Hormone replacement therapy and atherosclerosis—postmenopausal women and HRT: the fallen myth of the cardiovascular protective effects of hormone replacement therapy Emilio H. Moriguchi * , Jose ´ Luiz C. Vieira WHO/PAHO Collaborating Center for Prevention of Chronic Diseases Associated to Ageing, Pontifical Catholic University of Rio Grande do Sul,Porto Alegre, RS, Brazil Keywords: Hormone replacement therapy; Atherosclerosis; Coronary heart disease; Cardiovascular prevention The marked sex difference in risk of coronary heart disease (CHD) has been noted for many decades and was the impetus for early animal experiments of estrogen effects on atherosclerosis [1]. These studies demonstrated that estrogen could prevent atherogenesis in animal models for atherosclerosis. Moreover, in the last 2 decades of the last century, many observational studies have found lower prevalence of CHD both in women taking estrogen or estrogen/progestin than in women not receiving postmenopausal hormone replacement therapy (HRT) [2]. These results, besides the estrogen beneficial changes in intermediate markers such as lipid parameters [3,4], led to a belief that HRT could be an important weapon for preventing CHD. Regardless of those strong experimental, observational and mechanistic evidences, no large clinical trials had been done to evaluate HRT protection against CHD until 5 years ago. Women taking hormone therapy in observational studies differ from non-users in many aspects like general health status, health awareness (they are ‘‘compliant’’ per definition), profile of coronary risk factors or socioeconomic status. Observational data are not convincing as results from randomized placebo-controlled trials, in which randomi- zation hands out known and unknown biases in an even manner. Guiding therapy by mechanistic evidence is also not safe. The legacy of the CAST study has shown us that treating a patophysiologic processes (suppressing ventricular arrhythmia that is associated with sudden death) is not sufficient to warrant better outcome—patients can die with the surrogate outcome apparently corrected [5]. The results of the first large randomized trial evaluating HRT for prevention of CHD were published in 1998. The Heart and Estrogen/Progestin Replacement Study (HERS) 0531-5131/ D 2003 Elsevier B.V. All rights reserved. doi:10.1016/S0531-5131(03)01732-1 * Corresponding author. Tel.: +55-51-99012422; fax: +55-51-3315-9323. E-mail address: emoriguc@pucrs.br (E.H. Moriguchi). www.ics-elsevier.com International Congress Series 1262 (2004) 519 – 522