Risks and Considerations of Hormone Replacement Therapy in Menopausal Women

Cardiovascular and Thrombotic Risks

The American College of Physicians suggests that HRT increases stroke risk with a relative risk of 1.12 to 1.41, primarily thromboembolic strokes rather than hemorrhagic 1, 2
The absolute excess stroke risk is approximately 8 additional strokes per 10,000 women-years, as noted by the American Academy of Family Physicians 3
The risk of venous thromboembolism doubles with HRT use, with a relative risk of 2.14, and the highest danger occurring within the first year of therapy, according to the American College of Physicians 1, 2
Transdermal estrogen formulations significantly reduce the risk of venous thromboembolism compared to oral preparations, as recommended by the American College of Obstetricians and Gynecologists 4, 5

The American Cancer Society indicates that combined estrogen-progestin therapy increases invasive breast cancer risk, with a relative risk of 1.26, and an absolute excess of 8 cases per 10,000 women-years 4
Unopposed estrogen dramatically increases endometrial cancer risk, with a relative risk of 2.3, escalating to 9.5 with 10 years of use, as warned by the American College of Obstetricians and Gynecologists 1, 2, 4
Long-term HRT use associates with increased ovarian cancer mortality, with a relative risk of 1.8-2.2, according to the American College of Physicians 1, 2, 4

Current HRT users face increased cholecystitis risk, with a relative risk of 1.8, as reported by the American Gastroenterological Association 1, 2

The American Heart Association recommends using the lowest effective dose for the shortest duration needed for symptom control, to minimize risks such as venous thromboembolism and CHD 3, 6, 4
Transdermal 17-β estradiol is strongly preferred over oral formulations, particularly for women with hypertension or elevated thrombotic risk, as suggested by the American College of Cardiology 4, 5, 7

For 10,000 women taking combined estrogen-progestin therapy for one year, expect 8 additional strokes, 10 additional pulmonary emboli, and 8 additional invasive breast cancers, as estimated by the American Academy of Family Physicians 3

Never prescribe unopposed estrogen to women with an intact uterus, due to the unacceptable endometrial cancer risk, as advised by the American College of Obstetricians and Gynecologists 1, 2, 4
HRT should not be used for chronic disease prevention, given the unfavorable risk-benefit profile for this indication, as stated by the American Academy of Family Physicians 3, 6

The American College of Physicians recommends being aware that venous thromboembolism risk doubles with HRT use, with a relative risk of 2.14, and the highest danger occurring within the first year of therapy, with 12 additional deep venous thromboses and 9 additional pulmonary emboli per 10,000 women-years with combined estrogen-progestin therapy 8
Combined estrogen-progestin therapy increases coronary heart disease events, particularly evident shortly after initiation, with a hazard ratio of 1.29, and 7 additional coronary events per 10,000 women-years 8

The American College of Obstetricians and Gynecologists notes that unopposed estrogen dramatically increases endometrial cancer risk, with a relative risk of 2.3, escalating to 9.5-fold after 10 years of use, and this risk remains elevated for 5 or more years even after discontinuation 8
Estrogen-only therapy in women without a uterus may be protective against breast cancer, with a relative risk of 0.77-0.80 9

Most serious risks, including breast cancer, endometrial cancer, and cardiovascular risks, increase substantially after 5 years of continuous HRT use, with venous thromboembolism risk being highest within the first year, then remaining elevated at approximately 2-fold throughout continued use 8