Age or factors associated with aging attenuate testosterone's concentration-dependent enhancement of the regularity of luteinizing hormone secretion in healthy men

Journal of Clinical Endocrinology and Metabolism

Volumn 91, Issue 10, 2006, Pages 4077-4084

  Liu, Peter Y ^a   Takahashi, Paul Y ^a   Roebuck, Pamela D ^a   Veldhuis, Johannes D ^a  

^a MAYO CLINIC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

LUTEINIZING HORMONE; TESTOSTERONE;

ADULT; AGED; AGING; ARTICLE; BODY MASS; CONTROLLED STUDY; HEALTH CENTER; HORMONE RELEASE; HUMAN; HYPOTHALAMUS; LEYDIG CELL; NEUROENDOCRINE SYSTEM; NORMAL HUMAN; PRIORITY JOURNAL; REGRESSION ANALYSIS; SENSITIVITY AND SPECIFICITY; STEROIDOGENESIS;

EID: 33749561819     PISSN: 0021972X     EISSN: 0021972X     Source Type: Journal    
DOI: 10.1210/jc.2005-2811     Document Type: Article

References (69)

1. Hollander N, Hollander VP 1958 The microdetermination of testosterone in human spermatic vein blood. J Clin Endocrinol Metab 18:966-971
2. Giusti G, Gonnelli P, Borrelli D, Fiorelli G, Forti G, Pazzagli M, Serio M 1975 Age-related secretion of androstenedione, testosterone and dihydrotestosterone by the human testis. Exp Gerontol 10:241-245
3. Simon D, Preziosi P, Barrett-Connor E, Roger M, Saint-Paul M, Nahoul K, Papoz L 1992 The influence of aging on plasma sex hormones in men: the Telecom Study. Am J Epidemiol 135:783-791
4. Morley JE, Kaiser FE, Perry 3rd HM, Patrick P, Morley PM, Stauber PM, Vellas B, Baumgartner RN, Garry PJ 1997 Longitudinal changes in testosterone, luteinizing hormone, and follicle-stimulating hormone in healthy older men. Metab Clin Exp 46:410-413
5. Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR 2001 Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metab 86:724-731
6. Svartberg J, Midtby M, Bonaa KH, Sundsfjord J, Joakimsen RM, Jorde R 2003 The associations of age, lifestyle factors and chronic disease with testosterone in men: the Tromso Study. Eur J Endocrinol 149:145-152
7. Araujo AB, O'Donnell AB, Brambilla DJ, Simpson WB, Longcope C, Matsumoto AM, McKinlay JB 2004 Prevalence and incidence of androgen deficiency in middle-aged and older men: estimates from the Massachusetts Male Aging Study. J Clin Endocrinol Metab 89:5920-5926
8. Liu PY, Swerdloff RS, Veldhuis JD 2004 The rationale, efficacy and safety of androgen therapy in older men: future research and current practice recommendations. J Clin Endocrinol Metab 89:4789-4796
9. Allan CA, McLachlan RI 2004 Age-related changes in testosterone and the role of replacement therapy in older men. Clin Endocrinol (Oxf) 60:653-670
10. Veldhuis JD, Iranmanesh A, Keenan DM 2004 An ensemble perspective of aging-related hypoandrogenemia in men. In: Winters SJ, ed. Male hypogonadism: basic, clinical, and theoretical principles. Totowa, NJ: Humana Press; 261-284
11. Zmuda JM, Cauley JA, Kriska A, Glynn NW, Gutai JP, Kuller LH 1997 Longitudinal relation between endogenous testosterone and cardiovascular disease risk factors in middle-aged men. A 13-year follow-up of former Multiple Risk Factor Intervention Trial participants. Am J Epidemiol 146:609-617
12. Roy TA, Blackman MR, Harman SM, Tobin JD, Schrager M, Metter EJ 2002 Interrelationships of serum testosterone and free testosterone index with fat free mass and strength in aging men. Am J Physiol Endocrinol Metab 283:E284-E294
13. Ly LP, Jimenez M, Zhuang TN, Celermajer DS, Conway AJ, Handelsman DJ 2001 A double-blind, placebo-controlled, randomized clinical trial of transdermal dihydrotestosterone gel on muscular strength, mobility, and quality of life in older men with partial androgen deficiency. J Clin Endocrinol Metab 86:4078-4088
14. Urban RJ, Bodenburg YH, Gilkison C, Foxworth J, Coggan AR, Wolfe RR, Ferrando A 1995 Testosterone administration to elderly men increases skeletal muscle strength and protein synthesis. Am J Physiol 269:E280-E286
