Perspectives for metabolomics in testosterone replacement therapy

Journal of Endocrinology

Volumn 215, Issue 1, 2012, Pages 3-16

  Haring, Robin ^a  

^a UNIVERSITY MEDICINE GREIFSWALD   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

BIOLOGICAL MARKER; PARACETAMOL; TESTOSTERONE;

ANDROGEN DEFICIENCY; DRUG EFFICACY; DRUG RESPONSE; DRUG SAFETY; HORMONE SUBSTITUTION; HUMAN; LABORATORY DIAGNOSIS; MEDICAL LITERATURE; MEDLINE; METABOLOMICS; MONITORING; NONHUMAN; PHYSIOLOGY; PRIORITY JOURNAL; PROGNOSIS; REVIEW; SYSTEMATIC REVIEW; TESTOSTERONE REPLACEMENT THERAPY;

ANIMALS; ERECTILE DYSFUNCTION; HORMONE REPLACEMENT THERAPY; HUMANS; HYPOGONADISM; INDIVIDUALIZED MEDICINE; MALE; METABOLOMICS; TESTOSTERONE;

EID: 84869221950     PISSN: 00220795     EISSN: 14796805     Source Type: Journal    
DOI: 10.1530/JOE-12-0119     Document Type: Review

References (146)

1. Aardema MJ & MacGregor JT. 2002 Toxicology and genetic toxicology in the new era of "toxicogenomics": impact of "-omics" technologies. Mutation Research 499 13-25.
2. Aderem A. 2005 Systems biology: its practice and challenges. Cell 121 511-513.
3. 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. Journal of Clinical Endocrinology and Metabolism 89 5920-5926.
4. Araujo AB, Dixon JM, Suarez EA, Murad MH, Guey LT &Wittert GA. 2011 Endogenous testosterone and mortality in men: a systematic review and meta-analysis. Journal of Clinical Endocrinology and Metabolism 96 3007-3019.
5. Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T, Mende DR, Fernandes GR, Tap J, Bruls T, Batto JM et al. 2011 Enterotypes of the human gut microbiome. Nature 473 174-180.
6. Auffray C, Chen Z & Hood L. 2009 Systems medicine: the future of medical genomics and healthcare. Genome Medicine 1 2.
7. Badoud F, Grata E, Boccard J, Guillarme D, Veuthey JL, Rudaz S & Saugy M. 2011 Quantification of glucuronidated and sulfated steroids in human urine by ultra-high pressure liquid chromatography quadrupole time-of-flight mass spectrometry. Analytical and Bioanalytical Chemistry 400 503-516.
8. Bain JR, Stevens RD, Wenner BR, Ilkayeva O, Muoio DM & Newgard CB. 2009 Metabolomics applied to diabetes research: moving from information to knowledge. Diabetes 58 2429-2443.
9. Barderas MG, Laborde CM, Posada M, de la Cuesta F, Zubiri I, Vivanco F & Alvarez-Llamas G. 2011 Metabolomic profiling for identification of novel potential biomarkers in cardiovascular diseases. Journal of Biomedicine & Biotechnology 2011 790132.
10. Barrett-Connor E, Khaw KT & Yen SS. 1990 Endogenous sex hormone levels in older adult men with diabetes mellitus. American Journal of Epidemiology 132 895-901.
11. Basaria S, Coviello AD, Travison TG, Storer TW, Farwell WR, Jette AM, Eder R, Tennstedt S, Ulloor J, Zhang A et al. 2010 Adverse events associated with testosterone administration. New England Journal of Medicine 363 109-122.
12. Baumgartner C, Lewis GD, Netzer M, Pfeifer B & Gerszten RE. 2010 A new data mining approach for profiling and categorizing kinetic patterns of metabolic biomarkers after myocardial injury. Bioinformatics 26 1745-1751.doi:10.1093/bioinformatics/btq254)
13. Bean KA & Henion JD. 1997 Direct determination of anabolic steroid conjugates in human urine by combined high-performance liquid chromatography and tandem mass spectrometry. Journal of Chromatography. B, Biomedical Sciences and Applications 690 65-75.
14. Beckwith-Hall BM, Nicholson JK, Nicholls AW, Foxall PJ, Lindon JC, Connor SC, Abdi M, Connelly J & Holmes E. 1998 Nuclear magnetic resonance spectroscopic and principal components analysis investigations into biochemical effects of three model hepatotoxins. Chemical Research in Toxicology 11 260-272.
