Venous thromboembolism (VTE) is a condition in which clots form in the deep veins and travels in the circulation. People with cancer or undergoing surgery are at a greater risk of VTE, but recent studies also associate the increased risk of VTE with hormone replacement therapy. This study aims to investigate the use of hormone replacement therapy and the risk of VTE.

This is a combination of two nested case-control studies that included a total of 80,396 women aged 40-79 with a primary diagnosis of VTE, along with 391,494 controls. The primary outcome of the study was VTE recorded in general practice, hospital records, or mortality.

A total of 5,795 (7.2%) women who had VTE and 21,670 (5.5%) controls were exposed to hormone replacement therapy within 90 days of the index date. 4,915 (85%) and 16,938 (78%) women of the two groups, respectively, who received oral therapy were at a higher risk of VTE for both estrogen-only and combined preparations. The conjugated equine estrogen with medroxyprogesterone acetate had the highest risk (2.10), and estradiol with dydrogesterone had the lowest risk (1.18). Transdermal preparations were not associated with the risk of VTE. 

The research concluded that transdermal treatment is the safest, and conjugated equine estrogen with medroxyprogesterone acetate is the riskiest type of hormone therapy when considering the risk of VTE.