Advertisement

Endocrine

, Volume 63, Issue 1, pp 149–156 | Cite as

Oral glucose load and mixed meal feeding lowers testosterone levels in healthy eugonadal men

  • Thiago Gagliano-JucáEmail author
  • Zhuoying Li
  • Karol M. Pencina
  • Yusnie M. Beleva
  • Olga D. Carlson
  • Josephine M. Egan
  • Shehzad Basaria
Original Article

Abstract

Purpose

Precise evaluation of serum testosterone levels is important in making an accurate diagnosis of androgen deficiency. Recent practice guidelines on male androgen deficiency recommend that testosterone be measured in the morning while fasting. Although there is ample evidence regarding morning measurement of testosterone, studies that evaluated the effect of glucose load or meals were limited by inclusion of hypogonadal or diabetic men, and measurement of testosterone was not performed using mass spectrometry.

Methods

Sixty men (23–97 years) without pre-diabetes or diabetes who had normal total testosterone (TT) levels underwent either an oral glucose tolerance test (OGTT) or a mixed meal tolerance test (MMTT) after an overnight fast. Serum samples were collected before and at regular intervals for 2 h (OGTT cohort) or 3 h (MMTT cohort). TT was measured by LC-MS/MS. LH and prolactin were also measured.

Results

TT decreased after a glucose load (mean drop at nadir = 100 ng/dL) and after a mixed meal (drop at nadir = 123 ng/dL). Approximately 11% of men undergoing OGTT and 56% undergoing MMTT experienced a transient decrease in TT below 300 ng/dL, the lower normal limit. Testosterone started declining 20 min into the tests, with average maximum decline at 60 min. Most men still had TT lower than baseline at 120 min. This effect was independent of changes in LH or prolactin.

Conclusion

A glucose load or a mixed meal transiently, but significantly, lowers TT levels in healthy, non-diabetic eugonadal men. These findings support the recommendations that measurement of serum testosterone to diagnose androgen deficiency should be performed while fasting.

Keywords

Sex hormones Testosterone LH Oral glucose tolerance test Mixed meal tolerance test Hypogonadism 

Notes

Funding

National Institute on Aging Intramural research grants 03-AG-N035 and 15-AG-N074.

Compliance with ethical standards

Conflict of interest

Dr. Basaria has no conflict of interest related to the current work. He has previously received grant support from Abbott Pharmaceuticals for investigator-initiated studies unrelated to this study and has previously consulted for AbbVie, Eli Lilly, Inc and Regeneron Pharmaceuticals. The other authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The BLSA study protocol was reviewed by the National Institute of Environmental Health Sciences Institutional Review Board and the study with participants not from the BLSA cohort was approved by the Intramural Research Program of the National Institute on Aging and the institutional review board of the National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland.

Informed consent

Informed consent was obtained from all individual participants included in both studies.

