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Objective: To examine the effect of postmenopausal estrogen therapy (ET), including duration and recency of use, on all-cause mortality in older women., Design: As part of a prospective cohort study of residents of a California retirement community begun in the early 1980s, Leisure World Cohort women (median age, 73 y) completed a postal health survey including details on ET use and were followed up for 22 years (1981-2003). Age- and multivariate-adjusted risk ratios (RR) and 95% CIs were calculated using proportional hazard regression., Results: Of the 8,801 women, 6,626 died during follow-up (median age, 88 y). ET users had an age-adjusted mortality rate of 52.9 per 1,000 person-years compared with 56.5 among lifetime nonusers (RR = 0.91; 95% CI, 0.87-0.96). Risk of death decreased with both increasing duration of ET and decreasing years since last use (P for trend < 0.001). The risk was lowest 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 201 y). For long-term users, the age-adjusted mortality rate was 50.4 per 1,000 person-years. Lower-dose users (≤0.625 mg) had a slightly better survival rate than higher-dose users (RR = 0.84; 95% CI, 0.78-0.91 vs RR = 0.91; 95% CI, 0.83-0.97). Risk did not differ by route of administration (P = 0.56). Further adjustment for potential confounders had little effect on the observed RRs for ET., Conclusion: Long-term ET is associated with lower all-cause mortality in older women.

Observational studies and randomized controlled trials of menopausal hormone therapy (HT) and chronic disease risk appear to have divergent results for cardiovascular disease. However, differences may be related to a modifying effect of age, time since menopause, and HT formulation. In the Nurses' Health Study (NHS) (enrolling during 1980-1994 and following participants until 2002), we investigated associations between the use of oral conjugated equine estrogens (CEE) (0.625 mg/day) plus medroxyprogesterone acetate (MPA) (<10 mg/day) or oral CEE alone and cardiovascular disease, cancer, all-cause mortality, and other major endpoints among postmenopausal women, aged 50-79 years at HT initiation. Among women aged 50-59 years at HT initiation, associations of CEE alone or CEE+MPA with most clinical outcomes were highly concordant between NHS and Women's Health Initiative (WHI). However, for myocardial infarction, results for CEE+MPA were in the direction of risk elevation in WHI and in the direction of risk reduction in NHS. When examined according to years since menopause onset (<10 years) rather than age group, results were nonsignificant and concordant for both studies. Because few women in the NHS initiated HT after age 60 years, we did not examine associations in this group. Discrepancies between NHS and WHI could largely be attributed to differences in the age structure of the populations and age at HT initiation., (© The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To compare all-cause and specific-cause mortality rates in women who had or had not used long-term postmenopausal estrogen replacement therapy (ERT)., Methods: We identified women who used long-term postmenopausal ERT and compared them with a sample of age-matched postmenopausal nonusers. Through linking of these subjects' medical record numbers to various data bases, we examined survivorship and cause of death among estrogen users and nonusers. The risk of death in 232 postmenopausal women who began ERT within 3 years of menopause and used it for at least 5 years was compared with that of 222 age-matched postmenopausal nonusers. In the users, the mean length of estrogen use was 17.1 years., Results: Statistically significant reductions in all-cause mortality were found in users compared with nonusers. For death from any cause, the age-adjusted relative risk (RR) and associated 95% confidence interval (CI) in estrogen users was 0.54 (0.38-0.76). The reduction in all-cause mortality was largely due to reductions in coronary heart disease (RR 0.40, CI 0.16-1.02) and other cardiovascular disease (RR 0.27, CI 0.10-0.71). Overall cancer mortality was similar in the two groups (RR 0.85, CI 0.46-1.58), although estrogen users had a higher risk of death from breast cancer (RR 1.89, CI 0.43-8.36) and lower risk of death from lung cancer (RR 0.22, CI 0.04-1.15)., Conclusion: Long-term ERT use is associated with lower all-cause mortality and confers this apparent protection primarily through reduction in cardiovascular disease.