Cardiovascular risk associated with hormone replacement therapy: some critical questions about the type of estrogen used in most clinical trials

Abstract

Women’s Health Initiative (WHI) Hormone Replacement Trial (HRT) was stopped prematurely in 2002, because of increased risk for stroke, heart disease and thromboembolic events in women taking estrogen plus progestin combination [ [1] Writing Group for the Women’s Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women. Principal results from the Women’s Health Initiative randomized controlled trial. JAMA 2002;288:321–33. Google Scholar ]. Along with Heart and Estrogen/Progestin Replacement study (HERS) and The Estrogen and Atherosclerosis (ERA) trials [ 2 Hulley S Grady D Bush T Heart and Estrogen/progestin Replacement Study (HERS). Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. JAMA. 1998; 280: 605-612 Crossref PubMed Scopus (5615) Google Scholar , 3 Herrington D.M Reboussin D.M et al. Effects of estrogen replacement on the progression of coronary artery atherosclerosis. N. Eng. J. Med. 2000; 343: 522-529 Crossref PubMed Scopus (1139) Google Scholar ], WHI study was the third trial to suggest that HRT was not cardioprotective in postmenopausal women, but may actually increase the risk for thromboembolism and coronary heart disease (CHD). This stands in contrast to clinical and experimental studies which suggest cardioprotection and improvements in vascular reactivity following treatment with estrogens [ [4] Subbiah M.T.R Mechanisms of cardioprotection by estrogens. Proc. Soc. Expt. Biol. Med. 1998; 217: 23-29 Crossref PubMed Scopus (85) Google Scholar ].