Hyperprolactinemia Medication

Updated: Apr 10, 2020
  • Author: Donald Shenenberger, MD, FAAD, FAAFP; Chief Editor: George T Griffing, MD  more...
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Medication Summary

The dopamine agonist bromocriptine mesylate is often the initial drug of choice and may require high doses to achieve clinical improvement and shrinkage of prolactinomas. It can lower the prolactin level in 70-100% of patients. While the evidence supporting the use of medication therapy first is largely based on uncontrolled observational studies, they do strongly support the use of these medications. Agents other than bromocriptine have been used (eg, cabergoline, quinagolide). Cabergoline, in particular, probably is more effective and causes fewer adverse effects than bromocriptine. However, it is much more expensive. Cabergoline is often used in patients who cannot tolerate the adverse effects of bromocriptine or in those who do not respond to bromocriptine. [16, 17, 18, 19]

However, a study by Budayr et al indicated that compared with the use of bromocriptine, treatment of hyperprolactinemia with cabergoline poses a greater risk of valvular regurgitation, although the regurgitation itself was found to be primarily mild. Moreover, the adjusted odds ratio in the study for two or more valves with grade 2+ regurgitation was highest for cumulative cabergoline exposure of over 115 mg. [20]

Pergolide, a drug previously used for the treatment of hyperprolactinemia was withdrawn from the US market March 29, 2007, because of heart valve damage resulting in cardiac valve regurgitation. It is important not to stop pergolide abruptly. Health care professionals should assess patients’ need for dopamine agonist (DA) therapy and consider alternative treatment. If continued treatment with a DA is needed, another DA should be substituted for pergolide. For more information, see FDA MedWatch Product Safety Alert and Medscape Alerts: Pergolide Withdrawn From US Market.

Response to therapy should be monitored by checking fasting serum prolactin levels and checking tumor size with MRI. Most women (approximately 90%) regain cyclic menstruation and achieve resolution of galactorrhea. Testosterone levels in men increase but may remain below normal.

Therapy should be continued for approximately 12-24 months (depending on the degree of symptoms or tumor size) and then withdrawn if prolactin levels have returned to the normal range. After withdrawal, approximately one sixth of patients maintain normal prolactin levels.

Kharlip et al looked at the recurrence of hyperprolactinemia after withdrawal of cabergoline therapy in 46 patients who had undergone long-term treatment with the drug. [17]  At the beginning of the investigation, the study's patients were normoprolactinemic and had experienced tumor volume reduction after at least 2 years of treatment with cabergoline. The overall recurrence rate of hyperprolactinemia following cabergoline withdrawal was 54%; it was estimated that the recurrence risk by 18 months after the drug's discontinuation was 63%.

Kharlip et al also found that recurrence risk was related to the size of the tumor remnant remaining before therapy was discontinued, with an 18% risk increase for each millimeter of remnant. They concluded that withdrawal of cabergoline is safe in patients meeting the criteria used in the study but that close follow-up with these patients is essential, particular in the first year after the drug's discontinuation.

Bromocriptine is also used to shrink macroadenomas. Normalization of visual fields is observed in as many as 90% of patients. A failure to improve within 1-3 months is an indication for surgery. Tumors usually shrink to 50% of their original size in approximately 90% of patients treated for macroadenomas for 1 year. In patients with nonprolactinoma tumors (masses that are compressing the pituitary stalk), medical treatment reduces serum prolactin levels but does not reduce tumor size. Cabergoline is somewhat more effective than bromocriptine in terms of tumor shrinkage. [21]

Dekkers et al also investigated the effects of dopamine agonist withdrawal on patients with hyperprolactinemia, either the idiopathic form or that caused by prolactinomas. [22]  In a meta-analysis of 19 studies, encompassing a total of 743 patients, the authors found, just as Kharlip et al did, a high rate of recurrence of hyperprolactinemia following medication withdrawal. According to a stratified analysis, the treatment success rate (maintenance of normoprolactinemia after drug withdrawal) for patients with idiopathic hyperprolactinemia (32%) was greater than it was for individuals with prolactinomas (21% of patients with microprolactinomas, 16% of patients with macroprolactinomas). It was also found that the administration of cabergoline for at least 2 years provided the greatest probability of treatment success.


Dopamine agonists

Class Summary

These agents directly stimulate postsynaptic dopamine receptors. Dopaminergic neurons in tuberoinfundibular processes modulate the secretion of prolactin from the anterior pituitary by secreting a prolactin inhibitory factor, believed to be dopamine. [23, 24]

Bromocriptine (Parlodel)

Semisynthetic ergot alkaloid derivative; strong dopamine D2-receptor agonist; partial dopamine D1-receptor agonist. Inhibits prolactin secretion with no effect on other pituitary hormones. May be given with food to minimize possibility of GI irritation.

Cabergoline (Dostinex)

Semisynthetic ergot alkaloid derivative; strong dopamine D2-receptor agonist with low affinity for D1 receptors.

Quinagolide (Norprolac)

Pituitary selective dopamine-2 receptor agonist used in cases of bromocriptine resistance or intolerance. Used in the UK, not available in US.