Testosterone and sexual dysfunction, quality of life and mortality

Description

Emerging data show that erectile dysfunction is an actual risk factor for cardiovascular disease.1,2 A large prospective study of nearly 8 million patients aged 25-84 years - published in the British Medical Journal - showed that erectile dysfunction is likely to be an independent risk factor for cardiovascular disease.1 The cardiovascular disease risk (hazard ratio) is highest for men aged around 45 years and then declines gradually with increasing age.1

The importance of testosterone for type 2 diabetes is underscored by the American Association of Clinical Endocrinologists (AACE) / American College of Endocrinology (ACE) guidelines, which recommend:

  • R19. All men who have an increased waist circumference (102 cm or above) or who have obesity should be assessed for hypogonadism by history and physical examination and be tested for testosterone deficiency if indicated; all male patients with hypogonadism should be evaluated for the presence of overweight or obesity.
  • R20. All male patients with type 2 diabetes should be evaluated to exclude testosterone deficiency.
  • R54. Men with true hypogonadism and obesity who are not seeking fertility should be considered for testosterone therapy in addition to lifestyle intervention because testosterone in these patients results in weight loss, decreased waist circumference, and improvements in metabolic parameters (glucose, A1C, lipids, and blood pressure) (Grade A; BEL 1).

How common is hypogonadism in men with type 2 diabetes? In clinical practice, up to 50-80% of men with type 2 diabetes have testosterone levels below 12 nmol/L.4 In the general population, loss of libido / vigour is commonly one of the first symptoms that appears when testosterone levels fall below 15 nmol/L. Erectile dysfunction usually doesn’t manifest until testosterone levels fall below 8 nmol/L.5

Importantly, while weight loss increases testosterone levels to a small degree, this is not enough to improve symptoms.6 Data suggest that testosterone therapy is necessary to achieve symptomatic improvement, even in the context of weight loss.6

The BLAST study is the largest double-blind placebo-controlled study to date conducted exclusively in a male type 2 diabetes population to assess the metabolic changes with testosterone replacement.7 The BLAST study showed that treatment with injectable testosterone undecanoate for 30 weeks resulted in significant benefit in all the domains of sexual function in men with total testosterone levels ≤8 nmol/L or free testosterone levels ≤0.18 nmol/L (180 pmol/L).8 By contrast, only sexual desire improved significantly in those with mild hypogonadism (total testosterone 8.1–12 nmol/L or free testosterone 0.181 –0.25 nmol/L). The BLAST study also showed that therapeutic trials of testosterone therapy, especially with long-acting testosterone undecanoate, should have a duration of at least 7.5 months (30 weeks), not 3 months (12 weeks) as suggested by some guidelines.8 Even though men with lower testosterone levels respond better to testosterone therapy, it should be pointed out that the bulk of the burden of erectile dysfunction in type 2 diabetes is due to vascular and neuropathic disease, not just simply testosterone.

A long-term follow up of the BLAST patients for 5 years showed that continued testosterone therapy resulted in an improvement in IIEF score by 8.6 points, whereas discontinuation caused a drop by 2.6 points. Remarkably, with continued long-term treatment with testosterone undecanoate there was further improvement in IIEF.

Several studies show that the metabolic benefits of testosterone therapy and improvements in sexual function and quality of life are accompanied by improved survival.9,10,11 While it is not surprising that men with low testosterone have higher mortality risk than eugonadal men, what may come as a surprise is that hypogonadal men who are treated with testosterone therapy have lower mortality than eugonadal men (not receiving TTh).12

Symposium_QA180307

The panel answers the following questions:

How long does a patient need to stay on testosterone therapy?

What to do with patients who failed gel and pellets?


 

Speakers

Prof. Geoffrey Hackett

Prof. Geoffrey Hackett
Good Hope Hospital, Sutton Coldfield,
UK

References

  • Hippisley-Cox J, Coupland C, Brindle P. Development and validation of QRISK3 risk prediction algorithms to estimate future risk of cardiovascular disease: prospective cohort study. BMJ. 2017 May 23;357:j2099. Return to content
  • Vlachopoulos CV, Terentes-Printzios DG, Ioakeimidis NK, Aznaouridis KA, Stefanadis CI. Prediction of cardiovascular events and all-cause mortality with erectile dysfunction: a systematic review and meta-analysis of cohort studies. Circ Cardiovasc Qual Outcomes. 2013 Jan 1;6(1):99-109. Return to content
  • Garvey WT, Mechanick JI, Brett EM, Garber AJ, Hurley DL, Jastreboff AM, Nadolsky K, Pessah-Pollack R, Plodkowski R; Reviewers of the AACE/ACE Obesity Clinical Practice Guidelines. AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY COMPREHENSIVE CLINICAL PRACTICE GUIDELINES FOR MEDICAL CARE OF PATIENTS WITH OBESITY. Endocr Pract. 2016 Jul;22 Suppl 3:1-203. Return to content
  • Hackett, G. I., et al. Biochemical hypogonadism in men with type 2 diabetes in primary care practice." The British Journal of Diabetes & Vascular Disease 2009:9(5): 226-231. Return to content
  • Zitzmann M, Faber S, Nieschlag E. Association of specific symptoms and metabolic risks with serum testosterone in older men. J Clin Endocrinol Metab. 2006 Nov;91(11):4335-43 Return to content
  • Ng Tang Fui M, Hoermann R, Prendergast LA, Zajac JD, Grossmann M. Symptomatic response to testosterone treatment in dieting obese men with low testosterone levels in a randomized, placebo-controlled clinical trial. Int J Obes (Lond). 2017 Mar;41(3):420-426. Return to content
  • Hackett G, Cole N, Bhartia M, Kennedy D, Raju J, Wilkinson P, Saghir A; Blast Study Group. The response to testosterone undecanoate in men with type 2 diabetes is dependent on achieving threshold serum levels (the BLAST study). Int J Clin Pract. 2014 Feb;68(2):203-15. Return to content
  • Hackett G, Cole N, Saghir A, Jones P, Strange RC, Ramachandran S. Testosterone undecanoate improves sexual function in men with type 2 diabetes and severe hypogonadism: results from a 30-week randomized placebo-controlled study. BJU Int. 2016 Nov;118(5):804-813 Return to content
  • Muraleedharan V, Marsh H, Kapoor D, Channer KS, Jones TH. Testosterone deficiency is associated with increased risk of mortality and testosterone replacement improves survival in men with type 2 diabetes. Eur J Endocrinol. 2013;169(6):725-733. Return to content
  • Shores MM, Smith NL, Forsberg CW, Anawalt BD, Matsumoto AM. Testosterone treatment and mortality in men with low testosterone levels. J Clin Endocrinol Metab. 2012;97(6):2050-2058. Return to content
  • Hackett G, Jones PW, Strange RC, Ramachandran S. Statin, testosterone and phosphodiesterase 5-inhibitor treatments and age related mortality in diabetes. World J Diabetes. 2017 Mar 15;8(3):104-111. Return to content
  • Hackett G, Heald AH, Sinclair A, Jones PW, Strange RC, Ramachandran S. Serum testosterone, testosterone replacement therapy and all-cause mortality in men with type 2 diabetes: retrospective consideration of the impact of PDE5 inhibitors and statins. Int J Clin Pract. 2016 Mar;70(3):244-53. Return to content