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Menopausal hormone therapy with conjugated equine estrogen is associated with a higher risk of hemorrhagic stroke than therapy with estradiol: a retrospective population-based cohort study

  • Wei-Chuan Chang
    Affiliations
    Department of Medical Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Foundation, Tzu Chi University, Hualien, Taiwan
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  • Jen-Hung Wang
    Affiliations
    Department of Medical Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Foundation, Tzu Chi University, Hualien, Taiwan
    Search for articles by this author
  • Dah-Ching Ding
    Correspondence
    Corresponding author at: Department of Obstetrics and Gynecology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Foundation, Tzu Chi University, No. 707, Chung-Yang Rd., Sec. 3, Hualien, Taiwan.
    Affiliations
    Department of Obstetrics and Gynecology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Foundation, and Tzu Chi University, Hualien, Taiwan

    Department of Obstetrics and Gynecology, College of Medicine, Tzu Chi University, Hualien, Taiwan
    Search for articles by this author

      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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