Postmenopausal Hormone Therapy and Risk of Idiopathic Venous Thromboembolism

Abstract

Objective-Oral estrogen therapy increases venous thromboembolism risk among postmenopausal women. Although recent data showed transdermal estrogens may be safe with respect to thrombotic risk, the impact of the route of estrogen administration and concomitant progestogens is not fully established. Methods and Results-We used data from the E3N French prospective cohort of women born between 1925 and 1950 and biennially followed by questionnaires from 1990. Study population consisted of 80 308 postmenopausal women (average follow-up: 10.1 years) including 549 documented idiopathic first venous thromboembolism. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional models. Compared to never-users, past-users of hormone therapy had no increased thrombotic risk (HRϭ1.1; 95% CI: 0.8 to 1.5). Oral not transdermal estrogens were associated with increased thrombotic risk (HRϭ1.7; 95% CI: 1.1 to 2.8 and HRϭ1.1; 95% CI: 0.8 to 1.8; homogeneity: Pϭ0.01). The thrombotic risk significantly differed by concomitant progestogens type (homogeneity: PϽ0.01): there was no significant association with progesterone, pregnanes, and nortestosterones (HRϭ0.9; 95% CI: 0.6 to 1.5, HRϭ1.3; 95% CI: 0.9 to 2.0 and HRϭ1.4; 95% CI: 0.7 to 2.4). However, norpregnanes were associated with increased thrombotic risk (HRϭ1.8; 95% CI: 1.2 to 2.7). Conclusions-In this large study, we found that route of estrogen administration and concomitant progestogens type are 2 important determinants of thrombotic risk among postmenopausal women using hormone therapy. Transdermal estrogens alone or combined with progesterone might be safe with respect to thrombotic risk.

Menopausal hormone therapy and risk of cholecystectomy: a prospective study based on the French E3N cohort

“…27 Hepatobiliary effects of pro gestagens have been explored to a lesser extent than those of estrogens. 26 The E3N cohort study has assessed the impact of menopausal hormone therapy on several outcomes, including breast cancer, 17,28 diabetes onset, 29 thromboembolic events 30 and asthma. 31 Unlike most reports from cohort studies in which exposure to menopausal hormone therapy is assessed only at baseline, data on the use of menopausal hormone therapy and covariates in the E3N cohort were updated every 2 years during the follow-up period.…”

Transdermal hormone replacement therapy with nanostructured medicines

“…Drug carriers enhance the physicochemical properties of drugs, facilitate the penetration of drug molecules into the skin, and improve skin permeation by skin hydration and interaction with skin lipids [32]. Case-control studies have shown a lower risk of venous thromboembolism (VTE) with transdermal estrogen therapy than with the oral administration of estrogen [33]. This finding was confirmed by a cohort study in which transdermal estrogens and the risk of VTE recurrence were not correlated [34].…”

Menopausal hormone therapy: transdermal route of administration

“…W trzech dużych badaniach obserwacyjnych: Estrogen and THromboEmbolism Risk (ESTHER) [5], Etude Epidemiologique de Femmes de la Mutuelle Générale de l'Education Nationale (E3N) [9], UK General Practice Research Database (GPRD) [10] stwierdzono, że w trakcie stosowania MHT drogą przezskórną ryzyko wystąpienia ŻChZZ nie wzrasta. Względne ryzyko powikłań zakrzepowo-zatorowych wynosi 1,2 (95% CI 0,9-1,7) na podstawie metaanalizy 7 badań kliniczno-kontrolnych i 1 pracy kohortowej.…”