After eliminating 27 women who did not report their use of ET and 49 women with missing information on the other potential confounding variables, data from 8,801 women were analyzed. These women ranged in age from 44 to 101 years (median, 73 y). At study entry (completion of initial survey), 4,961 women (56%) reported having used ET. Estrogen users were on average younger than nonusers, and more estrogen users were past smokers, exercised daily, and had a history of angina and cancer, but fewer had a history of stroke and diabetes (). Among users, the median duration of ET was 8 years. Eighty-nine percent of estrogen users had used oral estrogen at least part of the time, and 61% had used only oral estrogen. Most estrogen use in this cohort was initiated in the immediate postmenopausal years and had been discontinued before entry into this study. Of those with a history of estrogen use, 1,298 (26%) had used ET within 1 year of study entry. The addition of progestogen to the treatment regimen is a recent phenomenon, and combination hormone therapy is uncommon in this cohort. In 1985, only 13% of estrogen users (1.6% of the cohort) were using progestogen. In 1992, these figures were 16% and 3.6%, respectively; in 1998, they were 18% and 5.8%.
Baseline characteristics of never vs ever users of estrogen therapy: the Leisure World Cohort Study, 1981–2003
By June 1, 2003, these 8,801 women had contributed 122,203 person-years of follow-up, and 6,626 had died. Age at death ranged from 59 to 110 years (median, 88 y). Ever use of ET was significantly related to increased longevity (RR = 0.91; 95% CI, 0.87–0.96; ). Women who had used ET had an age-adjusted mortality rate of 52.8 per 1,000 person-years, compared with 56.4 per 1,000 person-years among lifetime nonusers ().
Risk ratio of dying by use of estrogen therapy: the Leisure World Cohort Study, 1981–2003
Morality rate by age and use of estrogen therapy: the Leisure World Cohort Study, 1981–2003
Risk of death decreased with increasing duration of ET (P for trend <0.001; ). The lowest risks were observed among long-term (15+ y) users (RR = 0.83; 95% CI, 0.74–0.93 for 15–19 y and RR = 0.87; 95% CI, 0.80–0.94 for 20+ y compared with lifetime nonusers). The decreased risk among long-term users was evident within all age groups except those aged 95 years or older (). For long-term users, the age-adjusted mortality rate was 50.4 per 1,000 person-years.
Risk also decreased with increasing recency of use (P for trend <0.001; ). The relative risk for women who had used ET within 1 year of baseline compared with nonusers was 0.86 (95% CI, 0.79–0.93). Users of both lower (≤0.625 mg) and higher (≥1.25 mg) doses had significantly decreased risks of death compared with nonusers (RR = 0.84; 95% CI, 0.78–0.91 and RR = 0.91; 95% CI, 0.84–0.97, respectively). Although lower-dose users seemed to have a better survival rate than higher-dose users, the relative risk of death for higher-dose users compared with lower-dose users was not significant (RR = 1.07; 95% CI, 0.99–1.17). Likewise, risk did not differ significantly by route of administration (P = 0.56).
also shows the relation of the combined effect of duration and years since last use on mortality. Within each last use category, the lowest risk of death was observed for long-term users (15+ y). Long-term use significantly increased longevity in both recent users (within 4 y; RR = 0.85; 95% CI, 0.78–0.92) and in those who stopped using ET 5 to 14 years previously (RR = 0.86; 95% CI, 0.77–0.97). Long-term use also seemed to do so in those who stopped using ET 15 or more years previously (RR = 0.89; 95% CI, 0.71–1.11). However, the number of subjects in this category was small (n = 88), and the result was not significant. The largest risk and the only increased risk among estrogen users was in recent, short-term users (RR = 1.09; 95% CI, 0.86–1.38).
Adjustment for potential confounders (smoking, exercise, body mass index, and history of hypertension, angina, heart attack, stroke, diabetes, rheumatoid arthritis, and cancer) had little effect on the observed RRs for ET (). The risk of death among ever-users of ET changed from 0.91 with only age adjustment to 0.90 with adjustment for all potential confounders. For long-term users (20+ y), the risk changed from 0.87 to 0.84.