TAMOXIFEN AND TOREMIFENE LOWER SERUM-CHOLESTEROL BY INHIBITION OF DELTA(8)-CHOLESTENOL CONVERSION TO LATHOSTEROL IN WOMEN WITH BREAST-CANCER

被引:89
作者
GYLLING, H
PYRHONEN, S
MANTYLA, E
MAENPAA, H
KANGAS, L
MIETTINEN, TA
机构
[1] UNIV HELSINKI, DEPT MED, DIV INTERNAL MED & ONCOL, SF-00290 HELSINKI, FINLAND
[2] ORION CORP, ORION FARMOS, TURKU, FINLAND
关键词
D O I
10.1200/JCO.1995.13.12.2900
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: Long-term effects of tamoxifen and toremifene, a new antiestrogen that closely resembles tamoxifen, were investigated on serum lipids and cholesterol metabolism. Patients and Methods: The study group consisted of 24 postmenopausal Finnish women with advanced breast cancer from an international multicenter study of 415 patients. Cholesterol metabolism was evaluated by measuring the cholesterol precursor (Delta(8)-cholestenol, desmosterol, and lathosterol, reflecting cholesterol synthesis) and plant sterol (markers of cholesterol absorption) and cholestanol levels by gas-liquid chromatography. Results: Tamoxifen and toremifene lowered significantly serum low-density lipoprotein (LDL) cholesterol levels after 12 months of treatment by 16% and 15%, with no change in high-density lipoprotein (HDL) cholesterol or serum triglyceride levels, Serum Delta(8)-cholestenol was increased 40- and 55-fold during toremifene and tamoxifen treatment, respectively, while the increase of desmosterol less than doubled and was lacking for lathosterol by toremifene. Plant sterols and cholestanol were only inconsistently increased in serum. Conclusion: Tamoxifen and toremifene inhibit the conversion of Delta(8)-cholestenol to lathosterol so that serum total and LDL cholesterol levels ore lowered by downregulation of cholesterol synthesis. Thus, inhibition of the Delta(8)-isomerase may be the major hypolipidemic effect of these agents, Reduced risk of coronary artery disease will probably occur also during long-term toremifene treatment, because the drug reduces cholesterol and its synthesis, similarly to tamoxifen. (C) 1995 by American Society of Clinical Oncology.
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页码:2900 / 2905
页数:6
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