From the Guidelines
Hormone replacement therapy (HRT) increases the risk of blood clots, with oral estrogen formulations carrying the highest risk, and transdermal estrogen being a safer option for women with high baseline risk for blood clots. The degree of risk varies based on the type of HRT used, with oral estrogen formulations increasing blood clot risk by 2-4 times compared to non-users 1. Transdermal estrogen (patches, gels) carries significantly lower risk, with minimal to no increased clotting risk compared to non-users. The addition of progestins, especially synthetic ones like medroxyprogesterone acetate, may further increase clot risk.
Key Points to Consider
- The absolute risk remains relatively small for most women, with approximately 1-2 additional cases of venous thromboembolism per 1,000 women per year using oral HRT.
- Risk is highest in the first year of treatment and in women with other risk factors such as obesity, smoking, personal or family history of clots, or certain genetic conditions.
- For women with high baseline risk for blood clots, transdermal estrogen is the safer option if HRT is needed, as it does not increase VTE risk in healthy women, even those with prothrombotic mutations or high body mass index 1.
- The increased risk occurs because oral estrogen undergoes first-pass metabolism in the liver, altering clotting factor production, while transdermal delivery bypasses this effect by delivering hormones directly into the bloodstream.
Clinical Recommendations
- When considering HRT for women with high baseline risk for blood clots, transdermal estrogen should be considered as the initial therapy due to its lower VTE risk compared to oral estrogen-progestin preparations 1.
- Women with a history of blood clots or those at high risk for blood clots should be closely monitored while on HRT, and alternative treatments should be considered if possible.
- The benefits and risks of HRT should be carefully weighed for each individual patient, taking into account their medical history, risk factors, and personal preferences.
From the Research
Risk of Blood Clots with HRT
The risk of blood clots, also known as venous thromboembolism (VTE), is a significant concern for postmenopausal women undergoing hormone replacement therapy (HRT). Several studies have investigated this risk, focusing on the route of estrogen administration and the type of progestogen used.
Factors Influencing VTE Risk
- The route of estrogen administration: Oral estrogens have been shown to increase the risk of VTE, whereas transdermal estrogens have a minimal effect on hemostasis and may be safer 2, 3, 4.
- The type of progestogen: Medroxyprogesterone acetate has been associated with a higher VTE risk, while micronized progesterone appears to be safer 2, 5.
- Estrogen dosage: Higher doses of oral estrogen have been linked to an increased risk of VTE 4.
- Patient characteristics: Increasing age, weight, and the presence of thrombogenic mutations can further promote HRT's VTE risk 2, 6.
Comparison of Oral and Transdermal Estrogen
- Oral estrogens: Associated with an increased risk of VTE, particularly during the first year of use 2, 3, 4.
- Transdermal estrogens: Not associated with an increased risk of VTE, even in women with a history of VTE 3, 4.
- Transdermal estrogen combined with progesterone: Considered a safer option, especially for women at high risk for VTE 2, 5.
Key Findings
- The risk of VTE is higher with oral estrogen use, especially during the first year of treatment 2, 4.
- Transdermal estrogens may improve the benefit/risk ratio of postmenopausal hormone therapy and should be considered as a safer option 3.
- The choice of progestogen can modulate the estrogen-related VTE risk, with micronized progesterone being a safer option 5.