Controversies Regarding Postmenopausal Hormone Replacement Therapy for Primary Cardiovascular Disease Prevention in Women

The debate over the safety and benefit of hormone replacement therapy (HRT) in postmenopausal women for primary prevention of cardiovascular disease (CVD) has been ongoing for the past several decades. Observational trials in the 1980s suggested a benefit of HRT for primary CVD prevention. However, randomized controlled trials in the 1990s suggested potential harm. Because of these discrepancies, recommendations from authorities on the usage of postmenopausal HRT have fluctuated. Many believed that the timing of HRT initiation relative to the onset of menopause, also known as the "timing hypothesis," was the factor that could explain the differences among these studies. Some recent investigations have concluded that HRT initiated in postmenopausal women near the onset of menopause confers a cardioprotective benefit, while others simply showed that HRT does not cause harm. Research has expanded to evaluate alternative doses, preparations, routes, and formulations, including selective estrogen receptor modulators, to demonstrate their suitability for this purpose. This article is a review of the major research studies of HRT in postmenopausal women with respect to its safety and efficacy for the primary prevention of CVD.