Estrogen and Venous Thromboembolism -- More Details

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Summary and Comment

Estrogen and Venous Thromboembolism -- More Details

Older women, women with high BMIs, and women with factor V Leiden mutations might be at high risk for hormone-therapy complications.

The association of estrogen therapy with increased risk for venous thromboembolism (VTE) has been supported most recently by data from the Women's Health Initiative (WHI; Journal Watch Jul 26 2002). Results from two studies, including a further analysis from the WHI, extend these findings.

In the WHI, 16,608 postmenopausal women (age range, 50-79) were randomized to daily hormone therapy (conjugated equine estrogen [0.625 mg] plus medroxyprogesterone [2.5 mg]) or placebo. During nearly 6 years of follow-up, VTE occurred in 167 women who received HT and in 76 who received placebo (hazard ratio, 2.1). VTE risk with HT increased as age and body-mass index increased. Among women with factor V Leiden mutations, HT conferred higher VTE risk (HR, 6.7) than it did among those without such mutations, but among women with other prothrombotic genetic variants (e.g., factor V HR2, factor XIII mutation), HT was not associated with higher risk.

In a population-based observational study, a managed care database was used to evaluate risk for VTE among users of conjugated equine estrogen (CEE) and esterified estrogen (EE). The researchers identified 586 women (age range, 30-89) who experienced first episodes of VTE and 2268 controls (matched for age and hypertension status). Compared with women who used no HT, CEE users exhibited a significantly increased risk for VTE (odds ratio, 1.6), but EE users did not (OR, 0.9). CEE users had a significantly higher risk than did EE users (OR, 1.8).

Comment: These data extend our understanding of which patients have especially high risk for adverse events during therapy with conjugated equine estrogen therapy. The apparent lack of risk for VT among users of EE requires confirmation in prospective controlled studies before EE's clinical use can be recommended, especially given the widespread concerns about estrogens as a class that were raised by WHI findings.

— Thomas L. Schwenk, MD

Published in Journal Watch General Medicine October 26, 2004