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)
- Finasteride (Propecia; Proscar)
- 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
- Saw Palmetto (Serenoa repens)
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:
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hyperprolactinaemia and antipsychotic treatment: a review and lessons for
treatment of early psychosis. J Psychopharmacol 2012;36:42-51.
- Bostwick JR, Guthrie SK, Ellingrod VL.
Antipscyhotic-induced hyperprolactinemia. Pharmacotherapy
2009;29:64-73.
- Garcia Rodriquez LA, Jick H. Risk of gynaecomastia
associated with cimetidine, omeprazole, and other antiulcer drugs.
BMJ 1994;308:503-6.
- Wolfe CJ. Case report. Gynecomastia following
digitalis administration. J Fla Med Assoc 1975;62:54-5.
- 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.
- Green GR. Mechanism of hypogonadism in cirrhotic
males. GUT 1977;18:843-53.
- Eli C. Ketoconazole binds to the human androgen
receptor. Horm Metab Res 1992;24:367-70.
- 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.
- Thomas BL. Letter: Methadone-associated gynecomastia.
N Engl J Med 1976;294:169.
