From the Guidelines
Transdermal estradiol therapy may increase the risk of certain cancers, particularly breast cancer, but the risk depends on several factors, including duration of use, age, and personal and family history of cancer. The risk of breast cancer appears to increase with longer duration of use, especially beyond 5 years, and is higher with combined estrogen-progestin therapy than with estrogen alone 1. According to the NCCN clinical practice guidelines, the use of long-term menopausal hormone therapy (MHT) is controversial due to associated health risks, including an increased risk of stroke, pulmonary embolism, and invasive breast cancer 1.
Key Factors to Consider
- Duration of use: Longer duration of use, especially beyond 5 years, increases the risk of breast cancer
- Age: The risk of breast cancer varies based on a woman's age
- Personal and family history of cancer: Women with a personal or family history of cancer may be at higher risk
- Type of therapy: Combined estrogen-progestin therapy is associated with a higher risk of breast cancer than estrogen alone
Recommendations
- Women considering transdermal estradiol therapy should discuss their personal risk factors with their healthcare provider to make an informed decision about hormone therapy
- Lower doses and shorter durations of therapy can help minimize cancer risks
- Alternatives to MHT, such as non-hormonal treatments for menopausal symptoms, should be considered before initiating hormone therapy 1
Important Considerations
- The absolute increase in cancer risk for an individual woman is generally small, and for some women, the benefits of transdermal estradiol therapy for managing menopausal symptoms may outweigh the risks
- Women with a history of hormonally mediated cancers, such as breast cancer, should avoid MHT unless the benefits outweigh the risks and alternative treatments are not effective 1
From the Research
Transdermal Estradiol Therapy and Cancer Risk
- The relationship between transdermal estradiol therapy and cancer risk is complex and has been studied in various contexts 2, 3, 4, 5, 6.
- Studies have investigated the use of vaginal estrogen in women with a history of gynecologic malignancies, such as endometrial, ovarian, or cervical cancer, and found that adverse outcomes, including cancer recurrence, are infrequent 2.
- A review of the literature on hormone replacement therapy in cancer survivors suggests that the oncologic risk of HRT is difficult to assess, but that certain types of cancer may be more or less susceptible to the effects of estrogen therapy 3.
- Specifically, the use of vaginal estrogen in women with a history of estrogen-dependent breast cancer is generally reserved for those who are unresponsive to nonhormonal remedies, and the decision to use vaginal estrogen should be made in coordination with a woman's oncologist 4.
- Research has also investigated the effect of estradiol levels on the risk of breast, endometrial, and ovarian cancer, and found that high levels of estradiol may increase the risk of ovarian and ER-positive breast cancer 5.
- A study comparing the risk of gynecological cancers in users of estradiol/dydrogesterone or other HRT preparations found that the risk of breast cancer was lower for users of estradiol/dydrogesterone than for users of other HRT 6.
Types of Cancer and Estradiol Therapy
- Breast cancer: high levels of estradiol may increase the risk of ER-positive breast cancer 5, and the use of vaginal estrogen in women with a history of estrogen-dependent breast cancer should be approached with caution 4.
- Endometrial cancer: the relationship between estradiol levels and endometrial cancer risk is less clear, with some studies suggesting a possible link 5 and others finding no significant association 2.
- Ovarian cancer: high levels of estradiol may increase the risk of ovarian cancer 5.
- Cervical cancer: the use of vaginal estrogen in women with a history of cervical cancer has been studied, and adverse outcomes, including cancer recurrence, are infrequent 2.