What effects does tamoxifen (Tamaxin) have on the cardiovascular system, and in osteoporosis?

Fråga: What effects does tamoxifen (Tamaxin) have on the cardiovascular system, and in osteoporosis?

Sammanfattning: In reference to cardiovascular effects, tamoxifen seems to provide a cardioprotective effect whose exact mechanism is still under consideration. However, adverse effects such as venous and arterial thromboembolism have also been reported.

Tamoxifen also seems to increase bone mass in postmenopausal breast cancer patients. Although the effect is not seen throughout the skeletal system, it is measurable in some parts such as the lumbar spine.

Svar: Tamoxifen is a nonsteroidal anti-estrogen which competitively inhibits estradiol binding to estrogen receptors (1). It is indicated for the palliative and adjunct treatment of breast cancer (2).

CARDIOVASCULAR: One of the listed side effects of tamoxifen use is thromboembolism (1,3). However the manufacturer questions any relationship due to the increased chance of embolism seen in the cancer population (3).

Cases of both arterial and venous thrombosis were found in the literature (4-6). Dahan et al reported a fatality associated with tamoxifen induced thromboembolism. The patient developed total thrombosis of the left iliac and femoral arteries, and died 48 hours later. They also report on another patient who, although not fatal, developed serious thrombi in the left femoral artery which subsequently caused a pulmonary embolism. The patient died of unlisted causes 6 months later (4).

Deshmukh et al described the case of a breast cancer patient who suffered from numerous thrombi of the anterior and posterior tibial arteries as well as the peroneal arteries. Urokinase was started and the patient recovered without incident (5).

Nevasaari et al reported on four patients who experienced a deep vein thrombosis while on tamoxifen therapy. All of the patients recovered after being started on anticoagulation therapy (6).

Positive effects on the cardiovascular system have also been seen. Dewar et al demonstrated a significant reduction in fatal myocardial infarctions in postmenopausal women with breast cancer, taking 20 mg daily for five years or until relapse. The results showed that tamoxifen lowers serum cholesterol concentrations. This effect ends with the cessation of treatment (7).

Wiseman et al demonstrated that tamoxifen, as well as its metabolite 4-hydroxytamoxifen, protects LDL cholesterol against lipid peroxidation by exerting a membrane-stabilizing effect. They believe that this coupled with the decrease in the plasma LDL levels may account for tamoxifen´s cardioprotective effect (8).

McDonald et al has also demonstrated that, in the Scottish Adjuvant Tamoxifen Trial, tamoxifen given for at least five years in breast cancer patients has a cardioprotective effect in post menopausal women (9). The women taking tamoxifen had a significantly less number of fatal myocardial infarctions than did the control group. At the time the article was written, research was under way to see if there is a similar effect with non-fatal myocardial infarctions. Similar results were seen in study in California (9). It is not known whether this phenomenon is due to decreases in cholesterol concentrations or to other mechanisms such as decreased vascular tone or effects on insulin metabolism (9).

OSTEOPOROSIS: Due to its anti-estrogen effects, there has been some concern that the use of tamoxifen may promote the formation of osteoporosis (7, 10-12).

Kalef-Ezra et al studied 26 female breast cancer patients taking tamoxifen 20 mg daily. Their study showed that no osteopenia was seen after taking tamoxifen for 12-45 months (10).

Turken et al investigated the spinal bone density of 20 postmenopausal breast cancer patients. They report that in the tamoxifen group there was a nonsignificant gain in bone mass at 6 and 12 months, while the control group showed a decrease in bone mass at 6 months and a significant loss at 12 months (11).

Love et al demonstrated in a study of 140 postmenopausal women with breast cancer, given tamoxifen 10 mg twice daily, the bone mineral density of the lumbar spine increased by 0.61 per cent a year. The placebo group decreased by 1.00 per cent per year. However, the density of the radial bone decreased 0.88 per cent for tamoxifen users compared to 1.29 per cent for placebo (12).