DESIGN: A comprehensive search of medline, cinahl, and embase databases was performed to identify randomized controlled trials of hormone replacement therapy from 1966 to September 2002. The search was augmented by scanning selected journals through April 2003 and references of identified articles. Randomized trials of greater than 6 months’ duration were included if they compared hormone replacement with placebo or no treatment, and reported at least 1 death.

MEASUREMENTS: Outcomes measured were total deaths and deaths due to cardiovascular disease, cancer, or other causes. Odds ratios (OR) for total and cause-specific mortality were reported separately for trials with mean age of participants less than and greater than 60 years at baseline.

MAIN RESULTS: Pooled data from 30 trials with 26,708 participants showed that the OR for total mortality associated with hormone replacement was 0.98 (95% confidence interval [CI], 0.87 to 1.12). Hormone replacement reduced mortality in the younger age group (OR, 0.61; CI, 0.39 to 0.95), but not in the older age group (OR, 1.03; CI, 0.90 to 1.18). For all ages combined, treatment did not significantly affect the risk for cardiovascular or cancer mortality, but reduced mortality from other causes (OR, 0.67; CI, 0.51 to 0.88).

CONCLUSIONS: Hormone replacement therapy reduced total mortality in trials with mean age of participants under 60 years. No change in mortality was seen in trials with mean age over 60 years.