけるestrogenのpositive feedback機構に関するCB-154の効果

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Although CB-154 has been reported to be effective in the treatment of patients with normo-prolactinemic amenorrhea as well as those with hyperprolactinemic amenorrhea, the precise mechanism concerning its ovulation-inducing effect remains to be established. Several investigators declared that the prolactin (PRL) -lowering effect of CB-154 is responsible for the induction of ovulation, and others reported its direct action to the ovaries. However, a direct central action of CB-154, independent of its PRL-suppressing effect, on the LHRHgonadotropin releasing system has not been ruled out. On the other hand, some evidences have indicated that exogenously administered estrogen fails to produce a positive feedback effect on LH release in patients with hyperprolactinemic amenorrhea and early puerperal women. Therefore, the purpose of the present study was to evaluate the effect of CB-154 on the positive feedback mechanism of estrogen in amenorrheic patients with or without hyperprolactinemia and women in early puerperium. In addition, we investigated the influence of a high circulating PRL level on estrogen feedback action and gonadal function in the experimental model of artificial hyperprolactinemia induced by metoclopramide (MCP), a dopamine receptor antagonist, in normal cycling women. Serum PRL, LH, FSH, 17β-estradiol (E2), progesterone (P) and dehydroepiandrosterone-sulfate (DHAS) were measured by radioimmunoassy. 1) Normal cycling women (n = 6) and three groups of amenorrheic patients who were diagnosed as having Chiari-Frommel syndrome (n = 7), idiopathic hyperprolactinemic amenorrhea without clinically demonstrable pituitary tumor (n = 7) and normoprolactinemic secondary amenorrhea without polycystic ovary syndrome (n = 8), respectively, were selected. Twenty mg of conjugated estrogens (Premarin) was injected intravenously to these subjects 7-9 days (D 7-9) from the onset of menstruation or withdrawal bleeding. Blood samples were taken at 0, 24, 48 and 72 hours after Premarin injection. Changes in serum LH levels following the Premarin injection were expressed as percent net changes from the basal level. After the Premarin injection, the initial suppression of LH (negative feedback) was observed 24 hr later, followed by a rebound increase of LH (positive feedback) reaching about +200% above pre-injection values 48-72 hr later in normal women, though no rebound increase after the Premarin injection was recognized in three groups of amenorrheic patients. This impaired estrogen-induced LH release was not significantly different among the three groups of patients. The daily administration of 2.5mg of CB-154 brought about the restoration of the positive feedback effect of estrogen, accompanied by a significant decrease of PRL levels and occurrence of ovulation and/or menstruation in all groups of patients. No significant correlation between the decrement of PRL and the improvement of the positive feedback response was observed in any of the amenorrheic patients during the CB-154 treatment. 2) None of the 4 lactating women who wished to cease lactation showed a LHreleasing response following a Premarin injection at about one month post partum, however, the response was restored and menstruation occurred with a significant fall of serum PRL levels and cessation of lactation after the daily administration of 5mg of CB-154 for about one month, though the other 4 lactating women without CB-154 treatment continued to lack the response at the same period of puerperium. 3) The daily administration of 30mg of MCP for 1-3 months resulted in sustained hyperprolactinemia throughout the experiment in 6 normal cycling women. Serum PRL levels rose about 10-fold greater than pretreatment values, but the results of a Premarin provocation test on D 7-9 were unchanged before and during MCP treatment. Moreover,
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無月経婦人におけるestrogenのpositive feedback機構に関するCB-154の効果

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