Effects of hormone replacement therapy on C-reactive protein levels in healthy postmenopausal women: comparison between oral and transdermal administration of estrogen

Abstract

C-reactive protein, an acute phase reactant, is a sensitive marker of inflammation ( 1 Ridker P.M. Haughie P. Prospective studies of C-reactive protein as a risk factor for cardiovascular disease. J Invest Med. 1988; 46: 391-395 Google Scholar ). High plasma levels of C-reactive protein are associated with an increased risk of myocardial infarction and stroke among apparently healthy subjects, as well as among those at higher risk because of age, smoking, or previous coronary artery disease, and are useful in cardiovascular risk stratification ( 2 Ridker P.M. Cushman M. Stampher M.J. et al. Inflammation, aspirin, and risks of cardiovascular disease in apparently healthy men. N Engl J Med. 1997; 336: 973-979 Crossref PubMed Scopus (4851) Google Scholar , 3 Ridker P.M. Buring J.E. Shih J. et al. Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women. Circulation. 1998; 98: 731-733 Crossref PubMed Scopus (1444) Google Scholar , 4 Tracy R.P. Lemaitre R.N. Psaty B.M. et al. Relationship of C-reactive protein to risk of cardiovascular disease in the elderly results from the Cardiovascular Health Study and the Rural Health Promotion Project. Arterioscler Thromb Vasc Biol. 1997; 17: 1121-1127 Crossref PubMed Scopus (765) Google Scholar , 5 Kuller L.H. Tracy R.P. Shaten J. et al. MRFIT Research GroupRelationship of C-reactive protein and coronary heart disease in the MRFIT nested case-control study. Am J Epidemiol. 1996; 144: 537-547 Crossref PubMed Scopus (989) Google Scholar , 6 Haverkate F. Thompson S.G. Pyke S.D.M. et al. for the European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group. Production of C-reactive protein and risk of coronary events in stable and unstable angina. Lancet. 1997; 349: 462-466 Abstract Full Text Full Text PDF PubMed Scopus (1403) Google Scholar , 7 Ridker P.M. Rifai N. Pfeffer M.A. et al. for the Cholesterol And Recurrent Events (CARE) Investigators. Inflammation, pravastatin, and the risk of coronary events after myocardial infarction in patients with average cholesterol levels. Circulation. 1998; 98: 839-844 Crossref PubMed Scopus (1273) Google Scholar , 8 Liuzzo G. Biasucci L.M. Gallimore J.R. et al. The prognostic value of C-reactive protein and serum amyloid A protein in severe unstable angina. N Engl J Med. 1994; 331: 417-424 Crossref PubMed Scopus (2088) Google Scholar , 9 Ridker P.M. Glynn R.J. Hennekens C.H. C-reactive protein adds to the predictive value of total and HDL cholesterol in determining risk of first myocardial infarction. Circulation. 1998; 97: 2007-2011 Crossref PubMed Scopus (882) Google Scholar , 10 Ridker P.M. Hennekens C.H. Buring J.E. Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med. 2000; 342: 836-843 Crossref PubMed Scopus (4968) Google Scholar ). Moreover, statins have been shown to lower C-reactive protein levels ( 11 Ridker P.M. Rifai N. Pfeffer M.A. et al. Long-term effects of pravastatin on plasma concentration of C-reactive protein. The Cholesterol And Recurrent Events (CARE) Investigators. Circulation. 1999; 100: 230-235 Crossref PubMed Scopus (1398) Google Scholar , 12 Ridker P.M. Rifai N. Clearfield M. et al. Air Force/Texas Coronary Atherosclerosis Prevention Study Investigators. Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events. N Engl J Med. 2001; 344: 2016-2018 Crossref PubMed Scopus (1460) Google Scholar ). In contrast, oral hormone replacement therapy appears to increase C-reactive protein levels ( 13 Cushman M. Legault C. Barrett-Connor E. et al. Effect of postmenopausal hormones on inflammation-sensitive proteins the Postmenopausal Estrogen/Progestin Interventions (PEPI) Study. Circulation. 1999; 100: 717-722 Crossref PubMed Scopus (621) Google Scholar , 14 Ridker P.M. Hennekens C.H. Rifai N. et al. Hormone replacement therapy and increased plasma concentration of C-reactive protein. Circulation. 1999; 100: 713-716 Crossref PubMed Scopus (424) Google Scholar , 15 Cushman M. Meilahn E.N. Psaty B.M. et al. Hormone replacement therapy, inflammation, and hemostasis in elderly women. Arterioscler Thromb Vasc Biol. 1999; 19: 893-899 Crossref PubMed Scopus (220) Google Scholar ). However, the effects of different hormonal preparations and their routes of administration are not known. We therefore compared the effects of oral estrogen and transdermal estradiol on C-reactive protein plasma levels in healthy postmenopausal women.