15. Benton HP, Want E, Keun HC, Amberg A, Plumb RS, Goldfain-Blanc F, Walther B, Reily MD, Lindon JC, Holmes E et al. 2012 Intra- and interlaboratory reproducibility of ultra performance liquid chromatography-time-of-flight mass spectrometry for urinary metabolic profiling. Analytical Chemistry 84 2424-2432.
16. Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS & Montori VM. 2010 Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. Journal of Clinical Endocrinology and Metabolism 95 2536-2559.
17. Biomarkers Definitions Working Group 2001 Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clinical Pharmacology and Therapeutics 69 89-95.
18. Bollard ME, Holmes E, Lindon JC, Mitchell SC, Branstetter D, Zhang W & Nicholson JK. 2001 Investigations into biochemical changes due to diurnal variation and estrus cycle in female rats using high-resolution (1)H NMR spectroscopy of urine and pattern recognition. Analytical Biochemistry 295 194-202.
19. Bollard ME, Stanley EG, Lindon JC, Nicholson JK & Holmes E. 2005 NMR-based metabonomic approaches for evaluating physiological influences on biofluid composition. NMR in Biomedicine 18 143-162.
20. Brindle JT, Antti H, Holmes E, Tranter G, Nicholson JK, Bethell HW, Clarke S, Schofield PM, McKilligin E, Mosedale DE et al. 2002 Rapid and noninvasive diagnosis of the presence and severity of coronary heart disease using 1H-NMR-based metabonomics. Nature Medicine 8 1439-1444.
21. Brockmoller SF, Bucher E, Muller BM, Budczies J, Hilvo M, Griffin JL, Oresic M, Kallioniemi O, Iljin K, Loibl S et al. 2012 Integration of metabolomics and expression of glycerol-3-phosphate acyltransferase (GPAM) in breast cancer-link to patient survival, hormone receptor status, and metabolic profiling. Journal of Proteome Research 11 850-860.
22. Chen R, Mias GI, Li-Pook-Than J, Jiang L, Lam HYK, Chen R, Miriami E, Karczewski KJ, Hariharan M, Dewey FE et al. 2012 Personal omics profiling reveals dynamic molecular and medical phenotypes. Cell 148 1293-1307.
23. Clayton TA, Lindon JC, CloarecO, Antti H, CharuelC, Hanton G, Provost JP, Le Net JL, Baker D, Walley RJ et al. 2006 Pharmaco-metabonomic phenotyping and personalized drug treatment. Nature 440 1073-1077.
24. Clayton TA, Baker D, Lindon JC, Everett JR & Nicholson JK. 2009 Pharmacometabonomic identification of a significant host-microbiome metabolic interaction affecting human drug metabolism. PNAS 106 14728-14733.
25. Coen M, Lenz EM, Nicholson JK, Wilson ID, Pognan F & Lindon JC. 2003 An integrated metabonomic investigation of acetaminophen toxicity in the mouse using NMR spectroscopy. Chemical Research in Toxicology 16 295-303.
26. Comas I & Gagneux S. 2011 A role for systems epidemiology in tuberculosis research. Trends in Microbiology 19 492-500.
27. Dorgan JF, Fears TR, McMahon RP, Aronson Friedman L, Patterson BH & Greenhut SF. 2002 Measurement of steroid sex hormones in serum: a comparison of radioimmunoassay and mass spectrometry. Steroids 67 151-158.
28. Dumas ME, Wilder SP, Bihoreau MT, Barton RH, Fearnside JF, Argoud K, D'Amato L, Wallis RH, Blancher C, Keun HC, Baunsgaard D, Scott J, Sidelmann UG, Nicholson JK & Gauguier D. 2007 Direct quantitative trait locus mapping of mammalian metabolic phenotypes in diabetic and normoglycemic rat models. Nature Genetics 39 666-672.
29. Dunn WB, Broadhurst DI, Atherton HJ, Goodacre R & Griffin JL. 2011 Systems level studies of mammalian metabolomes: the roles of mass spectrometry and nuclear magnetic resonance spectroscopy. Chemical Society Reviews 40 387-426.
30. Feldman HA, Longcope C, Derby CA, Johannes CB, Araujo AB, Coviello AD, Bremner WJ & McKinlay JB. 2002 Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts male aging study. Journal of Clinical Endocrinology and Metabolism 87 589-598.
31. Fernandez-Balsells MM, Murad MH, Lane M, Lampropulos JF, Albuquerque F, Mullan RJ, Agrwal N, Elamin MB, Gallegos-Orozco JF, Wang AT et al. 2010 Clinical review 1: adverse effects of testosterone therapy in adult men: a systematic review and meta-analysis. Journal of Clinical Endocrinology and Metabolism 95 2560-2575.
