by Monica Mollica ~ trainergize.com
For reasons that are not readily apparent, there appears to be a conservative political movement that opposes the use of testosterone in older men. This was clearly demonstrated by the report of the Institute of Medicine, which felt that testosterone is not yet ready for prime time and that there is still a need for studies to prove its efficacy 1. Along the same lines, the guidelines of the Endocrine Society on testosterone use in older men seem to be ultra-cautious 2 . But fortunately, there are also other, more liberal guidelines and recommendations 3-5.
“It is dangerous to be right when the government is wrong.”
Probably no other medical issue has been bombarded by the influx of “expert” views from all walks of life; from endocrinologists and psychiatrists to urological surgeons and gerontologists, from the lay press to the regulatory agencies and from the pharmaceutical to the entertainment industries. The dismal result of all this free-for all cacophony of opinions is a great deal of confusion, erroneous information and significant detriment to patients and physicians alike.
Let’s take an in-depth look at the reasons for the negative attitudes to male testosterone replacement therapy (I will cover post-menopausal testosterone replacement in an upcoming article), and the hard scientific data that refutes it…
Unsubstantiated Claim 1:
There Is Insufficient Evidence That Testosterone Is Beneficial in Older Men
Numerous placebo-controlled studies have demonstrated salutary effects testosterone therapy in older men 6-11. Testosterone therapy clearly improves sexual function (both libido, erectile and ejaculatory function) in older men 12. In addition, testosterone supplementation in borderline hypo-gonadal men increases muscle mass 13-17, decreases fat mass 14, 15, 17, and improves strength 8, 13, 16, 17. There are also data showing that testosterone replacement in older men increases bone mineral density 18, 19 (and thereby and counteracts osteoporosis), improves cognition (in both Alzheimer and non-demented elderly) 20-22 and mood 16, 20, 23, and also alleviates depression 24.
Recent studies have also shown that testosterone therapy significantly improves not only symptoms of androgen deficiency (including erectile dysfunction), but also metabolic and control (lowering of blood glucose and glycated hemoglobin (HbA1c) (from 10.4 to 8.6%) 25, while decreasing abdominal obesity 25. These beneficial effects were seen without any adverse effects on blood pressure or hematological, biochemical and lipid parameters 25. Testosterone gel also has been shown to reverse the metabolic syndrome and improve glycemic control in men with sub-normal plasma testosterone 26. The improvements in glycaemic control, insulin resistance, cholesterol and visceral adiposity seen is these studies show that testosterone therapy contributes to an overall reduction in cardiovascular risk.
It is strange that treatment of testosterone deficiency caused by classical diseases affecting the hypothalamus, pituitary, and/or testes has been accepted for decades although there were no large multicenter trials, but that that treatment of testosterone deficiency caused by aging is taboo despite overwhelming scientific data showing significant benefits. It appears that physicians and regulatory agencies are much more comfortable treating older men with questionable drugs that pose more harm than benefit in terms of both quality of life, cancer and mortality 27-47, than using testosterone, a drug that not only improves important symptoms and risk factors, but also can reverse sarcopenia and frailty 48-54 which has well-documented detrimental effects on well-being, physical independence, morbidity and mortality. This is a poster-child example of “eminence” based medicine trumping evidence-based medicine.
Unsubstantiated Claim 2:
Testosterone Increases Prostate Cancer
The most prominent concern regarding testosterone treatment is its effect on prostate health. For decades, the concept that testosterone is “bad for the prostate” has gone unchallenged. Even though prostate-specific antigen (PSA) levels increase in response to testosterone supplementation 55, 56, recent research shows that the longstanding fear of stimulating prostate cancer with testosterone supplementation is without scientific basis 57-59.
Mechanistic studies have shown that the development and growth of prostate cancer are much more complex than simply an excess of lack of androgens: nonsteroidal hormones (e.g., insulin, leptin, glucocorticoids and growth hormone), genetic susceptibility, inflammation and environmental factors appear to be significant contributors 60. Further, there are a number of puzzling situations. For instance, prostate cancer cell lines that requires initial stimulation by androgens to grow is eventually suppressed by them 60. More evidence for the not so clear-cut relation between testosterone and prostate cancer lies in the fact that prostate cancer occurs in older men at a time when testosterone levels have already declined to low levels 61. In addition, there is no prospective evidence that testosterone is correlated with the development of prostate cancer 62, and retrospective studies have failed to demonstrate an increase in prostate cancer in men treated with testosterone 63.
