Testosterone replacement therapy: A new avenue for treating insulin resistance in diabetic men?

Testosterone is one of the oldest marketed drugs. It has been used in testosterone replacement therapy (TRT) to resolve sexual dysfunctions and other symptoms of hypogonadism in men since the 1930s.1 TRT has also been shown to improve numerous aspects of systemic health, including insulin metabolism. There is now considerable data that low testosterone levels are associated with insulin resistance.2 For example, 1 in 3 men with type 2 diabetes mellitus are also testosterone deficient.3 For diabetics, this may offer new avenues for treating insulin resistance, as evidence shows that TRT improves insulin metabolism in testosterone deficient diabetic men.4

About testosterone and testosterone deficiency

Testosterone is the key male hormone and regulates libido and the development of secondary male sex characteristics, including hair growth and genital development. In men, testosterone is primarily produced by the Leydig cells of the testes, in response to luteinising hormone (LH) signals from the pituitary gland. Dysfunction in either the pituitary gland or the testes may therefore impair testosterone production and lead to testosterone deficiency.⁵

How testosterone deficiency and diabetes are linked

Testosterone deficiency is associated with many chronic health conditions and the associations between low levels of testosterone and type 2 diabetes mellitus are well recognised.² Metabolic syndrome often precedes type 2 diabetes mellitus. It is characterised by the co-occurrence of several metabolic imbalances, including impaired insulin metabolism. There is also considerable evidence that metabolic syndrome increases the risk of hypogonadism, and vice versa.⁶

Testosterone production is affected in diabetic men because diabetes increases blood glucose levels, which in turn reduce the production of LH in the pituitary gland. As testosterone is only produced when LH is secreted from the pituitary, this reduces the amount of testosterone produced by the body.³ The associations between diabetes and hypogonadism are interdependent. Low testosterone is a risk factor for diabetes and the metabolic syndrome because testosterone levels affect body fat composition, glucose transport and the activity of androgen receptors. Diabetes is also a risk factor for hypogonadism because it is associated with increased body mass and altered hormone profiles (including reduced testosterone production in Leydig cells and increased aromatase activity).⁷

Studies have reported the prevalence of hypogonadism in type 2 diabetic men at 20–64%, depending on the age of participants.⁷ They have also consistently shown an inverse relationship between testosterone levels and insulin concentrations in healthy⁸ and type 2 diabetic men.⁹ Among type 2 diabetic men of all ages, approximately one third are testosterone deficient, and prevalence of testosterone deficiency increases further in men who are also obese.³ Recent evidence also demonstrates an association between insulin resistance and testosterone levels in type 1 diabetic men.¹⁰ Further, there is evidence of an association between testosterone levels and the progression of type 2 diabetes.¹¹

How TRT can improve outcomes in diabetic men

The good news is that testosterone replacement therapy has been shown to improve not only testosterone levels, but also insulin metabolism and other markers of diabetes in hypogonadal men with metabolic syndrome¹² and hypogonadal⁹ and mildly testosterone deficient¹³ men with type 2 diabetes mellitus. For example, 83% of hypogonadal men with metabolic syndrome who received TRT and a diet and exercise intervention reversed symptoms of the metabolic syndrome after one year of treatment, compared to 30% of men who received a diet and exercise intervention alone.¹²

Diagnosing testosterone deficiency in diabetic men

Despite mounting evidence of the associations between diabetes and hypogonadism, testosterone deficiency remains undiagnosed in many diabetic patients, who face considerable barriers to having their testosterone deficiency diagnosed and treated. Many of the symptoms of diabetes are also symptoms of testosterone deficiency. Providers may be uncomfortable raising sexual health issues in a consultation for diabetes, or may not have time to do so. Patients may also be embarrassed to discuss problems relating to sexual function, and those who experienced a slow onset of symptoms may not recognise their sexual function has declined.²

Screen diabetic men for testosterone deficiency

A pro-active approach to diagnosing and treating hypogonadism in diabetic and pre-diabetic patients can therefore identify hypogonadism in more diabetic men, and enable more effective treatment of both diabetes and testosterone deficiency through TRT.² Serum testosterone should be measured in all men with type 2 diabetes, and a clinical history of symptoms of testosterone deficiency (e.g. reduced libido) should be taken.⁴ Practitioners can help increase patient awareness of the association between testosterone levels and diabetes by providing patient education, either during consultations, or by providing educational materials in the waiting room.²

Prospective studies are needed to investigate the long term effects of TRT.¹⁰ However, there exists considerable evidence that, in addition to resolving symptoms of testosterone deficiency, TRT improves insulin markers in testosterone deficient men. TRT is therefore a viable treatment option for some diabetic men with testosterone deficiency,² and may be an important new avenue for improving insulin resistance and in turn the overall cardiovascular health of these men.⁷

For more information on testerone deficiency in men, see Testosterone Deficiency.

References

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