A Broad Spectrum of Prolactin Suppression by Bromocriptine in Hyperprolactinemic Women: A Study of Serum Prolactin and Bromocriptine Levels after Acute and Chronic Administration ofBromocriptine*

Abstract

Medical therapy with the semisynthetic ergot, bromocriptine (2-bromo-α-ergocryptine; CB 154), was assessed in 18 hyperprolactinemic women. Serum PRL and bromocriptine levels were measured after a single 2.5-mg oral dose and on chronic treatment at 3 and 6 months. All patients showed a marked decrease in circulating PRL concentrations after the single 2.5-mg dose of bromocriptine. Five patients did not decrease their PRL levels into the normal range on chronic therapy with 7.5 mg/day bromocriptine, although 3 of the 5 returned to normal ovulatory cycles. There is a broad spectrum of responsiveness to bromocriptine among hyperprolactinemic women, with afew patients showing relatively poor suppression; this relative lack of suppressibility persistseven after long term treatment and is not correlated with serum levels of bromocriptine. The effective concentration of bromocriptine measured in these patients was approximately 1 × 10⁻⁹ M (0.7 ng/ml),very nearly that required for maximal PRL suppression in vitro. The suppression of PRL continued for at least 11 h, with the peakbromocriptine concentration at 3 h, an effect consistent with the in vitro demonstration of prolonged bromocriptine effectiveness. Despite the variability of responsiveness to bromocriptine among hyperprolactinemic women, including a minority who respond less well to bromocriptine in terms of their circulating PRL concentrations, these patients, nevertheless, regain ovulatory menstrual cycles. We believe that these studies present evidence for the presence of a spectrum of dysfunction of dopamine mechanisms at the lactotroph in hyperprolactinemic states.