The benefits of treating hypogonadism

What are the Benefits of Treating Testosterone Deficiency (Hypogonadism)?

Sexual dysfunction and low libido are among the most easily reversible symptoms of testosterone deficiency (hypogonadism). Systematic reviews of randomised, placebo-controlled clinical trials of testosterone in men, including older men (aged 60 years and over) and middle-aged men, with sexual dysfunction and testosterone deficiency (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

Depression, well-being, cognitive function

Alterations in mood and depression are a symptom of, but not confined to, testosterone deficiency (hypogonadism).1,5 Outcomes in clinical trials of the effect of testosterone treatment on mood have varied. However, there is evidence that testosterone treatment can result in improvements in mood, particularly in older men with testosterone deficiency (hypogonadism).6,7 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.5,8-10,11

Body composition

Testosterone therapy has been shown to improve body composition (increase in lean body mass, decrease in fat mass) in men with testosterone deficiency (hypogonadism).1 There is a supplementary improvement in muscle strength and physical function. 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,1,5,7,12,13 and confirmed by systematic reviews or meta-analyses of randomised controlled trials.3,4,5,13

Cardiovascular risk

There is a large body of evidence linking cardiovascular risk 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 testosterone deficiency (hypogonadism).14 Current best evidence from systematic review of randomised controlled trials suggests that testosterone use in hypogonadal men is relatively well tolerated in terms of cardiovascular health and do not produce unfavorable elevations in blood pressure or glycaemic control, and does not adversely effect lipid profiles.3,15

Findings from some small registry studies have suggested that testosterone replacement therapy may invoke cardiovascular benefit.16 However, larger randomised controlled studies have only shown a cardiovascular-neutral effect at best following treatment, with no increased cardiovascular risk.17

Diabetes and metabolic syndrome

Testosterone deficiency (hypogonadism) is highly prevalent amongst men with diabetes mellitus type 2 or metabolic syndrome (insulin resistance, impaired glucose regulation, obesity, and hypertension).1,5,12,14,18 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 testosterone deficiency (hypogonadism).1,5 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 glycaemic control in hypogonadal men with diabetes are unclear. However, there are indications that treating testosterone deficiency (hypogonadism) may have benefits on metabolic status in men with diabetes, and there is evidence that testosterone replacement therapy has a beneficial effect on risk factors for diabetes such as central obesity, insulin sensitivity, glucose control and blood lipid profiles in hypogonadal men with type 2 diabetes.13,20,21

The American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology (ACE) Clinical Practice Guidelines advocate that testosterone deficiency (hypogonadism) should be evaluated in obese men with type 2 diabetes mellitus, and commencing testoterone replacement in these men if they are found to be testosterone deficient.22

Bone health

Low testosterone can lead to reduced bone mineral density and osteoporosis, and men with hip fractures have been found to have low testosterone.1,5 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.23

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.1,3,5,7,13 The effects may take several years to fully develop. At present no data on the role of testosterone in preventing fracture in men with testosterone deficiency (hypogonadism) are available.

References Show

  1. 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. Aging Male. 2009 Mar;12(1):5-12. doi: 10.1080/13685530802389628
  2. 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
  3. Gruenewald DA, Matsumoto AM. Testosterone supplementation therapy for older men: potential benefits and risks. J Am Geriatr Soc 2003; 51(1): 101-15
  4. 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
  5. 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. doi: 10.1210/jc.2009-2354. Review.
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  11. Resnick et al. JAMA 2017
  12. Qoubaitary A, Swerdloff RS, Wang C. Advances in male hormone substitution therapy. Expert Opin Pharmacother 2005; 6(9): 1493-506
  13. Stanworth RD, Jones TH. Testosterone for the aging male; current evidence and recommended practice. Clin Interv Aging 2008; 3(1): 25-44
  14. 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
  15. 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
  16. Cheetham et al JAMA 2017, Traish et al. 2017
  17. Onasyana et al Lancet diabetes endocrinol 2018, Maggi et al. IJCP 2016
  18. Barrett-Connor E. Lower endogenous androgen levels and dyslipidemia in men with non-insulin-dependent diabetes mellitus. Ann Intern Med 1992; 117(10): 807-11
  19. Gray A, Feldman HA, McKinlay JB, et al. Age, disease, and changing sex hormone levels in middle-aged men: results of the Massachusetts Male Aging Study. J Clin Endocrinol Metab 1991; 73(5): 1016-25
  20. Kapoor D, Goodwin E, Channer KS, et al. Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes. Eur J Endocrinol 2006; 154(6): 899-906
  21. Kapoor D, Jones TH. Androgen deficiency as a predictor of metabolic syndrome in aging men: an opportunity for intervention? Drugs Aging 2008; 25(5): 357-69
  22. Garvey et al.,&dl
  23. 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

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