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Osteoporosis International

, Volume 19, Issue 10, pp 1465–1471 | Cite as

Comparison of sex steroid measurements in men by immunoassay versus mass spectroscopy and relationships with cortical and trabecular volumetric bone mineral density

  • S. KhoslaEmail author
  • S. Amin
  • R. J. Singh
  • E. J. Atkinson
  • L. J. Melton III
  • B. L. Riggs
Original Article

Abstract

Summary

In men, measurement of serum testosterone and estradiol levels with immunoassays correlated with mass spectroscopic measurements, and correlations of sex steroids with volumetric bone mineral density were similar.

Introduction

While immunoassays have been used extensively for measurement of serum testosterone (T) and estradiol (E2) levels, there is concern about their specificity, particularly at low E2 levels as present in men.

Methods

We compared T and E2 measured by mass spectroscopy to levels measured by immunoassay in men (n = 313, age 22 to 91 years) and related these to volumetric bone mineral density (vBMD) at various skeletal sites.

Results

Serum T and non-SHBG bound (or bioavailable) T levels by immunoassay correlated well with the corresponding mass spectroscopy measurements (R = 0.90 and 0.95, respectively, P < 0.001); the correlations for serum E2 measured using the two techniques were less robust (R = 0.63 for total E2 and 0.84 for bioavailable E2, P < 0.001). Overall relationships between serum bioavailable T and E2 levels with vBMD at various skeletal sites were similar for the immunoassay and mass spectroscopic measures.

Conclusions

Although E2 levels with immunoassay correlate less well with the mass spectroscopic measurements than do the T measurements in men, our findings indicate that the fundamental relationships observed previously between vBMD and the sex steroids by immunoassay are also present with the mass spectroscopic measurements.

Keywords

Assays Bone Osteoporosis 

Notes

Acknowledgements

We would like to thank Lisa McDaniel, R.N. for recruitment of study subjects, Kelley Hoey for processing of the samples, Sara Achenbach for assistance with the statistical analyses, and Jim Peterson for making the figures.

Conflicts of interest

None.

