American Journal of Epidemiology Advance Access originally published online on August 5, 2008
American Journal of Epidemiology 2008 168(6):575-576; doi:10.1093/aje/kwn167
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Epplein et al. Respond to "Endometrial Hyperplasia—Getting Back to Normal"
1 Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA
2 Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, WA
3 Department of Obstetrics and Gynecology, School of Medicine, University of Washington, Seattle, WA
4 Group Health Center for Health Studies, Seattle, WA
5 Current affiliation: Epidemiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu, HI
Correspondence to Dr. Meira Epplein, Epidemiology Program, Cancer Research Center of Hawaii, 1236 Lauhala Street, Suite 407, Honolulu, HI 96822 (e-mail: mepplein{at}crch.hawaii.edu).
Received for publication May 8, 2008. Accepted for publication May 12, 2008.
We thank Dr. Lacey for his commentary (1). We share Dr. Lacey's concern that the inability to fully distinguish endometrial hyperplasia from carcinoma means that even if these conditions did not share risk factors, there would be some indication in a given study that they did. As he noted, we attempted to guard against this possibility by including as cases only those deemed by a pathology review panel to truly have hyperplasia (2). In addition, we redid our analyses after excluding those women initially diagnosed with hyperplasia who went on to have a diagnosis of endometrial cancer at hysterectomy performed within 8 weeks of the hyperplasia diagnosis (2). (Had we excluded women diagnosed as having hyperplasia who went on to be diagnosed with endometrial cancer later than this, we would have been studying the form of hyperplasia that tends not to progress. This was not our goal.)
Given that the boundary between atypical hyperplasia and endometrial carcinoma is not a precise one, we acknowledge that even these efforts are unlikely to have removed all of the misclassification. Nonetheless, the potential for misclassification of hyperplasia as cancer and vice versa is primarily an issue for atypical hyperplasia, not for complex hyperplasia. In addition, some of the associations we observed (e.g., that with morbid obesity) were so large as to not plausibly result solely from the inadvertent inclusion of women with endometrial cancer among the cases of hyperplasia. (Dr. Lacey correctly notes that the number of controls with morbid obesity was quite small but fails to note that the lower limits of the relevant confidence intervals around the odds ratios generously excluded the null value.)
On the other side of the spectrum, women with simple endometrial hyperplasia were not included in our study on the basis that simple hyperplasia is considered to be nonneoplastic, unlike complex hyperplasia and hyperplasia with atypia (3), and that approximately 80–100 percent of simple hyperplasias will spontaneously regress (4–7). While we appreciate Dr. Lacey's point that our study does not contribute to the debate about whether complex hyperplasia is more similar to low-risk simple hyperplasia or high-risk atypical hyperplasia, the exclusion of simple hyperplasias from our study does not alter our findings regarding the associations for either complex hyperplasia or atypical hyperplasia.
We sought to examine risk factors for complex and atypical hyperplasia in both pre- and postmenopausal women. Dr. Lacey suggests that rather than base the definition of postmenopause simply on age (as we did), a "precise" method should be used. Would that this were easy to accomplish, particularly when the cases have a condition in which uterine bleeding often figures as a prominent symptom! While some misclassification of menopausal status undoubtedly occurred as a result of our approach, the degrees of misclassification should have been approximately similar between cases and controls.
Finally, as was alluded to by Dr. Lacey, we are now exploring the association between oral contraceptives and postmenopausal hormone therapy and endometrial hyperplasia risk. A manuscript on this topic is currently under consideration for publication.
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ACKNOWLEDGMENTS |
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Conflict of interest: none declared.
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References |
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 TOP References |
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- Lacey JV Jr. Invited commentary: endometrial hyperplasia—getting back to normal. Am J Epidemiol (2008) 168:571–74.
[Abstract/Free Full Text] - Epplein M, Reed SD, Voight LF, et al. Risk of complex and atypical endometrial hyperplasia in relation to anthropometric measures and reproductive history. Am J Epidemiol (2008) 168:563–70.
[Abstract/Free Full Text] - Allison KH, Reed SD, Voigt LF, et al. Diagnosing endometrial hyperplasia: why is it so difficult to agree? Am J Surg Pathol (2008) 32:691–8.[CrossRef][Web of Science][Medline]
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[Abstract/Free Full Text] - Kurman RJ, Kaminski PF, Norris HJ. The behavior of endometrial hyperplasia: a long-term study of ‘untreated’ hyperplasia in 170 patients. Cancer (1985) 56:403–12.[CrossRef][Web of Science][Medline]
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Related articles in Am. J. Epidemiol.:
- Risk of Complex and Atypical Endometrial Hyperplasia in Relation to Anthropometric Measures and Reproductive History
- Meira Epplein, Susan D. Reed, Lynda F. Voigt, Katherine M. Newton, Victoria L. Holt, and Noel S. Weiss
Am. J. Epidemiol. 2008 168: 563-570.[Abstract] [FREE Full Text]
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