Supplementary material

12020_2018_1741_MOESM1_ESM.docx (15 kb)
Supplementary Information

References

  1. 1.
    S. Bhasin, J.P. Brito, G.R. Cunningham, F.J. Hayes, H.N. Hodis, A.M. Matsumoto, P.J. Snyder, R.S. Swerdloff, F.C. Wu, M.A. Yialamas, Testosterone therapy in men with hypogonadism: An Endocrine Society Clinical Practice Guideline. J. Clin. Endocrinol. Metab. 103(5), 1715–1744 (2018).  https://doi.org/10.1210/jc.2018-00229 CrossRefGoogle Scholar
  2. 2.
    L. Wartofsky, D.J. Handelsman, Standardization of hormonal assays for the 21st century. J. Clin. Endocrinol. Metab. 95(12), 5141–5143 (2010).  https://doi.org/10.1210/jc.2010-2369 CrossRefGoogle Scholar
  3. 3.
    W.J. Bremner, M.V. Vitiello, P.N. Prinz, Loss of circadian rhythmicity in blood testosterone levels with aging in normal men. J. Clin. Endocrinol. Metab. 56(6), 1278–1281 (1983).  https://doi.org/10.1210/jcem-56-6-1278 CrossRefGoogle Scholar
  4. 4.
    D.J. Brambilla, A.B. O’Donnell, A.M. Matsumoto, J.B. McKinlay, Intraindividual variation in levels of serum testosterone and other reproductive and adrenal hormones in men. Clin. Endocrinol. 67(6), 853–862 (2007).  https://doi.org/10.1111/j.1365-2265.2007.02976.x CrossRefGoogle Scholar
  5. 5.
    A.W. Meikle, J.D. Stringham, M.G. Woodward, M.P. McMurry, Effects of a fat-containing meal on sex hormones in men. Metab.: Clin. Exp. 39(9), 943–946 (1990)CrossRefGoogle Scholar
  6. 6.
    A. Jeibmann, S. Zahedi, M. Simoni, E. Nieschlag, M.M. Byrne, Glucagon-like peptide-1 reduces the pulsatile component of testosterone secretion in healthy males. Eur. J. Clin. Investig. 35(9), 565–572 (2005).  https://doi.org/10.1111/j.1365-2362.2005.01542.x CrossRefGoogle Scholar
  7. 7.
    J.R. Wall, R.J. Jarrett, P.Z. Zimmet, M. Bailes, C.M. Ramage, Fall in plasma-testosterone levels in normal male subjects in response to an oral glucose load. Lancet 1(7810), 967–968 (1973)CrossRefGoogle Scholar
  8. 8.
    M. Lehtihet, S. Arver, I. Bartuseviciene, A. Pousette, S-testosterone decrease after a mixed meal in healthy men independent of SHBG and gonadotrophin levels. Andrologia 44(6), 405–410 (2012).  https://doi.org/10.1111/j.1439-0272.2012.01296.x CrossRefGoogle Scholar
  9. 9.
    R.C. Habito, M.J. Ball, Postprandial changes in sex hormones after meals of different composition. Metab.: Clin. Exp. 50(5), 505–511 (2001).  https://doi.org/10.1053/meta.2001.20973 CrossRefGoogle Scholar
  10. 10.
    L.M. Caronia, A.A. Dwyer, D. Hayden, F. Amati, N. Pitteloud, F.J. Hayes, Abrupt decrease in serum testosterone levels after an oral glucose load in men: implications for screening for hypogonadism. Clin. Endocrinol. 78(2), 291–296 (2013).  https://doi.org/10.1111/j.1365-2265.2012.04486.x CrossRefGoogle Scholar
  11. 11.
    A. Hjalmarsen, U. Aasebo, A. Aakvaag, R. Jorde, Sex hormone responses in healthy men and male patients with chronic obstructive pulmonary disease during an oral glucose load. Scand. J. Clin. Lab. Investig. 56(7), 635–640 (1996)CrossRefGoogle Scholar
  12. 12.
    A. Iranmanesh, D. Lawson, J.D. Veldhuis, Glucose ingestion acutely lowers pulsatile LH and basal testosterone secretion in men. Am. J. Physiol. Endocrinol. Metab. 302(6), E724–730 (2012).  https://doi.org/10.1152/ajpendo.00520.2011 CrossRefGoogle Scholar
  13. 13.
