Impaired LH-RH release by estrogen in women with sulpiride-induced hyperprolactinemia

The effects of hyperprolactinemia on the release of immunoreactive luteinizing hormone-releasing hormone (LH-RH) and luteinizing hormone (LH) in response to iv injection of 20 mg conjugated estrogens (Premarin) were studied. Five normal cycling women were injected with Premarin on the morning of the 7th day of the first cycle (control cycle), and then the plasma levels of LH-RH, LH, and prolactin (PRL) were determined every 8 to 16 hours for 72 h. Two months later, the same women received 200 mg of oral sulpiride daily for 8 days from the 3rd day of the cycle (sulpiride treated cycle), and then the same protocol as in the control cycle was applied. Mean (+/- SE) plasma levels of PRL on day 7 in the sulpiride treated cycle were significantly higher than those in the control cycle (118 +/- 24 ng/ml vs. 14 +/- 4 ng/ml, p less than 0.001). After estrogen injection, the mean percent increases in immunoreactive LH-RH at 32 h (control: 71 +/- 38% vs. sulpiride: 6 +/- 36%) and 40 h (154 +/- 38% vs. -5 +/- 21%) and in LH at the 48 h (175 +/- 89% vs. 57 +/- 57%) and 56 h (99 +/- 32% vs. 7 +/- 21%) were significantly (p less than 0.01 or p less than 0.05) suppressed in the sulpiride cycle. These data suggest that the impaired positive feedback effect of estrogen on LH-release in hyperprolactinemic anovulatory women may be caused, at least in part, by disturbed LH-RH release.