From the Guidelines
Hormone replacement therapy (HRT) is associated with an increased risk of endometrial cancer, particularly with unopposed estrogen therapy, as well as a potential increased risk of ovarian cancer with long-term use, according to the USPSTF conclusions 1. The association between HRT and cancer risk is complex and depends on various factors, including the type of hormones used, duration of therapy, and individual risk factors.
- Endometrial cancer risk is significantly increased with estrogen-only therapy, which is why progestin is added for women who still have their uterus, as shown by cohort studies with a decreased risk for endometrial cancer (RR, 0.4 [95% CI, 0.2 to 0.6]) compared with nonusers 1.
- The risk for endometrial cancer remained elevated 5 or more years after discontinuation of unopposed estrogen therapy, highlighting the need for careful consideration of HRT use 1.
- Data on the association between HRT and ovarian cancer risk are inconsistent, but two good-quality cohort studies reported increased risks (RR, 1.8 to 2.2) for ovarian cancer or ovarian cancer mortality among women who had taken HRT for 10 years or more 1.
- Additionally, HRT has been associated with an increased risk of cholecystitis, with a good-quality cohort study reporting an increase in risk for cholecystitis among current HRT users (RR, 1.8 [95% CI, 1.6 to 2.0]) and long-term users (>5 years) (RR, 2.5 [95% CI, 2.0 to 2.9]) compared with nonusers 1. The potential benefits of HRT for menopausal symptom relief must be carefully weighed against these cancer risks, and therapy should be used at the lowest effective dose for the shortest duration necessary, as recommended by the USPSTF 1.
From the Research
Cancers Associated with Hormone Replacement Therapy
- Breast cancer: Studies have consistently shown that hormone replacement therapy (HRT) increases the risk of breast cancer, with the risk increasing proportionally with duration of HRT 2, 3, 4.
- Endometrial cancer: The risk of endometrial cancer is increased with estrogen-only therapy, but reduced with combined estrogen and progestin therapy 5, 6.
Types of HRT and Associated Cancer Risks
- Estrogen-only therapy: associated with an increased risk of endometrial cancer, but not breast cancer 5, 6.
- Combined estrogen and progestin therapy: associated with an increased risk of breast cancer, with the risk varying depending on the type of progestin used 3, 4.
- Continuous combined therapy: may be associated with a lower risk of endometrial cancer compared to sequential combined therapy 6.
Factors Influencing Cancer Risk
- Duration of HRT use: the risk of breast cancer increases with longer duration of HRT use 2, 4.
- Body weight: the risk of breast cancer may be higher in women who are leaner 2, 3.
- Breast density: the risk of breast cancer may be higher in women with dense breasts 2.
- Type of progestin: the risk of breast cancer may vary depending on the type of progestin used, with norethisterone associated with a higher risk and dydrogesterone associated with a lower risk 4.