INHIBITION OF MID-CYCLE GONADOTROPHIN RELEASE IN HEALTHY WOMEN BY PIMOZIDE AND FUSARIC ACID

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Abstract
The effects of pimozide, a drug blocking dopamine receptors, and fusaric acid, an inhibitor of dopamine .beta.-hydroxylase, on mid-cycle release of FSH [follicle stimulating hormone] and LH [luteinizing hormone] were studied in 8 healthy women 20-25 yr of age. None had used contraceptive drugs for the preceding 10 mo. From the menstrual history and serum LH determinations during the normal cycle, mid-cycle gonadotropin bursts were predicted for the following 3 cycles. Two days before and after the expected gonadotropin surge were regarded as sufficient for the drug tests. Pimozide (initially 2 mg, then 1 mg/day) and fusaric acid (600 mg/day) were administered in a randomized cross-over study. The mid-cycle LH values were reduced from the control level of 56 .+-. 10 mIU/ml (mean .+-. SE) to 22 .+-. 4 mIU/ml by pimozide (P < 0.001) and to 17 .+-. 5 mIU/ml by fusaric acid (P < 0.001). The serum FSH level was 9 .+-. 2 mIU/ml on the day of the LH surge and did not change significantly during treatment with either drug. The LH and FSH responses to synthetic LRF [luteinizing hormone releasing factor] (100 .mu.g i.v.) were not changed by pimozide or fusaric acid. The rise of basal temperature associated with ovulation was not affected by the drugs. Suprapituitary noradrenergic and dopaminergic neurotransmitters are involved in the regulation of mid-cycle gonadotropin secretion in women.

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