Testosterone Replacement Therapy - why is it so controversial?
"It is dangerous to be right when the government is wrong." - Voltaire
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 . Along the same lines, the guidelines of the Endocrine Society on testosterone use in older men seem to be ultra-cautious . But fortunately, there are also other, more liberal guidelines and recommendations [3-5].
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 . 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 .
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%) , while decreasing abdominal obesity . These beneficial effects were seen without any adverse effects on blood pressure or hematological, biochemical and lipid parameters . Testosterone gel also has been shown to reverse the metabolic syndrome and improve glycemic control in men with sub-normal plasma testosterone . 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 . 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 . 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 . In addition, there is no prospective evidence that testosterone is correlated with the development of prostate cancer , and retrospective studies have failed to demonstrate an increase in prostate cancer in men treated with testosterone .
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 . 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 . 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) , so this side-effect can actually be a good thing. And the hematocrit-induced increase in blood viscosity can be alleviated with fish oil , while the decrease in HDL can be counteracted by carbohydrate restriction  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 , and not with transdermal gel preparations .
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 . 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 . Randomized trials have even shown that testosterone supplementation in men with existing coronary artery disease can be protective against heart attack (myocardial ischaemia) .
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 . 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 . 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)” . 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 . 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 enjoyment. Even in the times of
Viagra, attitudes to sex remain embarrassingly silly “imagine if you give an old 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 might become abused by younger adults
Abuse of testosterone will occur whether or not it is available for older men.
Testosterone deficiency in 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 ), and yet only a small proportion of hypogonadal men are receiving testosterone replacement therapy . A large international web survey of over 10,000 men, mainly from the UK and USA, found that 80% had moderate or severe symptom scores likely to benefit from testosterone replacement therapy (TRT).
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 men despite overwhelming scientific research data supporting TRT as an appropriate strategy to prolong healthy longevity and wellbeing.
- Theisen, C., IOM report targets testosterone therapy. J Natl Cancer Inst, 2004. 96(4): p. 259.
- Bhasin, S., et al., Testosterone therapy in adult men with androgen deficiency syndromes: an endocrine society clinical practice guideline. J Clin Endocrinol Metab, 2006. 91(6): p. 1995-2010.
- Nieschlag, E., et al., Investigation, treatment and monitoring of late-onset hypogonadism in males. Aging Male, 2005. 8(2): p. 56-8.
- Asthana, S., et al., Masculine vitality: pros and cons of testosterone in treating the andropause. J Gerontol A Biol Sci Med Sci, 2004. 59(5): p. 461-5.
- Bain, J., G. Brock, and I. Kuzmarov, Canadian Society for the Study of the Aging Male: response to health Canada's position paper on testosterone treatment. J Sex Med, 2007. 4(3): p. 558-66.
- Isidori, A.M., et al., Effects of testosterone on body composition, bone metabolism and serum lipid profile in middle-aged men: a meta-analysis. Clin Endocrinol (Oxf), 2005. 63(3): p. 280-93.
- Isidori, A.M., et al., Effects of testosterone on sexual function in men: results of a meta-analysis. Clin Endocrinol (Oxf), 2005. 63(4): p. 381-94.
- Ottenbacher, K.J., et al., Androgen treatment and muscle strength in elderly men: A meta-analysis. J Am Geriatr Soc, 2006. 54(11): p. 1666-73.
- Morley, J.E., et al., Effects of testosterone replacement therapy in old hypogonadal males: a preliminary study. J Am Geriatr Soc, 1993. 41(2): p. 149-52.
- Sih, R., et al., Testosterone replacement in older hypogonadal men: a 12-month randomized controlled trial. J Clin Endocrinol Metab, 1997. 82(6): p. 1661-7.
- Tenover, J.S., Effects of testosterone supplementation in the aging male. J Clin Endocrinol Metab, 1992. 75(4): p. 1092-8.
- Khera, M., et al., Improved sexual function with testosterone replacement therapy in hypogonadal men: real-world data from the Testim Registry in the United States (TRiUS). J Sex Med, 2011. 8(11): p. 3204-13.
- Giannoulis, M.G., et al., Hormone replacement therapy and physical function in healthy older men. Time to talk hormones? Endocr Rev, 2012. 33(3): p. 314-77.
- Wittert, G.A., et al., Oral testosterone supplementation increases muscle and decreases fat mass in healthy elderly males with low-normal gonadal status. J Gerontol A Biol Sci Med Sci, 2003. 58(7): p. 618-25.
