How should I manage a post‑menopausal woman on long‑term combined estrogen‑progestogen hormone replacement therapy (Femaston (estradiol/levonorgestrel)) who presents with an acute ischemic stroke with MRI showing subacute infarction of the right thalamus and basal ganglia and mild small‑vessel disease (Fazekas grade I)?

Management of Acute Ischemic Stroke in a Patient on Long-Term HRT

Discontinue Femaston (estradiol/dydrogesterone) immediately and permanently—hormone replacement therapy is contraindicated after ischemic stroke and should never be restarted. 1, 2

Immediate Acute Stroke Management

Your patient requires standard acute ischemic stroke protocols without delay. The presence of oral HRT does not alter or contraindicate acute reperfusion therapy. 2

Acute Reperfusion Considerations

• Proceed with IV thrombolysis if she presents within 4.5 hours of symptom onset and meets eligibility criteria (no recent surgery, active bleeding, or coagulopathy). 2
• Consider mechanical thrombectomy for large-vessel occlusion if presenting within 24 hours, guided by perfusion imaging. 2
• Do not delay time-sensitive treatment to obtain detailed HRT history—acute stroke protocols take absolute priority. 2

Discontinue HRT Immediately

Stop Femaston upon diagnosis of acute stroke. This is a Class III recommendation with Level A evidence from the American Heart Association/American Stroke Association. 1, 2

Evidence of Harm

• The Women's Estrogen for Stroke Trial (WEST) demonstrated a 2.9-fold increased risk of fatal stroke (95% CI 0.9-9.0) in women with prior cerebrovascular disease who continued estrogen therapy. 1, 3
• Women who had recurrent strokes while on estrogen experienced significantly worse neurologic and functional outcomes compared to placebo. 1, 3
• Combined estrogen-progestin therapy increases stroke risk by 44% (HR 1.44; 95% CI 1.09-1.90), and estrogen alone by 53% (HR 1.53; 95% CI 1.16-2.02). 1, 4

Acute Hospitalization Management

VTE Prophylaxis

• Initiate subcutaneous unfractionated heparin or low-molecular-weight heparin for venous thromboembolism prophylaxis unless hemorrhagic transformation risk is high. 2
• Apply sequential compression devices to both lower extremities given her weakness. 2
• The combination of stroke-related immobilization and residual HRT effects creates a hypercoagulable state requiring aggressive prophylaxis. 2

Blood Pressure Control

• During the first 24 hours, allow permissive hypertension unless BP exceeds 220/120 mmHg (or maintain <180/105 mmHg if thrombolysis was given). 2
• After the acute phase, target BP <140/90 mmHg for secondary prevention. 2

Antiplatelet Therapy

• Start aspirin 325 mg within 24-48 hours if no thrombolysis was given; if thrombolysis was administered, delay aspirin until after 24 hours. 2
• For minor stroke, consider dual antiplatelet therapy (aspirin + clopidogrel) for 21 days. 2

Comprehensive Stroke Work-Up

Perform a complete evaluation to identify the stroke mechanism, which is critical given her pro-thrombotic risk profile from chronic HRT exposure:

• Transthoracic echocardiography to evaluate for cardioembolic sources. 2
• Cardiac telemetry (minimum 24-48 hours) to screen for atrial fibrillation. 2
• Carotid imaging (ultrasound, CTA, or MRA) to assess for large-vessel atherosclerosis. 2
• Hypercoagulable screening: Check antiphospholipid antibodies, factor V Leiden, and prothrombin 20210 mutation given her prothrombotic exposure history. 2

If atrial fibrillation is detected, initiate oral anticoagulation for secondary prevention. 2

Secondary Prevention Strategy

Cardiovascular Risk Factor Modification

• High-intensity statin therapy for lipid lowering regardless of baseline LDL. 2
• Aggressive hypertension control with target BP <140/90 mmHg (or <130/80 mmHg if diabetes or chronic kidney disease). 2
• Diabetes screening with HbA1c and fasting glucose. 2
• Weight reduction counseling and dietary modification. 2

Long-Term Antiplatelet or Anticoagulation

• Continue aspirin 81-325 mg daily for atherosclerotic stroke prevention if no indication for anticoagulation. 2
• Switch to oral anticoagulation if atrial fibrillation or high-risk cardioembolic source is identified. 2

HRT Management: Permanent Discontinuation

Never restart systemic HRT after stroke recovery under any circumstances. 1, 2, 5

Why HRT Cannot Be Restarted

• The American Heart Association issues a Class III recommendation (Level A evidence) against postmenopausal hormone therapy in women with prior ischemic stroke or TIA. 1, 2
• This contraindication applies to all formulations (oral, transdermal, combined, estrogen-alone) and is independent of time since stroke. 1, 5
• The increased stroke risk persists regardless of when HRT is initiated relative to menopause—the "window of opportunity" hypothesis has been refuted. 1

Alternative Management for Menopausal Symptoms

If she develops bothersome vasomotor symptoms after HRT discontinuation:

• Non-hormonal options: SSRIs (paroxetine, escitalopram), SNRIs (venlafaxine), or gabapentin for hot flashes. 6
• Low-dose vaginal estrogen may be considered with extreme caution for genitourinary symptoms only, though some systemic absorption occurs and theoretical risk remains. 2
• First-line for genitourinary symptoms: Non-hormonal vaginal moisturizers and lubricants. 2

Critical Pitfalls to Avoid

• Do not delay acute stroke treatment while obtaining HRT history—reperfusion therapy is time-critical. 2
• Do not consider "temporary" HRT discontinuation—this is a permanent contraindication. 1, 2
• Do not restart HRT for osteoporosis prevention or any other indication—the stroke risk outweighs all potential benefits. 1
• Do not assume transdermal or "bioidentical" formulations are safer—all systemic estrogen formulations carry the same stroke risk. 5, 4

Addressing Small-Vessel Disease (Fazekas Grade I)

Her MRI shows cerebral microangiopathy (Fazekas grade I), which represents early small-vessel disease:

• Aggressive vascular risk factor control is essential to prevent progression: optimize BP control, statin therapy, diabetes management, and smoking cessation. 2
• The combination of HRT-related thrombotic risk and underlying small-vessel disease makes permanent HRT discontinuation even more critical. 2
• Monitor for cognitive changes over time, as small-vessel disease can progress to vascular cognitive impairment. 2