Wells · Endocrine reviews 2002 · systematic review and meta-analysis of randomized controlled trials · n=57 studies

Meta-analyses of therapies for postmenopausal osteoporosis. V. Meta-analysis of the efficacy of hormone replacement therapy in treating and preventing osteoporosis in postmenopausal women.

Cited 370 times in the scientific literature.

Level 1 - systematic review of randomized trials

Systematic review and meta-analysis of randomized controlled trials

PubMed 12202468 · doi:10.1210/er.2001-5002 · record verified 2026-08-29

What was done

Authors conducted a systematic review and meta-analysis of randomized controlled trials (1966–1999) from MEDLINE, EMBASE, Cochrane Controlled Register, citations, and conference proceedings. Studies included postmenopausal women randomized to hormone replacement therapy (HRT) or a control (placebo or calcium/vitamin D) with a minimum duration of 1 year. Methodological quality assessment and data abstraction were performed independently by three reviewers.

What was found

A total of 57 randomized trials met inclusion criteria, 7 of which reported fracture outcomes. HRT showed a trend toward reduced incidence of vertebral fractures (relative risk [RR] 0.66, 95% CI 0.41–1.07; 5 trials) and nonvertebral fractures (RR 0.87, 95% CI 0.71–1.08; 6 trials). For bone mineral density (BMD), the percent change difference at 2 years significantly favored HRT across all assessed sites: 6.76% (95% CI 5.83–7.89; 21 trials) at the lumbar spine, 4.53% (95% CI 3.68–5.36; 14 trials) at the forearm, and 4.12% (95% CI 3.45–4.80; 9 trials) at the femoral neck.

Why it matters

The study synthesizes evidence confirming that HRT reliably increases bone mineral density at multiple skeletal sites, though pre-2000 trial evidence was underpowered to confirm statistically significant fracture reductions.

Limits

Fracture data were available in only 7 of 57 studies, resulting in wide confidence intervals spanning no effect. Total participant sample size, specific HRT regimens (types and doses), baseline bone health, and safety/adverse event outcomes were not reported in the abstract.

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