Medical Treatment Ergot alkaloids are the mainstay of therapy. In 1985, bromocriptine was approved for use in the United States to treat hyperprolactinemia caused by a pituitary adenoma. These agents act as strong dopamine agonists, thus decreasing prolactin levels. Effects on prolactin levels occur within hours, and lesion size may decrease within 1 or 2 weeks. Bromocriptine decreases prolactin synthesis, DNA synthesis, cell multiplication, and overall size of prolactinomas. Bromocriptine treatment results in normal prolactin blood levels or return of ovulatory menses in 80% to 90% of patients.
Because ergot alkaloids, like bromocriptine, are excreted via the biliary tree, caution is required when using it in the presence of liver disease. The major adverse effects include nausea, headaches, hypotension, dizziness, fatigue and drowsiness, vomiting, headaches, nasal congestion, and constipation. Many patients tolerate bromocriptine when the dose is increased gradually, by 1.25 mg (one-half tablet) daily each week until prolactin levels are normal or a dose of 2.5 mg twice daily is reached. A proposed regimen is as follows: one-half tablet every evening (1.25 mg) for 1 week, one-half tablet morning and evening (1.25 mg) during the second week, one-half tablet in the morning (1.25 mg) and a full tablet every evening (2.5 mg) during the third week, and one tablet every morning and every evening during the fourth week and thereafter (2.5 mg twice a day). The lowest dose that maintains the prolactin level in the normal range is continued (1.25 mg twice daily often is sufficient to normalize prolactin levels in individuals with levels less than 100 ng/mL). Pharmacokinetic studies show peak serum levels occur 3 hours after an oral dose, with a nadir at 7 hours. Because little detectable bromocriptine is in the serum by 11 to 14 hours, twice-a-day administration is required. Prolactin levels can be checked soon (6 to 24 hours) after the last dose.
One rare, but notable, adverse effect of bromocriptine is a psychotic reaction. Symptoms include auditory hallucinations, delusional ideas, and changes in mood that quickly resolve after discontinuation of the drug (294).
Many investigators report no difference in fibrosis, calcification, prolactin immunoreactivity, or the surgical success in patients pretreated with bromocriptine compared to those not receiving bromocriptine (291).
An alternative to oral administration is the vaginal administration of bromocriptine tablets, which is well tolerated, and actually results in increased pharmacokinetic measures (295). Cabergoline, another ergot alkaloid, has a very long half-life and can be given orally twice per week. Its long duration of action is attributable to slow elimination by pituitary tumor tissue, high affinity binding to pituitary dopamine receptors, and extensive enterohepatic recirculation.
Cabergoline, which appears to be as effective as bromocriptine in lowering prolactin levels and in reducing tumor size, has substantially fewer adverse effects than bromocriptine. Very rarely, patients experience nausea and vomiting or dizziness with cabergoline; they may be treated with intravaginal cabergoline as with bromocriptine. A gradually increasing dosage helps avoid the side effects of nausea, vomiting, and dizziness. Cabergoline at 0.25 mg twice per week is usually adequate for hyperprolactinemia with values less than 100 ng/mL. If required to normalize prolactin levels, the dosage can be increase by 0.25 mg per dose on a weekly basis to a maximum of 1 mg twice weekly.