All relevant English-language studies were identified in MEDLINE (1966-2001), HealthSTAR (1975-2001), Cochrane Library databases, and reference lists of key articles. Recent results of the Women's Health Initiative (WHI) and the Heart and
Estrogen/
progestin Replacement Study (HERS) are included for reported outcomes.
STUDY SELECTION AND DATA EXTRACTION: We used all published studies of HRT if they contained a comparison group of HRT nonusers and reported data relating to HRT use and clinical outcomes of interest. Studies were excluded if the population was selected according to prior events or presence of conditions associated with higher risks for targeted outcomes.
DATA SYNTHESIS: Meta-analyses of observational studies indicated summary relative risks (RRs) for
coronary heart disease (CHD) incidence and mortality that were significantly reduced among current HRT users only, although risk for incidence was not reduced when only studies that controlled for socioeconomic status were included. The WHI reported increased CHD events (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.02-1.63).
Stroke incidence but not mortality was significantly increased among HRT users in the meta-analysis and the WHI. The meta-analysis indicated that risk was significantly elevated for thromboembolic
stroke (RR, 1.20; 95% CI, 1.01-1.40) but not subarachnoid or intracerebral
stroke. Risk of
venous thromboembolism among current HRT users was increased overall (RR, 2.14; 95% CI, 1.64-2.81) and was highest during the first year of use (RR, 3.49; 95% CI, 2.33-5.59) according to a meta-analysis of 12 studies. Protection against
osteoporotic fractures is supported by a meta-analysis of 22
estrogen trials, cohort studies, results of the WHI, and trials with bone density outcomes. Current
estrogen users have an increased risk of
breast cancer that increases with duration of use.
Endometrial cancer incidence, but not mortality, is increased with unopposed
estrogen use but not with
estrogen with
progestin. A meta-analysis of 18 observational studies showed a 20% reduction in
colon cancer incidence among women who had ever used HRT (RR, 0.80; 95% CI, 0.74-0.86), a finding supported by the WHI. Women symptomatic from menopause had improvement in certain aspects of cognition. Current studies of
estrogen and
dementia are not definitive. In a cohort study, current HRT users had an age-adjusted RR for
cholecystitis of 1.8 (95% CI, 1.6-2.0), increasing to 2.5 (95% CI, 2.0-2.9) after 5 years of use.
CONCLUSIONS: