Is progesterone-only hormone replacement therapy (HRT) recommended for a patient with a total hysterectomy and a history of deep vein thrombosis (DVT)?

Progesterone-Only Hormone Replacement Therapy in Patients with Total Hysterectomy and History of DVT

Progesterone-only hormone replacement therapy is a reasonable option for patients with a total hysterectomy who have a history of DVT, as it carries a lower thrombotic risk compared to estrogen-containing regimens. 1

Risk Assessment for Hormone Replacement Therapy

DVT History Considerations

• Patients with a history of DVT are at higher risk for recurrent thrombotic events
• According to the International Society on Thrombosis and Haemostasis (ISTH), patients with unprovoked DVT have a higher recurrence risk than those with provoked DVT 1
• The risk stratification for recurrent DVT includes:
  • Higher risk: Estrogen-associated DVT, pregnancy-associated DVT, idiopathic DVT, known thrombophilia, active cancer, or history of recurrent DVT
  • Lower risk: DVT with no identified risk factors

Hormone Therapy Options After Hysterectomy

Estrogen-Only vs. Progesterone-Only Therapy

• Women with a total hysterectomy typically don't require progesterone for endometrial protection
• However, history of DVT significantly impacts hormone therapy selection:
  • Estrogen therapy (both oral and transdermal) increases DVT risk (HR 1.47 [CI, 1.06 to 2.05]) 1
  • Progesterone-only options have substantially lower thrombotic risk 1

Clinical Recommendation Algorithm

1. Assess DVT risk category:

   • If patient has higher risk factors for recurrent DVT (idiopathic DVT, known thrombophilia, etc.), proceed with extreme caution
   • If lower risk (provoked DVT with risk factor no longer present), progesterone-only HRT may be considered

2. Consider progesterone-only options:

   • Progestin-only pills (POPs) - Category 2 (benefits generally outweigh risks) for women with history of DVT 1
   • Depot medroxyprogesterone acetate (DMPA) - Category 2 for women with history of DVT 1
   • Progestin implants - Category 2 for women with history of DVT 1

3. If progesterone-only therapy is selected:

   • Start with lowest effective dose
   • Monitor for symptoms of recurrent DVT/PE
   • Consider concurrent anticoagulation in high-risk patients

Important Considerations and Caveats

• Thrombotic risk: While progesterone-only methods have lower thrombotic risk than estrogen-containing options, they still carry some risk 1
• Symptom management: Progesterone-only options may be less effective for certain menopausal symptoms compared to estrogen therapy
• Anticoagulation: For patients on established anticoagulant therapy (≥3 months), progesterone-only methods are classified as Category 2 (benefits generally outweigh risks) 1
• Monitoring: Regular follow-up is essential to assess symptom control and monitor for potential complications

Alternative Approaches

• Non-hormonal options for managing menopausal symptoms should be considered first:

  • SSRIs/SNRIs for vasomotor symptoms
  • Gabapentin for hot flashes
  • Vaginal moisturizers and lubricants for vaginal dryness

• Absolute contraindication: Combined estrogen-progestin therapy is contraindicated (Category 4) in women with a history of DVT 1, 2

The EVTET trial demonstrated a significantly increased risk of recurrent VTE in women with previous VTE who took combined hormone therapy (10.7% in HRT group vs 2.3% in placebo) 2, reinforcing the need to avoid estrogen-containing regimens in this population.