EFFECTS OF TAMOXIFEN TREATMENT ON PLASMA-LIPIDS AND LIPOPROTEIN LIPID-COMPOSITION

Concern has been raised that long term treatment with the antiestrogen tamoxifen might predispose women to the rapid development of cardiovascular disease. Since estrogen- induced changes in plasma lipids confer protection to females from coronary heart disease, we have examined the impact of tamoxifen on lipoprotein levels and composition on eight postmenopausal women. After 3 months of tamoxifen treatment (10 mg, twice daily), no significant changes were observed in either whole plasma triglyceride (pre-Rx, 137 ± 59; post-Rx, 157 ± 110 mg/dL) or cholesterol (pre-Rx, 193 ± 23; post-Rx, 204 ± 14 mg/dL); plasma free (unesterified) cholesterol (FC), however, fell significantly (pre-Rx, 66.5 ± 6.5; post-Rx, 59.6 ± 4.6 mg/dL; P < 0.05). Since plasma lecithin (L) was unchanged, the FC/L ratio declined significantly to levels observed in healthy menstruating women (pre-Rx, 95 ± 0.16; post-Rx, 0.74 ± 0.12 molar ratio; P < 0.025). In low density lipoprotein (LDL), the concentrations of cholesterol and FC and the FC/L ratio all fell significantly (P < 0.025, P < 0.05, and P < 0.025, respectively). Despite a tendency for high density lipoprotein2 cholesterol (HDL2-C) to increase (pre-Rx, 9.7 ± 3.6; post-Rx, and 14.4 ± 13.3 mg/dL; P < 0.4) and phosphoinositol to fall, there were few clear-cut alterations in either HDL2 or HDL3 surface or core lipid composition. The combination of reduced HDL3 lysolecithin (P < 0.025) associated with a posttreatment trend toward increased triglyceride/cholesterol esters ratios in both HDL subfractions are findings consistent with tamoxifen-induced inhibition of hepatic lipase. These changes in lipoprotein composition together with the fall in LDL cholesterol and increase in sex hormone-binding globulin (P < 0.005) indicate that tamoxifen acts as an estrogen agonist on the liver. Since elevated LDL cholesterol levels and qualitatively altered lipoproteins enriched in FC are both associated with increased coronary risk, the improvement noted in these parameters after tamoxifen should allay to some degree anxiety about its use with regard to cardiovascular risk. © 1990 by The Endocrine Society.