Can Nolvadex (tamoxifen) cause hypercholesterolemia?/nA 70-year old woman has been treated with Nol

Fråga: Can Nolvadex (tamoxifen) cause hypercholesterolemia? A 70-year old woman has been treated with Nolvadex at an unknown dose for one year because of breast cancer. The patient now has high levels of serum cholesterol, about twice the normal limit. She is not overweight or hypertensive and is on no other drug treatment.

Sammanfattning: Minor changes in plasma lipid levels have been described during treatment with tamoxifen. Increased levels of cholesterol have, however, not been reported as an isolated phenomenon.

Svar: Tamoxifen is an anti-oestrogenic drug that has intrinsic oestrogenic activity at high doses (1). Its effects on plasma lipids and lipoproteins have been monitored in a few studies in women with breast cancer. Bruning and coworkers (2) followed plasma lipids and lipoproteins in 46 postmenopausal and eight premenopausal women treated with tamoxifen for advanced breast cancer for up to six months. Total cholesterol levels (total-C) did not change significantly. High density lipoprotein cholesterol (HDL-C) and the HDL-C/total-C ratios, however showed a slight increase. Low density lipoprotein cholesterol (LDL-C) was slightly decreased. Triglycerides and free fatty acids did not change.

In a 12-month, randomized, double-blind, placebo-controlled study of tamoxifen (10 mg twice a day), 140 postmenopausal women with breast cancer and histologically negative axillary lymph nodes were followed (3). During 12 months, plasma triglyceride levels increased. Fasting plasma levels of total cholesterol and LDL-C decreased significantly. Small but significant deceases in HDL-C were observed in tamoxifen-treated women, but ratios of total-C to HDL-C and of LDL-C to HDL-C changed favourable i.e. decreased. Both studies thus indicate that tamoxifen does not seem to have any major unfavourable effects on the lipid profile in postmenopausal women.

Severe hypertriglyceridemia has, however, been reported in a case report in a woman treated with tamoxifen (4). Brun and coworkers (4) described high plasma triglyceride levels, increased very low density lipoprotein cholesterol (VLDL-C) levels and decreased LDL-C levels in a 61-year old woman treated with tamoxifen for breast cancer. A low activity of plasma lipoprotein lipase and hepatic triglyceride lipase was also noted. All these observations were reversed after tamoxifen withdrawal. The authors suggest that in some patients the weak hypertriglyceridemic effect of tamoxifen may be amplified.

No cases of hypercholesterolemia or hyperlipidemia during tamoxifen treatment have been reported to the side-effects committee at the MPA.