LETT ER T O TH E E DI TOR Letter to the Editor: “Harmonized Reference Ranges for Circulating Testosterone Levels in Men of Four Cohort Studies in the United States and Europe” 1 1 Xinguang Chen and Kai Wang Department of Epidemiology, University of Florida, Gainesville, Florida 32610 he report by Travison et al. (1) entitled “Harmonized either theory or practice and are very misleading. It violates TReference Ranges for Circulating Testosterone Levels in the basic knowledge of normal aging. To our understanding Men of Four Cohort Studies in the United States and as epidemiologists, one important source of bias for the Europe,” touched a very important area in contemporary results reported in this and other studies is the cohort effect. medical and health research. The reference ranges for an- Participants aged 80 years from a study cohort were born drogen levels are highly needed by researchers and physi- 80 years ago and participants aged 20 years were born cians alike to manage aging, male sexual and reproductive 20 years ago. This cohort effect must be adjusted for to health, and many other health-related issues. From the obtain unbiased estimates. One potential approach could description presented in their report, the process of research be the age-period-cohort modeling method. For example, is valid, including the research design, sample selection, the newly established hierarchical age-period-cohort mod- hormone measurement, measurement harmonization, and eling method for sociology can be used to model individual summarization analysis. However, we are deeply puzzled by level data (3). With this method, age-specific estimates of the results that the estimated median and interquartile range the total testosterone level can be estimated by adjusting (IQR) of the total testosterone level remain almost unchanged for the cohort effect and the period effect if a researcher for men from age 50 to 99 years, a period of five decades. suspects that participants recruited from different periods From the harmonized results, the median total testosterone will also be a confounding factor. level would be 531 ng/dL (IQR, 424 to 643) for men aged Acknowledgments 13 to 39 years; 481 ng/dL (IQR, 286 to 608) for men aged 40 to 49 years; 477 ng/dL (IQR, 604 to 374) for men aged 50 to Correspondence and Reprint Requests: Xinguang Chen, MD, 59 years and 60 to 68 years; 477 ng/dL (IQR, 604 to 372) PhD, Department of Epidemiology, University of Florida, 2004 for men aged 70 to 79 years, and 476 (IQR, 604 to 362) Mowry Road, Gainesville, Florida 32610. E-mail: jimax.chen@ for men aged 80 to 89 years. Although the authors did note ufl.edu. this issue in their statement “Notably, results obtained in References this study show a lesser age trend than that reported pre- viously in cross-sectional analyses of men of different ages, 1. Travison TG, Vesper HW, Orwoll E, Wu F, Kaufman JM, Wang Y, underscoring the need for longitudinal studies of the effects Lapauw B, Fiers T, Matsumoto AM, Bhasin S. Harmonized reference ranges for circulating testosterone levels in men of four cohort studies of aging on sex steroid concentrations.” No additional in the United States and Europe. J Clin Endocrinol Metab. 2017; explanation was provided. Similar results were also re- 102(4):1161–1173. ported in another study in PloS One, entitled “A Validated 2. Kelsey TW, Li LQ, Mitchell RT, Whelan A, Anderson RA, Wallace WH. A validated age-related normative model for male total tes- Age-Related Normative Model for Male Total Testosterone tosterone shows increasing variance but no decline after age 40 years. Shows Increasing Variance but No Decline After Age 40 PLoS One. 2014;9(10):e109346. Years” (2), with no explanation of why testosterone does 3. Yang Y, Land KC. Age-Period-Cohort Analysis: New Models, Methods, not decline with age. Such results are hardly acceptable in and Empirical Applications. Boca Raton, FL: CRC Press; 2013. ISSN Print 0021-972X ISSN Online 1945-7197 Printed in USA Copyright © 2018 Endocrine Society Received 23 August 2017. Accepted 13 November 2017. First Published Online 16 November 2017 698 https://academic.oup.com/jcem J Clin Endocrinol Metab, February 2018, 103(2):698 doi: 10.1210/jc.2017-01880 Downloaded from https://academic.oup.com/jcem/article-abstract/103/2/698/4634319 by Ed 'DeepDyve' Gillespie user on 16 March 2018
Journal of Clinical Endocrinology and Metabolism – Oxford University Press
Published: Feb 1, 2018
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