Treatment Options

What are the Benefits of Treating Hypogonadism?

Sexual function

Sexual dysfunction and low libido are among the most easily reversible symptoms of hypogonadism. Systematic reviews of randomized, placebo-controlled clinical trials of testosterone in men, including older men (aged 60 years and over) and middle-aged men, with sexual dysfunction and hypogonadism have shown large favourable effects on libido and moderate effects on satisfaction with erectile function.7-11 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.7

Depression, well-being, cognitive function

Alterations in mood and depression are a symptom of, but not confined to, hypogonadism.1,7 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, particularly in older men with hypogonadism.12-13 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.1,14-16 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.

Body composition

Testosterone therapy improves body composition (increase in lean body mass, decrease in fat mass) in men with hypogonadism.7 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,1,2,7,13,17 and confirmed by systematic reviews or meta-analyses of randomized controlled trials.1,10,11,17

Cardiovascular risk

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 hypogonadism.18 Current best evidence from systematic review of randomized controlled trials suggests that testosterone use in hypogonadal men is relatively safe in terms of cardiovascular health and do not produce unfavorable elevations in blood pressure or glycemic control, and does not adversely effect lipid profiles.10,19

In fact, there is increasing evidence of the potential benefits of testosterone replacement therapy on multiple cardiovascular risk factors. This evidence recently has been comprehensively reviewed by Traish et al. in the Journal of Andrology.20 Although the full effects of testosterone replacement therapy on cardiovascular risk are yet to be established, the balance of emerging evidence from clinical studies suggests that testosterone replacement therapy in hypogonadal men may improve endothelial function, reduce proinflammatory factors, reduce hypertension, and improve the lipid profile.

Diabetes and metabolic syndrome

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.1,7,17,18,21,22 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.1,7 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. However, there are indications that treating 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.18,23,24

Bone health

Low testosterone can lead to reduced bone mineral density and osteoporosis, and men with hip fractures tend to have low testosterone.1,7 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.25

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.1,7,10,13,17 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.

References:
1. Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone therapy in adult men with androgen deficiency syndromes: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2006; 91(6): 1995-2010.
2. Qoubaitary A, Swerdloff RS, Wang C. Advances in male hormone substitution therapy. Expert Opin Pharmacother 2005; 6(9): 1493-506.
3. Seftel A. Testosterone replacement therapy for male hypogonadism: part III. Pharmacologic and clinical profiles, monitoring, safety issues, and potential future agents. Int J Impot Res 2007; 19(1): 2-24
4. Sharma V, Perros P. The management of hypogonadism in aging male patients. Postgrad Med 2009; 121(1): 113-21
5. Tung DS, Cunningham GR. Androgen deficiency in men. The Endocrinologist 2007; 17(2): 101-115
6. Zitzmann M, Nieschlag E. Testosterone substitution: current modalities and perspectives. J Reproduktionsmed Endokrinol 2006; 3(2): 109-116
7. Wang, C., E. Nieschlag, R. Swerdloff, et al. Investigation, treatment and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA and ASA recommendations. Eur J Endocrinol 2008, 159(5): 507-514
8. Bayer Schering Pharma AG. Global Nebido Satisfaction Study 2009
9. 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
10. Gruenewald DA, Matsumoto AM. Testosterone supplementation therapy for older men: potential benefits and risks. J Am Geriatr Soc 2003; 51(1): 101-15
11. 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
12. 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
13. 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
14. 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
15. 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
16. 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
17. Stanworth RD, Jones TH. Testosterone for the aging male; current evidence and recommended practice. Clin Interv Aging 2008; 3(1): 25-44
18. 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
19. 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
20. Traish AM, Saad F, Feeley RJ, et al. The dark side of testosterone deficiency: III. Cardiovascular disease. J Androl 2009; 30(5): 477-94
21. 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
22. 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
23. 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
24. 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
25. 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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