Postmenopausal Estrogen Use and Mortality

The authors studied the association between postmenopausal estrogen use and mortality from cardiovascular disease, coronary heart disease, cancer, and all causes in a cohort of 1,868 women aged 50-79 years residing in a planned community. After 12 years, the age-adjusted all-cause mortality rate was lower in the 734 postmenopausal estrogen users (14.9/100 women) compared with the 1,134 nonusers (21.5/100 women) (relative risk (RR) = 0.69, 95% confidence interval (Cl) 0.55-0.87). After adjustment for age, systolic blood pressure, social class, fasting plasma cholesterol, fasting plasma glucose, Quetelet index (weight (lbs)/height (in)2 x 100), and cigarette smoking by the Cox model, the relative risk increased to 0.79 (95% Cl 0.62-1.01). Because a postmenopausal estrogen-smoking interaction term was significant (p = 0.025), separate Cox models were run for never, past, and current smokers. In never and current smokers, estrogen was protective for all-cause mortality, with relative risks of 0.67 (95% Cl 0.45-0.99) and 0.62 (95% Cl 0.39-0.98), respectively. However, past smokers were not protected by postmenopausal estrogen use (RR = 1.32, 95% Cl 0.84-2.08). Cause-specific models revealed differences in the association of postmenopausal estrogen use with cardiovascular disease mortality and coronary heart disease mortality that were dependent on smoking status. Postmenopausal estrogen use was strongly protective in current smokers but was associated with increased risk in past smokers. As expected, cancer mortality was increased in smokers. The confidence intervals for the relative risk estimate of postmenopausal estrogen use for cancer mortality in each smoking category included one. Finally, a separate analysis of subsequent three-year mortality in women surviving the first nine years of follow-up revealed reduced death rates only for women using estrogen at both baseline and nine years of follow-up, suggesting both a conservative bias in our data introduced by the large reduction in postmenopausal estrogen use during the study period and the possibility of a stronger protective effect for recent postmenopausal estrogen use.