Serum testosterone, dihydrotestosterone and estradiol concentrations in older men self-reporting very good health: the healthy man study (original) (raw)

Abstract

Objective To determine serum concentrations, intra-individual variability and impact of age-related co-morbidities on serum testosterone (T), dihydrotestosterone (DHT), estradiol (E 2) and estrone (E 1) in older men. Design Observational, repeated measures study. Participants Men (n = 325) with 40 years and older selfreporting very good or excellent health. Measurements Standardized history, physical examination and collection of nine blood samples at fixed time intervals were measured over 3 months (three at 20 min intervals on days 1 (fasting) and 2 (non-fasting), one at days 7, 30 and 90). Serum T, DHT, E 2 and E 1 (n = 2900, > 99% of scheduled samples) measured by liquid chromatography-tandem mass spectrometry (LC-MS) were analysed by linear mixed model analysis with fasting, age and obesity as covariables. Results Mean serum T did not vary with age (P = 0•76) but obesity (À0•35 nM per body mass index (BMI) unit, P < 0•0001) and ex-smoker status (À1•6 nM, P < 0•001) had significant effects. Serum DHT was increased with age (+0•011 nM per year, P = 0•001) but decreased with obesity (À0•05 nM per BMI unit, P < 0•0001). Serum E 2 did not vary with age (P = 0•31) or obesity (P = 0•12). Overnight fasting increased (by 9-16%, all P < 0•001) and reduced variability in morning serum T, DHT, E 2 and E 1. Non-fasting serum T and DHT were stable over time (day, week, month or 3 months; P > 0•28). Conclusions Serum T, DHT and E 2 displayed no decrease associated with age among men over 40 years of age who selfreport very good or excellent health although obesity and exsmoking status were associated with decreased serum androgens (T and DHT) but not E 2. These findings support the interpretation that the age-related decline in blood T accompanying non-specific symptoms in older men may be due to accumulating age-related co-morbidities rather than a symptomatic androgen deficiency state.

Loading...

Loading Preview

Sorry, preview is currently unavailable. You can download the paper by clicking the button above.

References (39)

