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• W2044512463 abstract "Epidemiologic studies support a primary preventative effect of estrogen on cardiovascular risk reduction in otherwise healthy postmenopausal women. 1 Stampfer M.J. Colditz G.A. Willett W.C. Manson J.E. Rosner B. Speizer F.E. Hennekens C.H. Postmenopausal estrogen therapy and cardiovascular disease ten-year follow-up from the Nurses’ Health Study. N Engl J Med. 1991; 325: 756-762 Crossref PubMed Scopus (1998) Google Scholar The mechanisms of benefit are likely multifactorial, including favorable effects on lipoprotein levels and vascular homeostasis. Studies of vascular effects of estrogen in men have been conflicting, with 1 group finding no effect of intracoronary infusion of 17β-estradiol on acetylcholine-stimulated coronary dynamics 2 Collins P. Rosano G.M.C. Sarrel P.M. Ulrich L. Adamopoulos S. Beale C.M. McNeill J.G. Poole-Wilson P.A. 17-beta-estradiol attenuates acetylcholine-induced coronary arterial constriction in women but not men with coronary heart disease. Circulation. 1995; 92: 24-30 Crossref PubMed Scopus (489) Google Scholar and another group showing postestrogen improvement in coronary endothelium-dependent responsiveness. 3 Reis S.E. Holubkov R. Zell K.A. Smith A.J. Cohen H.A. Feldman M.D. Blumenthal R.S. Estrogen acutely abolishes abnormal cold-induced coronary constriction in men. Chest. 1998; 114: 1556-1561 Crossref PubMed Scopus (21) Google Scholar , 4 Reis S.E. Bhoopalam V. Zell K.A. Counihan P.J. Smith A.J. Pham S. Murali S. Conjugated estrogens acutely abolish abnormal cold-induced coronary vasoconstriction in male cardiac allografts. Circulation. 1998; 97: 23-25 Crossref PubMed Scopus (28) Google Scholar Two groups from Australia reported vascular effects of chronic estrogen use in male-to-female transsexuals on estrogen preparations, with greater flow-mediated brachial artery dilator responses during postischemic hyperemia and greater dilator responses to nitroglycerin than in control men. 5 McCrohon J.A. Walters W.A. Robinson J.T. McCredie R.J. Turner L. Adams M.R. Handelsman D.J. Celermajer D.S. Arterial reactivity is enhanced in genetic males taking high dose estrogens. J Am Coll Cardiol. 1997; 29: 1432-1436 Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar , 6 New G. Timmins K.L. Duffy S.J. Tran B.T. O’Brien R.C. Harper R.W. Meredith I.T. Long-term estrogen therapy improves vascular function in male to female transsexuals. J Am Coll Cardiol. 1997; 29: 1437-1444 Abstract Full Text Full Text PDF PubMed Scopus (141) Google Scholar This vascular effect of estrogen may in part relate to increased nitric oxide activity: In the pig, estrogen treatment increases nitric oxide synthase activity in male animals, although longer treatment is required for this effect than in female animals. 7 Weiner C.P. Lizasoain I. Baylis S.A. Knowles R.G. Charles I.G. Moncada S. Induction of calcium-dependent nitric oxide synthase activity by sex hormones. Proc Natl Acad Sci USA. 1994; 91: 5212-5216 Crossref PubMed Scopus (1086) Google Scholar Further, estrogen has been shown to have lipoprotein effects in men similar to those seen in women on hormone replacement therapy, with reduction in low-density lipoprotein (LDL) cholesterol levels and increases in high-density lipoprotein (HDL) cholesterol levels. 8 Coronary Drug Project Research GroupThe Coronary Drug Project. JAMA. 1973; 226: 652-657 Crossref PubMed Scopus (398) Google Scholar , 9 Damewood M.D. Bellantoni J.J. Bachorik P.S. Kimball Jr, A.W. Rock J.A. Exogenous estrogen effect on lipid/lipoprotein cholesterol in transsexual males. J Endocrinol Invest. 1989; 12: 449-454 Crossref PubMed Scopus (22) Google Scholar However, despite the apparent vascular benefit of estrogen demonstrated in male transsexuals, the feminizing effects of estrogen would not be desirable for most men. Raloxifene is a benzothiophene compound classified as a selective estrogen receptor modulator that shares some of the biologic properties of estrogen, including reduction in LDL cholesterol and lipoprotein(a) levels, 10 Walsh B.W. Kuller L.H. Wild R.A. Paul S. Farmer M. Lawrence J.B. Shah A.S. Anderson P.W. Effects of raloxifene on serum lipids and coagulation factors in healthy postmenopausal women. JAMA. 1998; 279: 1445-1451 Crossref PubMed Scopus (674) Google Scholar which in turn may benefit vascular endothelial function through enhanced nitric oxide bioactivity. Therefore, we reasoned that raloxifene therapy could be a reasonable approach to the management of men who are at risk for atherosclerosis." @default.
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• W2044512463 title "Hormonal, lipoprotein, and vascular effects of the selective estrogen receptor modulator raloxifene in hypercholesterolemic men" @default.
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