Risks Associated with Estrogen Therapy in Postmenopausal Women

Thrombophlebitis/Deep Venous Thrombosis

Estrogen-only therapy is associated with a small increase in DVT risk 1, 3
Combined estrogen-progestin therapy carries convincing evidence of a small increased risk for DVT and pulmonary embolism 2

Unopposed estrogen therapy dramatically increases endometrial cancer risk, which is precisely why progestin must be added for women with an intact uterus 2, 3, 4
Unopposed estrogen significantly increases endometrial cancer risk (RR 2.3, 95% CI 2.1-2.5) 4
Risk escalates dramatically with duration: relative risk reaches 9.5 after 10 years of unopposed estrogen use 4
The elevated risk persists for at least 5 years after discontinuation 4
This is the fundamental reason estrogen without progestin has been restricted to women who have had a hysterectomy 1, 2, 3

Combined estrogen-progestin therapy increases invasive breast cancer risk (RR 1.26, 95% CI 1.00-1.59) with convincing evidence of a small increase in breast cancer incidence and deaths 2, 4
Estrogen-only therapy paradoxically shows a small reduction in invasive breast cancer risk (about 8 fewer cases per 10,000 person-years) and breast cancer deaths (about 2 fewer deaths per 10,000 person-years) 1, 3

Women with an intact uterus require progestin addition to prevent endometrial cancer, but this increases breast cancer risk 2, 4
Women who have had a hysterectomy can use estrogen alone, which paradoxically reduces breast cancer risk but still carries DVT, stroke, and gallbladder disease risks 1, 3