Canonico et al. carried out a systematic review and meta-analysis of both observational studies and randomised clinical trials to assess the overall risk of venous thromboembolism (VTE) in relation to hormone replacement therapy (HRT). The principal findings from the meta-analysis were that current use of oral estrogen increases the risk of VTE by 2-3 times and the elevation is much higher within the first year of treatment with HRT. In addition, a combination of oral estrogen and increased body-mass index was found to further increase in risk of VTE. The risk of VTE did not appear to be different when comparing unopposed and opposed oral estrogen therapy. The combined analysis of observational studies indicated that was no significant increase in the risk of VTE with the use of transdermal estrogen.