32. Gavaghan CL, Holmes E, Lenz E, Wilson ID & Nicholson JK. 2000 An NMR-based metabonomic approach to investigate the biochemical consequences of genetic strain differences: application to the C57BL10J and Alpk:ApfCD mouse. FEBS Letters 484 169-174.
33. Gavaghan CL, Nicholson JK, Connor SC, Wilson ID, Wright B & Holmes E. 2001 Directly coupled high-performance liquid chromatography and nuclear magnetic resonance spectroscopic with chemometric studies on metabolic variation in Sprague-Dawley rats. Analytical Biochemistry 291 245-252.
34. Gavaghan CL, Wilson ID & Nicholson JK. 2002 Physiological variation in metabolic phenotyping and functional genomic studies: use of orthogonal signal correction and PLS-DA. FEBS Letters 530 191-196.
35. Gould DC, Petty R & Jacobs HS. 2000 For and against: the male menopause - does it exist? BMJ 320 858-861.
36. Griffin JL, Atherton H, Shockcor J & Atzori L. 2011 Metabolomics as a tool for cardiac research. Nature Reviews. Cardiology 8 630-643.
37. Haring R & Wallaschofski H. 2012 Diving through the "-omics": the case for deep phenotyping and systems epidemiology. OMICS 16 231-234.
38. Haring R, Volzke H, Felix SB, Schipf S, Dorr M, Rosskopf D, Nauck M, Schofl C &Wallaschofski H. 2009 Prediction of metabolic syndrome by low serum testosterone levels in men: results from the study of health in Pomerania. Diabetes 58 2027-2031.
39. Haring R, Ittermann T, Volzke H, Krebs A, Zygmunt M, Felix SB, Grabe HJ, Nauck M &Wallaschofski H. 2010 Prevalence, incidence and risk factors of testosterone deficiency in a population-based cohort of men: results from the study of health in Pomerania. Aging Male 13 247-257.
40. Haring R, Baumeister S, Volzke H, Dorr M, Kocher T, Nauck M & Wallaschofski H. 2011a Prospective inverse associations of sex hormone concentrations in men with biomarkers of inflammation and oxidative stress. Journal of Andrology. In press.
41. Haring R, Baumeister SE, Völzke H, Dorr M, Felix SB, Kroemer HK, Nauck M & Wallaschofski H. 2011b Prospective association of low total testosterone concentrations with an adverse lipid profile and increased incident dyslipidemia. European Journal of Cardiovascular Prevention and Rehabilitation 18 86-96.
42. Haring R, Ernst F, Schurmann C, Homuth G, Volker U, Volzke H, Nauck M & Wallaschofski H. 2011c The androgen receptor CAG repeat polymorphism as a risk factor of low serum testosterone and its cardiometabolic effects in men. International Journal of Andrology. In press.
43. Haring R, Spielhagen C & NauckM. 2011d Challenges in the measurement of serum testosterone concentrations as a biomarker of men's health. Journal of Laboratory Medicine 35 1-5.
44. 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. Journal of Clinical Endocrinology and Metabolism 86 724-731.
45. Heijne WH, Lamers RJ, van Bladeren PJ, Groten JP, van Nesselrooij JH & van Ommen B. 2005 Profiles of metabolites and gene expression in rats with chemically induced hepatic necrosis. Toxicologic Pathology 33 425-433.
46. Heinzmann SS, Brown IJ, Chan Q, Bictash M, Dumas ME, Kochhar S, Stamler J, Holmes E, Elliott P & Nicholson JK. 2010 Metabolic profiling strategy for discovery of nutritional biomarkers: proline betaine as a marker of citrus consumption. American Journal of Clinical Nutrition 92 436-443.
47. Heinzmann SS, Merrifield CA, Rezzi S, Kochhar S, Lindon JC, Holmes E & Nicholson JK. 2012 Stability and robustness of human metabolic phenotypes in response to sequential food challenges. Journal of Proteome Research 11 643-655.
48. Holmes E & Nicholson JK. 2007 Human metabolic phenotyping and metabolome wide association studies. Ernst Schering Foundation Symposium Proceedings 227-249.
49. Holmes E, Bonner FW, Sweatman BC, Lindon JC, Beddell CR, Rahr E & Nicholson JK. 1992 Nuclear magnetic resonance spectroscopy and pattern recognition analysis of the biochemical processes associated with the progression of and recovery from nephrotoxic lesions in the rat induced by mercury(II) chloride and 2-bromoethanamine. Molecular Pharmacology 42 922-930.
50. Holmes E, Nicholls AW, Lindon JC, Ramos S, Spraul M, Neidig P, Connor SC, Connelly J, Damment SJ, Haselden J et al. 1998 Development of a model for classification of toxin-induced lesions using 1H NMR spectroscopy of urine combined with pattern recognition. NMR in Biomedicine 11 235-244.
