eMedicine Specialties > Endocrinology > Pituitary Gland
Hyperprolactinemia: Treatment & Medication
Updated: Aug 12, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
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 Patients on medications that cause hyperprolactinemia should have them withdrawn if possible.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.
- When symptoms are present, medical therapy is the treatment of choice. Patients with hyperprolactinemia and no symptoms (idiopathic or microprolactinoma) can be monitored without treatment. Consider treatment for women with amenorrhea. In addition, duel energy radiographic absorptiometry scanning should be considered to evaluate bone density.
- The persistent hypogonadism associated with hyperprolactinemia can lead to osteoporosis. 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.3
- 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. It lowers the prolactin level in 70-100% of patients. 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.4,5
- Pergolide, a drug previously used for the treatment of hyperprolactinemia was withdrawn from the US market March 29, 2007, because of heart valve damage resulting in cardiac valve regurgitation.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 For more information, see FDA MedWatch Product Safety Alert and Medscape Alerts: Pergolide Withdrawn From US Market.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.5 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.
Surgical Care
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.
Consultations
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.
Medication
The goals of pharmacotherapy are to reduce morbidity and to prevent complications.
Dopamine agonists
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.
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.
Adult
1.25-2.5 mg PO initially; increase gradually every few days to approximately 5-10 mg daily in divided doses.
Pediatric
Not recommended
Toxicity may increase with ergot alkaloids; amitriptyline, butyrophenones, imipramine, methyldopa, phenothiazines, and reserpine may decrease effects
Documented hypersensitivity; ischemic heart disease, uncontrolled hypertension, peripheral vascular disorders; breastfeeding
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in renal or hepatic disease; generally stopped during pregnancy but can be restarted if symptoms recur; perform regular visual-field testing during pregnancy to monitor for tumor growth; should be given hs to minimize postural hypotension or nausea
Cabergoline (Dostinex)
Semisynthetic ergot alkaloid derivative; strong dopamine D2-receptor agonist with low affinity for D1 receptors.
Adult
0.25-1 mg PO twice/wk; start with a low dose and increase q4wk based on prolactin levels
Pediatric
Not recommended
Toxicity may increase with ergot alkaloids; amitriptyline, butyrophenones, imipramine, methyldopa, phenothiazines, and reserpine may decrease effects
Documented hypersensitivity; ischemic heart disease, uncontrolled hypertension, peripheral vascular disorders; breastfeeding
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in renal or hepatic disease; generally stopped during pregnancy but can be restarted if symptoms recur; perform regular visual-field testing during pregnancy to monitor for tumor growth; can be given hs to minimize postural hypotension or nausea
Quinagolide (Norprolac)
Pituitary selective dopamine-2 receptor agonist used in cases of bromocriptine resistance or intolerance. Used in the UK, not available in US.
Adult
0.075 mg PO qd
Pediatric
Not recommended
Not established
Documented hypersensitivity; decreased kidney or liver function
Pregnancy
Precautions
May cause dizziness or hypotension
More on Hyperprolactinemia |
| Overview: Hyperprolactinemia |
| Differential Diagnoses & Workup: Hyperprolactinemia |
 Treatment & Medication: Hyperprolactinemia |
| Follow-up: Hyperprolactinemia |
| References |
| Further Reading |
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References
Nilsson LA, Roepstorff C, Kiens B, et al. Prolactin suppresses malonyl-CoA concentration in human adipose tissue. Horm Metab Res. Jun 23 2009;[Medline].
Schlechte JA. Long-term management of prolactinomas. J Clin Endocrinol Metab. August 2007;92(8):2861-5. [Medline].
Sathyapalan T, Gonzalez S, Atkin SL. Effect of long-term, high-dose estrogen treatment on prolactin levels: a retrospective analysis. Climacteric. Jul 21 2009;1-4. [Medline].
Nachtigall LB, Valassi E, Lo J, McCarty D, Passeri J, Biller BM, et al. Gender effects on cardiac valvular function in hyperprolactinaemic patients receiving cabergoline: a retrospective study. Clin Endocrinol (Oxf). Apr 17 2009;[Medline].