- Snyder, P.J., et al., Effect of testosterone treatment on body composition and muscle strength in men over 65 years of age. J Clin Endocrinol Metab, 1999. 84(8): p. 2647-53.
- Wang, C., 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. J Clin Endocrinol Metab, 1996. 81(10): p. 3654-62.
- Bhasin, S., Testosterone supplementation for aging-associated sarcopenia. J Gerontol A Biol Sci Med Sci, 2003. 58(11): p. 1002-8.
- Snyder, P.J., et al., Effect of testosterone treatment on bone mineral density in men over 65 years of age. J Clin Endocrinol Metab, 1999. 84(6): p. 1966-72.
- Katznelson, L., et al., Increase in bone density and lean body mass during testosterone administration in men with acquired hypogonadism. J Clin Endocrinol Metab, 1996. 81(12): p. 4358-65.
- Lu, P.H., et al., Effects of testosterone on cognition and mood in male patients with mild Alzheimer disease and healthy elderly men. Arch Neurol, 2006. 63(2): p. 177-85.
- Cherrier, M.M., et al., Testosterone improves spatial memory in men with Alzheimer disease and mild cognitive impairment. Neurology, 2005. 64(12): p. 2063-8.
- Azad, N., et al., Testosterone treatment enhances regional brain perfusion in hypogonadal men. J Clin Endocrinol Metab, 2003. 88(7): p. 3064-8.
- Wang, C., et al., Testosterone replacement therapy improves mood in hypogonadal men--a clinical research center study. J Clin Endocrinol Metab, 1996. 81(10): p. 3578-83.
- Pope, H.G., Jr., et al., Testosterone gel supplementation for men with refractory depression: a randomized, placebo-controlled trial. Am J Psychiatry, 2003. 160(1): p. 105-11.
- Boyanov, M.A., Z. Boneva, and V.G. Christov, Testosterone supplementation in men with type 2 diabetes, visceral obesity and partial androgen deficiency. Aging Male, 2003. 6(1): p. 1-7.
- Heufelder, A.E., 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. J Androl, 2009. 30(6): p. 726-33.
- Plonk, W.M., Jr., Most would fail to benefit from JUPITER Intervention. J Am Coll Cardiol, 2009. 54(8): p. 744; author reply 744-5.
- Hakansson, J., [The JUPITER study poses more questions than answers]. Lakartidningen, 2009. 106(26-27): p. 1757.
- Shepherd, J., et al., Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet, 2002. 360(9346): p. 1623-30.
- Silva, M.A., et al., Statin-related adverse events: a meta-analysis. Clin Ther, 2006. 28(1): p. 26-35.
- Sakaeda, T., K. Kadoyama, and Y. Okuno, 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): p. e28124.
- Bassuk, S.S., D. Wypij, and L.F. Berkman, Cognitive impairment and mortality in the community-dwelling elderly. Am J Epidemiol, 2000. 151(7): p. 676-88.
- Frisoni, G.B., et al., Mortality in nondemented subjects with cognitive impairment: the influence of health-related factors. Am J Epidemiol, 1999. 150(10): p. 1031-44.
- Guralnik, J.M., 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. J Gerontol A Biol Sci Med Sci, 2000. 55(4): p. M221-31.
- Guralnik, J.M., et al., Lower-extremity function in persons over the age of 70 years as a predictor of subsequent disability. N Engl J Med, 1995. 332(9): p. 556-61.
- King, D.S., et al., Cognitive impairment associated with atorvastatin and simvastatin. Pharmacotherapy, 2003. 23(12): p. 1663-7.
- Muldoon, M.F., et al., Effects of lovastatin on cognitive function and psychological well-being. Am J Med, 2000. 108(7): p. 538-46.
- Orsi, A., O. Sherman, and Z. Woldeselassie, Simvastatin-associated memory loss. Pharmacotherapy, 2001. 21(6): p. 767-9.
- Pasternak, R.C., et al., ACC/AHA/NHLBI Clinical Advisory on the Use and Safety of Statins. Stroke, 2002. 33(9): p. 2337-41.
- Penninx, B.W., et al., Lower extremity performance in nondisabled older persons as a predictor of subsequent hospitalization. J Gerontol A Biol Sci Med Sci, 2000. 55(11): p. M691-7.
- Schatz, I.J., et al., Cholesterol and all-cause mortality in elderly people from the Honolulu Heart Program: a cohort study. Lancet, 2001. 358(9279): p. 351-5.
- Smits, C.H., et al., Cognitive functioning and health as determinants of mortality in an older population. Am J Epidemiol, 1999. 150(9): p. 978-86.
