Venous Thrombosis and Conjugated Equine Estrogen in Women Without a Uterus

Leiden University, Leyden, South Holland, Netherlands
Archives of Internal Medicine (Impact Factor: 17.33). 05/2006; 166(7):772-80. DOI: 10.1001/archinte.166.7.772
Source: PubMed


Postmenopausal hormone therapy has been associated with a 2- to 3-fold increased risk of venous thromboembolism (VT) (including deep vein thrombosis and pulmonary embolism) in observational studies and secondary prevention clinical trials. Clinical trial data on the effects of estrogen alone on VT are limited.
The Women's Health Initiative estrogen trial enrolled 10 739 women aged 50 to 79 years without a uterus. Participants were randomly assigned to receive conjugated equine estrogen (0.625 mg/d) or placebo.
During a mean of 7.1 years, VT occurred in 111 women randomly assigned to receive estrogen (3.0 per 1000 person-years) and 86 randomly assigned to receive placebo (2.2 per 1000 person-years; hazard ratio, 1.32; 95% confidence interval, 0.99-1.75). Deep venous thrombosis was reported in 85 women randomly assigned to receive estrogen (2.3 per 1000 person-years) and 59 randomly assigned to receive placebo (1.5 per 1000 person-years; hazard ratio, 1.47; 95% confidence interval, 1.06-2.06). The VT risk was highest in the first 2 years. There were no significant interactions between estrogen use and age, body mass index, or most other VT risk factors. Comparison of Women's Health Initiative VT findings for estrogen and previous Women's Health Initiative findings for estrogen plus progestin showed that the hazard ratios for estrogen plus progestin were significantly higher than those for estrogen alone (P = .03), even after adjusting for VT risk factors.
An early increased VT risk is associated with use of estrogen, especially within the first 2 years, but this risk increase is less than that for estrogen plus progestin.

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Available from: Paul F Bray, Sep 02, 2014
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    • "Smoking itself is a weak risk factor for incident VT (Blondon et al, 2013). Therefore, our results suggest that smoking is not an important factor for the development VT in users of oral HT, similarly to those of the WHI clinical trial (Cushman et al, 2004; Curb et al, 2006). Our findings contrast with the observed synergistic effect of smoking and OC on the risk of VT (Pomp et al, 2008). "

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    • "Regarding pulmonary embolism, compared with those in the placebo group, women in the estrogen–progestin group experienced a statistically significant doubling of risk [15]. Assignment to estrogen alone appeared to raise the risk by 37%; this increase was not statistically significant [19]. No clear effect modification by age or time since menopause was apparent. "
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    • "In some studies, the observed effects were similar for the two preparations for some outcomes , including stroke (Hendrix et al., 2006; Wassertheil- Smoller et al., 2003) and hip fracture (Cauley et al., 2003; Jackson et al., 2006), whereas E þ P effects were unfavorable compared to those for E-alone for other outcomes, including coronary heart disease (CHD) (Hsia et al., 2006; Manson et al., 2003), breast cancer (Chlebowski et al., 2003; Stefanick et al., 2006), and venous thromboembolism (VT) (Curb et al., 2006; Cushman et al., 2004). The spectrum of biological changes induced by hormone therapy in relation to the outcome effects has remained unclear. "
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