    J.S. Volek, A.L. Gomez, D.M. Love, N.G. Avery, M.J. Sharman, W.J. Kraemer, Effects of a high-fat diet on postabsorptive and postprandial testosterone responses to a fat-rich meal. Metab.: Clin. Exp. 50(11), 1351–1355 (2001)CrossRefGoogle Scholar
  14. 14.
    S. Dhindsa, M.G. Miller, C.L. McWhirter, D.E. Mager, H. Ghanim, A. Chaudhuri, P. Dandona, Testosterone concentrations in diabetic and nondiabetic obese men. Diabetes care 33(6), 1186–1192 (2010).  https://doi.org/10.2337/dc09-1649 CrossRefGoogle Scholar
  15. 15.
    P. Dandona, S. Dhindsa, Update: Hypogonadotropic hypogonadism in type 2 diabetes and obesity. J. Clin. Endocrinol. Metab. 96(9), 2643–2651 (2011).  https://doi.org/10.1210/jc.2010-2724 CrossRefGoogle Scholar
  16. 16.
    D.J. Handelsman, L. Wartofsky, Requirement for mass spectrometry sex steroid assays in the Journal of Clinical Endocrinology and Metabolism. J. Clin. Endocrinol. Metab. 98(10), 3971–3973 (2013).  https://doi.org/10.1210/jc.2013-3375 CrossRefGoogle Scholar
  17. 17.
    J.L. Stone, A.H. Norris, Activities and attitudes of participants in the Baltimore longitudinal study. J. Gerontol. 21(4), 575–580 (1966)CrossRefGoogle Scholar
  18. 18.
    American Diabetes, A., Standards of medical care in diabetes--2010. Diabetes Care 33 Suppl 1, S11–61 (2010).  https://doi.org/10.2337/dc10-S011 CrossRefGoogle Scholar
  19. 19.
    S. Bhasin, M. Pencina, G.K. Jasuja, T.G. Travison, A. Coviello, E. Orwoll, P.Y. Wang, C. Nielson, F. Wu, A. Tajar, F. Labrie, H. Vesper, A. Zhang, J. Ulloor, R. Singh, R. D’Agostino, R.S. Vasan, Reference ranges for testosterone in men generated using liquid chromatography tandem mass spectrometry in a community-based sample of healthy nonobese young men in the Framingham Heart Study and applied to three geographically distinct cohorts. J. Clin. Endocrinol. Metab. 96(8), 2430–2439 (2011).  https://doi.org/10.1210/jc.2010-3012 CrossRefGoogle Scholar
  20. 20.
    S. Holm, A simple sequentially rejective multiple test procedure. Scand. J. Stat. 6(2), 65–70 (1979)Google Scholar
  21. 21.
    S. Bhasin, G.R. Cunningham, F.J. Hayes, A.M. Matsumoto, P.J. Snyder, R.S. Swerdloff, V.M. Montori, E.S. Task Force, Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab. 95(6), 2536–2559 (2010).  https://doi.org/10.1210/jc.2009-2354 CrossRefGoogle Scholar
  22. 22.
    S. Bhasin, G.R. Cunningham, F.J. Hayes, A.M. Matsumoto, P.J. Snyder, R.S. Swerdloff, V.M. Montori, Testosterone therapy in adult men with androgen deficiency syndromes: an endocrine society clinical practice guideline. J. Clin. Endocrinol. Metab. 91(6), 1995–2010 (2006).  https://doi.org/10.1210/jc.2005-2847 CrossRefGoogle Scholar
  23. 23.
    J.P. Mulhall, L.W. Trost, R.E. Brannigan, E.G. Kurtz, J.B. Redmon, K.A. Chiles, D.J. Lightner, M.M. Miner, M.H. Murad, C.J. Nelson, E.A. Platz, L.V. Ramanathan, R.W. Lewis, Evaluation and management of testosterone deficiency: AUA guideline. J. Urol. (2018).  https://doi.org/10.1016/j.juro.2018.03.115
  24. 24.
    J.D. Dean, C.G. McMahon, A.T. Guay, A. Morgentaler, S.E. Althof, E.F. Becher, T.J. Bivalacqua, A.L. Burnett, J. Buvat, A. El Meliegy, W.J. Hellstrom, E.A. Jannini, M. Maggi, A. McCullough, L.O. Torres, M. Zitzmann, The International Society for Sexual Medicine’s Process of Care for the assessment and management of testosterone deficiency in adult men. J. Sex. Med. 12(8), 1660–1686 (2015).  https://doi.org/10.1111/jsm.12952 CrossRefGoogle Scholar
