Is hormone replacement therapy (HRT) contraindicated in postmenopausal women with a history of acute stroke?

HRT is Contraindicated in Women with Acute Stroke

Yes, hormone replacement therapy (HRT) is absolutely contraindicated in postmenopausal women with a history of acute stroke. This is an FDA-labeled contraindication and a Class III recommendation from major cardiovascular societies.

FDA Contraindication

• Systemic estrogen therapy is explicitly contraindicated in women with active arterial thromboembolic disease (including stroke) or a history of these conditions 1
• The FDA labeling mandates immediate discontinuation of estrogen therapy if a stroke occurs or is suspected 1

Guideline Recommendations

The American Heart Association provides clear guidance:

• HRT should not be initiated for secondary prevention of cardiovascular disease in women with established cerebrovascular disease 2
• If a woman develops an acute cardiovascular event while on HRT, it is prudent to discontinue the therapy immediately to minimize risk of venous thromboembolism associated with immobilization 2
• The decision to reinstitute HRT after an acute event should be based on noncoronary benefits and risks, with full patient understanding of the increased stroke risk 2

The American Heart Association/American Stroke Association specifically recommends against postmenopausal hormone therapy for women who have had ischemic stroke or TIA (Class III recommendation; Level of Evidence A) 3

Evidence of Harm in Women with Prior Stroke

• The Women's Estrogen for Stroke Trial (WEST) demonstrated that women with established cerebrovascular disease randomized to estrogen had a hazard ratio of 2.9 for fatal stroke 3
• Women in the estrogen arm experienced significantly more severe neurological impairments after recurrent stroke 2
• The trial showed estrogen was not effective for preventing recurrent stroke or death in women with prior cerebrovascular disease 2

Stroke Risk in All Postmenopausal Women on HRT

Even in women without prior stroke, HRT increases stroke risk:

• Combined estrogen-progestin increases stroke risk by 41% (RR 1.41) 4
• Meta-analyses show 12-32% increased stroke incidence with HRT use, primarily thromboembolic strokes 5
• The Women's Health Initiative confirmed a 36-41% increased stroke risk with both estrogen-alone and combined therapy 5
• Oral HRT confers a 28% increased risk of stroke (RR 1.28) 6

Practical Management Algorithm

For women currently on HRT who experience acute stroke:

1. Immediately discontinue all systemic HRT (oral, transdermal patches at doses >50 mcg) 1
2. Ensure appropriate VTE prophylaxis during hospitalization, as both stroke-related immobilization and residual HRT effects create hypercoagulable states 2
3. Do not reinitiate systemic HRT after stroke recovery 3

For women with prior stroke requesting treatment for menopausal symptoms:

1. Systemic HRT (oral or transdermal) is contraindicated 1
2. For genitourinary symptoms only: low-dose vaginal estrogen may be considered with extreme caution, though some systemic absorption occurs 3
3. First-line therapy should be non-hormonal vaginal moisturizers 3

Critical Caveats

• The increased risk of fatal stroke (not just any stroke) is particularly concerning in women with prior cerebrovascular events 2, 3
• Even transdermal estrogen, while having lower stroke risk than oral formulations in primary prevention, is still contraindicated after stroke due to FDA labeling and the WEST trial findings 1, 7
• Vaginal estrogen preparations, despite lower systemic absorption, still carry theoretical risk and should be avoided or used only with extreme caution and informed consent in stroke survivors 3
• The combination of HRT with other prothrombotic conditions (immobilization, genetic thrombophilias, acute illness) creates multiplicative rather than additive risk 2

The evidence is unequivocal: systemic HRT must be discontinued immediately in acute stroke and should never be initiated in women with stroke history.