Kharlip J, Salvatori R, Yenokyan G, Wand GS. Recurrence of hyperprolactinemia after withdrawal of long-term cabergoline therapy. J Clin Endocrinol Metab. Jul 2009;94(7):2428-36. [Medline].
Biller MKB, Daniels GH. Neuroendocrine regulation and diseases of the anterior pituitary and hypothalamus. In: Braunwald E, Isselbacher KJ, Wilson J, et al. Harrison's Principles of Internal Medicine. 14th ed. New York, NY: McGraw-Hill; 1998:1974-8.
Blackwell RE. Hyperprolactinemia. Evaluation and management. Endocrinol Metab Clin North Am. Mar 1992;21(1):105-24. [Medline].
Conner P, Fried G. Hyperprolactinemia; etiology, diagnosis and treatment alternatives. Acta Obstet Gynecol Scand. Mar 1998;77(3):249-62. [Medline].
Davies PH. Drug-related hyperprolactinaemia. Adverse Drug React Toxicol Rev. Jun 1997;16(2):83-94. [Medline].
Hartog M, Hull MG. Hyperprolactinaemia. BMJ. Sep 17 1988;297(6650):701-2. [Medline].
Jones TH. The management of hyperprolactinaemia. Br J Hosp Med. Apr 19-May 2 1995;53(8):374-8. [Medline].
Kaye TB. Hyperprolactinemia. Causes, consequences, and treatment options. Postgrad Med. May 1996;99(5):265-8. [Medline].
Lancet. Management of prolactinoma. Lancet. Sep 15 1990;336(8716):661. [Medline].
Molitch ME. Medical treatment of prolactinomas. Endocrinol Metab Clin North Am. Mar 1999;28(1):143-69, vii. [Medline].
Prescrire International. Cabergoline and hyperprolactinaemia: new preparation. Better than bromocriptine. Prescrire Int. 2000;Feb;9(45):195-7. [Medline].
Serri O, Chik CL, Ur E, Ezzat S. Diagnosis and management of hyperprolactinemia. CMAJ. Sep 16 2003;169(6):575-81. [Medline].
Valdemarsson S. Macroprolactinemia. Risk of misdiagnosis and mismanagement in hyperprolactinemia. Lakartidningen. 2004;101(6):458-65. [Medline].
Wilson JD. Endocrine Disorders of the Breast. In: Braunwald E, Isselbacher KJ, Wilson J, et al,. Harrison's Principles of Internal Medicine. 1998. 14th ed. New York, NY: McGraw-Hill; 2116-7.
Further Reading
Related eMedicine topics:
Luteinizing Hormone Deficiency
Ovarian Insufficiency
Pituitary Adenoma
Pituitary Disease and Pregnancy
Pituitary Macroadenomas
Pituitary Microadenomas
Prolactinoma
Clinical guidelines:
ACR Appropriateness Criteria® neuroendocrine imaging.
American College of Radiology - Medical Specialty Society. 1999 (revised 2006). 11 pages. [NGC Update Pending] NGC:005121
Diagnosis of breast disease.
Institute for Clinical Systems Improvement - Private Nonprofit Organization. 1994 Jan (revised 2008 Jan). 47 pages. NGC:006317
Stereotactic radiosurgery for patients with pituitary adenomas.
IRSA - Professional Association. 2004 Apr. 12 pages. NGC:003598
Clinical trials:
Calcium and Vitamin D to Optimize Bone Mass in Boys With Risperidone-Induced Hyperprolactinemia
Substrate Metabolism and Insulin Sensitivity in Patients With Hyperprolactinemia Before and After Treatment
The Luveris In Vitro Fertilization Trial
Keywords
hyperprolactinemia, prolactin, prolactinoma, pituitary tumor, tumor pituitary, cabergoline, prolactin levels, macroprolactinomas, pituitary tumors, breast development, elevated serum prolactin level, pituitary adenoma, prolactin-secreting tumors, anterior pituitary gland, lactation, secondary amenorrhea, galactorrhea, oligomenorrhea, dopamine agonists, hypothyroidism
