Gynecomastia associated with low-dose methotrexate therapy for rheumatoid arthritis

Department of Orthopaedic Surgery, Chiba-Tokushukai Hospital, Funabashi, Japan.
Modern Rheumatology (Impact Factor: 2.4). 02/2007; 17(6):511-3. DOI: 10.1007/s10165-007-0619-2
Source: PubMed


A 68-year-old man with a 3-year history of rheumatoid arthritis (RA) developed gynecomastia 3 months after beginning oral low-dose methotrexate (MTX) therapy. Four months after MTX therapy was discontinued, the gynecomastia symptoms improved. Only eight cases of gynecomastia resulting from low-dose MTX administration have been reported worldwide, and no cases have previously been reported in Japan. Although it occurs infrequently, gynecomastia resulting from low-dose MTX therapy should be considered in male patients with RA.

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    ABSTRACT: Gynecomastia is often benign, but it can be the sign of serious endocrine disease and the source of significant embarrassment and psychological stress. Understanding its pathogenesis is crucial to distinguish a normal developmental variant from pathological causes. There is a growing list of potential causes of gynecomastia. Rare and unique case reports continue to supplement the literature to augment our understanding of this common physical finding. However, the exact basis for the pathogenesis of gynecomastia remains unknown. There appears to be a local imbalance between estrogen stimulation and the inhibitory action of androgens on breast tissue proliferation. Gynecomastia in a prepubertal boy is rare and should prompt an immediate evaluation for possible endocrine disorder. Pubertal gynecomastia, on the contrary, is common and usually physiological, with sympathetic reassurance and watchful waiting the mainstays of treatment. There is some evidence that early pharmacological intervention with antiestrogens may diminish persistent pubertal gynecomastia, but treatment with an aromatase inhibitor has not been shown to be more effective than placebo. Treatment of gynecomastia is geared toward its specific cause. Currently, there are insufficient data to recommend medical therapy in children with idiopathic gynecomastia.
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    ABSTRACT: A 62-year-old male with a 10-year history of seropositive rheumatoid arthritis (RA) developed gynecomastia 8 months after beginning oral low-dose methotrexate (MTX) therapy. Two months after folate supplementation, the gynecomastia symptoms improved. Gynecomastia associated with low-dose MTX is a rare occurrence, with only nine cases previously reported in the literature. This is the first report showing folate supplementation to be effective against gynecomastia following low-dose MTX. Although it occurs infrequently, gynecomastia associated with low-dose MTX therapy should be considered in male patients with RA.
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