15. Hak AE, Witteman JC, De Jong FH, Geerlings MI, Hofman A, Pols HA 2002 Low levels of endogenous androgens increase the risk of atherosclerosis in elderly men: the Rotterdam study. J Clin Endocrinol Metab 87:3632-3639
16. van den Beld AW, De Jong FH, Grobbee DE, Pols HA, Lamberts SW 2000 Measures of bioavailable serum testosterone and estradiol and their relationships with muscle strength, bone density, and body composition in elderly men. J Clin Endocrinol Metab 85:3276-3282
17. Liu PY, Wishart SM, Handelsman DJ 2002 A double-blind, placebo-controlled, randomized clinical trial of recombinant human chorionic gonadotropin on muscle strength and physical function and activity in older men with partial age-related androgen deficiency. J Clin Endocrinol Metab 87:3125-3135
18. Leifke E, Korner HC, Link TM, Behre HM, Peters PE, Nieschlag E 1998 Effects of testosterone replacement therapy on cortical and trabecular bone mineral density, vertebral body area and paraspinal muscle area in hypogonadal men. Eur J Endocrinol 138:51-58
19. Page ST, Amory JK, Bowman FD, Anawalt BD, Matsumoto AM, Bremner WJ, Tenover JL 2005 Exogenous testosterone (T) alone or with finasteride increases physical performance, grip strength, and lean body mass in older men with low serum T. J Clin Endocrinol Metab 90:1502-1510
20. Rolf C, von Eckardstein S, Koken U, Nieschlag E 2002 Testosterone substitution of hypogonadal men prevents the age-dependent increases in body mass index, body fat and leptin seen in healthy ageing men: results of a cross-sectional study. Eur J Endocrinol 146:505-511
21. Sih R, Morley JE, Kaiser FE, Perry HM, Patrick P, Ross C 1997 Testosterone replacement in older hypogonadal men: a 12-month randomized controlled trial. J Clin Endocrinol Metab 82:1661-1667
22. Janowsky JS, Oviatt SK, Orwoll ES 1994 Testosterone influences spatial cognition in older men. Behav Neurosci 108:325-332
23. Mulligan T, Iranmanesh A, Gheorghiu S, Godschalk M, Veldhuis JD 1995 Amplified nocturnal luteinizing hormone (LH) secretory burst frequency with selective attenuation of pulsatile (but not basal) testosterone secretion in healthy aged men: possible Leydig cell desensitization to endogenous LH signaling - a clinical research center study. J Clin Endocrinol Metab 80:3025-3031
24. Mulligan T, Iranmanesh A, Kerzner R, Demers LW, Veldhuis JD 1999 Two-week pulsatile gonadotropin releasing hormone infusion unmasks dual (hypothalamic and Leydig-cell) defects in the healthy aging male gonadotropic axis. Eur J Endocrinol 141:257-266
25. Keenan DM, Veldhuis JD 2004 Divergent gonadotropin-gonadal dose-responsive coupling in healthy young and aging men. Am J Physiol 286:R381-R389
26. Veldhuis JD, Veldhuis NJ, Keenan DM, Iranmanesh A 2005 Age diminishes the testicular steroidogenic response to repeated intravenous pulses of recombinant human LH during acute GnRH-receptor blockade in healthy men. Am J Physiol Endocrinol Metab 288:E775-E781
27. Mulligan T, Iranmanesh A, Veldhuis JD 2001 Pulsatile intravenous infusion of recombinant human LH in leuprolide-suppressed men unmasks impoverished Leydig-cell secretory responsiveness to midphysiological LH drive in the aging male. J Clin Endocrinol Metab 86:5547-5553
28. Veldhuis JD, Zwart A, Mulligan T, Iranmanesh A 2001 Muting of androgen negative feedback unveils impoverished gonadotropin-releasing hormone/luteinizing hormone secretory reactivity in healthy older men. J Clin Endocrinol Metab 86:529-535
29. Veldhuis JD, Urban RJ, Lizarralde G, Johnson ML, Iranmanesh A 1992 Attenuation of luteinizing hormone secretory burst amplitude is a proximate basis for the hypoandrogenism of healthy aging in men. J Clin Endocrinol Metab 75:52-58
30. Kaufman JM, Vermeulen A 2005 The decline of androgen levels in elderly men and its clinical and therapeutic implications. Endocr Rev 26:833-876
31. Deslypere JP, Kaufman JM, Vermeulen T, Vogelaers D, Vandalem JL, Vermeulen A 1987 Influence of age on pulsatile luteinizing hormone release and responsiveness of the gonadotrophs to sex hormone feedback in men. J Clin Endocrinol Metab 64:68-73
