Abstract
Background:
Measuring sex hormones is essential in diagnosing health issues such as testicular dysfunction, male infertility and feminization syndrome. However, there are no reports on reference intervals (RIs) in Chinese men. We conducted a nationwide multicenter study to establish RIs for seven sex hormones (luteinizing hormone [LH], follicle-stimulating hormone [FSH], prolactin [PRL], total testosterone [TT], free testosterone [FT], bioavailable testosterone [BAT] and estrogen [E2]), as well as sex hormone-binding globulin (SHBG).
Methods:
In 2013, 1043 apparently healthy adult men from five representative cities in China (Beijing, Hangzhou, Guangzhou, Dalian and Urumqi) were recruited; hormones were measured using an automated immunoassay analyzer. Multiple regression analysis (MRA) was performed to identify sources of variation (SVs) that might influence the hormone serum levels. RIs were computed using the parametric method.
Results:
Dalian and Hangzhou had significantly higher E2 values than other cities; age was a major source of variation for FSH, LH, PRL, SHBG, FT and BAT. FSH, LH and SHBG increased significantly with age, while PRL, FT and BAT decreased with age. TT showed no significant age-related changes. Median (RIs) derived without partition by age were as follows: FSH, 5.6 (1.9–16.3) IU/L; LH, 4.2 (1.6–10.0) IU/L; PRL, 189 (88–450) mIU/L; E2, 85 (4.7–195) pmol/L; SHBG, 29.4 (11.5–66.3) nmol/L; TT, 15.6 (7.4–24.5) nmol/L; FT, 0.31 (0.16–0.52) nmol/L; and BAT, 8.0 (3.7–13.2) nmol/L. RIs were also derived in accordance with between-city and between-age differences.
Conclusions: RIs were established for sex hormones and SHBG in apparently healthy Chinese men in consideration of age.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: This work was funded by the National Natural Science Foundation of China (81702060, 81201337), Funder Id: 10.13039/501100001809, and by research grants from the China National Clinical Key Subject Program and the National Key Technology Research and Development Support program (2015BAI32H00).
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Cheung KK, Lau ES, So WY, Ma RC, Ozaki R, Kong AP, et al. Low testosterone and clinical outcomes in Chinese men with type 2 diabetes mellitus – Hong Kong Diabetes Registry. Diabetes Res Clin Pract 2017;123:97–105.10.1016/j.diabres.2016.11.012Search in Google Scholar PubMed
2. Arnold AP, Cassis LA, Eghbali M, Reue K, Sandberg K. Sex hormones and sex chromosomes cause sex differences in the development of cardiovascular diseases. Arterioscler Thromb Vasc Biol 2017;37:746–56.10.1161/ATVBAHA.116.307301Search in Google Scholar PubMed PubMed Central
3. Liu S, Sun Q. Sex differences, endogenous sex-hormone hormones, sex-hormone binding globulin, and exogenous disruptors in diabetes and related metabolic outcomes. J Diabetes 2016. doi: 10.1111/1753-0407.12517. [Epub ahead of print].10.1111/1753-0407.12517Search in Google Scholar PubMed
4. Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, et al. Testosterone therapy in adult men with androgen deficiency syndromes: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2006;91:1995–2010.10.1210/jc.2005-2847Search in Google Scholar PubMed
5. Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 1999;84:3666–72.10.1210/jcem.84.10.6079Search in Google Scholar PubMed
6. Ozarda Y, Ichihara K, Barth JH, Klee G, Committee on Reference Intervals and Decision Limits (C-RIDL), International Federation for Clinical Chemistry and Laboratory Medicine. Protocol and standard operating procedures for common use in a worldwide multicenter study on reference values. Clin Chem Lab Med 2013;51:1027–40.10.1515/cclm-2013-0249Search in Google Scholar PubMed
7. Yu S, Fang H, Han J, Cheng X, Xia L, Li S, et al. The high prevalence of hypovitaminosis D in China: a multicenter vitamin D status survey. Medicine (Baltimore) 2015;94:e585.10.1097/MD.0000000000000585Search in Google Scholar PubMed PubMed Central
8. Xia L, Chen M, Liu M, Tao Z, Li S, Wang L, et al. Nationwide multicenter reference interval study for 28 common biochemical analytes in China. Medicine (Baltimore) 2016;95:e2915.10.1097/MD.0000000000002915Search in Google Scholar PubMed PubMed Central
9. Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 1999;84:3666–72.10.1210/jcem.84.10.6079Search in Google Scholar
10. Ichihara K, Boyd JC, IFCC Committee on Reference Intervals and Decision Limits (C-RIDL). An appraisal of statistical procedures used in derivation of reference intervals. Clin Chem Lab Med 2010;48:1537–51.10.1515/CCLM.2010.319Search in Google Scholar PubMed
11. Ichihara K, Yomamoto Y, Hotta T, Hosogaya S, Miyachi H, Itoh Y, et al. Collaborative derivation of reference intervals for major clinical laboratory tests in Japan. Ann Clin Biochem 2016;53:347–56.10.1177/0004563215608875Search in Google Scholar PubMed
