Potential secondary health benefits of testosterone therapy in men with hypogonadism

Testosterone, historically believed to be important only for male sexual function, has over the past decades transformed from niche hormone to multi-system player.19 There is increasing recognition of the harmful consequences of hypogonadism (also known as testosterone deficiency) and the potential, beneficial health effects of testosterone therapy.20,21

 

A growing number of studies have provided evidence that it takes several years for many of the beneficial health effects of testosterone therapy to manifest fully22, and that for most men maintenance of these health benefits requires lifelong testosterone therapy, as explained in the FAQ section.

 

Figure: Potential secondary health benefits of testosterone therapy in men with hypogonadism (low testosterone).

Blood

  • Prevents anemia

Sexual

  • Controls sexual function (sex drive, erectile function, orgasm)
  • Reduces lower urinary tract symptoms (LUTS)
Alt tag

Psychological

  • Improves mood, energy, wellbeing and quality of life
  • Prevents depression

Physical symptoms

  • Increases muscle mass
  • Increases strength
  • Decreases overall body fat mass
  • Decreases belly (visceral) fat mass
  • Increases bone mineral density

 

    Sexual dysfunction and low libido may be among the most easily reversed symptoms of hypogonadism. Systematic reviews of randomised, placebo-controlled clinical trials of testosterone in men, including older men (aged 60 years and over) and middleaged men, with sexual dysfunction and hypogonadism have shown large favourable effects on libido and moderate effects on satisfaction with erectile function.1-4 In men who do not respond sufficiently to testosterone therapy alone, the combination of phosphodiesterase 5-inhibitors and testosterone may be indicated, as there are suggestions that the combination may be synergistic.1

    Alterations in mood and depression are a symptom of, but not confined to, hypogonadism.1,6 Outcomes in clinical trials of the effect of testosterone treatment on mood have varied. However, there is evidence that testosterone treatment results in improvements in mood with hypogonadism.7,8 Similarly, although there is an established association between measures of cognitive ability and serum levels of testosterone, the benefits of testosterone treatment on cognition are less clearly established, with some studies reporting improvements in some measures of cognitive function and others failing to detect benefits.6,9-11 Although a potential role for testosterone in protecting cognitive function and preventing Alzheimer’s disease has been proposed by some researchers, confirmation from appropriately-designed clinical trials is awaited.

    Testosterone therapy may improve body composition (increase in lean body mass, decrease in fat mass) in men with hypogonadism.1 There may also be improvements in muscle strength and physical function.12 The benefits of testosterone treatment on body composition have consistently been demonstrated in clinical studies of testosterone therapy in hypogonadal men or men with borderline low testosterone levels,1,6,8,13,14 and confirmed by systematic reviews or meta-analyses of randomised controlled trials.4,5,6,14

    Hypogonadism is highly prevalent amongst men with diabetes mellitus type 2 or symptoms of the metabolic syndrome, including insulin resistance, impaired glucose regulation, obesity, and hypertension.1,6,14 Low testosterone in many men with diabetes remains undiagnosed and untreated, and current guidelines recommend measurement of testosterone levels in such patients and, equally, that such chronic diseases should be investigated and treated in men with hypogonadism.1,6 It is not yet fully known whether diabetes is a cause or a consequence of low testosterone, and the full effects of testosterone administration on glycemic control in hypogonadal men with diabetes are unclear.

    Low testosterone can lead to reduced bone mineral density and osteoporosis, and men with hip fractures tend to have low testosterone.1,6,18 For example, in a matched case-control study at a hospital orthopedic service, 71% of men with hip fractures had low testosterone levels, compared with 32% of age-matched controls.18

     

    A large number of trials have shown the positive effects of testosterone treatment on markers of bone formation and increased bone density in hypogonadal men treated with testosterone.1,4,6,8,14 Not surprisingly, the effects may take several years to fully develop. At present no data on the role of testosterone in preventing fracture in men with hypogonadism are available.

