What is the risk of venous thromboembolism with hormone therapy?

• A. Increased risk, especially with oral estrogens.
• B. Decreased risk
• C. No risk
• D. Only risk with transdermal routes

Answer: (A)

Estrogen-containing hormone therapy increases the risk of venous thromboembolism, and the risk varies by how the hormone is given. Oral estrogens raise VTE risk more than nonoral options because they go through the liver first (hepatic first-pass metabolism), which increases production of coagulation factors and shifts the balance toward clotting. Transdermal estrogens bypass this first-pass effect, producing a smaller impact on the coagulation system, so the VTE risk is substantially lower with the transdermal route. The overall risk is still higher than in non-users, especially with older age, higher body weight, prior VTE, smoking, or higher estrogen doses, but the principal idea is that VTE risk is increased with hormone therapy, particularly with oral estrogens.