12. Ichihara K, Ozarda Y, Barth JH, Klee G, Qiu L, Erasmus R, et al. A global multicenter study on reference values: 1. Assessment of methods for derivation and comparison of reference intervals. Clin Chim Acta 2017;467:70–82.10.1016/j.cca.2016.09.016Search in Google Scholar PubMed
13. Ichihara K, Ozarda Y, Barth JH, Klee G, Shimizu Y, Xia L, et al. A global multicenter study on reference values: 2. Exploration of sources of variation across the countries. Clin Chim Acta 2017;467:83–97.10.1016/j.cca.2016.09.015Search in Google Scholar PubMed
14. Qin X, Lv H, Mo Z, Chen Z, Lin L, Peng T, et al. Reference intervals for serum sex hormones in Han Chinese adult men from the Fangchenggang Area Male Health and Examination Survey. Clin Lab 2012;58:281–90.Search in Google Scholar
15. Schuring AN, Kelsch R, Pierscinski G, Nofer JR. Establishing reference intervals for sex hormones on the analytical platforms Advia Centaur and Immulite2000XP. Ann Lab Med 2016;36:55–9.10.3343/alm.2016.36.1.55Search in Google Scholar PubMed PubMed Central
16. Eskelinen S, Vahlberg T, Isoaho R, Kivela SL, Irjala K. Biochemical reference intervals for sex hormones with a new Auto Delfia method in aged men. Clin Chem Lab Med 2007;45:249–53.10.1515/CCLM.2007.042Search in Google Scholar PubMed
17. Sikaris K, McLachlan RI, Kazlauskas R, de Kretser D, Holden CA, Handelsman DJ. Reproductive hormone reference intervals for healthy fertile young men: evaluation of automated platform assays. J Clin Endocrinol Metab 2005;90:5928–36.10.1210/jc.2005-0962Search in Google Scholar PubMed
18. Qin X, Tang G, Qiu L, Li PC, Xia L, Chen M, et al. A multicenter reference intervals study for specific proteins in China. Medicine (Baltimore) 2015;94:e2211.10.1097/MD.0000000000002211Search in Google Scholar PubMed PubMed Central
19. Jobling S, Williams R, Johnson A, Taylor A, Gross-Sorokin M, Nolan M, et al. Predicted exposures to steroid estrogens in UK rivers correlate with widespread sexual disruption in wild fish populations. Environ Health Perspect 2006;114(Suppl 1):32–9.10.1289/ehp.8050Search in Google Scholar PubMed PubMed Central
20. Baynes A, Green C, Nicol E, Beresford N, Kanda R, Henshaw A, et al. Additional treatment of wastewater reduces endocrine disruption in wild fish – a comparative study of tertiary and advanced treatments. Environ Sci Technol 2012;46:5565–73.10.1021/es204590dSearch in Google Scholar PubMed
21. Frost M, Wraae K, Nielsen TL, Hougaard DM, Brixen K, Hagen C, et al. Similar reference intervals for total testosterone in healthy young and elderly men: results from the Odense Androgen Study. Clin Endocrinol (Oxf) 2013;78:743–51.10.1111/cen.12042Search in Google Scholar PubMed
22. Rosner W, Auchus RJ, Azziz R, Sluss PM, Raff H. Position statement: utility, limitations, and pitfalls in measuring testosterone: an Endocrine Society position statement. J Clin Endocrinol Metab 2007;92:405–13.10.1210/jc.2006-1864Search in Google Scholar PubMed
23. Morley JE, Patrick P, Perry HM. Evaluation of assays available to measure free testosterone. Metabolism 2002;51:554–9.10.1053/meta.2002.31975Search in Google Scholar PubMed
24. Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 1999;84:3666–72.10.1210/jcem.84.10.6079Search in Google Scholar PubMed
25. Yeap BB, Almeida OP, Hyde Z, Chubb SA, Hankey GJ, Jamrozik K, et al. Higher serum free testosterone is associated with better cognitive function in older men, while total testosterone is not. The Health In Men Study. Clin Endocrinol (Oxf) 2008;68:404–12.10.1111/j.1365-2265.2007.03055.xSearch in Google Scholar PubMed
26. Yeap BB, Grossmann M, McLachlan RI, Handelsman DJ, Wittert GA, Conway AJ, et al. Endocrine Society of Australia position statement on male hypogonadism (part 1): assessment and indications for testosterone therapy. Med J Aust 2016;205:173–8.10.5694/mja16.00393Search in Google Scholar PubMed
27. Gates MA, Mekary RA, Chiu GR, Ding EL, Wittert GA, Araujo AB. Sex steroid hormone levels and body composition in men. J Clin Endocrinol Metab 2013;98:2442–50.10.1210/jc.2012-2582Search in Google Scholar PubMed PubMed Central
28. Litman HJ, Bhasin S, Link CL, Araujo AB, McKinlay JB. Serum androgen levels in black, Hispanic, and white men. J Clin Endocrinol Metab 2006;91:4326–34.10.1210/jc.2006-0037Search in Google Scholar PubMed
29. Travison TG, Vesper HW, Orwoll E, Wu F, Kaufman JM, Wang Y, et al. Harmonized reference ranges for circulating testosterone levels in men of four cohort studies in the United States and Europe. J Clin Endocrinol Metab 2017;102:1161–73.10.1210/jc.2016-2935Search in Google Scholar PubMed PubMed Central
Supplemental Material:
The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2017-0749).
©2018 Walter de Gruyter GmbH, Berlin/Boston