51. Holmes E, Loo RL, Stamler J, Bictash M, Yap IK, Chan Q, Ebbels T, De Iorio M, Brown IJ, Veselkov KA et al. 2008a Human metabolic phenotype diversity and its association with diet and blood pressure. Nature 453 396-400.
52. Holmes E, Wilson ID & Nicholson JK. 2008b Metabolic phenotyping in health and disease. Cell 134 714-717.
53. Hsing AW, Stanczyk FZ, Belanger A, Schroeder P, Chang L, Falk RT & Fears TR. 2007 Reproducibility of serum sex steroid assays in men by RIA and mass spectrometry. Cancer Epidemiology, Biomarkers & Prevention 16 1004-1008.
54. Hu FB. 2011 Metabolic profiling of diabetes: from black-box epidemiology to systems epidemiology. Clinical Chemistry 57 1224-1226.
55. Isidori AM& Lenzi A. 2007 Testosterone replacement therapy: what we know is not yet enough. Mayo Clinic Proceedings 82 11-13.
56. Isidori AM, Giannetta E, Gianfrilli D, Greco EA, Bonifacio V, Aversa A, Isidori A, Fabbri A & Lenzi A. 2005 Effects of testosterone on sexual function in men: results of a meta-analysis. Clinical Endocrinology 63 381-394.
57. Kaplan SA, Meehan AG & Shah A. 2006 The age related decrease in testosterone is significantly exacerbated in obese men with the metabolic syndrome. What are the implications for the relatively high incidence of erectile dysfunction observed in these men? Journal of Urology 176 1524-1527 (discussion 1527-1528).
58. Kau AL, Ahern PP, Griffin NW, Goodman AL & Gordon JI. 2011 Human nutrition, the gut microbiome and the immune system. Nature 474 327-336.
59. Kaufman JM & Vermeulen A. 2005 The decline of androgen levels in elderly men and its clinical and therapeutic implications. Endocrine Reviews 26 833-876.
60. Kenny LC, Broadhurst DI, Dunn W, Brown M, North RA, McCowan L, Roberts C, Cooper GJ, Kell DB & Baker PN. 2010 Robust early pregnancy prediction of later preeclampsia using metabolomic biomarkers. Hypertension 56 741-749.
61. Kettunen J, Tukiainen T, Sarin AP, Ortega-Alonso A, Tikkanen E, Lyytikainen LP, Kangas AJ, Soininen P, Wurtz P, Silander K et al. 2012 Genome-wide association study identifies multiple loci influencing human serum metabolite levels. Nature Genetics 44 269-276.
62. Kinross JM, Alkhamesi N, Barton RH, Silk DB, Yap IK, Darzi AW, Holmes E & Nicholson JK. 2011 Global metabolic phenotyping in an experimental laparotomy model of surgical trauma. Journal of Proteome Research 10 277-287.
63. Kochhar S, Jacobs DM, Ramadan Z, Berruex F, Fuerholz A & Fay LB. 2006 Probing gender-specific metabolism differences in humans by nuclear magnetic resonance-based metabonomics. Analytical Biochemistry 352 274-281.
64. Kupelian V, Page ST, Araujo AB, Travison TG, Bremner WJ & McKinlay JB. 2006 Low sex hormone-binding globulin, total testosterone, and symptomatic androgen deficiency are associated with development of the metabolic syndrome in nonobese men. Journal of Clinical Endocrinology and Metabolism 91 843-850.
65. Laaksonen DE, Niskanen L, Punnonen K, Nyyssonen K, Tuomainen TP, Salonen R, Rauramaa R & Salonen JT. 2003 Sex hormones, inflammation and the metabolic syndrome: a population-based study. European Journal of Endocrinology 149 601-608.
66. Laaksonen DE, Niskanen L, Punnonen K, Nyyssonen K, Tuomainen TP, Valkonen VP, Salonen R & Salonen JT. 2004 Testosterone and sex hormone-binding globulin predict the metabolic syndrome and diabetes in middle-aged men. Diabetes Care 27 1036-1041.
67. Lamers RJ, van Nesselrooij JH, Kraus VB, Jordan JM, Renner JB, Dragomir AD, Luta G, van der Greef J & DeGroot J. 2005 Identification of an urinary metabolite profile associated with osteoarthritis. Osteoarthritis and Cartilage 13 762-768.
68. Lenfant C. 2003 Shattuck lecture - clinical research to clinical practice - lost in translation? New England Journal of Medicine 349 868-874.
