What are the guidelines for Hormone Replacement Therapy (HRT) in perimenopausal women?

Guidelines for Hormone Replacement Therapy in Perimenopause

Hormone replacement therapy (HRT) should be used at the lowest effective dose for the shortest possible time to manage moderate to severe vasomotor symptoms, sleep disturbances, and genitourinary symptoms in perimenopausal women, but not for prevention of chronic conditions. 1

Indications for HRT in Perimenopause

• Primary indication: Management of moderate to severe menopausal symptoms

  • Vasomotor symptoms (hot flashes, night sweats)
  • Sleep disturbances
  • Genitourinary symptoms (vaginal dryness, dyspareunia)

• HRT is not recommended for:

  • Primary prevention of chronic conditions 2, 1
  • Prevention of cardiovascular disease 2
  • Prevention of cognitive decline or dementia 2

Contraindications to HRT

Absolute Contraindications

• History of hormone-dependent cancers
• History of venous thromboembolism
• Active liver disease
• Unexplained vaginal bleeding
• History of stroke or coronary heart disease 1
• Obstetric and/or thrombotic antiphospholipid syndrome (APS) 2

Relative Contraindications

• Diabetes, obesity, or metabolic syndrome (increased VTE risk)
• Systemic lupus erythematosus (SLE) with active disease
• Positive antiphospholipid antibodies (aPL) 2, 1

Risk Assessment Before Initiating HRT

1. Check for absolute contraindications
2. Assess for autoimmune conditions (SLE, APS)
3. Evaluate metabolic risk factors
4. For women with an intact uterus, progestin must be added to estrogen therapy to reduce endometrial cancer risk 3, 4

Recommended Regimens

For Women with an Intact Uterus

• Transdermal estradiol (preferred) with oral micronized progesterone 1
  • Initial dose: 50-100 μg/24 hours (transdermal estradiol)
  • Oral micronized progesterone: 200 mg daily

For Women Without a Uterus

• Estrogen-only therapy is appropriate 3, 4
• Initial dosage range: 1-2 mg daily of estradiol 3

Administration Approaches

1. Cyclic Administration

   • Estrogen for 3 weeks followed by 1 week off 3
   • For women with a uterus: Add progestin for 10-14 days per month

2. Continuous Administration

   • Daily estrogen without interruption
   • For women with a uterus: Daily progestin without interruption

Risks of HRT

Based on data from the Women's Health Initiative study, per 10,000 women-years of HRT use 2, 1:

• 8 additional cases of breast cancer
• 8 additional strokes
• 7 additional coronary heart disease events
• 8 additional pulmonary emboli
• Increased risk of gallbladder disease (RR 1.8-2.5)

Benefits include:

• 6 fewer cases of colorectal cancer
• 5 fewer hip fractures

Monitoring and Follow-up

1. Schedule follow-up 8-10 weeks after initiation to:

   • Assess symptom improvement
   • Monitor for adverse effects
   • Adjust dosages as needed 1

2. Attempt to discontinue or taper medication at 3-6 month intervals to determine minimal effective dose 3, 4

3. Regular annual assessments of risks and benefits

Special Considerations

• For women with diabetes, obesity, or metabolic syndrome: Consider transdermal estrogen (lower VTE risk) 1
• For women with SLE: Only consider HRT if aPL-negative with stable, low-level disease 2
• The benefit-risk balance is most favorable for women ≤60 years or within 10 years of menopause onset 1
• Recent evidence suggests that different HRT formulations have different risk profiles, with transdermal routes potentially having fewer risks than oral administration 5

Key Takeaways

1. Use HRT for symptom management, not disease prevention
2. Individualize therapy based on risk factors and symptom severity
3. Use the lowest effective dose for the shortest duration
4. Regular monitoring and reassessment is essential
5. Consider transdermal estrogen for patients with metabolic risk factors