32. Winters SJ, Sherins RJ, Troen P 1984 The gonadotropin suppressive activity of androgen is increased in elderly men. Metabolism 33:1052-1059
33. Veldhuis JD, Iranmanesh A, Keenan DM 2004 Erosion of endogenous testosterone-driven negative feedback on pulsatile LH secretion in healthy aging men. J Clin Endocrinol Metab 89:5753-5761
34. Veldhuis JD, Urban RJ, Dufau ML 1992 Evidence that androgen negative-feedback regulates hypothalamic GnRH impulse strength and the burst-like secretion of biologically active luteinizing hormone in men. J Clin Endocrinol Metab 74:1227-1235
35. Veldhuis JD, Zwart AD, Iranmanesh A 1997 Neuroendocrine mechanisms by which selective Leydig-cell castration unleashes increased pulsatile LH release in the human: an experimental paradigm of short-term ketoconazole-induced hypoandrogenemia and deconvolution-estimated LH secretory enhancement. Am J Physiol 272:R464-R474
36. Keenan DM, Veldhuis JD 1998 A biomathematical model of time-delayed feedback in the human male hypothalamic-pituitary-Leydig cell axis. Am J Physiol 275:E157-E176
37. Keenan DM, Veldhuis JD 2001 Hypothesis testing of the aging male gonadal axis via a biomathematical construct. Am J Physiol 280:R1755-R1771
38. Keenan DM, Veldhuis JD 2001 Disruption of the hypothalamic luteinizing-hormone pulsing mechanism in aging men. Am J Physiol 281:R1917-R1924
39. Winters SJ, Atkinson L 1997 Serum LH concentrations in hypogonadal men during transdermal testosterone replacement through scrotal skin: further evidence that aging enhances testosterone negative feedback. Clin Endocrinol (Oxf) 47:317-322
40. Muta K, Kato K, Akamine Y, Ibayashi H 1981 Age-related changes in the feedback regulation of gonadotrophin secretion by sex steroids in men. Acta Endocrinol (Copenh) 96:154-162
41. Gentili A, Mulligan T, Godschalk M, Clore J, Patrie J, Iranmanesh A, Veldhuis JD 2002 Unequal impact of short-term testosterone repletion on the somatotropic axis of young and older men. J Clin Endocrinol Metab 87:825-834
42. Liu PY, Pincus SM, Keenan DM, Roelfsema F, Veldhuis JD 2005 Analysis of bidirectional pattern synchrony of concentration-secretion pairs: implementation in the human testicular and adrenal axes. Am J Physiol Regul Integr Comp 288:R440-R446
43. Pincus SM 1991 Approximate entropy as a measure of system complexity. Proc Natl Acad Sci USA 88:2297-2301
44. Zwart A, Iranmanesh A, Veldhuis JD 1997 Disparate serum free testosterone concentrations and degrees of hypothalamo-pituitary-LH suppression are achieved by continuous versus pulsatile intravenous androgen replacement in men: a clinical experimental model of ketoconazole-induced reversible hypoandrogenemia with controlled testosterone add-back. J Clin Endocrinol Metab 82:2062-2069
45. Wang C, Berman N, Longstreth JA, Chuapoco B, Hull L, Steiner B, Faulkner S, Dudley RE, Swerdloff RS 2000 Pharmacokinetics of transdermal testosterone gel in hypogonadal men: application of gel at one site versus four sites: a General Clinical Research Center Study. J Clin Endocrinol Metab 85:964-969
46. Veldhuis JD, Lizarralde G, Iranmanesh A 1992 Divergent effects of short-term glucocorticoid excess on the gonadotropic and somatotropic axes in normal men. J Clin Endocrinol Metab 74:96-102
47. Veldhuis JD, Iranmanesh A, Mulligan T, Pincus SM 1999 Disruption of the young-adult synchrony between luteinizing hormone release and oscillations in follicle-stimulating hormone, prolactin, and nocturnal penile tumescence (NPT) in healthy older men. J Clin Endocrinol Metab 84:3498-3505
48. Fitzgerald RL, Herold DA 1996 Serum total testosterone: immunoassay compared with negative chemical ionization gas chromatography-mass spectrometry. Clin Chem 42:749-755
