Hormone therapy and venous thromboembolism among postmenopausal women.

Venous thromboembolism (VTE) is a major harmful effect of hormone therapy (HT) among postmenopausal women. A large variety of HT can be used with significant differences in adverse effects. There is evidence that the VTE risk among HT users depends on the route of estrogen administration. Oral but not transdermal estrogens dose-dependently increase the VTE risk. This difference is supported by biological data. Whereas oral estrogens increase thrombin generation and induce resistance to activated protein C, transdermal estrogens have minimal effect on hemostasis. Past users of oral estrogens have a similar VTE risk to never users. Among users of oral estrogens, the VTE risk is higher within the 1st year of treatment. The combination of oral estrogen use and either obesity or thrombogenic mutations further enhances the VTE risk, whereas transdermal estrogens may not confer additional risk in women at high VTE risk. Significant differences in the VTE risk between HT preparations are also related to the type of concomitant progestogen. The VTE risk is greater in women using medroxyprogesterone acetate than in those receiving other progestins, whereas micronized progesterone appears safe. Based on the current data, transdermal estrogen alone or combined with progesterone could be the safer HT especially in women at high risk for thrombosis.