What are the risks and benefits of stopping continuous Hormone Replacement Therapy (HRT) annually?

Risks and Benefits of Stopping Continuous HRT Annually

Stopping continuous hormone replacement therapy (HRT) annually is not recommended as it can lead to significant bone loss and return of menopausal symptoms without providing any clear benefit. 1

Bone Health Implications

Discontinuing HRT, even temporarily, can have significant negative effects on bone health:

• When HRT is stopped, bone loss accelerates significantly within the first 2 years after withdrawal, with annual bone loss rates similar to those occurring in the early postmenopausal period (-1.64% ± 1.3% per year) 2
• This accelerated bone loss increases fracture risk, as women who stop HRT return to normal postmenopausal rates of bone loss 3
• Studies show that women who received continuous HRT had a significantly reduced risk of osteoporotic fractures (OR = 0.48,95% CI, 0.26-0.88) compared to those with interrupted treatment 3

Return of Menopausal Symptoms

Annual interruption of HRT can lead to:

• Recurrence of vasomotor symptoms (hot flashes) during the interruption period 4
• Return of urogenital atrophy symptoms, which may take weeks to months to resolve once HRT is restarted 4
• Sleep disturbances and mood changes that were previously controlled by continuous therapy 1

Cardiovascular Considerations

• Continuous HRT provides more stable protection against cardiovascular disease in eligible women 5
• Interrupting therapy may cause fluctuations in lipid profiles and hemostatic factors that could potentially increase cardiovascular risk 4
• Women who started HRT within 10 years of menopause show reduced all-cause mortality and coronary disease risk with continuous use 5

Cancer Risk Considerations

Annual interruption of HRT does not appear to reduce cancer risks:

• The increased risk of breast cancer with HRT is associated with prolonged use (15-20 years), not with continuous versus interrupted therapy 6
• The WHI study showed that combined estrogen-progestin therapy was associated with increased breast cancer risk (RH, 1.26 [95% CI, 1.00 to 1.59]) regardless of interruptions 7
• The protective effect against colorectal cancer (20% reduction) is more apparent with continuous use 8

Practical Considerations for HRT Management

Instead of annual interruption, the American College of Physicians recommends:

• Regular reassessment of HRT need every 3-6 months 1
• Dose adjustments rather than complete cessation:
  • Consider reducing oral estradiol from 1mg to 0.5mg daily if estradiol levels are elevated 1
  • For progesterone, consider reducing from 100mg to 50mg daily if levels are elevated 1
  • Consider transitioning to transdermal estradiol (25-50 μg/day patch) for better pharmacokinetic profile 1

Algorithm for HRT Management

1. Initial Assessment: Evaluate symptoms, risk factors, and treatment goals
2. Continuous Therapy: Maintain continuous HRT if benefits outweigh risks
3. Dose Optimization: Instead of interruption, consider dose adjustments:
   • Start with low doses (0.5 mg estradiol every other day)
   • Gradually increase as needed (0.5 mg daily after 12-18 months)
   • Monitor estradiol, FSH, LH levels 8-10 weeks after any dose adjustment 1
4. Regular Monitoring: Assess every 3-6 months for:
   • Symptom control
   • Side effects
   • New contraindications
5. Consider Discontinuation Only When:
   • Contraindications develop (breast cancer, venous thromboembolism, uncontrolled hypertension) 1
   • Patient no longer wishes to continue therapy
   • Long-term use (>5 years) requires reassessment of risk/benefit ratio 7

Common Pitfalls to Avoid

• Abrupt discontinuation: If discontinuation is necessary, gradual tapering is preferred to minimize rebound symptoms
• Ignoring bone health: If HRT must be discontinued, consider alternative osteoporosis prevention strategies
• Misunderstanding risk duration: Many HRT risks persist for 8-15 years after discontinuation 7
• Overlooking symptom recurrence: Patients should be warned that menopausal symptoms often return when HRT is interrupted

In conclusion, the evidence does not support a practice of annual interruption of HRT. Instead, continuous therapy with appropriate dose adjustments and regular monitoring provides better symptom control and bone protection while maintaining the risk/benefit profile established with the original treatment decision.