ABSTRACT
Introduction 454 What is the risk for venous thromboembolism with
different types of hormone replacement therapy? 455 What is the effect of the duration of hormone
replacement therapy on the risk for venous thromboembolism? 456
What is the mechanism for the association between hormone replacement therapy and venous thromboembolism? 457
What is the effect of thrombophilia on the risk for venous thromboembolism in hormone replacement therapy users? 458
Clinical management scenarios 459 Future research 462 References 462
The past decade has witnessed remarkable changes in our understanding of the risks and benefits of hormone replacement therapy (HRT), which is defined as an estrogen formulation with or without a progestin and is usually administered in an oral or transdermal (patch) form. Observational studies performed in the 1990s suggested that users of HRT had a two to three times greater risk of developing venous thromboembolism (VTE), which includes deep vein thrombosis and pulmonary embolism, than nonusers of HRT.1-7 These findings were subsequently confirmed in randomized placebo-controlled trials, the most important of which were the Hormone Replacement Therapy Study (HERS) and the Women’s Health Initiative (WHI) study.8,9
Based on the findings from these trials, HRT is no longer recommended for the primary or secondary prevention of cardiovascular disease or osteoporosis by gynecologic groups and other experts.10-13 However, HRT remains an
recommended for short-term (2 year) use in such patients.14 The scope of this clinical problem is considerable, as 25 percent of women will have menopausal symptoms for 1 year or longer and in 5 percent of such women these symptoms can be debilitating.15 Although there are nonhormonal treatments available for menopausal symptoms, such as clonidine or venlafaxine (an antidepressant), these agents require further investigation in clinical trials to assess efficacy compared with HRT. Consequently, it is likely that HRT will continue, at least for the foreseeable future, as an important and widely used treatment for menopausal women, although for short-time use.
