Primary Prevention of Cardiovascular Disease With HRT

Kate Maclaran; John C Stevenson


Women's Health. 2012;8(1):63-74. 

In This Article

Venous Thromboembolism

It is well recognized that HRT is associated with increased risk of VTE; although, as with stroke, there is increasing evidence that the route of administration and estrogen dose can influence risk. Meta-analyses have shown that oral HRT is associated with increased risk of VTE (OR: 2.5, 95% CI: 1.9–3.4);[60] however, there is no significant increase with transdermal therapy (OR: 1.2, 95% CI: 0.9–1.7). The risk with oral therapy is highest in the first year, declines thereafter and returns to that of never users on discontinuation.

Older studies failed to demonstrate a dose-dependent effect on VTE;[61,62] however, more recent data did find an association between oral estrogen dose and risk of VTE.[63] Of note, there was no association between estrogen dose and VTE risk when administered transdermally.

Data regarding thrombotic risk with estrogen alone compared with combination therapy remains contradictory, with one meta-analysis showing no significant difference between opposed and unopposed therapy,[60] and another reporting a twofold increase in risk in those using combination therapy.[57] A recent prospective cohort study examined the risk of thrombosis in 80,308 postmenopausal women in which there were 549 fatal and nonfatal events. They found that oral, but not transdermal, therapy was associated with increased risk of VTE and also that the thrombotic risk differed depending on the progestogen used. There was no increased risk with micronized progesterone, pregnane or nortestosterone derivatives, but significantly increased risk with norpregnane derivatives (OR: 1.8, 95% CI: 1.2–2.7).[64] Further data on the effects of progestogens are needed.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.