69. Lenz EM, Bright J, Wilson ID, Morgan SR & Nash AF. 2003 A 1H NMR-based metabonomic study of urine and plasma samples obtained from healthy human subjects. Journal of Pharmaceutical and Biomedical Analysis 33 1103-1115.
70. Lenz EM, Bright J, Knight R, Westwood FR, Davies D, Major H & Wilson ID. 2005 Metabonomics with 1H-NMR spectroscopy and liquid chromatography-mass spectrometry applied to the investigation of metabolic changes caused by gentamicin-induced nephrotoxicity in the rat. Biomarkers 10 173-187.
71. Lewis GD, Asnani A & Gerszten RE. 2008a Application of metabolomics to cardiovascular biomarker and pathway discovery. Journal of the American College of Cardiology 52 117-123.
72. Lewis GD, Wei R, Liu E, Yang E, Shi X, Martinovic M, Farrell L, Asnani A, Cyrille M, Ramanathan A et al. 2008b Metabolite profiling of blood from individuals undergoing planned myocardial infarction reveals early markers of myocardial injury. Journal of Clinical Investigation 118 3503-3512.
73. Lindon JC, Holmes E & Nicholson JK. 2006 Metabonomics techniques and applications to pharmaceutical research & development. Pharmaceutical Research 23 1075-1088.
74. Lindon JC & Nicholson JK. 2008 Spectroscopic and statistical techniques for information recovery in metabonomics and metabolomics. Annual Review of Analytical Chemistry 1 45-69.
75. Lindon JC, Nicholson JK, Holmes E, Antti H, Bollard ME, Keun H, Beckonert O, Ebbels TM, Reily MD, Robertson D et al. 2003 Contemporary issues in toxicology the role of metabonomics in toxicology and its evaluation by the COMET project. Toxicology and Applied Pharmacology 187 137-146.
76. Lund E & Dumeaux V. 2008 Systems epidemiology in cancer. Cancer Epidemiology, Biomarkers & Prevention 17 2954-2957.
77. Maclellan WR, Wang Y & Lusis AJ. 2012 Systems-based approaches to cardiovascular disease. Nature Reviews. Cardiology 9 172-184.
78. Madsen R, Lundstedt T & Trygg J. 2010 Chemometrics in metabolomics - a review in human disease diagnosis. Analytica Chimica Acta 659 23-33.
79. Maggio M & Basaria S. 2009 Welcoming low testosterone as a cardiovascular risk factor. International Journal of Impotence Research 21 261-264.
80. Makinen VP, Soininen P, Forsblom C, Parkkonen M, Ingman P, Kaski K, Groop PH & Ala-Korpela M. 2008 1H NMR metabonomics approach to the disease continuum of diabetic complications and premature death. Molecular Systems Biology 4 167.
81. Mamas M, Dunn WB, Neyses L & Goodacre R. 2011 The role of metabolites and metabolomics in clinically applicable biomarkers of disease. Archives of Toxicology 85 5-17.
82. Mareck U, Geyer H, Opfermann G, Thevis M & Schanzer W. 2008 Factors influencing the steroid profile in doping control analysis. Journal of Mass Spectrometry 43 877-891.
83. Mayr M, Yusuf S, Weir G, Chung YL, Mayr U, Yin X, Ladroue C, Madhu B, Roberts N, De Souza A et al. 2008 Combined metabolomic and proteomic analysis of human atrial fibrillation. Journal of the American College of Cardiology 51 585-594.
84. McLachlan RI. 2010 Certainly more guidelines than rules. Journal of Clinical Endocrinology and Metabolism 95 2610-2613.
85. Merrifield CA, Lewis M, Claus SP, Beckonert OP, Dumas ME, Duncker S, Kochhar S, Rezzi S, Lindon JC, Bailey M et al. 2011 A metabolic systemwide characterisation of the pig: a model for human physiology. Molecular BioSystems 7 2577-2588.
86. Mittelstrass K, Ried JS, Yu Z, Krumsiek J, Gieger C, Prehn C, Roemisch-MarglW, Polonikov A, Peters A, Theis FJ et al. 2011 Discovery of sexual dimorphisms in metabolic and genetic biomarkers. PLoS Genetics 7 e1002215.
87. Moolenaar SH, Engelke UF & Wevers RA. 2003 Proton nuclear magnetic resonance spectroscopy of body fluids in the field of inborn errors of metabolism. Annals of Clinical Biochemistry 40 16-24.
88. Mooradian AD, Morley JE & Korenman SG. 1987 Biological actions of androgens. Endocrine Reviews 8 1-28.
89. Morales A, Bella AJ, Chun S, Lee J, Assimakopoulos P, Bebb R, Gottesman I, Alarie P, Dugre H & Elliott S. 2010 A practical guide to diagnosis, management and treatment of testosterone deficiency for Canadian physicians. Canadian Urological Association Journal 4 269-275.
