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Though overall the risk remains low, oral estradiol is associated with increased venous thromboembolism (VTE) risk, whereas transdermal estradiol was not found to be associated with significant increased risk of VTE.7 The reason for the discrepancy is thought to be the result of procoagulant factors being formed as a result of first pass hepatic metabolism for estradiol, a factor that doesnt apply to the transdermal route

Discontinuation rates for the trial were over 50% across all dosage forms, compared to 40% discontinuation in the placebo group