Correspondence
Gynecomastia
N Engl J Med 2007; 357:2636-2637December 20, 2007
- Article
To the Editor:
In his review of gynecomastia, Dr. Braunstein (Sept. 20 issue)1 includes numerous medications that may be associated with gynecomastia but does not mention a potential link of statins to gynecomastia. The only medication used by the patient described in the clinical vignette was a statin, and case reports have suggested that statins might induce gynecomastia.2,3 In one case report, the gynecomastia was reversed after a change in statin medication.2 A possible mechanism for this relationship is a reduction in adrenal or gonadal steroid production through the effects of statins on the cholesterol pathway.2
3 ReferencesIsabela Romao, M.D.
Evan Klass, M.D.
North Shore–Long Island Jewish Health System, Lake Success, NY 110421
Braunstein GD . Gynecomastia. N Engl J Med 2007;357:1229-1237
Full Text | Web of Science | Medline2
Hammons KB ,Edwards RF ,Rice WY . Golf-inhibiting gynecomastia associated with atorvastatin therapy. Pharmacotherapy 2006;26:1165-1168
CrossRef | Web of Science | Medline3
Aerts J ,Karmochkine M ,Raguin G . Gynecomastia due to pravastatin. Presse Med 1999;28:787-787
Web of Science | Medline
To the Editor:
Braunstein stresses the importance of physical examination in the diagnosis of a breast mass in men and the addition of mammography in selected cases but does not discuss the role of fine-needle aspiration cytology and core biopsy in the diagnostic workup. In our hospital, fine-needle aspiration cytology or core biopsy is used in the evaluation of lesions that are equivocal or suggestive of cancer on physical examination, mammography, or both. In our experience and in the experience of others, fine-needle aspiration cytology has a negative predictive value that is close to 100% and, in almost all studies, a positive predictive value of 100%.1 In a small study of core biopsy, no false positive or false negative results were found.2 With the use of this strategy, diagnostic operations for gynecomastia may be avoided, and for men in whom breast cancer is diagnosed, appropriate treatment may be facilitated.3
3 ReferencesPieter J. Westenend, M.D.
Laboratory for Pathology, 3317 DA Dordrecht, the Netherlands
pwestenend@paldordt.nl Remmert Storm, M.D.
Rob J. Oostenbroek, M.D.
Albert Schweitzer Hospital, 3300 AK Dordrecht, the Netherlands1
Westenend PJ ,Jobse C . Evaluation of fine-needle aspiration cytology of breast masses in males. Cancer 2002;96:101-104
CrossRef | Web of Science | Medline2
Westenend PJ . Core needle biopsy in male breast lesions. J Clin Pathol 2003;56:863-865
CrossRef | Web of Science | Medline3
Giordano SH . A review of the diagnosis and management of male breast cancer. Oncologist 2005;10:471-479
CrossRef | Web of Science | Medline
Author/Editor Response
Romao and Klass raise the possibility that the patient in the case vignette had drug-induced gynecomastia from a statin. The only evidence of a relationship between the statin and the gynecomastia in the two patients in the case reports they referenced was the appearance of gynecomastia after treatment with pravastatin was started in one patient and after a switch was made from simvastatin to atorvastatin in the other; the breast enlargement resolved after withdrawal of the drug in the first patient and after a switch back to simvastatin in the second patient. Neither patient was rechallenged with the presumed culprit, and both patients were taking other medications that have been implicated in other case reports of gynecomastia. This illustrates the difficulty of evaluating most of these types of case reports, since they show only a temporal relationship. As to the postulated statin-induced reduction in adrenal or gonadal steroid production, multiple studies have shown no significant differences between basal or stimulated hormone levels in men before and after statin use or in men using statins versus those not using the drugs.1,2 In addition, double-blind, placebo-controlled trials of statin use in children and adolescents have not shown differences in adrenal or gonadal steroid levels or alterations in pubertal development between patients receiving statins and those receiving placebo.3,4
Westenend and colleagues advocate the use of fine-needle aspiration and core biopsy in the evaluation of breast masses. In most cases, one should be able to discriminate between gynecomastia and other breast lesions on physical examination. If not, the next step should be diagnostic (not screening) mammography, ultrasonography, or both. If the diagnosis is still uncertain, then fine-needle aspiration is reasonable as long as the pathologists have sufficient experience in interpreting the results of breast fine-needle aspiration. Unfortunately, there is a high rate of unsatisfactory specimens, and florid gynecomastia may be mistaken for breast cancer with this technique.5 Finally, Westenend's report on core biopsy in men with breast lesions demonstrates the potential usefulness of this technique. However, there is insufficient information from other centers to advocate widespread use at this time.
5 ReferencesGlenn D. Braunstein, M.D.
Cedars–Sinai Medical Center, Los Angeles, CA 90048
braunstein@cshs.org 1
Travia D ,Tosi F ,Negri C ,Faccini G ,Moghetti P ,Muggeo M . Sustained therapy with 3-hydroxy-3-methylglutaryl-coenzyme-A reductase inhibitors does not impair steroidogenesis by adrenals and gonads. J Clin Endocrinol Metab 1995;80:836-840
CrossRef | Web of Science | Medline2
Hall SA ,Page ST ,Travison TG ,Montgomery RB ,Link CL ,McKinlay JB . Do statins affect androgen levels in men? Results from the Boston area community health survey. Cancer Epidemiol Biomarkers Prev 2007;16:1587-1584
CrossRef | Web of Science | Medline3
de Jongh S ,Ose L ,Szamosi T , et al. Efficacy and safety of statin therapy in children with familial hypercholesterolemia: a randomized, double-blind, placebo-controlled trial with simvastatin. Circulation 2002;106:2231-2237
CrossRef | Web of Science | Medline4
Stein EA ,Illingworth DR ,Kwiterovich PO Jr , et al. Efficacy and safety of lovastatin in adolescent males with heterozygous familial hypercholesterolemia: a randomized controlled trial. JAMA 1999;281:137-144
CrossRef | Web of Science | Medline5
Siddiqui MT, Zakowski MF, Ashfaq R, Ali SZ. Breast masses in males: multi-institutional experience on fine-needle aspiration. Diagn Cytopathol 2002;26:87-91