90. Morley JE & Perry HM III. 2003 Androgen treatment of male hypogonadism in older males. Journal of Steroid Biochemistry and Molecular Biology 85 367-373.
91. Morley JE, Kaiser FE, Perry HM III, 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. Metabolism 46 410-413.
92. Nicholson JK & Lindon JC. 2008 Systems biology: metabonomics. Nature 455 1054-1056.
93. Nicholson JK & Wilson ID. 2003 Opinion: understanding 'global' systems biology: metabonomics and the continuum of metabolism. Nature Reviews. Drug Discovery 2 668-676.
94. Nicholson JK, Lindon JC & Holmes E. 1999 'Metabonomics': understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data. Xenobiotica 29 1181-1189.
95. Nicholson JK, Holmes E & Elliott P. 2008 The metabolome-wide association study: a new look at human disease risk factors. Journal of Proteome Research 7 3637-3638.
96. Nicholson G, Rantalainen M, Maher AD, Li JV, Malmodin D, Ahmadi KR, Faber JH, Hallgrimsdottir IB, Barrett A, Toft H et al. 2011 Human metabolic profiles are stably controlled by genetic and environmental variation. Molecular Systems Biology 7 525.
97. Nieschlag E & Behre H. 2004 Clinical uses of testosterone in hypogonadism and other conditions. In Testosterone: Action, Deficiency, Substitution, pp 375-404. Eds E Nieschlag & H Behre. Cambridge: University Press.
98. Nordstrom A & Lewensohn R. 2010 Metabolomics: moving to the clinic. Journal of Neuroimmune Pharmacology 5 4-17.
99. O'Connell MD, Roberts SA, Srinivas-Shankar U, Tajar A, Connolly MJ, Adams JE, Oldham JA & Wu FC. 2011 Do the effects of testosterone on muscle strength, physical function, body composition, and quality of life persist six months after treatment in intermediate-frail and frail elderly men? Journal of Clinical Endocrinology and Metabolism 96 454-458.
100. O'Donnell CJ & Nabel EG. 2011 Genomics of cardiovascular disease. New England Journal of Medicine 365 2098-2109.
101. Ohlsson C, Wallaschofski H, Lunetta KL, Stolk L, Perry JR, Koster A, Petersen AK, Eriksson J, Lehtimaki T, Huhtaniemi IT et al. 2011 Genetic determinants of serum testosterone concentrations in men. PLoS Genetics 7 e1002313.
102. O'Sullivan A, Gibney MJ & Brennan L. 2011 Dietary intake patterns are reflected in metabolomic profiles: potential role in dietary assessment studies. American Journal of Clinical Nutrition 93 314-321.
103. Perheentupa A & Huhtaniemi I. 2007 Does the andropause exist? Nature Clinical Practice. Endocrinology & Metabolism 3 670-671.
104. Psihogios NG, Gazi IF, Elisaf MS, Seferiadis KI & Bairaktari ET. 2008 Genderrelated and age-related urinalysis of healthy subjects by NMR-based metabonomics. NMR in Biomedicine 21 195-207.
105. Putluri N, Shojaie A, Vasu VT, Nalluri S, Vareed SK, Putluri V, Vivekanandan-Giri A, Byun J, Pennathur S, Sana TR et al. 2011 Metabolomic profiling reveals a role for androgen in activating amino acid metabolism and methylation in prostate cancer cells. PLoS ONE 6 e21417.
106. Rantalainen M, Cloarec O, Beckonert O, Wilson ID, Jackson D, Tonge R, Rowlinson R, Rayner S, Nickson J, Wilknson RW, Mills JD, Trygg J, Nicholson JK & Holmes E. 2006 Statistically integrated metabonomicproteomic studies on human prostate cancer xenograft model in mice. Journal of Proteome Research 5 2642-2655.
107. Rezzi S, Ramadan Z, Fay LB & Kochhar S. 2007 Nutritional metabonomics: applications and perspectives. Journal of Proteome Research 6 513-525.
108. Roddam AW, Allen NE, Appleby P & Key TJ. 2008 Endogenous sex hormones and prostate cancer: a collaborative analysis of 18 prospective studies. Journal of the National Cancer Institute 100 170-183.
109. Rommerts FFG. 2004 Testosterone: an overview of biosynthesis, transport, metabolism and non-genomic actions. In Testosterone: Action, Deficiency, Substitution, pp 1-38. Eds E Nieschlag & H Behre. Cambridge: University Press.
