Invasive breast cancer after initiation of testosterone replacement therapy in a man--a warning to endocrinologists

To alert fellow endocrinologists of a rare side effect of testosterone therapy, for which men with hypogonadism must receive appropriate counseling and monitoring.

We present clinical features, laboratory data, and histopathologic findings in a man with hypogonadism who received testosterone replacement therapy.

A 61-year-old man was referred to an endocrinologist after presenting to his general practitioner with erectile dysfunction and low libido. He had no history of hypothalamic, pituitary, or testicular disorders. There were no other illnesses or medications to account for low testosterone levels. Physical examination was unremarkable. There was no family history of malignant disease. Biochemical investigations confirmed the presence of primary hypogonadism, for which no cause (including Klinefelter syndrome) was identified. Testosterone therapy was initiated to improve sexual function and preserve bone density. Five weeks later, the patient returned to his general practitioner, complaining of a gradually enlarging lump in his right breast. When biopsy showed breast cancer, testosterone therapy was discontinued. Right mastectomy and axillary node clearance were performed. Further histologic examination revealed estrogen receptor-positive, invasive carcinoma, without nodal involvement. The patient remains on tamoxifen therapy and is undergoing follow-up in the breast clinic. After 6 months of treatment, estradiol levels were undetectable, and testosterone levels remained low.

Although breast cancer has been described in men with hypogonadism receiving long-term testosterone replacement therapy, to our knowledge this is the first report of breast cancer becoming clinically manifest after a short duration (5 weeks) of testosterone treatment. This case should remind clinicians that men receiving testosterone therapy should be warned of the risk of not only prostate cancer but also breast cancer. Patient self-monitoring and breast examinations by the attending physician are recommended.