    There is a large body of evidence linking the onset and/or progression of cardiovascular disease to low testosterone levels in men. It is now apparent that an increased cardiovascular risk and accelerated development of atherosclerosis occurs not only in elderly men or men with obesity or type 2 diabetes mellitus, but also in non-obese men with hypogonadism15

    References

    • ISA, ISSAM, EAU, EAA and ASA recommendations: investigation, treatment and monitoring of late-onset hypogonadism in males. Wang C, Nieschlag E, Swerdloff RS, Behre H, Hellstrom WJ, Gooren LJ, Kaufman JM, Legros JJ, Lunenfeld B, Morales A, Morley JE, Schulman C, Thompson IM, Weidner W, Wu FC. Ageing Male. 2009 Mar;12(1):5-12. Return to content
    • Bayer Pharma AG. Global Nebido Satisfaction Study 2009 Return to content
    • Boloña ER, Uraga MV, Haddad RM, et al. Testosterone use in men with sexual dysfunction: a systematic review and meta-analysis of randomized placebo-controlled trials. Mayo Clin Proc 2007; 82(1): 20-8 Return to content
    • Gruenewald DA, Matsumoto AM. Testosterone supplementation therapy for older men: potential benefits and risks. J Am Geriatr Soc 2003; 51(1): 101-15 Return to content
    • 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 (Oxf) 2005; 63(3): 280-93 Return to content
    • Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, Montori VM; Task Force, Endocrine Society. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010 Jun;95(6):2536-59. Return to content
    • Wang C, Alexander G, Berman N, et al. Testosterone replacement therapy improves mood in hypogonadal men--a clinical research center study. J Clin Endocrinol Metab 1996; 81(10): 3578-83 Return to content
    • Wang C, Cunningham G, Dobs A, et al. Long-term testosterone gel (AndroGel) treatment maintains beneficial effects on sexual function and mood, lean and fat mass, and bone mineral density in hypogonadal men. J Clin Endocrinol Metab 2004; 89(5): 2085-98 Return to content
    • Barrett-Connor E, Goodman-Gruen D, Patay B. Endogenous sex hormones and cognitive function in older men. J Clin Endocrinol Metab 1999; 84(10): 3681-5 Return to content
    • Moffat SD, Zonderman AB, Metter EJ, et al. Longitudinal assessment of serum free testosterone concentration predicts memory performance and cognitive status in elderly men. J Clin Endocrinol Metab 2002; 87(11): 5001-7 Return to content
    • Yaffe K, Lui LY, Zmuda J, et al. Sex hormones and cognitive function in older men. J Am Geriatr Soc 2002; 50(4): 707-12 Return to content
    • Saad F et al.gerentology 2017;63:44-156 Return to content
    • Qoubaitary A, Swerdloff RS, Wang C. Advances in male hormone substitution therapy. Expert Opin Pharmacother 2005; 6(9): 1493-506 Return to content
    • Stanworth RD, Jones TH. Testosterone for the ageing male; current evidence and recommended practice. Clin Interv Ageing 2008; 3(1): 25-44 Return to content
    • Traish AM, Saad F, Guay A. The dark side of testosterone deficiency: II. Type 2 diabetes and insulin resistance. J Androl 2009; 30(1): 23-32 Return to content
    • Haddad RM, Kennedy CC, Caples SM, et al. Testosterone and cardiovascular risk in men: a systematic review and meta-analysis of randomized placebo-controlled trials. Mayo Clin Proc 2007; 82(1): 29-39 Return to content
    • Traish AM, Saad F, Feeley RJ, et al. The dark side of testosterone deficiency: III. Cardiovascular disease. J Androl 2009; 30(5): 477-94 Return to content
    • Jackson JA, Riggs MW, Spiekerman AM. Testosterone deficiency as a risk factor for hip fractures in men: a case-control study. Am J Med Sci 1992; 304(1): 4-8 Return to content
    • Saad F. The emancipation of testosterone from niche hormone to multi-system player. Asian journal of andrology. 2015;17(1):58-60. Return to content
    • Traish AM. Adverse health effects of testosterone deficiency (TD) in men. Steroids. 2014;88:106-116. Return to content
    • Traish AM. Benefits and Health Implications of Testosterone Therapy in Men With Testosterone Deficiency. Sex Med Rev. 2018;6(1):86-105. Return to content
    • Saad F, Aversa A, Isidori AM, Zafalon L, Zitzmann M, Gooren L. Onset of effects of testosterone treatment and time span until maximum effects are achieved. Eur J Endocrinol. 2011;165(5):675-685. Return to content

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