Can Menopausal Hormone Therapy (MHT) cause neutropenia and low White Blood Cell (WBC) count?

Menopausal Hormone Therapy and Neutropenia/Low WBC Count

Menopausal hormone therapy (MHT) is not directly associated with neutropenia or low white blood cell counts based on current clinical evidence, but should be used with caution in patients with pre-existing neutropenia due to potential complications if infection develops.

Relationship Between MHT and Blood Counts

Current clinical guidelines do not identify MHT as a direct cause of neutropenia or low WBC counts:

• The 2024 American Heart Association/American Stroke Association guidelines on primary prevention of stroke discuss various risks of MHT but do not mention neutropenia or effects on white blood cell counts 1.
• Similarly, the 2020 JACC recommendations on cardiovascular disease prevention in women discuss MHT risks but do not include neutropenia among potential adverse effects 1.

Management Considerations for Patients with Neutropenia

For patients who already have neutropenia and are considering MHT:

• Regular monitoring of blood counts is recommended, particularly during the initial months of therapy 2.
• The severity of neutropenia should guide clinical decisions:
  • Mild to moderate neutropenia (0.5-1.5 × 10^9/L): MHT may be continued with careful monitoring
  • Severe neutropenia (<0.5 × 10^9/L): Consider withholding MHT until neutrophil recovery 2

Risk Assessment and Monitoring

When considering MHT in patients with or at risk for neutropenia:

• Baseline complete blood count with differential should be obtained before initiating therapy
• Monthly monitoring during initial therapy is recommended, with frequency adjusted based on clinical response 2
• Patients should be educated about signs of infection (fever, chills, malaise) that warrant immediate medical attention

Alternative Approaches

For patients with neutropenia who require treatment for menopausal symptoms:

• Transdermal estrogen formulations may be preferred over oral preparations as they have less impact on liver metabolism 2
• Non-hormonal options for managing vasomotor symptoms can be considered, including:
  • Antidepressants
  • Anticonvulsants
  • Certain antihypertensives 1

Special Considerations

• In cancer survivors, MHT decisions should be individualized based on cancer type and treatment history 1
• MHT is contraindicated in patients with active infection or severe neutropenia with high risk of infection 2
• In cases of drug-induced neutropenia, the causative medication should be identified and discontinued if possible 3, 4

Management of Neutropenia

If neutropenia develops during MHT use:

1. Assess for other potential causes (medications, infections, underlying conditions)
2. Consider temporary discontinuation of MHT if severe neutropenia develops
3. Granulocyte colony-stimulating factor (G-CSF) may be considered in severe cases 5
4. Broad-spectrum antibiotics should be initiated promptly if fever develops 2

While MHT itself is not established as a direct cause of neutropenia in the medical literature, clinicians should remain vigilant about monitoring blood counts in patients with risk factors for neutropenia who are using MHT.