Further evidence for promoting transdermal estrogens in the management of postmenopausal symptoms

Abstract

After a use in permanent increase until the end of the 90’ [1], prescription rates of postmenopausal hormone therapy (HT) have dramatically reduced in the wake of the findings from Women’s Health Initiative (WHI) clinical trials [2]. Yet, HT remains the most effective treatment to correct menopausal symptoms and therefore, many women are still prescribed this treatment worldwide. Nevertheless, medical guidelines have been modified and now recommend that only women suffering from moderate to severe symptoms be prescribe the lowest effective dose for the shortest possible duration [3]. In this context, middle-aged postmenopausal women represent the main candidate for this treatment and cardiovascular disease, including venous thromboembolism and stroke, becomes the major harmful effect of short-term oral HT. By contrast, short term use of HT little affects the risk of breast cancer and could be beneficial for coronary heart disease (CHD) among recently postmenopausal women [4]. In addition, HT reduces the risk of colorectal cancer and osteoporotic fractures [2]. Based on these observations, reducing the excess risk of venous thromboembolism appears as a relevant strategy to improve the benefit/risk profile of HT. In 2003, the EStrogen and THromboEmbolism Risk (ESTHER) study, a French case/control study, showed for the first time a differential association of oral and transdermal estrogens with the risk of venous thromboembolism. Contrary to oral estrogens, transdermal estrogens were not associated with an increased risk of venous thromboembolism [5]. Few years later, final results of the ESTHER study and the E3N French cohort study confirmed the potential safety of transdermal estrogens with respect to thrombotic risk [6, 7]. Recently, a large cohort study set-up in a United-Kingdom health insurance database provided further evidence for a better thrombotic profile of transdermal estrogens as compared to oral estrogens [8].