- Wagstaff, L.R., et al., Statin-associated memory loss: analysis of 60 case reports and review of the literature. Pharmacotherapy, 2003. 23(7): p. 871-80.
- Weverling-Rijnsburger, A.W., et al., Total cholesterol and risk of mortality in the oldest old. Lancet, 1997. 350(9085): p. 1119-23.
- Brescianini, S., 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. J Am Geriatr Soc, 2003. 51(7): p. 991-6.
- Curtis, L.H., et al., Inappropriate prescribing for elderly Americans in a large outpatient population. Arch Intern Med, 2004. 164(15): p. 1621-5.
- Gottlieb, S., Inappropriate drug prescribing in elderly people is common. BMJ, 2004. 329(7462): p. 367.
- Baumgartner, R.N., et al., Predictors of skeletal muscle mass in elderly men and women. Mech Ageing Dev, 1999. 107(2): p. 123-36.
- Kohn, F.M., Testosterone and body functions. Aging Male, 2006. 9(4): p. 183-8.
- Morley, J.E., Anorexia, sarcopenia, and aging. Nutrition, 2001. 17(7-8): p. 660-3.
- Morley, J.E., et al., Frailty. Med Clin North Am, 2006. 90(5): p. 837-47.
- van den Beld, A.W., et al., 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, 2000. 85(9): p. 3276-82.
- Lang, P.O., J.P. Michel, and D. Zekry, Frailty syndrome: a transitional state in a dynamic process. Gerontology, 2009. 55(5): p. 539-49.
- Kovacheva, E.L., 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): p. 628-38.
- Gerstenbluth, R.E., et al., Prostate-specific antigen changes in hypogonadal men treated with testosterone replacement. J Androl, 2002. 23(6): p. 922-6.
- Srinivas-Shankar, U., 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. J Clin Endocrinol Metab, 2010. 95(2): p. 639-50.
- Morgentaler, A., Testosterone and prostate cancer: an historical perspective on a modern myth. Eur Urol, 2006. 50(5): p. 935-9.
- Shabsigh, R., et al., Testosterone therapy in hypogonadal men and potential prostate cancer risk: a systematic review. Int J Impot Res, 2009. 21(1): p. 9-23.
- Fernandez-Balsells, M.M., et al., Clinical review 1: Adverse effects of testosterone therapy in adult men: a systematic review and meta-analysis. J Clin Endocrinol Metab, 2010. 95(6): p. 2560-75.
- Morales, A., The use of hormonal therapy in "andropause": the pro side. Can Urol Assoc J, 2008. 2(1): p. 43-6.
- Morley, J.E., Testosterone treatment in older men: effects on the prostate. Endocr Pract, 2000. 6(2): p. 218-21.
- Eaton, N.E., et al., Endogenous sex hormones and prostate cancer: a quantitative review of prospective studies. Br J Cancer, 1999. 80(7): p. 930-4.
- Hajjar, R.R., F.E. Kaiser, and J.E. Morley, Outcomes of long-term testosterone replacement in older hypogonadal males: a retrospective analysis. J Clin Endocrinol Metab, 1997. 82(11): p. 3793-6.
- Hartgens, F. and H. Kuipers, Effects of androgenic-anabolic steroids in athletes. Sports Med, 2004. 34(8): p. 513-54.
- Hall, R.C., Abuse of supraphysiologic doses of anabolic steroids. South Med J, 2005. 98(5): p. 550-5.
- Foster, Z.J. and J.A. Housner, Anabolic-androgenic steroids and testosterone precursors: ergogenic aids and sport. Curr Sports Med Rep, 2004. 3(4): p. 234-41.
- Basaria, S., et al., Adverse events associated with testosterone administration. N Engl J Med, 2010. 363(2): p. 109-22.
- Calof, O.M., et al., Adverse events associated with testosterone replacement in middle-aged and older men: a meta-analysis of randomized, placebo-controlled trials. J Gerontol A Biol Sci Med Sci, 2005. 60(11): p. 1451-7.
- Whitsel, E.A., et al., Intramuscular testosterone esters and plasma lipids in hypogonadal men: a meta-analysis. Am J Med, 2001. 111(4): p. 261-9.
- Bhatia, V., et al., Low testosterone and high C-reactive protein concentrations predict low hematocrit in type 2 diabetes. Diabetes Care, 2006. 29(10): p. 2289-94.
- Woodcock, B.E., et al., Beneficial effect of fish oil on blood viscosity in peripheral vascular disease. Br Med J (Clin Res Ed), 1984. 288(6417): p. 592-4.
