Cabergoline for Prolactinomas

Target Pituitary

Cabergoline for the Treatment of Prolactinomas

The treatment of choice for prolactinomas is dopamine agonist administration, which results in tumor shrinkage, normalization of prolactin, and restoration of gonadal function in the majority of patients. The original dopamine agonist available for this disorder in the United States was bromocriptine. Its use is limited by a high incidence of side effects, a short duration of action, and a lack of effectiveness in some patients. Cabergoline, a long-acting oral doparnine agonist specific for the D2 receptor, is the most potent and well-tolerated dopamine agonist available for the treatment of prolactinomas in the U.S. currently.

Neuroendocrine Center Bulletin Archives


Cabergoline - A Dopamine Agonist

Pituitary Home

Beverly M.K. Biller
by Beverly M.K. Biller, M.D.

The most interesting feature of cabergoline in terms of patient comphance is its extremely long half-life. Most patientscan be treated with a single weekly dose, is in contrast to the 1-3 times daily administration required for brornocriptine. Particularly in the population most prone to microprolactinomas, healthy young women without other medical disorders, a once weekly therapy is extremely appealing. What information is available about cabergoline and what is its current status in the United States?

Patient Study

Figure 1. The decline in serum prolactin level in a patient treated with cabergoline. The dotted line indicates the normal range.


Webster, et al. conducted a European study comparing cabergoline to bromocriptine in the treatment of hyperprolactinemic amenorrhea. A total of 459 women, the majority of whom had microprolactinomas or idiopathic hyperprolactinernia, were treated with either cabergoline or bromocriptine in a double blind study for 8 weeks, followed by an open label study for 16 weeks during which dose adjustments were made according to response Eighty-three percent of the women treated with cabergoline attained normal prolactin levels in comparison with 59% of women treated with bromocriptine. Seventy-two percent of cabergoline-treated women attained ovulatory cycles or became pregnant during therapy in contrast to only 52% of those treated with bromocriptine. Amenorrhea persisted in 7% of women treated with cabergoline versus 16% of women treated with bromocriptine. Cabergoline was better tolerated than bromocriptine with 3% of women discontinuing cabergoline versus 12% stopping bromocriptine due to intolerance. Gastrointestinal symptoms were significantly less frequent, less severe, and of shorter duration in cabergoline treated patients. The authors concluded that cabergoline is more effective and better tolerated than bromocriptine in women with hyperprolactinemic amenorrhea.

In a United States multicenter study of patients with macroprolactinomas, we also found cabergoline to he effective and well tolerated. Fifteen patients (8 women, 7 men) ages 18-76 years were followed in an open label, 48-week dose escalation trial of cabergoline administered once weekly. Eleven patients had received prior therapy with other dopamine agonists. The prolactin levels decreased by 93.6% with normal levels obtained in 73% of patients at doses of 0.5-3.0 mg per week. Three of 5 patients who had failed to normalize prolactin on prior dopamine agonists achieved normal levels. Gonadal function was restored in all hypogonadal men and in 75% of premenopausal women with amenorrhea. Tumor size decreased in 11 of 15 patients, but tumor shrinkage may have been compromised by the fact that many patients had achieved substantial decreases in tumor mass on prior dopamine agonists. Side effects were minimal, with no patients discontinuing the medication due to intolerance.

Subsequent studies have confirmed the effectiveness of cabergoline for the treatment of prolactinomas, with few side effects in most patients. It is now considered first-line therapy, except in patients with contraindications, such as in women who are pregnant or desire to become pregnant, and patients with psychiatric disease. There have also been studies to suggest that in a minority of patients, impulsivity and risk-taking behaviors may increase. Finally, there are data to suggest that at high doses, not usually prescribed to patients with pituitary tumors, cardiac valve dysfunction can occur.

In summary, cabergoline appears to be a more effective and better tolerated dopamine agonist in the therapy of prolactinomas. Patient compliance is high, related to the few mild side effects and once-weekly dosing.

References:

  1. Webster J, et al. 1994. Comparison of cabergoline and bromocriptine in the treatment of hyperprolactinemic amenorrhea. N Engl J Med 31:904-909.
  2. Biller BMK, et al. 1996. Treatment of prolactin secreting macroadenomas with once weekly agonist cabergoline. J Clin Endocrinol Metab 81:2338-43.
Updated 1/14/15 BS and KKM


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Physicians' Pituitary Information Service - Physicians with questions may contact Dr Biller or Dr Klibanski at 617.726.3965 or 1.888.429.6863 or via e-mail at - pituitary.info@partners.org :: Research Studies

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