Hyperprolactinemia Treatment & Management

  • Author: Donald Shenenberger, MD, FAAD, FAAFP; Chief Editor: George T Griffing, MD   more...
 
Updated: Aug 15, 2011
 

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 Patients on medications that cause hyperprolactinemia should have them withdrawn if possible.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.

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Pergolide, a drug previously used for the treatment of hyperprolactinemia was withdrawn from the US market March 29, 2007, because of heart valve damage resulting in cardiac valve regurgitation.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

Next

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. 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]

Previous
Next

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.

Previous
Proceed to Medication
 
 
Contributor Information and Disclosures
Author

Donald Shenenberger, MD, FAAD, FAAFP  Staff Dermatologist, Department of Dermatology, Naval Medical Center Portsmouth

Donald Shenenberger, MD, FAAD, FAAFP is a member of the following medical societies: American Academy of Dermatology, American Academy of Family Physicians, Association of Military Dermatologists, and Uniformed Services Academy of Family Physicians

Disclosure: Nothing to disclose.

Specialty Editor Board

David M Klachko, MD, MEd  Professor Emeritus, Department of Internal Medicine, Division of Endocrinology, Diabetes, and Metabolism, University of Missouri-Columbia School of Medicine

David M Klachko, MD, MEd is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American Diabetes Association, American Federation for Medical Research, Endocrine Society, Missouri State Medical Association, and Sigma Xi

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Yoram Shenker, MD  Chief of Endocrinology Section, Veterans Affairs Medical Center of Madison; Interim Chief, Associate Professor, Department of Internal Medicine, Section of Endocrinology, Diabetes and Metabolism, University of Wisconsin at Madison

Yoram Shenker, MD is a member of the following medical societies: American Heart Association, Central Society for Clinical Research, and Endocrine Society

Disclosure: Nothing to disclose.

Mark Cooper, MBBS, PhD, FRACP  Head, Diabetes & Metabolism Division, Baker Heart Research Institute, Professor of Medicine, Monash University

Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD  Professor of Medicine, St Louis University School of Medicine

George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Medical Practice Executives, American College of Physician Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical Research, Endocrine Society, International Society for Clinical Densitometry, and Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Acknowledgments

The editors would like to thank Treyce Knee, MD, for previous contributions to this article.

References
  1. Nilsson LA, Roepstorff C, Kiens B, et al. Prolactin suppresses malonyl-CoA concentration in human adipose tissue. Horm Metab Res. Jun 23 2009;[Medline].

  2. [Guideline] Melmed S, Casanueva FF, Hoffman AR, et al. Diagnosis and treatment of hyperprolactinemia: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. Feb 2011;96(2):273-88. [Medline].

  3. Erem C, Kocak M, Nuhoglu I, et al. Blood coagulation, fibrinolysis and lipid profile in patients with prolactinoma. Clin Endocrinol (Oxf). Dec 18 2009;[Medline].

  4. Berinder K, Akre O, Granath F, Hulting AL. Cancer risk in hyperprolactinemia patients: a population-based cohort study. Eur J Endocrinol. Aug 2011;165(2):209-15. [Medline].

  5. Schlechte JA. Long-term management of prolactinomas. J Clin Endocrinol Metab. August 2007;92(8):2861-5. [Medline].

  6. 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].

  7. 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].

  8. 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].

  9. Lafeber M, Stades A, Valk G, et al. Absence of major fibrotic adverse events in hyperprolactinemic patients treated with cabergoline. Eur J Endocrinol. Jan 13 2010;[Medline].

  10. Valassi E, Klibanski A, Biller BM. Potential cardiac valve effects of dopamine agonists in hyperprolactinemia. J Clin Endocrinol Metab. Mar 2010;95(3):1025-33. [Medline].

  11. Dekkers OM, Lagro J, Burman P, et al. Recurrence of hyperprolactinemia after withdrawal of dopamine agonists: systematic review and meta-analysis. J Clin Endocrinol Metab. Jan 2010;95(1):43-51. [Medline].

  12. 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.

  13. Blackwell RE. Hyperprolactinemia. Evaluation and management. Endocrinol Metab Clin North Am. Mar 1992;21(1):105-24. [Medline].

  14. Bolanowski M, Zadrozna-Sliwka B, Jawiarczyk A, et al. The influence of other than prolactin hormones on bone mineral density in women with hyperprolactinaemia of various origins. Gynecol Endocrinol. Mar 10 2010;[Medline].

  15. Conner P, Fried G. Hyperprolactinemia; etiology, diagnosis and treatment alternatives. Acta Obstet Gynecol Scand. Mar 1998;77(3):249-62. [Medline].

  16. Davies PH. Drug-related hyperprolactinaemia. Adverse Drug React Toxicol Rev. Jun 1997;16(2):83-94. [Medline].

  17. Hartog M, Hull MG. Hyperprolactinaemia. BMJ. Sep 17 1988;297(6650):701-2. [Medline].

  18. Jones TH. The management of hyperprolactinaemia. Br J Hosp Med. Apr 19-May 2 1995;53(8):374-8. [Medline].

  19. Kaye TB. Hyperprolactinemia. Causes, consequences, and treatment options. Postgrad Med. May 1996;99(5):265-8. [Medline].

  20. Lancet. Management of prolactinoma. Lancet. Sep 15 1990;336(8716):661. [Medline].

  21. Molitch ME. Medical treatment of prolactinomas. Endocrinol Metab Clin North Am. Mar 1999;28(1):143-69, vii. [Medline].

  22. Prescrire International. Cabergoline and hyperprolactinaemia: new preparation. Better than bromocriptine. Prescrire Int. 2000;Feb;9(45):195-7. [Medline].

  23. Serri O, Chik CL, Ur E, Ezzat S. Diagnosis and management of hyperprolactinemia. CMAJ. Sep 16 2003;169(6):575-81. [Medline].

  24. Valdemarsson S. Macroprolactinemia. Risk of misdiagnosis and mismanagement in hyperprolactinemia. Lakartidningen. 2004;101(6):458-65. [Medline].

  25. 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.

Previous
Next
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.