Is estradiol contraindicated in pulmonary embolism (PE)/deep vein thrombosis (DVT)?

From the Guidelines

Estradiol is not absolutely contraindicated in patients with a history of pulmonary embolism (PE) or deep vein thrombosis (DVT), but its use should be carefully considered and typically avoided when possible due to the increased risk of clot formation. Patients with current or history of venous thromboembolism should avoid estrogen-containing medications when possible due to the increased risk of clot formation. Estrogens, including estradiol, increase production of clotting factors and decrease natural anticoagulants, creating a prothrombotic state. For patients requiring hormone therapy who have a history of PE/DVT, non-estrogen alternatives should be considered first. If estrogen is deemed necessary, transdermal estradiol may pose less thrombotic risk than oral formulations since it bypasses first-pass liver metabolism, as suggested by the general understanding of estrogen therapy and thrombosis risk 1. However, any estrogen use in these patients should only occur after careful risk-benefit assessment and with concurrent anticoagulation therapy, as indicated by guidelines for management of venous thromboembolism 1. The absolute risk varies based on individual factors including age, weight, smoking status, and genetic predisposition to clotting disorders.

Some key points to consider in the management of patients with PE/DVT who require hormonal treatment include:

• The risk for recurrent VTE is low following completion of a course of anticoagulant therapy as primary treatment for patients who sustain a thromboembolism in the setting of a transient risk factor, such as estrogen therapy 1.
• A longer course of therapeutic anticoagulation for the primary treatment phase may decrease the risk of recurrent VTE while on treatment, but this is offset by an increased risk for bleeding complications 1.
• Patients with PE/DVT requiring hormonal treatment should consult with both their hematologist and the prescribing physician to develop an appropriate management plan, taking into account the latest guidelines and individual patient factors.
• The most recent guidelines suggest a shorter course (3-6 months) of anticoagulant therapy over a longer duration (6-12 months) for the primary treatment phase, based on moderate certainty in the evidence of effects 1.

From the Research

Estradiol and Pulmonary Embolism/Deep Vein Thrombosis

• The use of estradiol in patients with a history of pulmonary embolism (PE) or deep vein thrombosis (DVT) is a concern due to the potential increased risk of recurrent venous thromboembolism (VTE) 2.
• A study published in 2000 found that hormone replacement therapy (HRT) with estradiol increased the risk of recurrent VTE in women with a history of VTE, with an incidence of 10.7% in the HRT group compared to 2.3% in the placebo group 2.
• However, a more recent study published in 2024 found that vaginal estradiol use was not associated with an increased risk of recurrent VTE in women with prior VTE, with a hazard ratio of 0.75 for current use and 0.83 for prior use 3.
• Another study published in 2014 found that high endogenous concentrations of estradiol were not associated with an increased risk of VTE in women and men in the general population 4.
• A review published in 2010 found that transdermal estrogens may be safer than oral estrogens in terms of VTE risk, with a pooled risk ratio of 1.0 for transdermal estrogens compared to 1.9 for oral estrogens 5.
• A review published in 2020 highlighted the importance of careful evaluation and counseling for women at high-risk of thrombosis who are using estrogen for contraception, pregnancy, or menopausal hormonal therapy 6.

Key Findings

• Estradiol may increase the risk of recurrent VTE in women with a history of VTE 2.
• Vaginal estradiol use may not be associated with an increased risk of recurrent VTE in women with prior VTE 3.
• High endogenous concentrations of estradiol are not associated with an increased risk of VTE in the general population 4.
• Transdermal estrogens may be safer than oral estrogens in terms of VTE risk 5.
• Women at high-risk of thrombosis require careful evaluation and counseling when using estrogen 6.