Leg cramps associated with tamoxifen use--possible mechanism and treatment recommendations.

Since 1970s, tamoxifen has widely been used in the adjuvant and metastatic settings and also in risk reduction of hormone receptor positive breast cancer. Long-term use of tamoxifen in the adjuvant setting of hormone receptor positive breast cancer, such as up to 5 or 10 years duration, is standard of care and associated with favorable survival outcomes, almost in all stages of disease. Symptomatic side effects such as painful cramps due to tamoxifen are as important as adverse effects which might lead to treatment discontinuation. Today, we have been experiencing leg and foot cramps in our patients receiving tamoxifen in our clinic, this condition being severe enough to lead to treatment discontinuation with negative impact on the quality of life in breast cancer survivors. Recurrent leg cramp associated with tamoxifen use is a common side effect and causes severe acute leg pain. However, the mechanism of this side effect remains obscure [1,2]. In the literature, there are several reports suggesting that estrogen increases blood flow in muscle tissue and vessels by releasing nitric oxide (NO) and producing direct vaso-myorelaxant effect. In a study, basal blood flow was found to be lower in estrogen-deficient postmenopausal women compared to premenopausal counterparts [3]. In two other studies, estrogen replacement therapy has been found to increase serum NO levels in postmenopausal women [4,5]. We favor the explanation that leg cramps, particularly developing in night sleep, may be triggered by reduced blood flow due to postural changes. Instead of using vitamin D or magnesium tablets which have been mostly used for these cramps and failed to show efficience, systemic or local treatments (e.g. sildenafil, nitrates, pentoxyfylline etc) which increase NO levels may be useful and may improve the symptoms. Our hypothesis on this issue should be supported with relevant trials. References