Is it safe for a woman to take Hormone Replacement Therapy (HRT) if she had one unprovoked Pulmonary Embolism (PE) 3 years ago?

From the Guidelines

Taking hormone replacement therapy (HRT) in 2025 is not recommended for a woman who experienced an unprovoked pulmonary embolism (PE) three years ago, due to the increased risk of recurrent blood clots associated with HRT, especially formulations containing estrogen. This recommendation is based on the understanding that an unprovoked PE indicates an underlying thrombophilic tendency, and adding hormonal therapy could further elevate this risk 1. The risk of venous thromboembolism (VTE) is significantly increased in women with a history of unprovoked PE, and HRT has been shown to further increase this risk 1.

If menopausal symptom management is necessary, non-hormonal options should be considered first, such as:

• Selective serotonin reuptake inhibitors (SSRIs) like paroxetine or escitalopram for hot flashes
• Vaginal moisturizers for vaginal dryness
• Lifestyle modifications including regular exercise and avoiding triggers. In rare cases where severe menopausal symptoms significantly impact quality of life and other treatments have failed, transdermal estrogen (patches or gels) with micronized progesterone might be considered, but only after thorough consultation with both a hematologist and gynecologist, and with ongoing anticoagulation therapy 1. The risk-benefit analysis must be individualized, considering the severity of menopausal symptoms against the substantial risk of potentially life-threatening recurrent blood clots.

Key factors to consider in this decision include:

• The increased risk of VTE associated with HRT, especially in women with a history of unprovoked PE
• The potential benefits of HRT in managing menopausal symptoms
• The availability of alternative, non-hormonal treatments for menopausal symptoms
• The need for ongoing anticoagulation therapy to mitigate the risk of recurrent blood clots. Ultimately, the decision to use HRT in a woman with a history of unprovoked PE should be made on a case-by-case basis, taking into account the individual's unique medical history, risk factors, and preferences 1.

From the Research

HRT and Venous Thromboembolism Risk

• The risk of venous thromboembolism (VTE) is increased in women taking hormone replacement therapy (HRT), although the absolute risk is small 2.
• The risk of VTE appears to be greatest soon after the initiation of HRT and returns to the baseline level of risk of non-HRT users after discontinuation 2.
• Women who have previously suffered a VTE have an increased risk of recurrence on HRT, with a study showing an incidence of VTE of 10.7% in the HRT group and 2.3% in the placebo group 3.

Route of Estrogen Administration and VTE Risk

• Transdermal HRT may not be as prothrombotic as oral HRT, although this has not been evaluated in randomized clinical trials 2.
• A meta-analysis found that oral but not transdermal estrogen-only preparations increased VTE risk, with a relative risk (RR) of 1.48 (95% CI 1.39-1.58) for oral preparations and RR 0.97 (95% CI 0.87-1.09) for transdermal preparations 4.

Progestogens and VTE Risk

• Progestogens may modulate the estrogen-related VTE risk, with some progestogens associated with increased VTE risk 4.
• A study found that micronized progesterone did not increase VTE risk in women using transdermal estrogen, whereas norpregnane derivatives were associated with increased VTE risk (RR 2.42,95% CI 1.84-3.18) 4.

Recurrence Risk in Women with Previous VTE

• Women who had their first VTE while using estrogens have a low risk of recurrent VTE, with a cumulative probability of recurrence of 1% (95% CI, 0-2) after 1 year and 6% (95% CI, 3-9) after 5 years 5.
• The adjusted relative risk of recurrent VTE was 0.4 (95% CI, 0.2-0.8) in estrogen users compared with non-users 5.