From the Guidelines
Hormone replacement therapy (HRT) is associated with significant risks, including increased chances of blood clots, stroke, and heart disease, and should be used with caution, considering individual risk factors and preferences, as the harms of estrogen-progestin therapy are likely to outweigh the chronic disease prevention benefits for most women. The main risks of HRT include an increased chance of cardiovascular events, such as coronary heart disease (CHD) and stroke, with 10,000 women taking estrogen and progestin for 1 year experiencing 7 additional CHD events and 8 more strokes, as reported in the study by 1. Additionally, women taking combined estrogen-progestin therapy face a small increased risk of breast cancer after several years of use, with 8 more invasive breast cancers expected in 10,000 women taking estrogen and progestin for 1 year, according to 1. Other risks include gallbladder disease, with estrogen increasing the likelihood of gallstones, and a slight increase in ovarian cancer risk with long-term use. Specific formulations carry different risk profiles, with oral estrogens posing higher clotting risks than transdermal patches or gels, as noted in the study by 1. Side effects may include breast tenderness, bloating, headaches, mood changes, and vaginal bleeding. The risk-benefit profile varies significantly based on age, health history, family history, and specific symptoms being treated, and clinicians should develop a shared decision-making approach to preventing chronic diseases in perimenopausal and postmenopausal women, considering individual risk factors and preferences, as recommended by 1. Women with a history of hormone-sensitive cancers, liver disease, unexplained vaginal bleeding, or previous blood clots should generally avoid HRT, and regular monitoring by healthcare providers is essential to assess ongoing risks versus benefits throughout treatment. Key considerations for HRT use include:
- Individual risk factors, such as age, health history, and family history
- Specific symptoms being treated, such as menopausal symptoms or osteoporosis
- Formulation and dosage of HRT, with oral estrogens posing higher clotting risks than transdermal patches or gels
- Regular monitoring by healthcare providers to assess ongoing risks versus benefits throughout treatment.
From the FDA Drug Label
In the WHI estrogen plus progestin substudy, a statistically significant 2-fold greater rate of VTE (DVT and pulmonary embolism [PE]) was reported in women receiving daily CE (0.625 mg) plus MPA (2. 5 mg) compared to women receiving placebo (35 versus 17 per 10,000 women-years). The most important randomized clinical trial providing information about breast cancer in estrogen plus progestin users is the Women's Health Initiative (WHI) substudy of daily CE (0.625 mg) plus MPA (2.5 mg). After a mean follow-up of 5. 6 years, the estrogen plus progestin substudy reported an increased risk of invasive breast cancer in women who took daily CE plus MPA. An increased risk of endometrial cancer has been reported with the use of unopposed estrogen therapy in a woman with a uterus The reported endometrial cancer risk among unopposed estrogen users is about 2 to 12 times greater than in non-users, and appears dependent on duration of treatment and on estrogen dose.
The risks of HRT include:
- Venous Thromboembolism (VTE): a 2-fold greater rate of VTE was reported in women receiving daily CE plus MPA compared to women receiving placebo 2
- Breast Cancer: an increased risk of invasive breast cancer was reported in women who took daily CE plus MPA, with a relative risk of 1.24 and an absolute risk of 41 versus 33 cases per 10,000 women-years 2
- Endometrial Cancer: an increased risk of endometrial cancer has been reported with the use of unopposed estrogen therapy, with a risk 2 to 12 times greater than in non-users 2
From the Research
Risks of Hormone Replacement Therapy (HRT)
The risks associated with HRT are a significant concern for menopausal women. Some of the potential risks include:
- Coronary Heart Disease (CHD) 3
- Stroke 3
- Thromboembolic events 3
- Breast cancer, particularly with 5 or more years of use 3
- Cholecystitis 3
- Increased risk of dementia 4
- Adverse effects on hemostatic balance and inflammatory and immune factors 4
Factors Influencing HRT Risks
The risk-benefit ratio of HRT differs markedly by clinical characteristics of the participants, especially:
Minimizing HRT Risks
Some studies suggest that physiologic sex steroid therapy with transdermal delivery may offer a different risk-benefit profile 4. Additionally, a daily combination of micronized estradiol and progesterone may result in symptomatic improvement, minimal side effects, and an improved lipid profile 6. However, it is essential to weigh the benefits and harms of HRT based on scientific evidence and consider patient-specific factors when prescribing HRT 3.