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Etiology

Postmenopausal hormone use was associated with decreased total mortality

ACP J Club. 1998 Jan-Feb;128:14. doi:10.7326/ACPJC-1998-128-1-014


Source Citation

Grodstein F, Stampfer MJ, Colditz GA, et al. Postmenopausal hormone therapy and mortality. N Engl J Med. 1997 Jun 19;336:1769-75.


Abstract

Objective

To determine whether postmenopausal hormone use was associated with total mortality.

Design

A nested case-control study of participants in the Nurses' Health Study.

Setting

Community-based study in the United States.

Participants

121 700 nurses (women) aged 30 to 55 years in 1976 completed questionnaires in 1976 and every 2 years until 1994. Postmenopausal women were included in the analysis. Exclusion criteria were cardiovascular disease or cancer before menopause. 3637 women died during follow-up and were considered to be the case-patients. Each woman who died was matched with 10 control-women who were alive either at the date of death or diagnosis of the fatal illness (34 625 control-patients).

Assessment of risk factors

Hormone use (current, past, never) was defined according to the report on the last questionnaire completed before death, before the diagnosis of the disease that led to death, or on the questionnaire that matched the date of death for control-women.

Main outcome measures

All-cause mortality and mortality from coronary heart disease, stroke, all types of cancer, and breast cancer.

Main results

Adjustment was done for age, age at menopause, type of menopause, body mass index, diabetes, high blood pressure, high cholesterol levels, smoking, past use of oral contraceptives, family history of myocardial infarction or breast cancer, parity, age at menarche, and time period (8 biennial questionnaire periods). Never use of postmenopausal hormones was taken as the reference standard. Compared with never use, current use was associated with a lower adjusted risk for all-cause mortality (relative risk [RR], 0.63, 95% CI 0.56 to 0.70), coronary heart disease mortality (RR 0.47, CI 0.32 to 0.69), and all cancer mortality (RR 0.71, CI 0.62 to 0.81) but not with mortality from stroke (RR 0.68, CI 0.39 to 1.16) or breast cancer (RR 0.76, CI 0.56 to 1.02). Past use of postmenopausal hormones was not associated with decreased risk for any outcome. The magnitude of the risk reduction for all-cause mortality decreased with the length of time postmenopausal hormones ! were taken (RR for < 5 y 0.56, CI 0.48 to 0.65; RR for 5 to 9 y 0.60, CI 0.50 to 0.72; and RR for ≥ 10 y 0.80, CI 0.67 to 0.96). Subgroup analysis showed that women who were at high risk for cardiovascular disease had a greater benefit in terms of all-cause mortality (RR 0.51, CI 0.45 to 0.57 vs RR for low-risk women 0.89, CI 0.62 to 1.28).

Conclusions

Current use of postmenopausal hormones reduced all-cause mortality in women. The magnitude of the reduction decreased with increasing duration of use. Women with cardiovascular risk factors had the greatest benefit from use of postmenopausal hormones.

Source of funding: National Institutes of Health.

For article reprint: Dr. F. Grodstein, Channing Laboratory, 181 Longwood Avenue, Boston, MA 02115, USA. FAX 617-525-2008.


Commentary

The high-quality design of the study by Grodstein and colleagues lends substantial weight to the results. The strengths of the study include careful matching of cases and controls, the ascertainment of hormone use before the diagnosis of terminal disease, adjustment of results using the major risk factors for both heart disease and breast cancer, and a 98% follow-up for mortality. This study supports previous research that postmenopausal hormones lower heart disease mortality by approximately 50%, with greatest benefit for women with ≥ 1 cardiovascular risk factor. It also extends these findings to include all-cause mortality and the contribution of such variables as duration of hormone use and risk factors for heart disease and breast cancer. Physicians should now feel more confident recommending hormone use, especially for women with 1 or more cardiovascular risk factors.

It is of interest that a positive family history of breast cancer did not diminish the protective effects of hormone use on all-cause mortality. The protective effects of hormones were lost 5 years after the discontinuation of use, and women who plan to discontinue hormones should be made aware of this. Of note, generalizability may be somewhat limited because the proportion of deaths in the study cohort (even among never users) from breast cancer was higher and from heart disease was lower than that in the general population of U.S. women (1).

One puzzling issue remains. In 1995, data from the same cohort of women revealed an adjusted RR for breast cancer mortality in current hormone users of 1.14 (CI 0.85 to 1.51) in comparison with never users (2), but in the present study this same RR decreased to 0.76 (CI 0.56 to 1.02). Despite a significant increase in breast cancer mortality with longer duration of use in the 1995 report, the present study reports a nonsignificant association after 10 years of use (RR 1.43, CI 0.82 to 2.48). Until results from ongoing randomized trials resolve such discrepancies, this study highlights the fact that the large protective effect of hormones on all-cause mortality and specifically on heart disease mortality outweighs a possible increase in breast cancer mortality.

Sally E. McNagny, MD, MPH
Emory UniversityAtlanta, Georgia, USA

Sally E. McNagny, MD, MPH
Emory University
Atlanta, Georgia, USA


References

1. Bureau of the Census. Statistical Abstract of the United States. 1996. The National Data Book. Washington, DC: U.S. Department of Commerce; 1996.

2. Colditz GA, Hankinson SE, Hunter DJ, et al. The use of estrogens and progestins and the risk of breast cancer in postmenopausal women. N Engl J Med. 1995;332:1589-93.