Risks of Estrogen Replacement Therapy

Cardiovascular and Thromboembolic Risks

The American College of Family Physicians notes that stroke risk increases by 8 additional events per 10,000 women-years of combined estrogen-progestin therapy 1, 2
The American College of Family Physicians also reports that venous thromboembolism (VTE) risk increases by 8 additional pulmonary emboli per 10,000 women-years 1, 2
Coronary heart disease events increase by 7 additional cases per 10,000 women-years with combined therapy, according to the American College of Family Physicians 1, 2
The risk-benefit profile is critically dependent on timing, with women under 60 or within 10 years of menopause onset having the most favorable risk-benefit profile 2, 3

The American College of Family Physicians states that combined estrogen-progestin therapy increases breast cancer risk with a hazard ratio of 1.26, translating to 8 additional invasive breast cancers per 10,000 women-years 1, 2
The addition of synthetic progestins drives the increased breast cancer risk, not estrogen alone, as noted by the American College of Family Physicians 2
Unopposed estrogen in women with hysterectomy shows no increase in breast cancer risk after 5-7 years, with some evidence suggesting a small protective effect, according to the American College of Family Physicians 2, 3

Unopposed estrogen dramatically increases endometrial cancer risk in women with an intact uterus, as reported by the National Comprehensive Cancer Network 4, 1
Adding progestin for 10-14 days monthly reduces endometrial cancer risk by approximately 90%, according to the National Comprehensive Cancer Network 2

The National Comprehensive Cancer Network strongly contraindicates HRT in women with prior breast cancer, regardless of hormone receptor status of the tumor 4, 2
Women with surgical menopause before age 45 should receive HRT immediately to prevent long-term cardiovascular, bone, and cognitive consequences, continuing at least until age 51, as recommended by the American College of Family Physicians 2, 3

The American College of Family Physicians lists absolute contraindications to HRT, including history of breast cancer 4, coronary heart disease or prior myocardial infarction 2, and previous venous thromboembolic event or stroke 2

The American College of Family Physicians recommends using transdermal estradiol as first-line rather than oral formulations to reduce VTE and stroke risk 2, 3
Prescribing the lowest effective dose for the shortest duration necessary is also recommended by the American College of Family Physicians 1, 2