Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Persons: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized controlled trials and prospective cohort studies
PubMed 36318128 · doi:10.1001/jama.2022.18324
What was done
This systematic review updated evidence for the US Preventive Services Task Force on the benefits and harms of hormone therapy for the primary prevention of chronic conditions in postmenopausal persons. Searches of PubMed/MEDLINE, Cochrane Library, EMBASE, and trial registries spanned January 1, 2016, through October 12, 2021, with surveillance through July 2022. English-language randomized clinical trials and prospective cohort studies of fair or good quality were included. Abstract and full-text review and study quality assessments were conducted in duplicate, and meta-analyses were performed when at least three similar studies were available.
What was found
Twenty trials (N = 39,145) and 3 cohort studies (N = 1,155,410) met inclusion criteria. - Estrogen only vs placebo (per 10,000 persons): - Benefits: significantly lower risks for diabetes over 7.1 years (1050 vs 903 cases; 134 fewer [95% CI, 18-237]) and fractures over 7.2 years (1024 vs 1413 cases; 388 fewer [95% CI, 277-489]). - Harms: significantly increased risks for gallbladder disease over 7.1 years (1113 vs 737 cases; 377 more [95% CI, 234-540]), stroke over 7.2 years (318 vs 239 cases; 79 more [95% CI, 15-159]), venous thromboembolism over 7.2 years (258 vs 181 cases; 77 more [95% CI, 19-153]), and urinary incontinence over 1 year (2331 vs 1446 cases; 885 more [95% CI, 659-1135]). - Estrogen plus progestin vs placebo (per 10,000 persons): - Benefits: significantly lower risks for colorectal cancer over 5.6 years (59 vs 93 cases; 34 fewer [95% CI, 9-51]), diabetes over 5.6 years (403 vs 482 cases; 78 fewer [95% CI, 15-133]), and fractures over 5 years (864 vs 1094 cases; 230 fewer [95% CI, 66-372]). - Harms: significantly increased risks for invasive breast cancer (242 vs 191 cases; 51 more [95% CI, 6-106]), gallbladder disease (723 vs 463 cases; 260 more [95% CI, 169-364]), stroke (187 vs 135 cases; 52 more [95% CI, 12-104]), and venous thromboembolism (246 vs 126 cases; 120 more [95% CI, 68-185]) over 5.6 years; probable dementia over 4.0 years (179 vs 91 cases; 88 more [95% CI, 15-212]); and urinary incontinence over 1 year (1707 vs 1145 cases; 562 more [95% CI, 412-726]).
Why it matters
This review provides the updated evidence foundation for preventive guidelines, showing that postmenopausal hormone therapy confers some preventive benefits (fewer fractures, reduced diabetes incidence) but carries substantial, statistically significant risks of serious multi-organ adverse events.
Limits
The review was restricted to English-language publications and studies of fair or good quality. The abstract does not report effects stratified by participant age, time since menopause onset, baseline cardiovascular risk, specific hormone formulation, or route of administration, and observational cohort inclusions carry inherent residual confounding.
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