Hormone therapy and risk of venous thromboembolism among postmenopausal women

Despite a decrease in the use of postmenopausal hormone therapy (HT) over the last decade, many women are still prescribed this treatment, as it remains the most effective means of counteracting climacteric symptoms. Its use declined when it was shown that HT increases the risk of breast cancer, stroke and venous thromboembolism (VTE). Nevertheless, that benefit/risk ratio was established among women using oral estrogens alone or combined with a specific progestogen and it cannot necessarily be extrapolated to other HTs. Oral estrogens increase the risk of VTE especially during the first year of treatment and past users revert to a similar risk as women who have never used them. There is now growing evidence that VTE risk among HT users strongly depends on the route of administration. Indeed, transdermal estrogens, unlike oral estrogens, are not associated with an increased VTE risk and biological data support this difference between oral and transdermal estrogens. In addition, transdermal estrogens may not confer additional risk in women at high risk of VTE. Significant differences in thrombotic risk between HT preparations also relate to the concomitant progestogen. Studies have consistently shown that VTE risk is higher among users of combined estrogens plus progestogens than among users of estrogens alone. With respect to the different pharmacological classes of progestogens, two observational studies found that norpregnane derivatives are associated with an increased VTE risk, whereas micronized progesterone may be safe with respect to thrombotic risk. In conclusion, transdermal estrogens alone or combined with micronized progesterone may represent the safest alternative for women who require HT.