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Statistical adjustment for a measure of healthy lifestyle doesn’t yield the truth about hormone therapy

Diana B. Petitti and Wansu Chen

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Abstract

The Women’s Health Initiative randomized clinical trial of hormone therapy found no benefit of hormones in preventive cardiovascular disease, a finding in striking contrast with a large body of observational research. Understanding whether better methodology and/or statistical adjustment might have prevented the erroneous conclusions of observational research is important. This is a re-analysis of data from a case-control study examining the relationship of postmenopausal hormone therapy and the risks of myocardial infarction (MI) and ischemic stroke in which we reported no overall increase or decrease in the risk of either event. Variables measuring health behavior/lifestyle that are not likely to be causally with the risks of MI and stroke (e.g., sunscreen use) were included in multivariate analysis along with traditional confounders (age, hypertension, diabetes, smoking, body mass index, ethnicity, education, prior coronary heart disease for MI and prior stroke/TIA for stroke) to determine whether adjustment for the health behavior/lifestyle variables could reproduce or bring the results closer to the findings in a large and definitive randomized clinical trial of hormone therapy, the Women’s Health Initiative.

For both MI and stroke, measures of health behavior/lifestyle were associated with odds ratios (ORs) less than 1.0. Adjustment for traditional cardiovascular disease confounders did not alter the magnitude of the ORs for MI or stroke. Addition of a subset of these variables selected using stepwise regression to the final MI or stroke models along with the traditional cardiovascular disease confounders moved the ORs for estrogen and estrogen/progestin use closer to values observed in the Women Health Initiative clinical trial, but did not reliably reproduce the clinical trial results for these two endpoints.

Chapter information

Source
Deborah Nolan and Terry Speed, eds., Probability and Statistics: Essays in Honor of David A. Freedman (Beachwood, Ohio, USA: Institute of Mathematical Statistics, 2008), 142-152

Dates
First available in Project Euclid: 7 April 2008

Permanent link to this document
https://projecteuclid.org/euclid.imsc/1207580083

Digital Object Identifier
doi:10.1214/193940307000000437

Zentralblatt MATH identifier
1166.62362

Subjects
Primary: 92C60: Medical epidemiology
Secondary: 62P10: Applications to biology and medical sciences 00B30: Festschriften

Keywords
cerebrovascular disorders cerebral infarction stroke coronary epidemiological methods estrogen heart disease hormone replacement myocardial infarction

Rights
Copyright © 2008, Institute of Mathematical Statistics

Citation

Petitti, Diana B.; Chen, Wansu. Statistical adjustment for a measure of healthy lifestyle doesn’t yield the truth about hormone therapy. Probability and Statistics: Essays in Honor of David A. Freedman, 142--152, Institute of Mathematical Statistics, Beachwood, Ohio, USA, 2008. doi:10.1214/193940307000000437. https://projecteuclid.org/euclid.imsc/1207580083


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References

  • [1] Anderson, G., Limacher, M., Assaf, A. et al. (2004). Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: The women’s health initiative randomized controlled trial. JAMA 291 1701–1–2.
  • [2] DeMets, D. (2005). Invited commentary on prentice, pettinger and anderson. Biometrics 61 914–918.
  • [3] Freedman, D. and Petitti, D. (2005). Invited commentary on prentice, pettinger and anderson. Biometrics 61 918–920.
  • [4] Greenland, S. (2005). Invited commentary on prentice, pettinger and anderson. Biometrics 61 920–921.
  • [5] Petitti, D. and Freedman, D. (2005). Invited commentary: How far can epidemiologists get with statistical adjustment? Am. J. Epidemiol. 162 415–418.
  • [6] Petitti, D., Sidney, S., Quesenberry, C. and Bernstein, A. (1998). Ischemic stroke and use of estrogen and estrogen/progestogen as hormone replacement therapy. Stroke 29 23–28.
  • [7] Prentice, R., Langer, R., Stefanick, M., Howard, B., Pettinger, M., Anderson, G., Barad, D., Curb, J., Kotchen, J., Kuller, L., Limacher, M. and Wactawski-Wende, J. (2006). Combined analysis of women’s health initiative observational and clinical trial data on postmenopausal hormone treatment and cardiovascular disease. Am. J. Epidemiol. 163 589–599.
  • [8] Prentice, R., Pettinger, M. and Anderson, G. (2005). Statistical issues arising in the women’s health initiative. Biometrics 61 899–911.
  • [9] Psaty, B., Heckbert, S., Atkins, D., Siscovick, D., Koepsell, T., Wahl, P., Longstreth, W. J., Weiss, N., Wagner, E. and Prentice, R. (1993). A review of the association of estrogens and progestins with cardiovascular disease in postmenopausal women. Arch. Intern. Med. 153 1421–1427.
  • [10] Rossouw, J., Anderson, G., Prentice, R. et al. (2002). Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the women’s health initiative randomized controlled trial. JAMA 288 321–333.
  • [11] Sidney, S., Petitti, D. and Quesenberry, C. (1997). Myocardial infarction and the use of estrogen and estrogen-progestogen in postmenopausal women. Ann. Intern. Med. 127 501–508.
  • [12] Stampfer, M. and Colditz, G. (1991). Estrogen replacement therapy and coronary heart disease: A quantitative assessment of the epidemiologic evidence. Prev. Med. 20 47–63.