10.1371/journal.pmed.1003731 Menopausal hormone therapy and women's health: an umbrella review. [Dataset] Zhang, Guo-Qiang Guo-Qiang Zhang Chen, Jin-Liang Jin-Liang Chen Luo, Ying Ying Luo Mathur, Maya B. Maya B. Mathur Anagnostis, Panagiotis Panagiotis Anagnostis Nurmatov, Ulugbek Ulugbek Nurmatov Talibov, Madar Madar Talibov Zhang, Jing Jing Zhang Hawrylowicz, Catherine M. Catherine M. Hawrylowicz Ann Lumsden, Mary Mary Ann Lumsden Critchley, Hilary Hilary Critchley Sheikh, Aziz Aziz Sheikh Lundbäck, Bo Bo Lundbäck Lässer, Cecilia Cecilia Lässer Kankaanranta, Hannu Hannu Kankaanranta Lee, Siew Hwa Siew Hwa Lee Nwaru, Bright I. Bright I. Nwaru Public Library of Science 2021 Estrogen; Menopausal hormone therapy; Meta-analysis; Progestin; Umbrella review 2021-07-12 2021-06-07 Dataset 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 hypothesisâ€) 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.