Unsubstantiated Claim 3:
Testosterone increases cardiovascular disease risk
Another debate centers on the putative increased cardiovascular risk of testosterone therapy. While it is true that supra-physiological doses of testosterone, such as those administered by athletes, doe increase several risk factors for cardiovascular disease and cardiac events 64-66, this is not the case when testosterone therapy is used to restore low age-related testosterone levels to the normal range 59. To counter this, the anti-testosterone maffia often points to a study that was stopped before completion because much more adverse cardiovascular events were measured in the treatment group 67. However, the adverse cardiovascular events in this study could be explained by the pre-study high prevalence of cardiovascular risk factors within the study participants.
The adverse effects of testosterone therapy include an increase in hemoglobin and hematocrit (volume percentage (%) of red blood cells in blood) 59, 68, and a small decrease in HDL (the “good” cholesterol) 59, 69. However, elderly men with low testosterone tend to have a low hematocrit and also frequently present with anemia (hemoglobin deficiency) 70, so this side-effect can actually be a good thing. And the hematocrit-induced increase in blood viscosity can be alleviated with fish oil 71, while the decrease in HDL can be counteracted by carbohydrate restriction 72 and/or niacin (vitamin B3, the most effective way for increasing HDL) 73, 74, and a moderately increased physical activity 75-78. It should be noted that the small HDL reduction is primarily observed with intramuscular testosterone injections 69, and not with transdermal gel preparations 79.
To the contrary, it is well documented that low testosterone levels actually increase cardiovascular disease risk 80, 81. Following the recent reevaluation of the estrogen-protection orthodoxy, empirical research has flourished into the role of androgens in cardiovascular health. Observational studies show that blood testosterone levels are consistently lower among men with cardiovascular disease 80, 81, suggesting a preventive role for testosterone therapy.
In middle-aged and older men, lower testosterone levels are associated with insulin resistance, metabolic syndrome and diabetes, and related conditions that predispose to cardiovascular disease 82. Lower testosterone levels predict cardiovascular events, such as stroke and transient ischaemic attack, in older men and are associated with higher cardiovascular and overall mortality 82. Randomized trials have even shown that testosterone supplementation in men with existing coronary artery disease can be protective against heart attack (myocardial ischaemia) 82.
Unsubstantiated Claim 4:
Andropause doesn’t exist
While andropause, the progressive decline in testosterone production in aging men, unquestionably does exist and warrants treatment, whether the term “andropause” per see is a good descriptor for this phenomenon has been debated.
The terms “andropause” or “male menopause” are not completely accurate because androgen secretion does not cease altogether, as the term “pause” indicates 83, 84. The term menopause is correct in that in women the reproductive cycle invariably ends with ovarian failure and an abrupt cessation of estrogen production and onset of symptoms. In men however, the reduction in testosterone levels is a gradual process and the appearance of its clinical manifestations is more subtle and develop over time. This has unfortunately led to a tendency among many suffering older men to ignore the symptoms and accept it as an unavoidable and untreatable result of aging. In a survey of health care professionals, half reported that their patients rarely or never asked about low testosterone 85. Several prominent scientists have strongly recommended that awareness of andropause and its consequences be increased 83, 86, 87.
The term “male climacteric” is more appropriate as it suggests a decline and not a precipitous drop in hormones levels 88. The term “male climacteric” refers to the syndrome of endocrine, somatic, and psychic changes that occur in normal men with aging. This term is good in that it emphasizes the multidimensional nature of age-related changes, including age-related decreases in other important hormones such as growth hormone (GH), insulin-like growth factor-1 (IGF-1), dehydroepiandrosterone (DHEA), and melatonin 89-91, and not only relates aspects of the male aging syndrome specifically with testosterone levels.
Andropause has also been referred to by some medical professionals as “androgen deficiency in the aging male (ADAM),” “partial androgen deficiency in the aging male (PADAM),” or “aging-associated androgen deficiency (AAAD)” 84. However, andropause is the term that is used commonly by experts in the field and by lay persons alike because it retains some analogy to the term menopause in women 83. After all, what’s in a name?
Unsubstantiated Claim 5:
Estrogen replacement in post-menopausal women turned out to be bad, and therefore testosterone replacement in men must also be bad.
