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Cardiovascular effects of droloxifene, a new selective estrogen receptor modulator, in healthy postmenopausal women.
Herrington, D M; Pusser, B E; Riley, W A; Thuren, T Y; Brosnihan, K B; Brinton, E A; MacLean, D B.
Afiliación
  • Herrington DM; Departments of Internal Medicine/Cardiology, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1045, USA. dherring@wfubmc.edu
Arterioscler Thromb Vasc Biol ; 20(6): 1606-12, 2000 Jun.
Article en En | MEDLINE | ID: mdl-10845879
Selective estrogen receptor modulators, like tamoxifen and related compounds, have mixed estrogen agonistic/antagonistic effects. Tamoxifen may confer significant cardiovascular benefits without the estrogen-associated risks of endometrial and breast cancer. Droloxifene, a structural analogue of tamoxifen, has estrogen agonistic effects on bone and antagonistic effects on endometrial and breast tissue. Its cardiovascular effects in women are unknown. We enrolled 24 healthy postmenopausal women in a randomized, double-blind, 2-period crossover trial comparing the effects of droloxifene (60 mg/d) with conjugated estrogen (0.625 mg/d). Plasma lipids, coagulation and fibrinolytic factors, and brachial flow-mediated vasodilator responses were measured at the beginning and end of each treatment period. Droloxifene and estrogen resulted in 16.6% and 12.0% reductions, respectively, in low density lipoprotein cholesterol (P<0.001) and 13.2% and 9.5% reductions, respectively, in lipoprotein(a) (P<0.05). In contrast, estrogen, but not droloxifene, increased high density lipoprotein (18.5%, P<0.001). Droloxifene also reduced fibrinogen by 17.8% versus a 7.3% reduction with estrogen (P=0.004) but produced no estrogen-like changes in plasminogen, plasminogen activator inhibitor-1, or tissue plasminogen activator. Droloxifene and estrogen produced 36.4% and 27.3% increases, respectively, in flow-mediated vasodilation (percent change from baseline, P<0.05 for both). Droloxifene has estrogen agonistic properties regarding low density lipoprotein and lipoprotein(a) metabolism, certain coagulation factors, and endothelium-dependent vasodilation but, unlike estrogen, has no effect on high density lipoprotein/triglyceride metabolism and the fibrinolytic cascade. It remains unknown whether droloxifene can confer a true cardiovascular benefit.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tamoxifeno / Sistema Cardiovascular / Posmenopausia / Antagonistas de Estrógenos / Estrógenos Tipo de estudio: Clinical_trials Límite: Aged / Female / Humans / Middle aged Idioma: En Revista: Arterioscler Thromb Vasc Biol Asunto de la revista: ANGIOLOGIA Año: 2000 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tamoxifeno / Sistema Cardiovascular / Posmenopausia / Antagonistas de Estrógenos / Estrógenos Tipo de estudio: Clinical_trials Límite: Aged / Female / Humans / Middle aged Idioma: En Revista: Arterioscler Thromb Vasc Biol Asunto de la revista: ANGIOLOGIA Año: 2000 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos