正常プロラクチン血性無排卵症におけるCB-154の排卵誘発効果

抄録

Several investigators have reported that CB-154 induces ovulation in patients with normoprolactinemic anovulation as well as those with hyperprolactinemic amenorrhea. In the present research, the ovulation-inducing effects of CB-154 were studied in normoprolactinemic subjects with special reference to the feedback effect of estradiol on LH release. Thirty female subjects aged 20-32 years with ovulatory disturbances were studied. Basal serum PRL, LH and FSH were determined by radioimmunoassay, and both hyperprolactinemic and hypergonadotropic anovulatory patients were excluded.
A 2mg dose of estradiol benzoate was administered intramuscularly to each subject and 8ml samples of venous blood were taken at 0, 6, 24, 30, 48, 54, 72, 78 hr. The subjects under study were divided into two groups, A and B, according to the effect the estradiol benzoate had on LH release. Group A subjects (nine in all) failed to show any positive feed-back release of LH in response to the estradiol benzoate. Group B subjects (twenty-one in all) showed a more than twofold increase in circulating LH as compared with the initial serum LH value, and this was taken as an indication of positive feedback release. All the subjects in group B were given clomiphene (50-100mg daily for five days). The clomiphene therapy was effective in eleven subjects, and four became pregnant (three in the first or second cycle of treatment and one in the third). The therapy was ineffective in the remain-ing six subjects, four of whom were diagnosed as suffering from polycystic overy syndrome. Clomiphene was judged to be effective when the subjects undergoing therapy with this drug ovulated during three successive treatment cycles, and ineffective when the subjects did not fulfill this criterion (criterion for effectiveness of clomiphene). With the exception of four cases of polycystic ovary syndrome and three pregnancies which occurred in the first or second cycle, the rate of effectiveness of clomiphene in group B was 12 our of 14. It was concluded from these results that clomiphene was effective in group B subjects except in cases of polycycstic ovary syndrome. Treatment with clomiphene alone was effective in none of the seven subjects in group A. However, administration of CB-154 for several weeks prior to and during the clomiphene treatment cycle (combined therapy of CB-154 and clomiphene) led to remarkably improved ovulation rates in five subjects in gorup A. Four patients in group A were selected, and given estradiol benzoate prior to (control) and during (study) CB-154 administration. In each case administration of CB-154 elicited marked posi-tive feedback release of LH as compared with the control period, that is to say, CB-154 transformed group A patients into group B patients. This effect of CB-154 may explain why therapy combining CB-154 and clomiphene improved ovulation rates in group A. We concluded from these results that CB-154 restored the positive feedback release of LH in the group A subjects so that they ovulate on therapy which combines CB-154 and clomiphene.