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Menopausal hormone therapy and women's health: an umbrella review. [Dataset]


Guo-Qiang Zhang
Data Collector

Jin-Liang Chen
Data Collector

Ying Luo
Data Collector

Maya B. Mathur
Data Collector

Panagiotis Anagnostis
Data Collector

Ulugbek Nurmatov
Data Collector

Madar Talibov
Data Collector

Jing Zhang
Data Collector

Catherine M. Hawrylowicz
Data Collector

Mary Ann Lumsden
Data Collector

Hilary Critchley
Data Collector

Aziz Sheikh
Data Collector

Bo Lundb�ck
Data Collector

Cecilia L�sser
Data Collector

Hannu Kankaanranta
Data Collector

Bright I. Nwaru
Data Collector


Why was this study done? By 2050, it is estimated that worldwide more than 1.6 billion women will have reached menopause or be postmenopausal, up from 1 billion in 2020 and up to 75% of menopausal women are affected by bothersome menopausal symptoms, such as hot flashes and night sweats. Menopausal hormone therapy (MHT) is the most effective treatment for alleviating menopausal symptoms, but its effects on numerous health outcomes remain uncertain. What did the researchers do and find? The authors included 60 published systematic reviews of MHT use in menopausal women, involving 102 meta-analyses of randomized controlled trials and 38 of observational studies, and synthesized the evidence on 102 health outcomes. Overall, MHT had a complex balance of benefits and harms; for example, beyond alleviation of menopausal symptoms, it was associated with decreased risks of bone fracture, diabetes mellitus, and esophageal, gastric, and colorectal cancer, but increased risks of stroke, venous thromboembolism, gallbladder disease, and breast and ovarian cancer. The available clinical data in support of MHT reducing the risk of coronary heart disease and all-cause mortality in women aged [more than] 60 years or within 10 years from menopause (known as the “timing hypothesis”) were only suggestive. The overall quality of included systematic reviews was moderate to poor. What do these findings mean? This overview of the evidence landscape could help guideline developers and decision-makers better appreciate the trade-offs between the benefits and harms associated with MHT use in menopausal women. More data are needed to evaluate the timing hypothesis for coronary heart disease and all-cause mortality. Clinicians should evaluate the scientific strength of systematic reviews prior to considering applying their results in clinical practice.


ZHANG, G.-Q., CHEN, J.-L., LUO, Y., et al. 2021. Menopausal hormone therapy and women's health: an umbrella review. [Dataset]. PLoS medicine [online], 18(8), article e1003731. Available from:

Acceptance Date Jul 12, 2021
Online Publication Date Aug 2, 2021
Publication Date Dec 31, 2021
Deposit Date Aug 17, 2021
Publicly Available Date Aug 17, 2021
Publisher Public Library of Science
Keywords Estrogen; Menopausal hormone therapy; Meta-analysis; Progestin; Umbrella review
Public URL
Related Public URLs
Type of Data XLSX files, PDF files, DOCX, R file and accompanying TXT file.
Collection Date Jun 7, 2021
Collection Method MEDLINE, EMBASE, and 10 other databases were searched from inception to November 26, 2017, updated on December 17, 2020, to identify systematic reviews or meta-analyses of randomized controlled trials (RCTs) and observational studies investigating effects of MHT, including estrogen-alone therapy (ET) and estrogen plus progestin therapy (EPT), in perimenopausal or postmenopausal women in all countries and settings. All health outcomes in previous systematic reviews were included, including menopausal symptoms, surrogate endpoints, biomarkers, various morbidity outcomes, and mortality. Two investigators independently extracted data and assessed methodological quality of systematic reviews using the updated 16-item AMSTAR 2 instrument. Random-effects robust variance estimation was used to combine effect estimates, and 95% prediction intervals (PIs) were calculated whenever possible. The term MHT was used to encompass ET and EPT, and results are presented for MHT for each outcome, unless otherwise indicated. Sixty systematic reviews were included, involving 102 meta-analyses of RCTs and 38 of observational studies, with 102 unique outcomes. The overall quality of included systematic reviews was moderate to poor. In meta-analyses of RCTs, MHT was beneficial for vasomotor symptoms (frequency: 9 trials, 1,104 women, risk ratio [RR] 0.43, 95% CI 0.33 to 0.57, p < 0.001; severity: 7 trials, 503 women, RR 0.29, 95% CI 0.17 to 0.50, p = 0.002) and all fracture (30 trials, 43,188 women, RR 0.72, 95% CI 0.62 to 0.84, p = 0.002, 95% PI 0.58 to 0.87), as well as vaginal atrophy (intravaginal ET), sexual function, vertebral and nonvertebral fracture, diabetes mellitus, cardiovascular mortality (ET), and colorectal cancer (EPT), but harmful for stroke (17 trials, 37,272 women, RR 1.17, 95% CI 1.05 to 1.29, p = 0.027) and venous thromboembolism (23 trials, 42,292 women, RR 1.60, 95% CI 0.99 to 2.58, p = 0.052, 95% PI 1.03 to 2.99), as well as cardiovascular disease incidence and recurrence, cerebrovascular disease, nonfatal stroke, deep vein thrombosis, gallbladder disease requiring surgery, and lung cancer mortality (EPT). In meta-analyses of observational studies, MHT was associated with decreased risks of cataract, glioma, and esophageal, gastric, and colorectal cancer, but increased risks of pulmonary embolism, cholelithiasis, asthma, meningioma, and thyroid, breast, and ovarian cancer. ET and EPT had opposite effects for endometrial cancer, endometrial hyperplasia, and Alzheimer disease. The major limitations include the inability to address the varying effects of MHT by type, dose, formulation, duration of use, route of administration, and age of initiation and to take into account the quality of individual studies included in the systematic reviews. The study protocol is publicly available on PROSPERO (CRD42017083412).