What are the guidelines for estrogen and progesterone (hormone replacement therapy (HRT)) therapy in women's health?

Guidelines for Hormone Replacement Therapy (HRT) in Women's Health

Hormone replacement therapy should be prescribed at the lowest effective dose for the shortest duration consistent with treatment goals and risks, with different recommendations based on specific indications and patient characteristics.

Indications for HRT

Menopausal Symptoms

• HRT is the gold standard for management of vasomotor symptoms (hot flashes) and vaginal atrophy 1
• For moderate to severe vasomotor symptoms, start with lowest effective dose and attempt to discontinue or taper at 3-6 month intervals 2
• For genitourinary symptoms, local vaginal estrogen preparations can be used with minimal systemic absorption

Premature Ovarian Insufficiency (POI)

• HRT is indicated for treatment of low estrogen symptoms in women with POI 3
• HRT may have a role in primary prevention of cardiovascular disease and bone protection in POI patients 3
• Women with POI should be informed that HRT has not been found to increase breast cancer risk before the age of natural menopause 3

Contraindications to HRT

Absolute Contraindications

• Active liver disease 4
• History of breast cancer 4
• History of coronary heart disease 4
• Previous venous thromboembolism or stroke 4
• Undiagnosed abnormal vaginal bleeding 2

Relative Contraindications

• Hypertension (consider transdermal route) 3
• Migraine (not an absolute contraindication, but consider changing dose or route if worsens) 3

HRT Regimens

Estrogen Component

• 17-β estradiol is preferred to ethinylestradiol or conjugated equine estrogens 3
• Recommended dosages:
  • Oral estradiol: 1-2 mg daily 2
  • Transdermal estradiol: 0.025-0.05 mg/day patch (applied twice weekly) 4

Progestogen Component (for women with intact uterus)

• Progestogen must be given with estrogen to protect the endometrium 3, 2
• Options include:
  • Micronized progesterone: 200 mg daily for 12-14 days per month 4
  • Medroxyprogesterone acetate: 2.5 mg daily 4

Administration Patterns

• Cyclic regimen: Estrogen daily with progestogen for 12-14 days per month 4
• Continuous combined: Both estrogen and progestogen daily (for established menopause) 5
• Women without a uterus require estrogen-only therapy 4, 2

Special Populations

Women with Cardiovascular Risk

• HRT should not be used for primary or secondary prevention of cardiovascular disease 3
• The Women's Health Initiative (WHI) study showed increased risks of myocardial infarction and stroke with oral HRT 2
• For women with hypertension who require HRT, transdermal estradiol is preferred 3, 6

Women with History of Breast Cancer

• HRT is generally contraindicated in breast cancer survivors 3, 7
• Alternative approaches for symptom management include:
  • Selective serotonin reuptake inhibitors (SSRIs) like venlafaxine 4, 7
  • Gabapentin 4
  • Non-pharmacological approaches (cognitive behavioral therapy, physical activity) 4

Women with BRCA1/2 Mutations

• HRT is a treatment option for BRCA1/2 mutation carriers without personal history of breast cancer after prophylactic bilateral salpingo-oophorectomy 3

Women with Endometriosis

• Combined estrogen/progestogen therapy can be effective for vasomotor symptoms and may reduce risk of disease reactivation 3

Risks of HRT

Breast Cancer

• Combined estrogen/progestogen therapy increases breast cancer risk when used for more than 3-5 years 4
• Estrogen-only therapy appears to have lower breast cancer risk than combined therapy 8
• Natural progesterone may confer less risk of breast cancer compared to synthetic progestins 6

Cardiovascular Risks

• Increased risk of venous thromboembolism (highest in first year of use) 4
• Increased risk of stroke (RR 1.20) 4
• Transdermal estrogen has lower risk of venous thromboembolism compared to oral administration 5, 6

Other Risks

• Increased risk of cholecystitis 3, 4
• Possible increased risk of dementia in women over 65 2

Monitoring and Follow-up

• Initial follow-up at 3 months, then annual follow-up 4
• Assessment should include:
  • Blood pressure and weight
  • Symptom control
  • Bleeding patterns
  • Lipid profile

Discontinuation

• Gradual reduction of HRT dose by 25-50% every 4-8 weeks 4
• Monitor for return of vasomotor symptoms
• Reevaluate need for therapy every 3-6 months 2

Optimizing HRT Safety

• Use lowest effective dose for shortest duration needed 2
• Consider transdermal estrogen to reduce VTE and stroke risk 5, 6
• Consider natural micronized progesterone instead of synthetic progestins when possible 5, 6
• For women with an intact uterus, continuous combined regimens provide better endometrial protection than sequential regimens for long-term use 5

HRT remains an important treatment option for menopausal symptoms when used appropriately, with careful consideration of individual risk factors and regular monitoring.