Correspondence

Postmenopausal Hormone Therapy

N Engl J Med 2003; 348:2363-2364June 5, 2003

Article

To the Editor:

The assertion by Grodstein et al. (Feb. 13 issue)1 in their Sounding Board article that confounding due to socioeconomic status is unlikely to explain the different reported associations between postmenopausal hormone therapy and cardiovascular disease in observational studies and in randomized clinical trials rests on flawed assumptions. Among these are the assumptions that the Nurses' Health Study “controlled for educational level and occupation by including only registered nurses” (with some adjustment for husband's educational level) and that the Leisure World study “adjusted for income by recruiting exclusively from a middle-class retirement community.”

These three socioeconomic variables — education, occupation, and a surrogate for income — are at best partial measures, with occupation particularly ill-suited for analyses of women's health.2 Evidence, including some from the Nurses' Health Study,3 indicates that the risk of cardiovascular disease among women (and men) is shaped by lifetime socioeconomic status, beginning in utero4; lifetime socioeconomic factors may also affect age at menopause.5 Greater precision in socioeconomic as well as biologic variables is needed in order to resolve discrepancies in research about postmenopausal hormone therapy.

Nancy Krieger, Ph.D.
Harvard School of Public Health, Boston, MA 02115

5 References

1. 1

   Grodstein F, Clarkson TB, Manson JE. Understanding the divergent data on postmenopausal hormone therapy. N Engl J Med 2003;348:645-650
   Full Text | Web of Science | Medline

2. 2

   Krieger N, Williams DR, Moss NE. Measuring social class in US public health research: concepts, methodologies, and guidelines. Annu Rev Public Health 1997;18:341-378
   CrossRef | Web of Science | Medline

3. 3

   Gliksman MD, Kawachi I, Hunter D, et al. Childhood socioeconomic status and risk of cardiovascular disease in middle aged US women: a prospective study. J Epidemiol Community Health 1995;49:10-15
   CrossRef | Web of Science | Medline

4. 4

   Davey Smith G, Gunnell D, Ben-Shlomo Y. Lifecourse approaches to socio-economic differentials in cause-specific adult mortality. In: Leon D, Walt G, eds. Poverty, inequality, and health: an international perspective. Oxford, England: Oxford University Press, 2000:88-124.
   

5. 5

   Wise LA, Krieger N, Zierler S, Harlow BL. Lifetime socioeconomic position in relation to onset of perimenopause. J Epidemiol Community Health 2002;56:851-860
   CrossRef | Web of Science | Medline

Author/Editor Response

We explored the issue of confounding by socioeconomic status in epidemiologic studies of postmenopausal hormone therapy and coronary heart disease; we did not seek to review the complex relation between socioeconomic status and coronary heart disease. In many observational studies, postmenopausal hormone users are of higher socioeconomic status than nonusers,1 which may lead to lower rates of coronary heart disease that are attributable to improved access to health care and healthier lifestyles. Use of cohorts such as that in the Nurses' Health Study inherently provides adjustment (although not complete adjustment) for such potential confounding, since all participants are registered nurses and have access to health care and knowledge about health. For example, in the Nurses' Health Study, the rates of cholesterol and blood-pressure screening and the intake of saturated fats are similar among hormone users and nonusers; adjustment for husband's education, childhood socioeconomic status, or household income did not change the reported results.2 Although numerous diseases are related to socioeconomic status, associations between hormone therapy and cancer, stroke, and fractures were similar in the Women's Health Initiative trial and in observational investigations. These findings indicate that confounding by socioeconomic status may not completely explain findings from observational studies regarding the relation between postmenopausal hormone therapy and coronary heart disease.

Francine Grodstein, Sc.D.
JoAnn Manson, M.D., Dr.P.H.
Brigham and Women's Hospital, Boston, MA 02115

Thomas B. Clarkson, D.V.M.
Wake Forest University School of Medicine, Winston-Salem, NC 27157

2 References

1. 1

   Barrett-Connor E. Postmenopausal estrogen and prevention bias. Ann Intern Med 1991;115:455-456
   Web of Science | Medline

2. 2

   Grodstein F, Stampfer MJ, Manson JE, et al. Postmenopausal estrogen and progestin use and the risk of cardiovascular disease. N Engl J Med 1996;335:453-461[Erratum, N Engl J Med 1996;335:1406.]
   Full Text | Web of Science | Medline

Citing Articles (5)

Citing Articles

1. 1

   N. Krieger. (2008) Hormone therapy and the rise and perhaps fall of US breast cancer incidence rates: critical reflections. International Journal of Epidemiology 37:3, 627-637
   CrossRef

2. 2

   W. Maziak. (2008) The triumph of the null hypothesis: epidemiology in an age of change. International Journal of Epidemiology 38:2, 393-402
   CrossRef

3. 3

   Nancy Krieger. (2007) Why Epidemiologists Cannot Afford to Ignore Poverty. Epidemiology 18:6, 658-663
   CrossRef

4. 4

   D. A Lawlor, G. Davey Smith, S. Ebrahim. (2004) Socioeconomic Position and Hormone Replacement Therapy Use: Explaining the Discrepancy in Evidence From Observational and Randomized Controlled Trials. American Journal of Public Health 94:12, 2149-2154
   CrossRef

5. 5

   Lamberto Manzoli, Pamela Di Giovanni, Livio Del Duca, Domenico De Aloysio, Davide Festi, Simona Capodicasa, Giovanni Monastra, Ferdinando Romano, Tommaso Staniscia. (2004) Use of hormone replacement therapy in Italian women aged 50–70 years. Maturitas 49:3, 241-251
   CrossRef