Highlights
- •Studies show that menopausal hormone therapy decreases the risk of hemorrhagic stroke, but the risk with the use of estradiol versus the use of conjugated estrogens remains undetermined.
- •In this study the incidence of hemorrhagic stroke was 1.23-fold higher in women treated with conjugated estrogens than in those treated with estradiol, with an adjusted hazard ratio of 1.50.
- •Menopausal hormone therapy with conjugated estrogens initiated within 5 years of menopause was associated with a higher risk of hemorrhagic stroke than menopausal hormone therapy with estradiol (hazard ratio 1.47).
Abstract
Background
Several studies have shown that menopausal hormone therapy (MHT) reduces the risk
of hemorrhagic stroke (HS), but there are no studies comparing the effect of different
estrogen types (conjugated equine estrogen [CEE] and estradiol [E2]).
Methods
This retrospective cohort study included menopausal women aged 40–65 years diagnosed
between 2000 and 2016 who received MHT with oral CEE or E2 and were registered in
Taiwan's National Health Insurance Research Database. The primary outcome was HS.
Propensity score matching with menopausal age and comorbidities was performed. Cox
proportional hazard regression models were used to calculate the incidence and hazard
ratios (HRs) of HS.
Results
A total of 14,586 pairs of women were included. The mean menopausal ages of the CEE
and E2 groups were 50.45 ± 5.31 and 50.31 ± 4.99 years, respectively. After adjusting
for age and comorbidities, the incidence of HS was 1.23-fold higher in women treated
with CEE than in those treated with E2 (8.04 vs. 6.49/10,000 person-years), with an
adjusted HR of 1.50 (95 % confidence interval [CI] 1.04–2.17). MHT with CEE initiated
within 5 years of menopause was associated with a higher risk of HS than MHT with
E2 (HR = 1.47, 95 % CI: 1.01–2.14).
Conclusions
In postmenopausal Taiwanese women, MHT with CEE was associated with an increased risk
of HS compared to MHT with E2, a risk that women using CEE should discuss with their
clinicians. Further large-scale investigations of this population are warranted.
Keywords
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References
- Serum estradiol level according to dose and formulation of oral estrogens in postmenopausal women.Sci. Rep. 2021; 11: 3585
- Continuous combined estrogen plus progestin and endometrial cancer: the women’s health initiative randomized trial.J. Natl. Cancer Inst. 2016; 108https://doi.org/10.1093/jnci/djv350
- Conjugated equine estrogen used in postmenopausal women associated with a higher risk of stroke than estradiol.Sci. Rep. 2021; 11: 10801
- Comparison of neurological clinical manifestation in patients with hemorrhagic and ischemic stroke.World J. Emerg. Med. 2017; 8: 34-38
- Risk of stroke with various types of menopausal hormone therapies: a national cohort study.Stroke. 2017; 48: 2266-2269
- Effects of conjugated equine estrogen on stroke in the women’s health initiative.Circulation. 2006; 113: 2425-2434
- Hormone replacement therapy and associated risk of stroke in postmenopausal women.Arch. Intern. Med. 2002; 162: 1954-1960
- Lower risk of cardiovascular events in postmenopausal women taking oral estradiol compared with oral conjugated equine estrogens.JAMA Intern. Med. 2014; 174: 25-31
- Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases.BMJ. 2019; 364k4810
- Postmenopausal hormone therapy and stroke: role of time since menopause and age at initiation of hormone therapy.Arch. Intern. Med. 2008; 168: 861-866
- Hormone replacement therapy and the risk of subarachnoid hemorrhage in postmenopausal women.J. Neurosurg. 2016; 124: 45-50
- Hormone therapy in postmenopausal women associated with risk of stroke and venous thromboembolism: a population-based cohort study in Taiwan.Menopause. 2018; 26: 197-202
- Propensity scores: uses and limitations.PM R. 2012; 4: 693-697
- Propensity score methods in health technology assessment: principles, extended applications, and recent advances.Front. Pharmacol. 2019; 10: 973
- Oral contraceptives and menopausal hormone therapy: relative and attributable risks of cardiovascular disease, cancer, and other health outcomes.Ann. Epidemiol. 2015; 25: 193-200
- American Heart Association stroke council, council on cardiovascular surgery and anesthesia, council on cardiovascular radiology and intervention, council on cardiovascular and stroke nursing, council on epidemiology and prevention, council on peripheral vascular disease, council on nutrition, physical activity and metabolism, an updated definition of stroke for the 21st century: a statement for healthcare professionals from the American Heart Association/American Stroke Association.Stroke. 2013; 44: 2064-2089
- Pathophysiology of blood-brain barrier permeability throughout the different stages of ischemic stroke and its implication on hemorrhagic transformation and recovery.Front. Neurol. 2020; 11594672
- Gender-related differences in migraine.Neurol. Sci. 2020; 41: 429-436
- Postmenopausal hormone therapy and risk of stroke: a pooled analysis of data from population-based cohort studies.PLoS Med. 2017; 14e1002445
- Changes in U.S. Prescribing patterns of menopausal hormone therapy, 2001–2003.Obstet. Gynecol. 2006; 108: 33-40
Article info
Publication history
Published online: August 01, 2022
Accepted:
July 13,
2022
Received in revised form:
April 18,
2022
Received:
February 15,
2022
Identification
Copyright
© 2022 Elsevier B.V. All rights reserved.
