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Common Medications That Can Cause Gynecomastia in Males

  • Gynecomastia is known as breast enlargement and tenderness.
  • A list of common medications known to cause gynecomastia are listed below. 

Editor-in-Chief: Anthony J. Busti, MD, PharmD, FNLA, FAHA
Last Reviewed: October 2015

Explanation

  • Gynecomastia is an enlargement or swelling of the breast tissue in males.  It is most commonly caused by too much influence from estrogen and not enough testosterone.  In addition to breast enlargement, most male patients will experience breast tenderness and/or pain.  In some cases, patients can also have nipple discharge.  If the medication is removed, the enlarged breast tissue will regress over time and return to normal. 

    The following medications are most commonly known to increase the risk for gynecomastia (breast enlargement and tenderness) in males.  If known or reported the incidence is also provided.

    Medications Known to Cause Gynecomastia:

    • Aldosterone Antagonists
      • Eplerenone (Inspra) [up to 1%]
      • Spironolactone (Aldactone)
    • Antipsychotics
      • Typical or First Generation
        • Chlorpromazine (Thorazine)
        • Fluphenazine (Prolixin)
        • Haloperidol (Haldol)
        • Perphenazine (Trilafon)
        • Thioridazine (Mellaril)
        • Trifluoperazine (Stelazine)
      • Atypical or Second Generation
        • Aripiprazole (Abilify; Abilify Discmelt)
        • Asenapine sublingual tablets (Saphris)
        • Clozapine (Clozaril; Fazaclo)
        • Iloperidone (Fanapt)
        • Olanzapine (Zyprexa; Zydis, Zyprexa Relprevv)
        • Paliperidone (Invega; Invega Sustenna)
        • Quetiapine (Seroquel; Seroquel XR)
        • Ziprasidone (Geodon)
        • Cimetidine (Tagamet) [1-4%]
    • Digoxin (Lanoxin) [<1%]
    • Efavirenz (Sustiva)
    • Estrogen use
    • Ethanol (Alcohol)
    • Ketoconazole (Nizoral) [<1%]
    • Methadone

    The mechanisms by which these medications are known to cause this this effect are different and/or may not be fully known.  We do know that antipsychotics contribute to this side effect through their antagonism of the dopamine receptors in the central nervous system, which causes an increase in prolactin secretion from the pituitary.  Eplerenone and spironolactone have varying degrees of binding to the androgen and progesterone receptors with eplerenone being the least likely to inhibit it.  Ketoconazole is known to inhibit androgen synthesis thus creating an imbalance that favors breast tissue growth.

    If you know of other medications that should be added to this list, please let us know.  We appreciate your contribution.

    References:
    1. Cookson J, Hodgson R, Wildgust HJ.  Prolactin, hyperprolactinaemia and antipsychotic treatment: a review and lessons for treatment of early psychosis.  J Psychopharmacol 2012;36:42-51. 
    2. Bostwick JR, Guthrie SK, Ellingrod VL.  Antipscyhotic-induced hyperprolactinemia.  Pharmacotherapy 2009;29:64-73.
    3. Garcia Rodriquez LA, Jick H. Risk of gynaecomastia associated with cimetidine, omeprazole, and other antiulcer drugs.  BMJ 1994;308:503-6.
    4. Wolfe CJ.  Case report. Gynecomastia following digitalis administration. J Fla Med Assoc 1975;62:54-5.
    5. Sikora MJ, Rae JM, Johnson MD et al.  Efavirenz directly modulates the oesterogen receptor and induces cancer cell growth.  HIV Med 2010;11:603-7.   
    6. Green GR. Mechanism of hypogonadism in cirrhotic males.  GUT 1977;18:843-53. 
    7. Eli C.  Ketoconazole binds to the human androgen receptor.  Horm Metab Res  1992;24:367-70. 
    8. De la Rosa RE, Hennessey JV.  Hypogonadism and methadone: Hypothalamic hypogonadism after long-term use of high-dose methadone.  Endocr Pract 1996;2:4-7.
    9. Thomas BL. Letter: Methadone-associated gynecomastia.  N Engl J Med 1976;294:169.

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MESH Terms & Keywords

  • Gynecomastia, Drug Induced Breast Enlargement, Drug Induced Breast Tenderness