World J Mens Health.  2019 Jan;37(1):31-44. 10.5534/wjmh.180027.

Type 2 Diabetes and Testosterone Therapy

Affiliations
  • 1Department of Urology, Good Hope Hospital, Heart of England Foundation Trust and University of Aston, Birmingham, UK. hackettgeoff@gmail.com

Abstract

A third of men with type 2 diabetes (T2DM) have hypogonadotrophic hypogonadism (HH) and associated increased risk of cardiovascular and all-cause mortality. Men with HH are at increased risk of developing incident T2DM. We conducted MEDLINE, EMBASE, and COCHRANE reviews on T2DM, HH, testosterone deficiency, cardiovascular and all-cause mortality from May 2005 to October 2017, yielding 1,714 articles, 52 clinical trials and 32 randomized controlled trials (RCT). Studies with testosterone therapy suggest significant benefits in sexual function, quality of life, glycaemic control, anaemia, bone density, fat, and lean muscle mass. Meta-analyses of RCT, rather than providing clarification, have further confused the issue by including under-powered studies of inadequate duration, multiple regimes, some discontinued, and inbuilt bias in terms of studies included or excluded from analysis.

Keyword

Cardiovascular diseases; Diabetes mellitus, type 2; Hypogonadism; Major adverse coronary events; Testosterone deficiency

MeSH Terms

Bias (Epidemiology)
Bone Density
Cardiovascular Diseases
Diabetes Mellitus, Type 2
Humans
Hypogonadism
Male
Mortality
Quality of Life
Testosterone*
Testosterone

Figure

  • Fig. 1 Changes from baseline in body composition after 56 weeks treatment with intramuscular testosterone undecanoate (plus intense exercise) or placebo (plus intensive exercise). Data from Ng Tang Fui et al (BMC Med 2016;14:153) [41].

  • Fig. 2 Changes in HbA1c from baseline with 30 weeks double blind therapy with intramuscular testosterone undecanoate or placebo in poorly controlled type 2 diabetes (T2DM) (HbA1c= or >7.5%) vs. well controlled (HbA1c<7.5%). Data from Hackett et al (Int J Clin Pract 2014;68:203–15) [46].

  • Fig. 3 Changes in international index of erectile function (IIEF) from baseline with 30 weeks double blind therapy with intramuscular testosterone undecanoate (TU) or placebo (P) in men with type 2 diabetes and mild hypogonadism (HG) (8–12 nmol/L) or severe HG (<8 nmol/L). Data from Hackett et al (Int J Clin Pract 2014;68:203–15) [46].

  • Fig. 4 Meta-analysis of 59 randomized controlled trials of testosterone substitution in hypogonadism (3,029 treated vs. 2,049 controls) (mean duration=32.5 weeks). Highlight boxes indicate significant changes. diff: difference, LL: lower limit, UL: upper limit, BMI: body mass index, HOMA: homeostatic model assessment, HDL: high density lipoprotein, SBP: systolic blood pressure, DBP: diastolic blood pressure. Cited from Corona et al (Eur J Endocrinol 2016;174:R99–116) [70].

  • Fig. 5 Estimated mortality probability and 95% confidence intervals (CIs) from the fitted logistic regression: Men stratified by testosterone (T) replacement therapy. Data from Hackett et al (World J Diabetes 2017;8:104–11) [67].

  • Fig. 6 Estimated mortality probability and 95% confidence intervals (CIs) from fitted logistic regression: men on all or none of the treatments testosterone replacement therapy, phosphodiesterase type 5 inhibitor, or statin). Data from Hackett et al (World J Diabetes 2017;8:104–11) [67].


Cited by  1 articles

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