This claim is screams irrational logic and an unwarranted extrapolation.
Unsubstantiated Claim 6:
Bad Kharma: It’s All about Sex
Testosterone therapy is a touchy topic because it improves sexual capacity and enjoyment. Even in the times of Viagra, attitudes to sex remain embarrassingly silly “imagine if you give an older man testosterone, he may want to have sex!!” The use of testosterone in women is facing a similar issue 92-95.
Unsubstantiated Claim 7:
If testosterone becomes mainstream treatment in elderly it will become abused by younger adults
Abuse of testosterone will occur whether or not it is available for older men.
Testosterone deficiency in older men (hypogonadism) is very common 52, 96, 97 (up to 50% of men over the age of 50 are deficient in free testosterone when compared with peak morning concentrations in young men 91), and yet only a small proportion of hypogonadal men are receiving testosteone replacement therapy 98. In the end, a particular political viewpoint is in the eye of the beholder. Nevertheless, it is obvious that the political climate is working against testosterone replacement therapy in older men despite overwhelming scientific data supporting this appropriate pursuit as a strategy to prolong healthy longevity.
About the Author:
Monica Mollica has a Bachelor’s and Master’s degree in Nutrition from the University of Stockholm, Sweden, and is an ISSA Certified Personal Trainer. She works a dietary consultant, health journalist and writer for www.BrinkZone.com, and is also a web designer and videographer.
Monica has admired and been fascinated by muscular and sculptured strong athletic bodies since childhood, and discovered bodybuilding as an young teenager. Realizing the importance of nutrition for maximal results in the gym, she went for a BSc and MSc with a major in Nutrition at the University.
During her years at the University she was a regular contributor to the Swedish bodybuilding magazine BODY, and she has published the book (in Swedish) “Functional Foods for Health and Energy Balance”, and authored several book chapters in Swedish publications.
It was her insatiable thirst for knowledge and scientific research in the area of bodybuilding and health that brought her to the US. She has completed one semester at the PhD-program “Exercise, Nutrition and Preventive Health” at Baylor University Texas, at the department of Health Human Performance and Recreation, and worked as an ISSA certified personal trainer. Today, Monica is sharing her solid experience by doing dietary consultations and writing about topics related to health, fitness, bodybuilding, anti-aging and longevity.
1. Theisen C. IOM report targets testosterone therapy. Journal of the National Cancer Institute. 2004;96(4):259.
2. Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone therapy in adult men with androgen deficiency syndromes: an endocrine society clinical practice guideline. The Journal of clinical endocrinology and metabolism. 2006;91(6):1995-2010.
3. Nieschlag E, Swerdloff R, Behre HM, et al. Investigation, treatment and monitoring of late-onset hypogonadism in males. The aging male : the official journal of the International Society for the Study of the Aging Male. 2005;8(2):56-58.
4. Asthana S, Bhasin S, Butler RN, et al. Masculine vitality: pros and cons of testosterone in treating the andropause. The journals of gerontology Series A, Biological sciences and medical sciences. 2004;59(5):461-465.
5. Bain J, Brock G, Kuzmarov I. Canadian Society for the Study of the Aging Male: response to health Canada’s position paper on testosterone treatment. The journal of sexual medicine. 2007;4(3):558-566.
6. Isidori AM, Giannetta E, Greco EA, et al. Effects of testosterone on body composition, bone metabolism and serum lipid profile in middle-aged men: a meta-analysis. Clinical endocrinology. 2005;63(3):280-293.
7. Isidori AM, Giannetta E, Gianfrilli D, et al. Effects of testosterone on sexual function in men: results of a meta-analysis. Clinical endocrinology. 2005;63(4):381-394.
8. Ottenbacher KJ, Ottenbacher ME, Ottenbacher AJ, et al. Androgen treatment and muscle strength in elderly men: A meta-analysis. Journal of the American Geriatrics Society. 2006;54(11):1666-1673.
9. Morley JE, Perry HM, 3rd, Kaiser FE, et al. Effects of testosterone replacement therapy in old hypogonadal males: a preliminary study. Journal of the American Geriatrics Society. 1993;41(2):149-152.
10. Sih R, Morley JE, Kaiser FE, et al. Testosterone replacement in older hypogonadal men: a 12-month randomized controlled trial. The Journal of clinical endocrinology and metabolism. 1997;82(6):1661-1667.