49. Veldhuis JD, Iranmanesh A, Demers LM, Mulligan T 1999 Joint basal and pulsatile hypersecretory mechanisms drive the monotropic follicle-stimulating hormone (FSH) elevation in healthy older men: concurrent preservation of the orderliness of the FSH release process. J Clin Endocrinol Metab 84:3506-3514
50. Veldhuis JD, Johnson ML 1986 Cluster analysis: a simple, versatile and robust algorithm for endocrine pulse detection. Am J Physiol 250:E486-E493
51. Urban RJ, Johnson ML, Veldhuis JD 1989 In vivo biological validation and biophysical modeling of the sensitivity and positive accuracy of endocrine peak detection: I. The LH pulse signal. Endocrinology 124:2541-2547
52. Veldhuis JD, Straume M, Iranmanesh A, Mulligan T, Jaffe CA, Barkan A, Johnson ML, Pincus SM 2001 Secretory process regularity monitors neuroendocrine feedback and feedforward signaling strength in humans. Am J Physiol 280:R721-R729
53. Pincus SM, Mulligan T, Iranmanesh A, Gheorghiu S, Godschalk M, Veldhuis JD 1996 Older males secrete luteinizing hormone and testosterone more irregularly, and jointly more asynchronously, than younger males. Proc Natl Acad Sci USA 93:14100-14105
54. Pincus SM, Keefe DL 1992 Quantification of hormone pulsatility via an approximate entropy algorithm. Am J Physiol 262:E741-E754
55. Pincus SM, Hartman ML, Roelfsema F, Thorner MO, Veldhuis JD 1999 Hormone pulsatility discrimination via coarse and short time sampling. Am J Physiol 277:E948-E957
56. Veldhuis JD, Johnson ML, Veldhuis OL, Straume M, Pincus S 2001 Impact of pulsatility on the ensemble orderliness (approximate entropy) of neurohormone secretion. Am J Physiol 281:R1975-R1985
57. Pincus SM, Kalman RE 1997 Not all (possibly) "random" sequences are created equal. Proc Natl Acad Sci USA 94:3513-3518
58. Fisher LD, van Belle G 1996 Descriptive statistics. Biostatistics: a methodology for the health sciences. New York: John Wiley, Sons; 58-74
59. O'Brien PC 1983 The appropriateness of analysis of variance and multiplecomparison procedures. Biometrics 39:787-794
60. Liu PY, Pincus SM, Takahashi PY, Roebuck PD, Iranmanesh A, Keenan DM, Veldhuis JD 2006 Aging attenuates both the regularity and joint synchrony of LH and testosterone secretion in normal men: analyses via a model of graded GnRH receptor blockade. Am J Physiol Endocrinol Metab 290:E34-E41
61. O'Connor JC, Frame SR, Ladics GS 2002 Evaluation of a 15-day screening assay using intact male rats for identifying steroid biosynthesis inhibitors and thyroid modulators. Toxicol Sci 69:79-91
62. Haji M, Kato KI, Nawata H, Ibayashi H 1980 Age-related changes in the concentrations of cytosol receptors for sex steroid hormones in the hypothalamus and pituitary gland of the rat. Brain Res 204:373-386
63. Roth GS 1979 Hormone receptor changes during adulthood and senescence: significance for aging research. Fed Proc 38:1910-1914
64. Wilson ME, Rosewell KL, Kashon ML, Shughrue PJ, Merchenthaler I, Wise PM 2002 Age differentially influences estrogen receptor-α(ERα) and estrogen receptor-β (ERβ) gene expression in specific regions of the rat brain. Mech Ageing Dev 123:593-601
65. Hayes FJ, Seminara SB, DeCruz S, Boepple PA, Crowley Jr WF 2000 Aromatase inhibition in the human male reveals a hypothalamic site of estrogen feedback. J Clin Endocrinol Metab 85:3027-3035
66. Schnorr JA, Bray MJ, Veldhuis JD 2001 Aromatization mediates testosterone's short-term feedback restraint of 24-hour endogenously driven and acute exogenous GnRH-stimulated LH and FSH secretion in young men. J Clin Endocrinol Metab 86:2600-2606
67. Clarke IJ, Cummins JT 1982 The temporal relationship between gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) secretion in ovariectomized ewes. Endocrinology 111:1737-1739
68. Urbanski HF, Pickle RL, Ramirez VD 1988 Simultaneous measurement of gonadotropin-releasing hormone, luteinizing hormone, and follicle-stimulating hormone in the orchidectomized rat. Endocrinology 123:413-419
69. Terasawa E 1995 Control of luteinizing hormone-releasing hormone pulse generation in nonhuman primates. Cell Mol Neurobiol 15:141-164