Recommended Combined Hormone Replacement Therapy for Postmenopausal Women
Combined hormone replacement therapy (HRT) is not recommended for the primary prevention of chronic conditions in postmenopausal women due to the unfavorable balance of benefits and harms. 1
Evidence Against Routine Use of Combined HRT
- The U.S. Preventive Services Task Force (USPSTF) explicitly recommends against the use of combined estrogen and progestin for the prevention of chronic conditions in postmenopausal women (Grade D recommendation) 1
- The USPSTF also recommends against the use of estrogen alone for the prevention of chronic conditions in postmenopausal women who have had a hysterectomy (Grade D recommendation) 1
- The USPSTF concluded with high certainty that the chronic disease prevention benefits of combined estrogen and progestin do not outweigh the harms in most postmenopausal women 1
Risks and Benefits of Combined HRT
Risks of Combined Estrogen and Progestin Therapy:
- Increased risk of stroke 1
- Increased risk of invasive breast cancer 1
- Increased risk of dementia 1
- Increased risk of gallbladder disease 1
- Increased risk of urinary incontinence 1
- Increased risk of deep venous thrombosis (DVT) and pulmonary embolism 1
- Possible increased risk of coronary heart disease (CHD) events (HR, 1.22 [95% CI, 0.99 to 1.51]) 1
Benefits of Combined Estrogen and Progestin Therapy:
- Reduced risk of fractures (approximately 46 fractures of any type prevented per 10,000 person-years) 1
When HRT is Used for Symptom Management
While HRT is not recommended for prevention of chronic conditions, it may be used for management of menopausal symptoms. In such cases:
- The FDA has approved HRT indications limited to treatment of menopausal symptoms and prevention of osteoporosis 1
- When HRT is used for symptom management, the FDA recommends using the lowest effective dose for the shortest duration consistent with treatment goals 1
Recommended Regimen When HRT is Used for Symptom Management
If HRT is being used specifically for menopausal symptom management (not for prevention of chronic conditions):
For women with an intact uterus requiring combined therapy:
- The American College of Obstetricians and Gynecologists recommends micronized progesterone (200 mg daily for 12-14 days every 28 days) as the first choice for progestin therapy 2
- Medroxyprogesterone acetate (10 mg daily for 12-14 days per month) is considered an alternative 2
- Lower doses of combined therapy may be considered: conjugated equine estrogen (CEE) 0.3-0.45 mg/day with medroxyprogesterone acetate (MPA) 1.5 mg/day, which has shown favorable endometrial protection with higher rates of amenorrhea compared to higher doses 3, 4
For route of administration:
Important Caveats and Considerations
- The USPSTF recommendations explicitly do not apply to women using HRT for management of menopausal symptoms such as hot flashes or vaginal dryness 1
- The recommendations also do not apply to women younger than 50 years who have had surgical menopause 1
- Continuous combined regimens (daily estrogen plus daily progestin) have been shown to result in higher rates of amenorrhea compared to sequential regimens 6, 4
- Lower-dose regimens of CEE and MPA produce higher rates of amenorrhea and less bleeding compared with standard doses 4
Common Pitfalls to Avoid
- Using HRT primarily for prevention of chronic conditions rather than symptom management 1
- Failing to recognize that combined HRT increases the risk of several serious conditions including stroke, breast cancer, and venous thromboembolism 1
- Not using progestin therapy in women with an intact uterus, which increases the risk of endometrial cancer 2, 3
- Using higher doses than necessary, which may increase side effects without providing additional symptom relief 5, 4