11. Tenover JS. Effects of testosterone supplementation in the aging male. The Journal of clinical endocrinology and metabolism. 1992;75(4):1092-1098.
12. Khera M, Bhattacharya RK, Blick G, et al. Improved sexual function with testosterone replacement therapy in hypogonadal men: real-world data from the Testim Registry in the United States (TRiUS). The journal of sexual medicine. 2011;8(11):3204-3213.
13. Giannoulis MG, Martin FC, Nair KS, et al. Hormone replacement therapy and physical function in healthy older men. Time to talk hormones? Endocrine reviews. 2012;33(3):314-377.
14. Wittert GA, Chapman IM, Haren MT, et al. Oral testosterone supplementation increases muscle and decreases fat mass in healthy elderly males with low-normal gonadal status. The journals of gerontology Series A, Biological sciences and medical sciences. 2003;58(7):618-625.
15. Snyder PJ, Peachey H, Hannoush P, et al. Effect of testosterone treatment on body composition and muscle strength in men over 65 years of age. The Journal of clinical endocrinology and metabolism. 1999;84(8):2647-2653.
16. Wang C, Eyre DR, Clark R, et al. Sublingual testosterone replacement improves muscle mass and strength, decreases bone resorption, and increases bone formation markers in hypogonadal men–a clinical research center study. The Journal of clinical endocrinology and metabolism. 1996;81(10):3654-3662.
17. Bhasin S. Testosterone supplementation for aging-associated sarcopenia. The journals of gerontology Series A, Biological sciences and medical sciences. 2003;58(11):1002-1008.
18. Snyder PJ, Peachey H, Hannoush P, et al. Effect of testosterone treatment on bone mineral density in men over 65 years of age. The Journal of clinical endocrinology and metabolism. 1999;84(6):1966-1972.
19. Katznelson L, Finkelstein JS, Schoenfeld DA, et al. Increase in bone density and lean body mass during testosterone administration in men with acquired hypogonadism. The Journal of clinical endocrinology and metabolism. 1996;81(12):4358-4365.
20. Lu PH, Masterman DA, Mulnard R, et al. Effects of testosterone on cognition and mood in male patients with mild Alzheimer disease and healthy elderly men. Archives of neurology. 2006;63(2):177-185.
21. Cherrier MM, Matsumoto AM, Amory JK, et al. Testosterone improves spatial memory in men with Alzheimer disease and mild cognitive impairment. Neurology. 2005;64(12):2063-2068.
22. Azad N, Pitale S, Barnes WE, et al. Testosterone treatment enhances regional brain perfusion in hypogonadal men. The Journal of clinical endocrinology and metabolism. 2003;88(7):3064-3068.
23. Wang C, Alexander G, Berman N, et al. Testosterone replacement therapy improves mood in hypogonadal men–a clinical research center study. The Journal of clinical endocrinology and metabolism. 1996;81(10):3578-3583.
24. Pope HG, Jr., Cohane GH, Kanayama G, et al. Testosterone gel supplementation for men with refractory depression: a randomized, placebo-controlled trial. The American journal of psychiatry. 2003;160(1):105-111.
25. Boyanov MA, Boneva Z, Christov VG. Testosterone supplementation in men with type 2 diabetes, visceral obesity and partial androgen deficiency. The aging male : the official journal of the International Society for the Study of the Aging Male. 2003;6(1):1-7.
26. Heufelder AE, Saad F, Bunck MC, et al. Fifty-two-week treatment with diet and exercise plus transdermal testosterone reverses the metabolic syndrome and improves glycemic control in men with newly diagnosed type 2 diabetes and subnormal plasma testosterone. Journal of andrology. 2009;30(6):726-733.
27. Plonk WM, Jr. Most would fail to benefit from JUPITER Intervention. Journal of the American College of Cardiology. 2009;54(8):744; author reply 744-745.
28. Hakansson J. [The JUPITER study poses more questions than answers]. Lakartidningen. 2009;106(26-27):1757.
29. Shepherd J, Blauw GJ, Murphy MB, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet. 2002;360(9346):1623-1630.
30. Silva MA, Swanson AC, Gandhi PJ, et al. Statin-related adverse events: a meta-analysis. Clinical therapeutics. 2006;28(1):26-35.