110. Ruige JB, Mahmoud AM, De Bacquer D & Kaufman JM. 2010 Endogenous testosterone and cardiovascular disease in healthy men: a meta-analysis. Heart 97 870-875.
111. Saad F, Aversa A, Isidori AM, Zafalon L, Zitzmann M & Gooren L. 2011 Onset of effects of testosterone treatment and time span until maximum effects are achieved. European Journal of Endocrinology 165 675-685.
112. Sabatine MS, Liu E, Morrow DA, Heller E, McCarroll R, Wiegand R, Berriz GF, Roth FP & Gerszten RE. 2005 Metabolomic identification of novel biomarkers of myocardial ischemia. Circulation 112 3868-3875.
113. Sadovsky R, Dhindsa S & Margo K. 2007 Testosterone deficiency: which patients should you screen and treat? Journal of Family Practice 56 S1-S20 (quiz S21-23).
114. Schipf S, Haring R, Friedrich N, Nauck M, Lau K, Alte D, Stang A, Volzke H & Wallaschofski H. 2011 Low total testosterone is associated with increased risk of incident type 2 diabetes mellitus in men: results from the Study of Health in Pomerania (SHIP). Aging Male 14 168-175.
115. Seidman SN. 2006 Normative hypogonadism and depression: does 'andropause' exist? International Journal of Impotence Research 18 415-422.
116. Shah SH, Bain JR, Muehlbauer MJ, Stevens RD, Crosslin DR, Haynes C, Dungan J, Newby LK, Hauser ER, Ginsburg GS et al. 2010 Association of a peripheral blood metabolic profile with coronary artery disease and risk of subsequent cardiovascular events. Circulation. Cardiovascular Genetics 3 207-214.
117. Shaham O, Wei R, Wang TJ, Ricciardi C, Lewis GD, Vasan RS, Carr SA, Thadhani R, Gerszten RE & Mootha VK. 2008 Metabolic profiling of the human response to a glucose challenge reveals distinct axes of insulin sensitivity. Molecular Systems Biology 4 214.
118. Shulaev V. 2006 Metabolomics technology and bioinformatics. Briefings in Bioinformatics 7 128-139.
119. Slupsky CM, Rankin KN, Wagner J, Fu H, Chang D, Weljie AM, Saude EJ, Lix B, Adamko DJ, Shah S et al. 2007 Investigations of the effects of gender, diurnal variation, and age in human urinary metabolomic profiles. Analytical Chemistry 79 6995-7004.
120. Snyder PJ. 2008 Decreasing testosterone with increasing age: more factors, more questions. Journal of Clinical Endocrinology and Metabolism 93 2477-2478.
121. Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y et al. 2009 Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature 457 910-914.
122. Stanczyk FZ & Clarke NJ. 2010 Advantages and challenges of mass spectrometry assays for steroid hormones. Journal of Steroid Biochemistry and Molecular Biology 121 491-495.
123. Strahm E, Kohler I, Rudaz S, Martel S, Carrupt PA, Veuthey JL, Saugy M & Saudan C. 2008 Isolation and quantification by high-performance liquid chromatography-ion-trap mass spectrometry of androgen sulfoconjugates in human urine. Journal of Chromatography. A 1196-1197 153-160.
124. Suhre K, Shin SY, Petersen AK, Mohney RP, Meredith D, Wagele B, Altmaier E, Deloukas P, Erdmann J, Grundberg E et al. 2011 Human metabolic individuality in biomedical and pharmaceutical research. Nature 477 54-60.
125. Svartberg J, von Muhlen D, Sundsfjord J & Jorde R. 2004Waist circumference and testosterone levels in community dwelling men. The Tromso study. European Journal of Epidemiology 19 657-663.
126. Taieb J, Mathian B, Millot F, Patricot MC, Mathieu E, Queyrel N, Lacroix I, Somma-Delpero C & Boudou P. 2003 Testosterone measured by 10 immunoassays and by isotope-dilution gas chromatography-mass spectrometry in sera from 116 men, women, and children. Clinical Chemistry 49 1381-1395.
127. Thienpont LM, Van Uytfanghe K, Blincko S, Ramsay CS, Xie H, Doss RC, Keevil BG, Owen LJ, Rockwood AL, Kushnir MM et al. 2008 Stateof-the-art of serum testosterone measurement by isotope dilution-liquid chromatography-tandem mass spectrometry. Clinical Chemistry 54 1290-1297.
128. Torkler S, Wallaschofski H, Baumeister SE, Volzke H, Dorr M, Felix S, Rettig R, Nauck M & Haring R. 2011 Inverse association between total testosterone concentrations, incident hypertension and blood pressure. Aging Male 14 176-182.
