Cabergoline in the Treatment of Hyperprolactinemia: A Study in 455 Patients

Abstract

Many hyperprolactinemic patients do not tolerate bromocriptine or other dopamine agonists and, even if they do, often must take them two or three times each day. Cabergoline is a long-lasting dopamine agonist whose action lasts up to 2 weeks after a single dose so that it may be taken once or twice a week. This study evaluated cabergoline in 353 women and 102 men with pathologic hyperprolactinemia. Roughly 40 percent of the group had a microadenoma, and the same proportion had a macroadenoma. No cause was evident in 16 percent of cases. Of 292 patients who previously had received bromocriptine, 140 were intolerant and 58 were resistant to the drug. The median baseline serum prolactin was 124 μg/liter. Cabergoline therapy usually began at a dose of 0.25 or 0.5 mg twice weekly, and the dose was adjusted at 2- to 3-month intervals as needed to consistently reduce the prolactin level. Patients then were followed up every 4 to 6 months. Menstrual function became normal during cabergoline therapy in 89 percent of the women evaluated, several of whom became pregnant and delivered healthy children. The visual fields became normal in 70 percent of 47 patients. Migraine symptoms lessened significantly in 72 percent of 71 patients. Prolactin levels became normal in 86 percent of all patients and decreased by 75 percent or more in more than half of the others. The median lowest serum prolactin level, achieved in 8 months on average, was 5.6 μg/liter. The tumor shrank to some degree in two thirds of patients. At the end of follow-up, the median dose of cabergoline was 0.5 mg/week. Minor side effects were reported by 8.5 percent of patients, and major or persistent symptoms were reported by 4 percent. Headache and postural hypotension were the most common adverse effects. Of the 14 patients who withdrew because of intolerance, 12 had also failed to tolerate bromocriptine. Only 9 percent of bromocriptine-intolerant patients were also intolerant of cabergoline. Patients harboring a microprolactinoma required lower doses and were more likely than those with macroadenomas to achieve a normal serum prolactin level. The baseline and lowest serum prolactin levels correlated weakly but significantly. In more than two thirds of patients who had been resistant to bromocriptine, control was achieved with cabergoline. This large-scale study affirms the effectiveness and tolerance of cabergoline when used to treat pathologic hyperprolactinemia. J Clin Endocrinol Metab 1999;84:2518–2522