- Hauner, H., et al., Evidence-based guideline of the German Nutrition Society: carbohydrate intake and prevention of nutrition-related diseases. Ann Nutr Metab, 2012. 60 Suppl 1: p. 1-58.
- Bodor, E.T. and S. Offermanns, Nicotinic acid: an old drug with a promising future. Br J Pharmacol, 2008. 153 Suppl 1: p. S68-75.
- Vosper, H., Niacin: a re-emerging pharmaceutical for the treatment of dyslipidaemia. Br J Pharmacol, 2009. 158(2): p. 429-41.
- Sunami, Y., et al., Effects of low-intensity aerobic training on the high-density lipoprotein cholesterol concentration in healthy elderly subjects. Metabolism, 1999. 48(8): p. 984-8.
- King, A.C., 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): p. 2596-604.
- Blumenthal, J.A., et al., Effects of exercise training on cardiorespiratory function in men and women older than 60 years of age. Am J Cardiol, 1991. 67(7): p. 633-9.
- Despres, J.P., et al., Long-term exercise training with constant energy intake. 3: Effects on plasma lipoprotein levels. Int J Obes, 1990. 14(1): p. 85-94.
- Snyder, P.J., et al., Effect of transdermal testosterone treatment on serum lipid and apolipoprotein levels in men more than 65 years of age. Am J Med, 2001. 111(4): p. 255-60.
- Liu, P.Y., A.K. Death, and D.J. Handelsman, Androgens and cardiovascular disease. Endocr Rev, 2003. 24(3): p. 313-40.
- Kaushik, M., S.P. Sontineni, and C. Hunter, Cardiovascular disease and androgens: a review. Int J Cardiol, 2010. 142(1): p. 8-14.
- Yeap, B.B., Androgens and cardiovascular disease. Curr Opin Endocrinol Diabetes Obes, 2010. 17(3): p. 269-76.
- Matsumoto, A.M., Andropause: clinical implications of the decline in serum testosterone levels with aging in men. J Gerontol A Biol Sci Med Sci, 2002. 57(2): p. M76-99.
- Morales, A., J.P. Heaton, and C.C. Carson, 3rd, Andropause: a misnomer for a true clinical entity. J Urol, 2000. 163(3): p. 705-12.
- Anderson, J.K., et al., Andropause: knowledge and perceptions among the general public and health care professionals. J Gerontol A Biol Sci Med Sci, 2002. 57(12): p. M793-6.
- Morley, J.E., Drugs, aging, and the future. J Gerontol A Biol Sci Med Sci, 2002. 57(1): p. M2-6.
- Morley, J.E., Andropause: is it time for the geriatrician to treat it? J Gerontol A Biol Sci Med Sci, 2001. 56(5): p. M263-5.
- Gould, D.C., R. Petty, and H.S. Jacobs, For and against: The male menopause--does it exist? BMJ, 2000. 320(7238): p. 858-61.
- Morley, J.E., 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. Proc Natl Acad Sci U S A, 1997. 94(14): p. 7537-42.
- van den Beld, A.W. and S.W. Lamberts, The male climacterium: clinical signs and symptoms of a changing endocrine environment. Prostate Suppl, 2000. 10: p. 2-8.
- Lamberts, S.W., A.W. van den Beld, and A.J. van der Lely, The endocrinology of aging. Science, 1997. 278(5337): p. 419-24.
- Morley, J.E. and H.M. Perry, 3rd, Androgens and women at the menopause and beyond. J Gerontol A Biol Sci Med Sci, 2003. 58(5): p. M409-16.
- Bolour, S. and G. Braunstein, Testosterone therapy in women: a review. Int J Impot Res, 2005. 17(5): p. 399-408.
- Davis, S.R. and H.G. Burger, Use of androgens in postmenopausal women. Curr Opin Obstet Gynecol, 1997. 9(3): p. 177-80.
- Rivera-Woll, L.M., et al., Androgen insufficiency in women: diagnostic and therapeutic implications. Hum Reprod Update, 2004. 10(5): p. 421-32.
- Harman, S.M., et al., Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metab, 2001. 86(2): p. 724-31.
- Morley, J.E., Androgens and aging. Maturitas, 2001. 38(1): p. 61-71; discussion 71-3.
- Tariq, S.H., Knowledge about low testosterone in older men. J Gerontol A Biol Sci Med Sci, 2003. 58(4): p. 382-3.
- Trinick, T.R., et al., International web survey shows high prevalence of symptomatic testosterone deficiency in men. Aging Male, 2011. 14(1): p. 10-5.