31. Sakaeda T, Kadoyama K, Okuno Y. Statin-associated muscular and renal adverse events: data mining of the public version of the FDA adverse event reporting system. PloS one. 2011;6(12):e28124.
32. Bassuk SS, Wypij D, Berkman LF. Cognitive impairment and mortality in the community-dwelling elderly. American journal of epidemiology. 2000;151(7):676-688.
33. Frisoni GB, Fratiglioni L, Fastbom J, et al. Mortality in nondemented subjects with cognitive impairment: the influence of health-related factors. American journal of epidemiology. 1999;150(10):1031-1044.
34. Guralnik JM, Ferrucci L, Pieper CF, et al. Lower extremity function and subsequent disability: consistency across studies, predictive models, and value of gait speed alone compared with the short physical performance battery. The journals of gerontology Series A, Biological sciences and medical sciences. 2000;55(4):M221-231.
35. Guralnik JM, Ferrucci L, Simonsick EM, et al. Lower-extremity function in persons over the age of 70 years as a predictor of subsequent disability. The New England journal of medicine. 1995;332(9):556-561.
36. King DS, Wilburn AJ, Wofford MR, et al. Cognitive impairment associated with atorvastatin and simvastatin. Pharmacotherapy. 2003;23(12):1663-1667.
37. Muldoon MF, Barger SD, Ryan CM, et al. Effects of lovastatin on cognitive function and psychological well-being. The American journal of medicine. 2000;108(7):538-546.
38. Orsi A, Sherman O, Woldeselassie Z. Simvastatin-associated memory loss. Pharmacotherapy. 2001;21(6):767-769.
39. Pasternak RC, Smith SC, Jr., Bairey-Merz CN, et al. ACC/AHA/NHLBI Clinical Advisory on the Use and Safety of Statins. Stroke; a journal of cerebral circulation. 2002;33(9):2337-2341.
40. Penninx BW, Ferrucci L, Leveille SG, et al. Lower extremity performance in nondisabled older persons as a predictor of subsequent hospitalization. The journals of gerontology Series A, Biological sciences and medical sciences. 2000;55(11):M691-697.
41. Schatz IJ, Masaki K, Yano K, et al. Cholesterol and all-cause mortality in elderly people from the Honolulu Heart Program: a cohort study. Lancet. 2001;358(9279):351-355.
42. Smits CH, Deeg DJ, Kriegsman DM, et al. Cognitive functioning and health as determinants of mortality in an older population. American journal of epidemiology. 1999;150(9):978-986.
43. Wagstaff LR, Mitton MW, Arvik BM, et al. Statin-associated memory loss: analysis of 60 case reports and review of the literature. Pharmacotherapy. 2003;23(7):871-880.
44. Weverling-Rijnsburger AW, Blauw GJ, Lagaay AM, et al. Total cholesterol and risk of mortality in the oldest old. Lancet. 1997;350(9085):1119-1123.
45. Brescianini S, Maggi S, Farchi G, et al. Low total cholesterol and increased risk of dying: are low levels clinical warning signs in the elderly? Results from the Italian Longitudinal Study on Aging. Journal of the American Geriatrics Society. 2003;51(7):991-996.
46. Curtis LH, Ostbye T, Sendersky V, et al. Inappropriate prescribing for elderly Americans in a large outpatient population. Archives of internal medicine. 2004;164(15):1621-1625.
47. Gottlieb S. Inappropriate drug prescribing in elderly people is common. BMJ. 2004;329(7462):367.
48. Baumgartner RN, Waters DL, Gallagher D, et al. Predictors of skeletal muscle mass in elderly men and women. Mechanisms of ageing and development. 1999;107(2):123-136.
49. Kohn FM. Testosterone and body functions. The aging male : the official journal of the International Society for the Study of the Aging Male. 2006;9(4):183-188.
50. Morley JE. Anorexia, sarcopenia, and aging. Nutrition. 2001;17(7-8):660-663.
51. Morley JE, Haren MT, Rolland Y, et al. Frailty. The Medical clinics of North America. 2006;90(5):837-847.
52. van den Beld AW, de Jong FH, Grobbee DE, et al. Measures of bioavailable serum testosterone and estradiol and their relationships with muscle strength, bone density, and body composition in elderly men. The Journal of clinical endocrinology and metabolism. 2000;85(9):3276-3282.
