Correspondence

Gynecomastia and Breast Cancer during Finasteride Therapy

N Engl J Med 1996; 335:823September 12, 1996

Article

To the Editor:

From June 1992, when finasteride (Proscar) was approved for the treatment of prostatic hyperplasia, to February 1995, the Food and Drug Administration (FDA) received reports of gynecomastia in 214 men (ages, 47 to 90 years; median, 71) in the United States who were taking the drug. Gynecomastia has been the most frequently reported adverse effect of this drug, with an onset ranging from 14 days to 2 1/2 years (median, 180 days) after the initiation of therapy. Most of the men were taking the recommended daily dose of 5 mg. About 30 percent had unilateral gynecomastia, and 25 percent had bilateral involvement; the side or sides involved were not specified in 45 percent. Sixteen men (7 percent) had biopsies, 17 (8 percent) had mammography, and 12 (6 percent) underwent mastectomy. Fifty-eight (27 percent) were also taking other medications (such as digoxin, histamine H₂ -receptor antagonists, spironolactone, lovastatin, and verapamil) known to be associated with gynecomastia.1 One hundred five men stopped taking finasteride. At the time of the report to the FDA, 69 of the 86 (80 percent) for whom information on the results after discontinuation was available had partial or complete remission of gynecomastia, and 17 (20 percent) had no change.

Two men in whom gynecomastia developed during finasteride therapy were subsequently found to have primary intraductal breast carcinoma. One was a 59-year-old man who had taken finasteride for only 35 days, and the other was a 63-year-old man who had taken finasteride for about 1 3/4 years.

Finasteride blocks the conversion of testosterone to dihydrotestosterone. Because gynecomastia is due to an increased ratio of estrogen to androgen,1 it is biologically plausible that finasteride causes gynecomastia. In addition to the reports of gynecomastia received by the FDA, one case has been reported in the English-language literature.2 A study monitoring events related to prescription-drug use in England3 reported that gynecomastia or mastalgia occurred in 0.4 percent of men taking finasteride (4 of 1000). In this study the rate of gynecomastia was 0.26 per 1000 patient-months of finasteride therapy, the highest rate of any of 18 drugs studied.

Gynecomastia and drugs that cause it have been associated with breast cancer in men.4 However, of the two men who were given a diagnosis of breast cancer after beginning finasteride therapy, the breast cancer was probably present in at least one before treatment was initiated. Whether finasteride therapy and breast cancer in men are related is unknown at this time, and continued surveillance is required.

This letter contains the professional views of the authors and does not necessarily represent the official position of the FDA.

Lanh Green, R.Ph., M.P.H.
Diane K. Wysowski, Ph.D.
Jean L. Fourcroy, M.D., Ph.D.
Food and Drug Administration, Rockville, MD 20857

4 References

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   Abdulmaged M. Traish, John Hassani, Andre T. Guay, Michael Zitzmann, Michael L. Hansen. (2011) Adverse Side Effects of 5α-Reductase Inhibitors Therapy: Persistent Diminished Libido and Erectile Dysfunction and Depression in a Subset of Patients. The Journal of Sexual Medicine 8:3, 872-884
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   Daibes Rachid-Filho, Andre G. Cavalcanti, Luciano A. Favorito, Waldemar S. Costa, Francisco J.B. Sampaio. (2009) Treatment of Recurrent Priapism in Sickle Cell Anemia With Finasteride: A New Approach. Urology 74:5, 1054-1057
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   Ricardo Augusto Santana Davanço, Miguel Sabino Neto, Élvio Bueno Garcia, Priscila Katsumi Matsuoka, Juliana Perez Rodrigues Huijsmans, Lydia Masako Ferreira. (2009) Quality of Life in the Surgical Treatment of Gynecomastia. Aesthetic Plastic Surgery 33:4, 514-517
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   Ari Eckman, Adrian Dobs. (2008) Drug-induced gynecomastia. Expert Opinion on Drug Safety 7:6, 691-702
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   Rajiv Kumar, Bhupinder Singh, Gautam Bakshi, Om Prakash Katare. (2007) Development of Liposomal Systems of Finasteride for Topical Applications: Design, Characterization, and In Vitro Evaluation. Pharmaceutical Development and Technology 12:6, 591-601
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   Marek Medras, Filus Alicja, Jozkow Pawel, Winowski Jacek, Sicinska Werner Teresa. (2006) Breast cancer and long-term hormonal treatment of male hypogonadism. Breast Cancer Research and Treatment 96:3, 263-265
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   Gilbert J. Wise, Andrew K. Roorda, Robert Kalter. (2005) Male breast disease1. Journal of the American College of Surgeons 200:2, 255-269
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   W. Krause. (2004) Review article Male breast cancer - an andrological disease: risk factors and diagnosis. Andrologia 36:6, 346-354
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   J.-L. Schmutz, A. Barbaud, P. Trechot. (2004) Gynécomastie et finastéride (Propecia®) : 4 nouveaux cas. Annales de Dermatologie et de Vénéréologie 131:6-7, 615
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    James F Libecco, Wilma F Bergfeld. (2004) Finasteride in the treatment of alopecia. Expert Opinion on Pharmacotherapy 5:4, 933-940
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    (2004) Finasteride in Benign Prostatic Hyperplasia. New England Journal of Medicine 350:13, 1359-1361
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    (2003) Prevention of Prostate Cancer with Finasteride. New England Journal of Medicine 349:16, 1569-1572
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    Patrick Merci??, Jean-Fran??ois Viallard, Rodolphe Thi??baut, Isabelle Faure, Patrick Rispal, Bernard Leng, Jean-Luc Pellegrin. (2001) Efavirenz-associated breast hypertrophy in HIV-infected patients. AIDS 15:1, 126-129
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14. 14

    &NA;. (1996) Finasteride-induced gynaecomastia and breast cancer?. Reactions Weekly &NA;:619, 2
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