  25. 25.
    L. Pal, H.P. Chu, J. Shu, I. Topalli, N. Santoro, G. Karkanias, In vitro evidence of glucose-induced toxicity in GnRH secreting neurons: high glucose concentrations influence GnRH secretion, impair cell viability, and induce apoptosis in the GT1-1 neuronal cell line. Fertil. Steril. 88(4 Suppl), 1143–1149 (2007).  https://doi.org/10.1016/j.fertnstert.2007.01.007 CrossRefGoogle Scholar
  26. 26.
    C.Y. Cheung, Prolactin suppresses luteinizing hormone secretion and pituitary responsiveness to luteinizing hormone-releasing hormone by a direct action at the anterior pituitary. Endocrinology 113(2), 632–638 (1983).  https://doi.org/10.1210/endo-113-2-632 CrossRefGoogle Scholar
  27. 27.
    M.O. Thorner, S.M. Ryan, J.A. Wass, A. Jones, P. Bouloux, S. Williams, G.M. Besser, Effect of the dopamine agonist, lergotrile mesylate, on circulating anterior pituitary hormones in man. J. Clin. Endocrinol. Metab. 47(2), 372–378 (1978).  https://doi.org/10.1210/jcem-47-2-372 CrossRefGoogle Scholar
  28. 28.
    B. Ishizuka, M.E. Quigley, S.S. Yen, Pituitary hormone release in response to food ingestion: evidence for neuroendocrine signals from gut to brain. J. Clin. Endocrinol. Metab. 57(6), 1111–1116 (1983).  https://doi.org/10.1210/jcem-57-6-1111 CrossRefGoogle Scholar
  29. 29.
    H.E. Carlson, H.L. Wasser, S.R. Levin, J.N. Wilkins, Prolactin stimulation by meals is related to protein content. J. Clin. Endocrinol. Metab. 57(2), 334–338 (1983).  https://doi.org/10.1210/jcem-57-2-334 CrossRefGoogle Scholar
  30. 30.
    H.E. Carlson, Prolactin stimulation by protein is mediated by amino acids in humans. J. Clin. Endocrinol. Metab. 69(1), 7–14 (1989).  https://doi.org/10.1210/jcem-69-1-7 CrossRefGoogle Scholar
  31. 31.
    K. Esposito, F. Nappo, R. Marfella, G. Giugliano, F. Giugliano, M. Ciotola, L. Quagliaro, A. Ceriello, D. Giugliano, Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress. Circulation 106(16), 2067–2072 (2002)CrossRefGoogle Scholar
  32. 32.
    R.C. Gaillard, D. Turnill, P. Sappino, A.F. Muller, Tumor necrosis factor alpha inhibits the hormonal response of the pituitary gland to hypothalamic releasing factors. Endocrinology 127(1), 101–106 (1990).  https://doi.org/10.1210/endo-127-1-101 CrossRefGoogle Scholar
  33. 33.
    C. Mauduit, F. Gasnier, C. Rey, M.A. Chauvin, D.M. Stocco, P. Louisot, M. Benahmed, Tumor necrosis factor-alpha inhibits leydig cell steroidogenesis through a decrease in steroidogenic acute regulatory protein expression. Endocrinology 139(6), 2863–2868 (1998).  https://doi.org/10.1210/endo.139.6.6077 CrossRefGoogle Scholar
  34. 34.
    V. Morales, P. Santana, R. Diaz, C. Tabraue, G. Gallardo, F. Lopez Blanco, I. Hernandez, L.F. Fanjul, C.M. Ruiz de Galarreta, Intratesticular delivery of tumor necrosis factor-alpha and ceramide directly abrogates steroidogenic acute regulatory protein expression and Leydig cell steroidogenesis in adult rats. Endocrinology 144(11), 4763–4772 (2003).  https://doi.org/10.1210/en.2003-0569 CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Research Program in Men’s Health: Aging and Metabolism, Brigham and Women’s HospitalHarvard Medical SchoolBostonUSA
  2. 2.Laboratory of Clinical InvestigationNational Institute on AgingBaltimoreUSA

Personalised recommendations