Menopause: The Journal of The North American Menopause Society Vol. 18, No. 5, pp. 488/493 DOI: 10.1097/gme.0b013e3181f9f7c3 * 2011 by The North American Menopause Society Hormone therapy and recurrence of venous thromboembolism among postmenopausal women Vale ´rie Olie ´, MSc, 1,2 Genevie `ve Plu-Bureau, MD, 1,3,4 Jacqueline Conard, PhD, 3,4 Marie-He ´le `ne Horellou, MD, 3,4 Marianne Canonico, PhD, 1,2 and Pierre-Yves Scarabin, MD 1,2 Abstract Objectives: The route of estrogen administration is an important determinant of the risk of the first venous thromboembolism (VTE) event in postmenopausal women using hormone therapy (HT). However, the impact of transdermal estrogens on VTE recurrence risk has not been investigated. The aim of our study was to assess the impact of HT by route of estrogen administration on the risk of recurrent VTE. Methods: A total of 1,023 consecutive postmenopausal women aged 45 to 70 years with a confirmed first VTE were recruited from an outpatient clinic of a hemostasis hospital unit between January 2000 and December 2008 and were followed for an average of 79 months after discontinuation of anticoagulation therapy. Results: Recurrent VTE occurred in 77 women (1.1% per year). During the follow-up, 130 women used HT (12.7%), including 103 transdermal estrogen users (10.0%) and 10 oral estrogen users (1.0%). After adjustment for potential confounders, there was no significant association between recurrent VTE and use of transdermal estrogens (hazard ratio, 1.0; 95% CI, 0.4-2.4), with the nonusers as a reference group. In contrast, women using oral estro- gens had an increased risk of recurrent VTE (hazard ratio, 6.4; 95% CI, 1.5-27.3). Consistently, no subgroup of women had evidence of a risk of recurrent VTE with transdermal HT that significantly differed from that observed for all women. Conclusions: Oral but not transdermal estrogens are associated with a higher risk of recurrent VTE among postmenopausal women. This result provides further epidemiological evidence that transdermal estrogens may be safe with respect to VTE risk. Key Words: Hormone therapy Y Venous thromboembolism Y Transdermal estrogens Y Recurrence. V enous thromboembolism (VTE) is a common disease affecting 1.5 per 1,000 persons every year, with a potential fatal outcome in approximately 5% to 10% of cases. 1,2 Moreover, individuals who experience a first event are at high risk for a recurrent VTE during many years after discontinuation of anticoagulant treatment. 3 Although several clinical risk factors have already been identified as risk factors for recurrent VTE, 4,5 data regarding the influence of hormone use on VTE recurrence are scarce. Despite an important decrease in hormone therapy (HT) use since the publication of the Women Health Initiative trials results, 6,7 many postmen- opausal women experiencing severe climacteric symptoms remain eligible for this treatment, which is the most effective for hot flashes. Because oral estrogen therapy is contra- indicated in postmenopausal women with a personal history of VTE, it is important to identify a safe therapy to counter- act severe climacteric symptoms in women at high risk of recurrent VTE. Although there is evidence that oral estrogen therapy increases the risk of VTE among postmenopausal women, 6,7 recent epidemiological data suggest that trans- dermal estrogen use does not expose a woman to an excess risk of a first VTE event. 8,9 Transdermal estrogens are widely used in Europe, especially in France, but the impact of this route of administration on the risk of recurrent VTE has not been investigated yet. In this context, we set up the MEVE (Menopause, Estrogen, and Veins) cohort study aimed to evaluate the safety of trans- dermal estrogens among postmenopausal women with a per- sonal history of VTE. METHODS Participants and study design Between January 1, 2000, and December 31, 2008, all postmenopausal women aged 45 to 70 who came to the out- patient clinic of the hemostasis unit in the Hotel-Dieu Hospital because of a first objectively confirmed episode of Received July 16, 2010; revised and accepted August 26, 2010. From the 1 Hormones and Cardiovascular disease team, CEPH Centre for research in Epidemiology and Population Health, U1018, Inserm, F94807, Villejuit, France; 2 Universite ´ Paris-Sud, UMRS-1018, F94807 Villejuit, France; 3 Biological Hematology Department, Hotel-Dieu Hos- pital, Paris, France; and 4 Universite ´ Paris Descartes, Paris, France. Funding/support: This study was partially supported by a grant from Pierre Fabre Sante ´. The sponsor had no role in the design and conduct of this study (collection, management, analysis, and interpretation of the data). Financial disclosure/conflicts of interest: None reported. Address correspondence to: Vale ´rie Olie ´, MSc, Hormones and Cardio- vascular disease team, CEPH Centre for research in Epidemiology and Public Health, U1018, Inserm, 16 avenue Paul Vaillant Coufurier, F94807 Villejuit, France. E-mail: valerie.olie@inserm.fr 488 Menopause, Vol. 18, No. 5, 2011 Copyright © 2011 The North American Menopause Society. Unauthorized reproduction of this article is prohibited.