Testosterone Replacement Therapy Has Limited Effect on Increasing Bone Mass Density in Older Men: a Meta-analysis

Author(s): Wang Junjie, Hao Dongsheng, Sun Lei, Li Hongzhuo*, Sun Changying*.

Journal Name: Current Pharmaceutical Design

Volume 25 , Issue 1 , 2019

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Abstract:

Background: Testosterone insufficiency may play a role in age-related decreases in bone mass density (BMD) and osteoporosis in aging men. Testosterone replacement therapy (T therapy) seems to be a simple and convenient way to increase BMD and improve the condition of osteoporosis.

Objective: To evaluate the effects of T therapy in increasing BMD among older men with low serum testosterone concentrations.

Methods: A comprehensive search in the PubMed, EMBASE, Web of Science and Cochrane Central databases was undertaken for randomized controlled trials (RCTs) on the effect of T therapy on osteoporosis in aging men. Primary outcome measures were the change in BMD, bone turnover markers, prostate symptoms, body composition, metabolic and endocrine system markers. The final search was performed in October 2018.

Results: Seven RCTs were included. A total of 800 patients met the inclusion criteria. T therapy did not significantly reverse the trend toward decreasing BMD in the spine, femoral neck, Ward’s triangle and the whole body, with the exception of the trochanter and total hip. In addition, T therapy increased prostate size, lean mass, sex hormone levels; reduced HDL concentration; and had no statistical effect on prostate symptoms, body composition, serum hormones and metabolism.

Conclusion: T therapy is not effective in increasing BMD in older men. In addition, it has limited effects on prostate-specific antigen (PSA), the International Prostate Symptom Score (IPSS), body mass index (BMI), fat mass, parathyroid hormone (PTH), 25-VitD and lipid metabolism, although it can increase prostate size, lean mass, and sex hormone levels, and reduce glucose levels and HDL concentrations.

Keywords: Testosterone, aging men, bone mass density, osteoporosis, meta-analysis, randomized controlled trials.

