What are the contraindications for starting Hormone Replacement Therapy (HRT)?

Contraindications for Starting Hormone Replacement Therapy (HRT)

Hormone replacement therapy (HRT) is contraindicated in several conditions where the risks significantly outweigh the benefits, including history of breast cancer, coronary heart disease, previous venous thromboembolism, stroke, active liver disease, and antiphospholipid syndrome. 1, 2

Absolute Contraindications

• Breast cancer (current or history) - HRT is generally contraindicated in breast cancer survivors due to potential stimulation of hormone-sensitive cancer cells 1, 2
• Endometrial cancer or other estrogen-dependent neoplasia - Due to potential stimulation of hormone-sensitive cancer cells 2
• Cardiovascular disease - Including history of myocardial infarction or coronary artery disease 1, 2
• Thromboembolic disorders - Current or past history of deep vein thrombosis, pulmonary embolism, or thrombophilia 2, 3
• Cerebrovascular disease - History of stroke 1, 2
• Active liver disease - Including cholestatic jaundice of pregnancy or jaundice with prior estrogen use 1, 2
• Antiphospholipid syndrome (APS) - Both obstetric and thrombotic APS are strong contraindications to HRT 1
• Positive antiphospholipid antibodies (aPL) - Even without APS diagnosis, positive aPL titers contraindicate HRT 1
• Undiagnosed abnormal genital bleeding - Until malignancy is ruled out 2
• Known or suspected pregnancy 2

Relative Contraindications and Special Considerations

Systemic Lupus Erythematosus (SLE)

• HRT may be considered in SLE patients with all of the following:
  • Negative aPL antibodies
  • Stable, low-level disease activity
  • Severe vasomotor symptoms
  • No other contraindications 1
• HRT should be avoided in SLE patients with:
  • Positive aPL antibodies
  • Moderate to high disease activity 1

Cardiovascular Risk Factors

• Age ≥60 years or >10 years post-menopause - Oral estrogen-containing HRT carries excess stroke risk in this population 1
• Hypertension - Not an absolute contraindication, but transdermal estradiol is preferred over oral formulations 1
• Diabetes with vascular involvement - Increased risk with HRT 2

Migraine

• Migraine with focal neurological symptoms - Contraindication for oral HRT 2
• Migraine without aura - Not a contraindication but may require route adjustment if symptoms worsen 1

Other Considerations

• Major surgery with prolonged immobilization - Temporary contraindication due to increased thrombosis risk 2
• Valvular heart disease with complications - Increased risk of thromboembolism 2
• Hypersensitivity to any component of HRT products 2

Special Populations

BRCA Mutation Carriers

• HRT is a treatment option for BRCA1/2 mutation carriers without personal history of breast cancer after prophylactic bilateral salpingo-oophorectomy 1

Premature Ovarian Insufficiency (POI)

• Most contraindications that apply to standard menopausal HRT do not apply with the same strength to women with POI
• Benefits generally outweigh risks in this population, except in cases of:
  • Hormone-sensitive cancers
  • History of thromboembolism 1

Decision-Making Algorithm for HRT Initiation

1. Assess for absolute contraindications:

   • History of breast cancer or estrogen-dependent neoplasia
   • Cardiovascular or cerebrovascular disease
   • Thromboembolic disorders
   • Active liver disease
   • APS or positive aPL antibodies 1, 2

2. If no absolute contraindications, evaluate for SLE and aPL status:

   • If SLE present: Check aPL status and disease activity
   • If aPL positive: Avoid HRT regardless of SLE status
   • If SLE with negative aPL and stable disease: Consider HRT for severe symptoms 1

3. Assess cardiovascular risk profile:

   • Age ≥60 or >10 years post-menopause: Higher risk with oral HRT
   • Hypertension: Consider transdermal route
   • Diabetes with vascular involvement: Avoid HRT 1, 2

4. Consider special circumstances:

   • POI: More liberal use of HRT (fewer contraindications)
   • BRCA mutation without breast cancer: HRT may be appropriate
   • Endometriosis: Combined estrogen/progestogen therapy may be effective 1

Important Caveats

• The route of administration affects risk profile - transdermal estrogen has lower thrombotic risk than oral formulations 1
• For women with an intact uterus, estrogen must be combined with progestogen to prevent endometrial hyperplasia 1
• When HRT is prescribed, use the lowest effective dose for the shortest duration necessary 1, 3
• Clinical trials of HRT in SLE patients did not include those with active disease, so caution is warranted 1