53. Lang PO, Michel JP, Zekry D. Frailty syndrome: a transitional state in a dynamic process. Gerontology. 2009;55(5):539-549.
54. Kovacheva EL, Hikim AP, Shen R, et al. Testosterone supplementation reverses sarcopenia in aging through regulation of myostatin, c-Jun NH2-terminal kinase, Notch, and Akt signaling pathways. Endocrinology. 2010;151(2):628-638.
55. Gerstenbluth RE, Maniam PN, Corty EW, et al. Prostate-specific antigen changes in hypogonadal men treated with testosterone replacement. Journal of andrology. 2002;23(6):922-926.
56. Srinivas-Shankar U, Roberts SA, Connolly MJ, et al. Effects of testosterone on muscle strength, physical function, body composition, and quality of life in intermediate-frail and frail elderly men: a randomized, double-blind, placebo-controlled study. The Journal of clinical endocrinology and metabolism. 2010;95(2):639-650.
57. Morgentaler A. Testosterone and prostate cancer: an historical perspective on a modern myth. European urology. 2006;50(5):935-939.
58. Shabsigh R, Crawford ED, Nehra A, et al. Testosterone therapy in hypogonadal men and potential prostate cancer risk: a systematic review. International journal of impotence research. 2009;21(1):9-23.
59. Fernandez-Balsells MM, Murad MH, Lane M, et al. Clinical review 1: Adverse effects of testosterone therapy in adult men: a systematic review and meta-analysis. The Journal of clinical endocrinology and metabolism. 2010;95(6):2560-2575.
60. Morales A. The use of hormonal therapy in “andropause”: the pro side. Canadian Urological Association journal = Journal de l’Association des urologues du Canada. 2008;2(1):43-46.
61. Morley JE. Testosterone treatment in older men: effects on the prostate. Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2000;6(2):218-221.
62. Eaton NE, Reeves GK, Appleby PN, et al. Endogenous sex hormones and prostate cancer: a quantitative review of prospective studies. British journal of cancer. 1999;80(7):930-934.
63. Hajjar RR, Kaiser FE, Morley JE. Outcomes of long-term testosterone replacement in older hypogonadal males: a retrospective analysis. The Journal of clinical endocrinology and metabolism. 1997;82(11):3793-3796.
64. Hartgens F, Kuipers H. Effects of androgenic-anabolic steroids in athletes. Sports Med. 2004;34(8):513-554.
65. Hall RC. Abuse of supraphysiologic doses of anabolic steroids. Southern medical journal. 2005;98(5):550-555.
66. Foster ZJ, Housner JA. Anabolic-androgenic steroids and testosterone precursors: ergogenic aids and sport. Current sports medicine reports. 2004;3(4):234-241.
67. Basaria S, Coviello AD, Travison TG, et al. Adverse events associated with testosterone administration. The New England journal of medicine. 2010;363(2):109-122.
68. Calof OM, Singh AB, Lee ML, et al. Adverse events associated with testosterone replacement in middle-aged and older men: a meta-analysis of randomized, placebo-controlled trials. The journals of gerontology Series A, Biological sciences and medical sciences. 2005;60(11):1451-1457.
69. Whitsel EA, Boyko EJ, Matsumoto AM, et al. Intramuscular testosterone esters and plasma lipids in hypogonadal men: a meta-analysis. The American journal of medicine. 2001;111(4):261-269.
70. Bhatia V, Chaudhuri A, Tomar R, et al. Low testosterone and high C-reactive protein concentrations predict low hematocrit in type 2 diabetes. Diabetes care. 2006;29(10):2289-2294.
71. Woodcock BE, Smith E, Lambert WH, et al. Beneficial effect of fish oil on blood viscosity in peripheral vascular disease. Br Med J (Clin Res Ed). 1984;288(6417):592-594.
72. Hauner H, Bechthold A, Boeing H, et al. Evidence-based guideline of the German Nutrition Society: carbohydrate intake and prevention of nutrition-related diseases. Annals of nutrition & metabolism. 2012;60 Suppl 1:1-58.
73. Bodor ET, Offermanns S. Nicotinic acid: an old drug with a promising future. British journal of pharmacology. 2008;153 Suppl 1:S68-75.
74. Vosper H. Niacin: a re-emerging pharmaceutical for the treatment of dyslipidaemia. British journal of pharmacology. 2009;158(2):429-441.
