Hyperprolactinemia Treatment & Management

Direct treatment is geared toward resolving hyperprolactinemic symptoms or reducing tumor size. Patients on medications that cause hyperprolactinemia should have them withdrawn if possible. Patients with hypothyroidism should be given thyroid hormone replacement therapy.

In cases of pharmacologic-induced hyperprolactinemia, an evaluation of the risk-benefit of the causative agent is imperative. Stopping the drug is ideal but may not be feasible. A good example is a patient with schizophrenia in whom a single antipsychotic agent is the cause, but in whom that drug is keeping the patient’s psychoses under control. The cautious addition of a dopamine agonist may be considered.^[2]

The persistent hypogonadism associated with hyperprolactinemia can lead to osteoporosis. Baseline dual-energy X-ray absorptiometry (DXA) scanning is appropriate. Treatment significantly improves the patient's quality of life. If the goal is to treat hypogonadism only, patients with idiopathic hyperprolactinemia or microadenoma can be treated with estrogen replacement and prolactin levels can be monitored.^[6]

Radiation treatment is another option. However, the risk of hypopituitarism makes this a poor choice. It may be necessary for rapidly growing tumors, but its benefits in routine treatment have not been shown to outweigh the risks.

Medication

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. Although the evidence supporting initial medication therapy is largely based on uncontrolled observational studies, it does strongly support the use of these medications.^[2]

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.^{[7, 8, 9, 10]}

Pergolide, a drug previously used for the treatment of hyperprolactinemia was withdrawn from the US market March 29, 2007, because of heart valve damage resulting in cardiac valve regurgitation.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.^[8] 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%. The authors 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.

Dekkers et al also investigated the effects of dopamine agonist withdrawal on patients with hyperprolactinemia, either the idiopathic form or that caused by prolactinomas. 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.^[11]

General indications for pituitary surgery include patient drug intolerance, tumors resistant to medical therapy, patients who have persistent visual-field defects in spite of medical treatment, and patients with large cystic or hemorrhagic tumors. In patients with symptomatic prolactinomas who are either not responding to high doses of dopamine agonists or cannot tolerate the high doses necessary, transspenoidal surgery has been suggested as the best treatment. However, no controlled studies have evaluated the surgical outcomes in medically resistant tumors.^[2]

Physicians who are comfortable with the initial evaluation of a patient (without evidence of tumor mass effect) can easily initiate therapy and provide follow-up. However, given the time constraints of modern ambulatory medicine, consultation with an endocrinologist is often necessary.