What are the indications for hormone replacement therapy (HRT) in postmenopausal women?

From the Guidelines

Hormone therapy in menopause is primarily indicated for the management of moderate to severe vasomotor symptoms, genitourinary syndrome of menopause, and for prevention of bone loss and fractures in women at elevated risk. The U.S. Food and Drug Administration (FDA)–approved indications for hormone therapy in postmenopausal women are limited to the treatment of menopausal symptoms and the prevention of osteoporosis 1.

Key Considerations

• Systemic hormone therapy typically includes estrogen alone (for women without a uterus) or estrogen plus progestogen (for women with an intact uterus to prevent endometrial hyperplasia) 1.
• Common estrogen preparations include oral conjugated equine estrogens (0.3-0.625 mg daily), oral estradiol (0.5-1 mg daily), or transdermal estradiol patches (0.025-0.1 mg/day), while progestogens include medroxyprogesterone acetate (2.5 mg daily) or micronized progesterone (100-200 mg daily) 1.
• For isolated vaginal symptoms, low-dose vaginal estrogen products (creams, tablets, or rings) are preferred.
• Treatment should be initiated at the lowest effective dose and continued for the shortest duration needed to achieve treatment goals, typically reassessing annually.
• Hormone therapy is not recommended for women with a history of breast cancer, coronary heart disease, previous venous thromboembolism, stroke, active liver disease, or unexplained vaginal bleeding.

Benefits and Risks

• The benefits of hormone therapy are greatest when started before age 60 or within 10 years of menopause onset, as this timing is associated with the most favorable benefit-risk ratio for symptom relief and quality of life improvement 1.
• Estrogen-only therapy is also associated with important harms, such as an increased likelihood of stroke, DVT, and gallbladder disease 1.
• Combined oral estrogen and progestin and oral estrogen-only therapy have both been shown to be associated with an increased incidence of stress, mixed, or any urinary incontinence in previously asymptomatic women after 1 year 1.

From the FDA Drug Label

For treatment of moderate to severe vasomotor symptoms, vulval and vaginal atrophy associated with the menopause, the lowest dose and regimen that will control symptoms should be chosen and medication should be discontinued as promptly as possible. For women who have a uterus, adequate diagnostic measures, such as endometrial sampling, when indicated, should be undertaken to rule out malignancy in cases of undiagnosed persistent or recurring abnormal vaginal bleeding. The usual initial dosage range is 1 to 2 mg daily of estradiol adjusted as necessary to control presenting symptoms.

The indications for hormonal treatment in menopause include:

• Moderate to severe vasomotor symptoms
• Vulval and vaginal atrophy
• Prevention of osteoporosis in women at significant risk of osteoporosis and for whom non-estrogen medications are not considered to be appropriate. Hormonal treatment should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman 2.

From the Research

Indications for Hormonal Treatment in Menopause

• Hormonal treatment is indicated for menopausal symptoms such as vasomotor symptoms (hot flashes, night sweats) and vulvar-vaginal atrophy (VVA) 3, 4, 5.
• Estrogen therapy is the most consistently effective treatment for menopausal vasomotor symptoms and is approved by the FDA for this indication 3, 5.
• Low-dose estrogen preparations, including transdermal preparations with ultra-low doses of estrogen, are available and can effectively relieve menopausal symptoms while minimizing risks 3.
• Tissue-selective estrogen complexes (TSECs), which combine a selective estrogen receptor modulator (SERM) with estrogen, may offer a promising new option for the treatment of menopause, alleviating symptoms while maintaining bone mass and having a neutral or beneficial effect on the cardiovascular system 4.
• Selective estrogen receptor modulators (SERMs) can be used as an alternative to estrogen therapy for the treatment of VVA, with some SERMs (such as ospemifene) demonstrating positive vaginal effects 6.
• Menopause hormone therapy (MHT) is the most efficient treatment for symptoms of acute climacteric syndrome and for prevention of long-term estrogen deficiency, with vaginal administration of low doses of estrogen being a therapy of choice for treatment and prevention of urogenital atrophy 7.

Treatment Options

• Estrogen therapy (oral or transdermal) for vasomotor symptoms and VVA 3, 5.
• Tissue-selective estrogen complexes (TSECs) for alleviating menopausal symptoms and maintaining bone mass 4.
• Selective estrogen receptor modulators (SERMs) for the treatment of VVA, particularly for women who cannot use or choose not to use estrogen therapy 6.
• Nonhormonal therapy, including phytoestrogens, black cohosh extract, and serotonin reuptake inhibitors, for women who cannot use or choose not to use hormonal therapy 7.