  1. Kaufman, J.M. & Vermeulen, A. (2005) The decline of androgen levels in elderly men and its clinical and therapeutic implications. Endocrine Reviews, 26, 833-876.
  2. Morley, J.E., Kaiser, F.E., Perry, H.M. III et al. (1997) Longitudi- nal changes in testosterone, luteinizing hormone, and follicle- stimulating hormone in healthy older men. Metabolism: Clinical and Experimental, 46, 410-413.
  3. Liu, P.Y., Beilin, J., Meier, C. et al. (2007) Age-related changes in serum testosterone and sex hormone binding globulin in Aus- tralian men: longitudinal analyses of two geographically separate regional cohorts. Journal of Clinical Endocrinology and Metabo- lism, 92, 3599-3603.
  4. Travison, T.G., Nguyen, A.H., Naganathan, V. et al. (2011) Changes in reproductive hormone concentrations predict the prevalence and progression of the frailty syndrome in older men: the concord health and ageing in men project. Journal of Clinical Endocrinology and Metabolism, 96, 2464-2474.
  5. Haring, R., Ittermann, T., Volzke, H. et al. (2010) Prevalence, incidence and risk factors of testosterone deficiency in a popula- tion-based cohort of men: results from the study of health in Pomerania. Aging Male, 13, 247-257.
  6. Travison, T.G., Shackelton, R., Araujo, A.B. et al. (2008) The natural history of symptomatic androgen deficiency in men: onset, progression, and spontaneous remission. Journal of the American Geriatrics Society, 56, 831-839.
  7. Kelleher, S., Conway, A.J. & Handelsman, D.J. (2004) Blood tes- tosterone threshold for androgen deficiency symptoms. Journal of Clinical Endocrinology and Metabolism, 89, 3813-3817.
  8. T'Sjoen, G., Goemaere, S., De Meyere, M. et al. (2004) Percep- tion of males' aging symptoms, health and well-being in elderly community-dwelling men is not related to circulating androgen levels. Psychoneuroendocrinology, 29, 201-214.
  9. 9 Zitzmann, M., Faber, S. & Nieschlag, E. (2006) Association of specific symptoms and metabolic risks with serum testosterone in older men. Journal of Clinical Endocrinology and Metabolism, 91, 4335-4343.
  10. Bhasin, S., Cunningham, G.R., Hayes, F.J. et al. (2010) Testoster- one therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. Journal of Clinical Endocrinology and Metabolism, 95, 2536-2559.
  11. Wu, F.C., Tajar, A., Beynon, J.M. et al. (2010) Identification of Late-Onset Hypogonadism in Middle-Aged and Elderly Men. New England Journal of Medicine, 363, 123-135.
  12. Liverman, C.T. & Blazer, D.G., eds. (2004) Testosterone and Aging: Clinical Research Directions. Institute of Medicine: The National Academies Press, Washington, DC.
  13. Wang, C., Nieschlag, E., Swerdloff, R. et al. (2009) Investigation, treatment, and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA, and ASA recommendations. Journal of Andrology, 30, 1-9.
  14. Handelsman, D.J. (2011) An old emperor finds new clothing: rejuvenation in our time. Asian Journal of Andrology, 13, 125- 129.
  15. Idan, A., Griffiths, K.A., Harwood, D.T. et al. (2010) Long-term effects of dihydrotestosterone treatment on prostate growth in healthy, middle-aged men without prostate disease: a random- ized, placebo-controlled trial. Annals of Internal Medicine, 153, 621-632.
  16. Harwood, D.T. & Handelsman, D.J. (2009) Development and validation of a sensitive liquid chromatography-tandem mass spectrometry assay to simultaneously measure androgens and estrogens in serum without derivatization. Clinica Chimica Acta, 409, 78-84.
  17. Vesper, H.W. & Botelho, J.C. (2010) Standardization of testos- terone measurements in humans. Journal of Steroid Biochemistry and Molecular Biology, 121, 513-519.
  18. Sartorius, G., Ly, L.P., Sikaris, K. et al. (2009) Predictive accu- racy and sources of variability in calculated free testosterone esti- mates. Annals of Clinical Biochemistry, 46, 137-143.
  19. Ly, L.P. & Handelsman, D.J. (2005) Empirical estimation of free testosterone from testosterone and sex hormone-binding globu- lin immunoassays. European Journal of Endocrinology, 152, 471- 478.
  20. Ly, L.P., Sartorius, G., Hull, L. et al. (2010) Accuracy of calcu- lated free testosterone formulae in men. Clinical Endocrinology, 73, 382-388.
  21. Carrington, M.J., Jennings, G.L. & Stewart, S. (2010) Pattern of blood pressure in Australian adults: results from a national blood pressure screening day of 13 825 adults. International Jour- nal of Cardiology, 145, 461-467.
  22. Cameron, A.J., Welborn, T.A., Zimmet, P.Z. et al. (2003) Over- weight and obesity in Australia: the 1999-2000 Australian diabe- tes, obesity and lifestyle study (AusDiab). Medical Journal of Australia, 178, 427-432.
  23. Nieschlag, E., Lammers, U., Freischem, C.W. et al. (1982) Repro- ductive function in young fathers and grandfathers. Journal of Clinical Endocrinology and Metabolism, 55, 676-681.
  24. Harman, S.M. & Tsitouras, P.D. (1980) Reproductive hormones in aging men I: measurement of sex steroids, basal luteinizing hormone, and Leydig cell response to human chorionic gonado- tropin. Journal of Clinical Endocrinology and Metabolism, 51, 35- 40.
  25. Sikaris, K., McLachlan, R.I., Kazlauskas, R. et al. (2005) Repro- ductive hormone reference intervals for healthy fertile young men: evaluation of automated platform assays. Journal of Clinical Endocrinology and Metabolism, 90, 5928-5936.
  26. Yeap, B.B., Almeida, O.P., Hyde, Z. et al. (2007) In men older than 70 years, total testosterone remains stable while free testos- terone declines with age. The Health in Men Study. European Journal of Endocrinology, 156, 585-594.
  27. Handelsman, D.J. & Staraj, S. (1985) Testicular size: the effects of aging, malnutrition and illness. Journal of Andrology, 6, 144- 151.
  28. Shackleton, C. (2010) Clinical steroid mass spectrometry: a 45- year history culminating in HPLC-MS/MS becoming an essential tool for patient diagnosis. Journal of Steroid Biochemistry and Molecular Biology, 121, 481-490.
  29. Lee, J.S., Ettinger, B., Stanczyk, F.Z. et al. (2006) Comparison of methods to measure low serum estradiol levels in postmeno- pausal women. Journal of Clinical Endocrinology and Metabolism, 91, 3791-3797.
  30. Vermeulen, A. & Verdonck, G. (1992) Representativeness of a single point plasma testosterone level for the long term hor- monal milieu in men. Journal of Clinical Endocrinology and Metabolism, 74, 939-942.
  31. Brambilla, D.J., O'Donnell, A.B., Matsumoto, A.M. et al. (2007) Intraindividual variation in levels of serum testosterone and other reproductive and adrenal hormones in men. Clinical Endo- crinology, 67, 853-862.
  32. Iranmanesh, A., Lawson, D. & Veldhuis, J.D. (2012) Glucose ingestion acutely lowers pulsatile LH and basal testosterone secretion in men. American Journal of Physiology. Endocrinology and Metabolism, 302, E724-E730.
  33. Bergendahl, M., Aloi, J.A., Iranmanesh, A. et al. (1998) Fasting suppresses pulsatile luteinizing hormone (LH) secretion and enhances orderliness of LH release in young but not older men. Journal of Clinical Endocrinology and Metabolism, 83, 1967-1975.
  34. Rojdmark, S., Asplund, A. & Rossner, S. (1989) Pituitary-testicu- lar axis in obese men during short-term fasting. Acta Endocrinol- ogica, 121, 727-732.
  35. Judelson, D.A., Maresh, C.M., Yamamoto, L.M. et al. (2008) Effect of hydration state on resistance exercise-induced endocrine markers of anabolism, catabolism, and metabolism. Journal of Applied Physiology, 105, 816-824.
  36. Allan, C.A. & McLachlan, R.I. (2010) Androgens and obesity. Cur- rent opinion in Endocrinology, Diabetes, and Obesity, 17, 224-232.
  37. Vine, M.F. (1996) Smoking and male reproduction: a review. International Journal of Andrology, 19, 323-337.
  38. Huhtaniemi, I.T., Pye, S.R., Limer, K.L. et al. (2009) Increased estrogen rather than decreased androgen action is associated with longer androgen receptor CAG repeats. Journal of Clinical Endo- crinology and Metabolism, 94, 277-284.
  39. Orwoll, E.S., Nielson, C.M., Labrie, F. et al. (2010) Evidence for geographical and racial variation in serum sex steroid levels in older men. Journal of Clinical Endocrinology and Metabolism, 95, E151-E160.