OESTROGEN MODULATION OF GONADOTROPHIN AND PROLACTIN RELEASE IN WOMEN WITH ANOVULATION AND THEIR RESPONSES TO CLOMIPHENE

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Abstract
An LHRH [luliberin] test was performed before and at both 44 and 92 h after the administration of 2.5 mg estradiol benzoate in 11 patients with hyperprolactinemia, 8 with idiopathic secondary amenorrhea and 7 with oligomenorrhea. The basal serum hormone concentrations and the responses to LHRH were compared with the same tests performed on 10 normal subjects during the early follicular phase of their menstrual cycles (days 4-6). Mean basal concentrations of estradiol in each group of patients and estrone in those with hyperprolactinemia were significantly lower than in the normal subjects. The mean concentration of prolactin [PRL] in women with secondary amenorrhea remained lower than in the normal women throughout the tests (P < 0.05). The LH [lutropin] and FSH [follitropin] responses to LHRH before estrogen in patients with hyperprolactinemia and of FSH in those with secondary amenorrhea, were greater than in the normal subjects (P < 0.001). After estrogen treatment the responses were similar in all groups except in those with oligomenorrhea where LH and FSH responses at 44 h (P < 0.05 and P < 0.01 respectively) and LH responses at 92 h (P < 0.01) were lower than in normal controls. The responses at 92 h in all groups were greater than at 44 h (amplification ) but the amplification at 92 h and at 44 h compared to the pretreatment responses, tended to be lower in each group of patients compared to the normal controls. In the hyperprolactinemic group of patients there was a negative correlation between the basal PL concentration and the gonadotropin amplifications at 92 h (P < 0.01), and a positive correlation between the basal estrone levels and the amplifications at 92 h (P < 0.01). The results of the estrogen amplifications test in 11 of the non-hyperprolactinemic anovular patients were compared with the ovulatory response to 100 mg clomiphene given for 5 days. Six showed a normal estrogen amplification and they all ovulated. Two patients failed to show greater amplification at 92 than at 44 h and required human chorionic gonadotropin (hCG) and clomiphene to ovulate. The other 3 showed a diminished LH amplification at 92 h; they required 200 mg clomiphene and showed a prolonged follicular phase. The responses of the hyperprolactinemic patients to clomiphene were poor and there was a negative correlation between PL concentration and estrogen production (P < 0.01). All 10 hyperprolactinemic patients treated with bromicriptine ovulated and 8 conceived. The estrogen amplification test appears to have some value in predicting the subsequent response to clomiphene in non-hyperprolactinemic anovular women.