Context Hormone replacement therapy (HRT) is widely considered to reduce fractures,
but this belief is based on observational data; evidence from randomized trials
Objective To conduct a systematic review of all randomized trials of HRT that
have reported or collected nonvertebral fracture data but that may not have
focused on fracture prevention.
Data Sources The MEDLINE, EMBASE, Science Citation Index, and Cochrane Controlled
Trials Register databases were searched from 1997 through 2000 and a search
was conducted of all recent systematic reviews to identify older studies.
Authors were contacted to establish whether fracture data had been collected
but not reported. Researchers in the field and pharmaceutical companies also
were contacted to try to identify unpublished studies.
Study Selection Trials were included in which participants had been randomized to at
least 12 months of therapy and data on nonvertebral fractures at any other
site and due to any cause were available. Of 70 initially identified studies,
22 were included in the analysis.
Data Extraction Both investigators extracted data independently and appraised trial
quality according to the Jadad scale, which assesses the methods of randomization,
concealment allocation, and reporting of withdrawals and dropouts. Disagreements
were resolved by discussion.
Data Synthesis There was an overall 27% reduction in nonvertebral fractures in a pooled
analysis (reduction favoring HRT in relative risk [RR], 0.73; 95% confidence
interval [CI], 0.56-0.94; P = .02). This effect was
greater among women randomized to HRT who had a mean age younger than 60 years
(RR, 0.67; 95% CI, 0.46-0.98; P = .03). Among women
with a mean age of 60 years or older, there was a reduced effect (RR, 0.88;
95% CI, 0.71-1.08; P = .22). For hip and wrist fractures
alone, the effectiveness of HRT appeared more marked (RR, 0.60; 95% CI, 0.40-0.91; P = .02), particularly for women younger than 60 years
(RR, 0.45; 95% CI, 0.26-0.79; P = .005).
Conclusions Our meta-analysis of randomized controlled trials of HRT noted a statistically
significant reduction in nonvertebral fractures. However, this effect may
be attenuated in older women.