Menopause: The Journal of The North American Menopause Society Vol. 21, No. 11, pp. 1204/1210 DOI: 10.1097/gme.0000000000000227 * 2014 by The North American Menopause Society
Risk of stroke in healthy postmenopausal women during and after hormone therapy: a meta-analysis Haifeng Gu, MD, MS,1 Xiaohong Zhao, MD, MS,1 Xiaoping Zhao, MD, MS,2 Yunmei Yang, MD, PhD,1 and Xueying Lv, MD1 Abstract Objective: This meta-analysis aims to examine the risk of stroke in healthy postmenopausal women during and after hormone therapy (HT). Methods: Medline, The Cochrane Library, EMBASE, and Google Scholar were searched for randomized controlled trials involving healthy postmenopausal women who received HT and were followed up for at least 3 years after starting treatment. The primary outcome measures were stroke hazard ratio (HR) for the intervention phase, stroke HR for the postintervention phase, and overall stroke HR. Results: Four studies, involving 15,423 participants who received HT and 14,582 participants who received placebo, met the criteria for inclusion in the meta-analysis. The mean age of participants ranged from approximately 50 to 64 years. HT was given as conjugated equine estrogens in three studies and as 17A-estradiol in one study. The duration of HT ranged from 3.0 to 10.1 years. The length of follow-up after the start of HT ranged from 3.0 to 15.8 years. Meta-analysis revealed that the stroke HR during the intervention phase and the overall stroke HR were significantly increased among women who received HT (intervention phase: pooled HR, 1.32; 95% CI, 1.12-1.56; P = 0.001; overall: pooled HR, 1.15; 95% CI, 1.03-1.28; P = 0.017). The stroke HR during the postintervention phase was not increased among women who received HT (pooled HR, 1.00; 95% CI, 0.85-1.16; P = 0.958). Sensitivity analysis confirmed the reliability of the meta-analysis for both outcomes. Conclusions: These findings suggest that HT may increase the risk of stroke during, but not after, HT in healthy postmenopausal women. Key Words: Hormone therapy Y Intervention Y Meta-analysis Y Postintervention Y Postmenopause Y Stroke Y Women.
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ntil 2002, hormone therapy (HT) was commonly prescribed to treat menopause symptoms and to treat or prevent chronic diseases such as cardiovascular disease and osteoporosis. This changed with the release of the initial findings from the Women’s Health Initiative (WHI) study in 2002,1 which suggested that the overall health risk of HT exceeded the health benefit. More specifically, the findings from this randomized controlled trial indicated that HT (estrogen + progesterone) was associated with an increased risk (compared with placebo) of invasive breast cancer, cardiovascular disease, coronary heart disease, venous thromboembolism, and stroke.1 Subsequent analyses of WHI data and findings from other studies suggest that these risks may be related to the timing of HT after menopause and/or indeed the Received October 17, 2013; revised and accepted January 30, 2014. From 1The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China; and 2Nursing Department, Zhejiang Medical College, Hangzhou, China. Funding/support: This work is supported by the Foundation for General Project in the Health Department of Zhejiang province (Grant No. 2012KYB08). Financial disclosure/conflicts of interest: None reported. Address correspondence to: Xueying Lv, MD, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China. E-mail: [email protected]
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HT regimen.2 Nevertheless, HT in postmenopausal women has continued to be a topic of intense interest and investigation, reflecting the fact that our understanding of the pros and cons of HT is far from complete. A number of reviews and meta-analyses have reported on the relationship between HT and stroke among postmenopausal women who have received HT.3
Risk of stroke in healthy postmenopausal women during and after hormone therapy: a meta-analysis Haifeng Gu, MD, MS,1 Xiaohong Zhao, MD, MS,1 Xiaoping Zhao, MD, MS,2 Yunmei Yang, MD, PhD,1 and Xueying Lv, MD1 Abstract Objective: This meta-analysis aims to examine the risk of stroke in healthy postmenopausal women during and after hormone therapy (HT). Methods: Medline, The Cochrane Library, EMBASE, and Google Scholar were searched for randomized controlled trials involving healthy postmenopausal women who received HT and were followed up for at least 3 years after starting treatment. The primary outcome measures were stroke hazard ratio (HR) for the intervention phase, stroke HR for the postintervention phase, and overall stroke HR. Results: Four studies, involving 15,423 participants who received HT and 14,582 participants who received placebo, met the criteria for inclusion in the meta-analysis. The mean age of participants ranged from approximately 50 to 64 years. HT was given as conjugated equine estrogens in three studies and as 17A-estradiol in one study. The duration of HT ranged from 3.0 to 10.1 years. The length of follow-up after the start of HT ranged from 3.0 to 15.8 years. Meta-analysis revealed that the stroke HR during the intervention phase and the overall stroke HR were significantly increased among women who received HT (intervention phase: pooled HR, 1.32; 95% CI, 1.12-1.56; P = 0.001; overall: pooled HR, 1.15; 95% CI, 1.03-1.28; P = 0.017). The stroke HR during the postintervention phase was not increased among women who received HT (pooled HR, 1.00; 95% CI, 0.85-1.16; P = 0.958). Sensitivity analysis confirmed the reliability of the meta-analysis for both outcomes. Conclusions: These findings suggest that HT may increase the risk of stroke during, but not after, HT in healthy postmenopausal women. Key Words: Hormone therapy Y Intervention Y Meta-analysis Y Postintervention Y Postmenopause Y Stroke Y Women.
U
ntil 2002, hormone therapy (HT) was commonly prescribed to treat menopause symptoms and to treat or prevent chronic diseases such as cardiovascular disease and osteoporosis. This changed with the release of the initial findings from the Women’s Health Initiative (WHI) study in 2002,1 which suggested that the overall health risk of HT exceeded the health benefit. More specifically, the findings from this randomized controlled trial indicated that HT (estrogen + progesterone) was associated with an increased risk (compared with placebo) of invasive breast cancer, cardiovascular disease, coronary heart disease, venous thromboembolism, and stroke.1 Subsequent analyses of WHI data and findings from other studies suggest that these risks may be related to the timing of HT after menopause and/or indeed the Received October 17, 2013; revised and accepted January 30, 2014. From 1The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China; and 2Nursing Department, Zhejiang Medical College, Hangzhou, China. Funding/support: This work is supported by the Foundation for General Project in the Health Department of Zhejiang province (Grant No. 2012KYB08). Financial disclosure/conflicts of interest: None reported. Address correspondence to: Xueying Lv, MD, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China. E-mail: [email protected]
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HT regimen.2 Nevertheless, HT in postmenopausal women has continued to be a topic of intense interest and investigation, reflecting the fact that our understanding of the pros and cons of HT is far from complete. A number of reviews and meta-analyses have reported on the relationship between HT and stroke among postmenopausal women who have received HT.3