75. Sunami Y, Motoyama M, Kinoshita F, et al. Effects of low-intensity aerobic training on the high-density lipoprotein cholesterol concentration in healthy elderly subjects. Metabolism: clinical and experimental. 1999;48(8):984-988.
76. King AC, Haskell WL, Young DR, et al. Long-term effects of varying intensities and formats of physical activity on participation rates, fitness, and lipoproteins in men and women aged 50 to 65 years. Circulation. 1995;91(10):2596-2604.
77. Blumenthal JA, Emery CF, Madden DJ, et al. Effects of exercise training on cardiorespiratory function in men and women older than 60 years of age. The American journal of cardiology. 1991;67(7):633-639.
78. Despres JP, Tremblay A, Moorjani S, et al. Long-term exercise training with constant energy intake. 3: Effects on plasma lipoprotein levels. International journal of obesity. 1990;14(1):85-94.
79. Snyder PJ, Peachey H, Berlin JA, et al. Effect of transdermal testosterone treatment on serum lipid and apolipoprotein levels in men more than 65 years of age. The American journal of medicine. 2001;111(4):255-260.
80. Liu PY, Death AK, Handelsman DJ. Androgens and cardiovascular disease. Endocrine reviews. 2003;24(3):313-340.
81. Kaushik M, Sontineni SP, Hunter C. Cardiovascular disease and androgens: a review. International journal of cardiology. 2010;142(1):8-14.
82. Yeap BB. Androgens and cardiovascular disease. Current opinion in endocrinology, diabetes, and obesity. 2010;17(3):269-276.
83. Matsumoto AM. Andropause: clinical implications of the decline in serum testosterone levels with aging in men. The journals of gerontology Series A, Biological sciences and medical sciences. 2002;57(2):M76-99.
84. Morales A, Heaton JP, Carson CC, 3rd. Andropause: a misnomer for a true clinical entity. The Journal of urology. 2000;163(3):705-712.
85. Anderson JK, Faulkner S, Cranor C, et al. Andropause: knowledge and perceptions among the general public and health care professionals. The journals of gerontology Series A, Biological sciences and medical sciences. 2002;57(12):M793-796.
86. Morley JE. Drugs, aging, and the future. The journals of gerontology Series A, Biological sciences and medical sciences. 2002;57(1):M2-6.
87. Morley JE. Andropause: is it time for the geriatrician to treat it? The journals of gerontology Series A, Biological sciences and medical sciences. 2001;56(5):M263-265.
88. Gould DC, Petty R, Jacobs HS. For and against: The male menopause–does it exist? BMJ. 2000;320(7238):858-861.
89. Morley JE, Kaiser F, Raum WJ, et al. Potentially predictive and manipulable blood serum correlates of aging in the healthy human male: progressive decreases in bioavailable testosterone, dehydroepiandrosterone sulfate, and the ratio of insulin-like growth factor 1 to growth hormone. Proceedings of the National Academy of Sciences of the United States of America. 1997;94(14):7537-7542.
90. van den Beld AW, Lamberts SW. The male climacterium: clinical signs and symptoms of a changing endocrine environment. The Prostate Supplement. 2000;10:2-8.
91. Lamberts SW, van den Beld AW, van der Lely AJ. The endocrinology of aging. Science. 1997;278(5337):419-424.
92. Morley JE, Perry HM, 3rd. Androgens and women at the menopause and beyond. The journals of gerontology Series A, Biological sciences and medical sciences. 2003;58(5):M409-416.
93. Bolour S, Braunstein G. Testosterone therapy in women: a review. International journal of impotence research. 2005;17(5):399-408.
94. Davis SR, Burger HG. Use of androgens in postmenopausal women. Current opinion in obstetrics & gynecology. 1997;9(3):177-180.
95. Rivera-Woll LM, Papalia M, Davis SR, et al. Androgen insufficiency in women: diagnostic and therapeutic implications. Human reproduction update. 2004;10(5):421-432.
96. Harman SM, Metter EJ, Tobin JD, et al. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. The Journal of clinical endocrinology and metabolism. 2001;86(2):724-731.
97. Morley JE. Androgens and aging. Maturitas. 2001;38(1):61-71; discussion 71-63.
98. Tariq SH. Knowledge about low testosterone in older men. The journals of gerontology Series A, Biological sciences and medical sciences. 2003;58(4):382-383.