Using nested case-control studies, British researches have explored the association between risk of venous thromboembolism and use of different types of hormone replacement therapy. 80 396 women aged 40-79 with a primary diagnosis of venous thromboembolism were matched by age, general practice, and index date to 391 494 female controls. Odds ratios were adjusted for demographic factors, smoking status, alcohol consumption, comorbidities, recent medical events, and other prescribed drugs. They found that 5795 (7.2%) women who had venous thromboembolism and 21 670 (5.5%) controls had been exposed to hormone replacement therapy within 90 days before the index date. Among those women with VTE, 85% had used oral HRT, whilst compared to 78% of controls (adjusted odds ratio 1.58, 95% confidence interval 1.52 to 1.64). The increased odds for VTE were demonstrable for both oestrogen only preparations (OR 1.40, 1.32 to 1.48) and combined preparations (OR 1.73, 1.65 to 1.81). Estradiol alone had a lower risk than the use of conjugated equine oestrogen (for oestrogen only preparations) (OR 0.85, 0.76 to 0.95) and combined preparations (OR 0.83, 0.76 to 0.91). Compared with no exposure, conjugated equine oestrogen with medroxyprogesterone acetate carried the highest risk (OR 2.10, 1.92 to 2.31), and estradiol with dydrogesterone had the lowest risk (OR 1.18, 0.98 to 1.42). Transdermal preparations were not associated with risk of venous thromboembolism, which was consistent for different regimens (overall adjusted OR 0.93, 95% confidence interval 0.87 to 1.01). Transdermal treatment was the safest type of hormone replacement therapy with respect to the risk of venous thromboembolism, but this treatment approach appears to be underused, as oral HRT preparations continue to be the most widely used products. Read more in the BMJ
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