References

  1. 1.
    Khosla S, Melton LJ, Riggs BL (2002) Estrogen and the male skeleton. J Clin Endocrinol Metab 87:1443–1450PubMedCrossRefGoogle Scholar
  2. 2.
    Kaufman JM, Vermeulen A (2005) The decline of androgen levels in elderly men and its clinical and therapeutic implications. Endocr Rev 26:833–876PubMedCrossRefGoogle Scholar
  3. 3.
    Khosla S, Melton LJ III, Atkinson EJ, O’Fallon WM, Klee GG, Riggs BL (1998) Relationship of serum sex steroid levels and bone turnover markers with bone mineral density in men and women: A key role for bioavailable estrogen. J Clin Endocrinol Metab 83:2266–2274PubMedCrossRefGoogle Scholar
  4. 4.
    Khosla S, Melton LJ, Atkinson EJ, O’Fallon WM (2001) Relationship of serum sex steroid levels to longitudinal changes in bone density in young versus elderly men. J Clin Endocrinol Metab 86:3555–3561PubMedCrossRefGoogle Scholar
  5. 5.
    Khosla S, Melton LJ III, Robb RA, Camp JJ, Atkinson EJ, Oberg AL, Rouleau PA, Riggs BL (2005) Relationship of volumetric BMD and structural parameters at different skeletal sites to sex steroid levels in men. J Bone Miner Res 20:730–740PubMedCrossRefGoogle Scholar
  6. 6.
    Khosla S, Melton LJ III, Achenbach SJ, Oberg AL, Riggs BL (2006) Hormonal and biochemical determinants of trabecular microstructure at the ultradistal radius in women and men. J Clin Endocrinol Metab 91:885–891PubMedCrossRefGoogle Scholar
  7. 7.
    Van Pottelbergh I, Goemaere S, Kaufman JM (2003) Bioavailable estradiol and an aromatase gene polymorphism are determinants of bone mineral density changes in men over 70 years of age. J Clin Endocrinol Metab 88:3075–3081PubMedCrossRefGoogle Scholar
  8. 8.
    Gennari L, Merlotti D, Martini G, Gonnelli S, Franci B, Campagna S, Lucani B, Canto ND, Valenti R, Gennari C, Nuti R (2003) Longitudinal association between sex hormone levels, bone loss, and bone turnover in elderly men. J Clin Endocrinol Metab 88:5327–5333PubMedCrossRefGoogle Scholar
  9. 9.
    Eriksson AL, Lorentzon M, Mellstrom D, Vandenput L, Swanson C, Andersson N, Hammond GL, Jakobsson J, Rane A, Orwoll ES, Ljunggren O, Johnell O, Labrie F, Windahl SH, Ohlsson C (2006) SHBG gene promoter polymorphisms in men are associated with serum sex hormone-binding globulin, androgen and androgen metabolite levels, and hip bone mineral density. J Clin Endocrinol Metab 91:5029–5037PubMedCrossRefGoogle Scholar
  10. 10.
    Ensrud KE, Lewis CE, Lambert LC, Taylor BC, Fink HA, Barrett-Connor E, Cauley JA, Stefanick ML, Orwoll E, Group OFiMSR (2006) Endogenous sex steroids, weight change and rates of hip bone loss in older men: the MrOS study 17:1329–1336Google Scholar
  11. 11.
    Amin S, Zhang Y, Sawin CT, Evans SR, Hannan MT, Kiel DP, Wilson PWF, Felson DT (2000) Association of hypogonadism and estradiol levels with bone mineral density in elderly men from the Framingham study. Ann Intern Med 133:951–963PubMedGoogle Scholar
  12. 12.
    Amin S, Zhang Y, Felson DT, Sawin CT, Hannan MT, Wilson PWF, Kiel DP (2006) Estradiol, testosterone, and the risk for hip fractures in elderly men from the Framingham Study. Am J Med 119:426–433PubMedCrossRefGoogle Scholar
  13. 13.
    O’Connor S, Baker HWG, Dulmanis A, Hudson B (1973) The measurement of sex steroid binding globulin by differential ammonium sulphate precipitation. J Steroid Biochem 4:331–339PubMedCrossRefGoogle Scholar
  14. 14.
    Tremblay RR, Dube JY (1974) Plasma concentrations of free and non-TeBG bound testosterone in women on oral contraceptives. Contraception 10:599–605PubMedCrossRefGoogle Scholar
  15. 15.
    Vermeulen A, Verdonck L, Kaufman JM (1999) A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 84:3666–3672PubMedCrossRefGoogle Scholar
  16. 16.
    Sodergard R, Backstrom T, Shanbhag V, Carstensen H (1982) Calculation of free and bound fractions of testosterone and estradiol-17 beta to human plasma proteins at body temperature. J Steroid Biochem 16:801–810PubMedCrossRefGoogle Scholar
  17. 17.
    Lee JS, Ettinger B, Stanczyk FZ, Vittinghoff E, Hanes V, Cauley JA, Chandler W, Settlage J, Beattie MS, Folkerd E, Dowsett M, Grady D, Cummings SR (2006) Comparison of methods to measure low serum estradiol levels in postmenopausal women. J Clin Endocrinol Metab 91:3791–3797PubMedCrossRefGoogle Scholar
  18. 18.
    Melton LJ III (1996) History of the Rochester Epidemiology Project. Mayo Clin Proc 71:266–274PubMedCrossRefGoogle Scholar
  19. 19.
    Riggs BL, Melton LJ III, Robb RA, Camp JJ, Atkinson EJ, Peterson JM, Rouleau PA, McCollough CH, Bouxsein ML, Khosla S (2004) Population-based study of age and sex differences in bone volumetric density, size, geometry, and structure at different skeletal sites. J Bone Miner Res 19:1945–1954PubMedCrossRefGoogle Scholar
  20. 20.
    Camp JJ, Karwoski RA, Stacy MC, Atkinson EJ, Khosla S, Melton LJ, Riggs BL, Robb RA (2004) A system for the analysis of whole-bone strength from helical CT images. Proceedings of SPIE 5369:74–88CrossRefGoogle Scholar
  21. 21.
    Cann CE (1988) Quantitative CT for determination of bone mineral density: a review. Radiology 166:509–522PubMedGoogle Scholar
  22. 22.
    Pardridge WM (1986) Serum bioavailability of sex steroid hormones. Clin Endocrinol Metab 15:259–278PubMedCrossRefGoogle Scholar
  23. 23.
    Nguyen TV, Meier C, Handelsman DJ, Kraenzlin M, Kushnir MM, Rockwood AL, Meikle AW, Center JR, Eisman JA, Seibel MJ (2007) Serum testosterone in elderly men measured by liquid chromatography-tandem mass spectrometry and radioimmunoassay: concordance and effect on epidemiologic association. In J Bone Miner Res 22(Suppl 1):S277 (Abstract)Google Scholar
  24. 24.
    Khosla S (2006) Editorial: Sex hormone binding globulin: inhibitor or facilitator (or both) of sex steroid action? J Clin Endocrinol Metab 91:4764–4766PubMedCrossRefGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2008

Authors and Affiliations

  • S. Khosla
    • 1
    Email author
  • S. Amin
    • 1
  • R. J. Singh
    • 1
  • E. J. Atkinson
    • 1
  • L. J. Melton III
    • 1
  • B. L. Riggs
    • 1
  1. 1.From the Endocrine Research Unit, Division of Rheumatology, Department of Laboratory Medicine, and Health Sciences ResearchMayo Clinic College of MedicineRochesterUSA

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