What is the best hormone replacement therapy (HRT) for menopause?

Best Hormone Replacement Therapy for Menopause

Transdermal estradiol with natural micronized progesterone is the best hormone replacement therapy for menopause, used at the lowest effective dose for the shortest duration needed to manage symptoms.

Key Considerations for HRT Selection

Benefits vs. Risks Assessment

The decision to use HRT must carefully weigh benefits against risks, as HRT is associated with both positive and negative health outcomes:

• Benefits:

  • Effective relief of vasomotor symptoms (hot flashes, night sweats)
  • Protection against vaginal atrophy and dryness
  • Increased bone mineral density and reduced fracture risk 1
  • Reduced risk of colorectal cancer (20% reduction) 1

• Risks:

  • Combined estrogen-progestin therapy increases risk of breast cancer, stroke, deep venous thrombosis, pulmonary embolism, and gallbladder disease 1, 2, 3
  • Estrogen alone increases risk of stroke, deep venous thrombosis, and gallbladder disease 1
  • Dementia risk may increase in women starting HRT after age 65 3

Formulation Recommendations

For Women with Intact Uterus:

• Preferred regimen: Transdermal estradiol (0.025-0.0375 mg/day patch) with natural micronized progesterone 1
  • Transdermal delivery has lower thrombotic risk compared to oral formulations, particularly beneficial for women with cardiovascular risk factors 1
  • Natural micronized progesterone has better cardiovascular and thrombotic risk profile than synthetic progestins like medroxyprogesterone acetate 1, 4

For Women Post-Hysterectomy:

• Estrogen-only therapy (no progesterone needed) 1, 5
• Transdermal formulation preferred for same reasons as above

Administration Regimens

Continuous vs. Sequential Therapy

• Sequential therapy: Estrogen daily with progesterone 10-14 days per month

  • Less irregular bleeding in first year of therapy 5
  • Monthly sequential preferred over long-cycle (quarterly) sequential 5

• Continuous combined therapy: Daily estrogen and progesterone

  • More irregular bleeding in first year but less in subsequent years 5
  • More effective than sequential therapy for preventing endometrial hyperplasia with long-term use 5

Contraindications to HRT

HRT should be avoided in women with:

• History of breast cancer
• History of venous thromboembolism
• Undiagnosed vaginal bleeding
• Active liver disease
• Uncontrolled hypertension 1

Duration of Therapy

• Use lowest effective dose for shortest duration consistent with treatment goals 1
• Typically not exceeding 5 years 1
• Regular reassessment every 3-6 months to monitor effectiveness and side effects 1
• Attempt to taper or discontinue medication at these intervals 1

Special Considerations

Timing of Initiation

The WHI trials showed that starting HRT closer to menopause onset (ages 50-59) may have more favorable effects on coronary heart disease and all-cause mortality compared to starting more than a decade past menopause 6

Common Pitfalls to Avoid

1. Using unopposed estrogen in women with intact uterus - significantly increases risk of endometrial hyperplasia and cancer 5
2. Long-cycle sequential therapy (progestogen every three months) has higher risk of endometrial hyperplasia than monthly sequential therapy 5
3. Overlooking non-hormonal alternatives for women with contraindications to HRT:
   • SSRIs/SNRIs (venlafaxine, paroxetine)
   • Gabapentin
   • Clonidine
   • Cognitive behavioral therapy 1

Monitoring

• Initial follow-up at 2-4 weeks to assess symptom control and side effects
• Regular reassessment every 3-6 months 1
• Annual mammograms as appropriate for age and risk factors 3

The USPSTF recommends against using HRT for the primary prevention of chronic conditions in postmenopausal women (Grade D recommendation) 7, but this recommendation does not apply to women considering HRT for management of menopausal symptoms.