Abstract
The results of the Women’s Health Initiative, a randomized controlled primary prevention trial evaluating the risks and benefits of estrogen plus progestin in healthy postmenopausal women, were published in July 2002.1 After a mean of 5.2 years of follow-up, the data and safety monitoring board recommended cessation of the trial because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits. More surprisingly, this trial revealed that hormone replacement therapy (HRT) does not confer vasculoprotection, but even slightly increases the risk of a cardiovascular event early after the start of HRT. These results are quite similar to those reported concerning the effect of HRT in secondary prevention (Heart and Estrogen/Progestin Replacement Study [HERS, 1998]).2 These data clearly conflict with previous clinical observations and experimental studies. Indeed, the clinical rationale for these two large randomized controlled trials was based on the epidemiological evidence that women are protected against the clinical complications of atherosclerosis until menopause. However, this protection, probably attributable to sex hormones, is steadily lost within the years after menopause. In addition, all experimental studies that use animal models of atherosclerosis, by feeding monkeys, swine, or rabbits an atherogenic diet,3 have clearly demonstrated that estrogens prevent fatty streak deposit, the first step of atherosclerosis. More recently, the effect of estrogens was also studied in genetically modified mice, which allowed evaluation of the expression of various genes in physiological or various pathophysiological processes. Mice deficient in apolipoprotein E demonstrate an endogenous hypercholesterolemia on a chow diet and …
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.