[1]
Consensus development conference diagnosis, prophylaxis, and treatment of osteoporosis. Am J Med 1993; 94(6): 646-50.
[2]
Cooper C. Epidemiology of osteoporosis. Osteoporos Int 1999; 9(Suppl. 2): S2-8.
[3]
Holroyd C, Cooper C, Dennison E. Epidemiology of osteoporosis. Best Pract Res Clin Endocrinol Metab 2008; 22(5): 671-85.
[4]
Bliuc D, Nguyen N, Milch V, Nguyen T, Eisman J, Center J. Mortality risk associated with low-trauma osteoporotic fracture and subsequent fracture in men and women. JAMA 2009; 301(5): 513-21.
[5]
Svartberg J, Midtby M, Bønaa K, Sundsfjord J, Joakimsen R, Jorde R. The associations of age, lifestyle factors and chronic disease with testosterone in men: the Tromsø Study. Eur J Endocrinol 2003; 149(2): 145-52.
[6]
Morley J, Perry H, Kaiser F, et al. Effects of testosterone replacement therapy in old hypogonadal males: a preliminary study. J Am Geriatr Soc 1993; 41(2): 149-52.
[7]
Tenover JS. Effects of testosterone supplementation in the aging male. J Clin Endocrinol Metab 1992; 75(4): 1092-8.
[8]
Devogelaer JP, De Cooman S, Nagant de Deuxchaisnes C. Low bone mass in hypogonadal males. Effect of testosterone substitution therapy, a densitometric study. Maturitas 1992; 15(1): 17-23.
[9]
Katznelson L, Finkelstein JS, Schoenfeld DA, Rosenthal DI, Anderson EJ, Klibanski A. Increase in bone density and lean body mass during testosterone administration in men with acquired hypogonadism. J Clin Endocrinol Metab 1996; 81(12): 4358-65.
[10]
Snyder P, Peachey H, Hannoush P, et al. Effect of testosterone treatment on bone mineral density in men over 65 years of age. J Clin Endocrinol Metab 1999; 84(6): 1966-72.
[11]
Kenny A, Prestwood K, Gruman C, Marcello K, Raisz L. Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels. J Gerontol A Biol Sci Med Sci 2001; 56(5): M266-72.
[12]
Amory J, Watts N, Easley K, et al. Exogenous testosterone or testosterone with finasteride increases bone mineral density in older men with low serum testosterone. J Clin Endocrinol Metab 2004; 89(2): 503-10.
[13]
Tracz MJ, Sideras K, Bolona ER, et al. Testosterone use in men and its effects on bone health. A systematic review and meta-analysis of randomized placebo-controlled trials. J Clin Endocrinol Metab 2006; 91(6): 2011-6.
[14]
Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ (Clinical research ed) 1997; 315(7109): 629-34.
[15]
Kenny AM, Kleppinger A, Annis K, et al. Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels, low bone mass, and physical frailty. J Am Geriatr Soc 2010; 58(6): 1134-43.
[16]
Snyder P, Kopperdahl D, Stephens-Shields A, et al. Effect of testosterone treatment on volumetric bone density and strength in older men with low testosterone: A controlled clinical trial. JAMA Intern Med 2017; 177(4): 471-9.
[17]
Adams J. Quantitative computed tomography. Eur J Radiol 2009; 71(3): 415-24.
[18]
Hlaing TT, Compston JE. Biochemical markers of bone turnover - uses and limitations. Ann Clin Biochem 2014; 51(Pt 2): 189-202.
[19]
Camozzi V, Bonanni G, Frigo A, et al. Effect of a single injection of testosterone enanthate on 17beta estradiol and bone turnover markers in hypogonadal male patients. J Endocrinol Invest 2015; 38(4): 389-97.
[20]
Robinson J, Hodges E, Davison J. Prostate-specific antigen screening: a critical review of current research and guidelines. J Am Assoc Nurse Pract 2014; 26(10): 574-81.
[21]
Kang DY, Li HJ. The effect of testosterone replacement therapy on prostate-specific antigen (PSA) levels in men being treated for hypogonadism: a systematic review and meta-analysis. Medicine 2015; 94(3): e410.
[22]
Shim J, Kim J, Yoon Y, Choi H, Park J, Bae J. Serum Testosterone Levels Are Negatively Correlated with International Prostate Symptom Score and Transitional Prostate Volume. Low Urin Tract Symptoms 2018; 10(2): 143-7.
[23]
Kohn T, Mata D, Ramasamy R, Lipshultz L. Effects of Testosterone Replacement Therapy on Lower Urinary Tract Symptoms: A Systematic Review and Meta-analysis. Eur Urol 2016; 69(6): 1083-90.
[24]
Karazindiyanoğlu S, Cayan S. The effect of testosterone therapy on lower urinary tract symptoms/bladder and sexual functions in men with symptomatic late-onset hypogonadism. Aging Male 2008; 11(3): 146-9.
[25]
Holmäng S, Mårin P, Lindstedt G, Hedelin H. Effect of long-term oral testosterone undecanoate treatment on prostate volume and serum prostate-specific antigen concentration in eugonadal middle-aged men. Prostate 1993; 23(2): 99-106.
[26]
Sih R, Morley JE, Kaiser FE, Perry HM III, Patrick P, Ross C. Testosterone replacement in older hypogonadal men: a 12-month randomized controlled trial. J Clin Endocrinol Metab 1997; 82(6): 1661-7.
[27]
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. Clin Endocrinol 2005; 63(3): 280-93.
[28]
Cauley JA. Estrogen and bone health in men and women. Steroids 2015; 99(Pt A): 11-5.
[29]
Boyanov M, Boneva Z, Christov V. Testosterone supplementation in men with type 2 diabetes, visceral obesity and partial androgen deficiency. Aging Male 2003; 6(1): 1-7.
[30]
Mårin P, Andersson B, Ottosson M, et al. The morphology and metabolism of intraabdominal adipose tissue in men. Metab Clin Exp 1992; 41(11): 1242-8.
[31]
Zmuda JM, Fahrenbach MC, Younkin BT, et al. The effect of testosterone aromatization on high-density lipoprotein cholesterol level and postheparin lipolytic activity. Metab Clin Exp 1993; 42(4): 446-50.
[32]
Wu Y, Fan Z, Tian Y, Liu S, Liu S. Relation between high density lipoprotein particles concentration and cardiovascular events: a meta-analysis. Lipids in Health and Disease 2018; 17(1): 142.
[33]
Francomano D, Bruzziches R, Barbaro G, Lenzi A, Aversa A. Effects of testosterone undecanoate replacement and withdrawal on cardio-metabolic, hormonal and body composition outcomes in severely obese hypogonadal men: a pilot study. J Endocrinol Invest 2014; 37(4): 401-11.
[34]
Krysiak R, Gilowski W, Okopień B. The effect of testosterone on cardiometabolic risk factors in atorvastatin-treated men with late-onset hypogonadism. Pharmacol Rep 2016; 68(1): 196-200.


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Article Details

VOLUME: 25
ISSUE: 1
Year: 2019
Page: [73 - 84]
Pages: 12
DOI: 10.2174/1381612825666190206223244
Price: $58

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