PLoS Medicine (Aug 2021)

Menopausal hormone therapy and women's health: An umbrella review.

  • Guo-Qiang Zhang,
  • Jin-Liang Chen,
  • Ying Luo,
  • Maya B Mathur,
  • Panagiotis Anagnostis,
  • Ulugbek Nurmatov,
  • Madar Talibov,
  • Jing Zhang,
  • Catherine M Hawrylowicz,
  • Mary Ann Lumsden,
  • Hilary Critchley,
  • Aziz Sheikh,
  • Bo Lundbäck,
  • Cecilia Lässer,
  • Hannu Kankaanranta,
  • Siew Hwa Lee,
  • Bright I Nwaru

DOI
https://doi.org/10.1371/journal.pmed.1003731
Journal volume & issue
Vol. 18, no. 8
p. e1003731

Abstract

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BackgroundThere remains uncertainty about the impact of menopausal hormone therapy (MHT) on women's health. A systematic, comprehensive assessment of the effects on multiple outcomes is lacking. We conducted an umbrella review to comprehensively summarize evidence on the benefits and harms of MHT across diverse health outcomes.Methods and findingsWe searched MEDLINE, EMBASE, and 10 other databases 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. We used the term MHT 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 ConclusionsMHT has a complex balance of benefits and harms on multiple health outcomes. Some effects differ qualitatively between ET and EPT. The quality of available evidence is only moderate to poor.