129. Traish AM, Miner MM, Morgentaler A & Zitzmann M. 2011 Testosterone deficiency. American Journal of Medicine 124 578-587.
130. Travison TG, Araujo AB, Kupelian V, O'Donnell AB & McKinlay JB. 2007 The relative contributions of aging, health, and lifestyle factors to serum testosterone decline in men. Journal of Clinical Endocrinology and Metabolism 92 549-555.
131. Vasan RS. 2006 Biomarkers of cardiovascular disease: molecular basis and practical considerations. Circulation 113 2335-2362.
132. Vermeulen A, Kaufman JM & Giagulli VA. 1996 Influence of some biological indexes on sex hormone-binding globulin and androgen levels in aging or obese males. Journal of Clinical Endocrinology and Metabolism 81 1821-1826.
133. Vesper HW, Bhasin S, Wang C, Tai SS, Dodge LA, Singh RJ, Nelson J, Ohorodnik S, Clarke NJ, Salameh WA et al. 2009 Interlaboratory comparison study of serum total testosterone [corrected] measurements performed by mass spectrometry methods. Steroids 74 498-503.
134. Vikan T, Schirmer H, Njolstad I & Svartberg J. 2010 Low testosterone and sex hormone-binding globulin levels and high estradiol levels are independent predictors of type 2 diabetes in men. European Journal of Endocrinology 162 747-754.
135. Wang C, Catlin DH, Demers LM, Starcevic B & Swerdloff RS. 2004 Measurement of total serum testosterone in adult men: comparison of current laboratory methods versus liquid chromatography-tandem mass spectrometry. Journal of Clinical Endocrinology and Metabolism 89 534-543.
136. Wang C, Nieschlag E, Swerdloff R, Behre HM, Hellstrom WJ, Gooren LJ, Kaufman JM, Legros JJ, Lunenfeld B, Morales A et al. 2009a Investigation, treatment, and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA, and ASA recommendations. Journal of Andrology 30 1-9.
137. Wang Z, Tang WH, Cho L, Brennan DM & Hazen SL. 2009b Targeted metabolomic evaluation of arginine methylation and cardiovascular risks: potential mechanisms beyond nitric oxide synthase inhibition. Arteriosclerosis, Thrombosis, and Vascular Biology 29 1383-1391.
138. Wang HP, Liang YJ, Zhang Q, Long DX, Li W, Li L, Yang L, Yan XZ & Wu YJ. 2011a Changes in metabolic profiles of urine from rats following chronic exposure to anticholinesterase pesticides. Pesticide Biochemistry and Physiology 101 232-239.
139. Wang TJ, Larson MG, Vasan RS, Cheng S, Rhee EP, McCabe E, Lewis GD, Fox CS, Jacques PF, Fernandez C et al. 2011b Metabolite profiles and the risk of developing diabetes. Nature Medicine 17 448-453.
140. Wheeler MJ & Barnes SC. 2008 Measurement of testosterone in the diagnosis of hypogonadism in the ageing male. Clinical Endocrinology 69 515-525.
141. Winnike JH, Li Z, Wright FA, Macdonald JM, O'Connell TM &Watkins PB. 2010 Use of pharmaco-metabonomics for early prediction of acetaminophen-induced hepatotoxicity in humans. Clinical Pharmacology and Therapeutics 88 45-51.
142. Wopereis S, Rubingh CM, van Erk MJ, Verheij ER, van Vliet T, Cnubben NH, Smilde AK, van der Greef J, van Ommen B & Hendriks HF. 2009 Metabolic profiling of the response to an oral glucose tolerance test detects subtle metabolic changes. PLoS ONE 4 e4525.
143. Wu FC, Tajar A, Pye SR, Silman AJ, Finn JD, O'Neill TW, Bartfai G, Casanueva F, Forti G, Giwercman A et al. 2008 Hypothalamic-pituitary- testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: the European Male Aging Study. Journal of Clinical Endocrinology and Metabolism 93 2737-2745.
144. Wu FC, Tajar A, Beynon JM, Pye SR, Silman AJ, Finn JD, O'Neill TW, Bartfai G, Casanueva FF, Forti G et al. 2010 Identification of late-onset hypogonadism in middle-aged and elderly men. New England Journal of Medicine 363 123-135.
145. Yap IK, Angley M, Veselkov KA, Holmes E, Lindon JC & Nicholson JK. 2010 Urinary metabolic phenotyping differentiates children with autism from their unaffected siblings and age-matched controls. Journal of Proteome Research 9 2996-3004.
146. 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. American Journal of Epidemiology 146 609-617.