Testosterone Deficiency, Diabetes and Metabolic Syndrome

• Introduction
• Testosterone deficiency, diabetes and the metabolic syndrome
  • Testosterone and testosterone metabolism
  • Insulin and insulin metabolism
  • How does insulin resistance affect testosterone levels?
  • Evidence of the associations between diabetes, metabolic syndrome and testosterone deficiency
• Diagnosing hypogonadism in men with diabetes and metabolic syndrome
  • Screening for testosterone deficiency in men with diabetes and metabolic syndrome
  • Diagnosing diabetes and metabolic syndrome in men with symptoms of testosterone deficiency
• Testosterone replacement therapy for men with diabetes and metabolic syndrome
  • Starting testosterone replacement therapy
  • Administering testosterone
  • How will sexual performance change while undergoing testosterone replacement therapy?
• Assessing and managing lifestyle risk factors
  • Diet and exercise
  • Alcohol, smoking and other recreational drug use
  • Stress

Introduction

Testosterone is the key male hormone. It regulates a man’s libido (sex drive) and the development of secondary male sex characteristics, such as facial and body hair, the testes and the penis. Testosterone also protects the health of bone and muscle tissues. Testosterone deficiency is associated with many chronic health conditions, including type 2 diabetes mellitus and other metabolic disorders.

Testosterone deficiency has been estimated to affect about 1 in 200 Australian men, although this may under-represent the true number due to not all cases being diagnosed. In men from Boston, USA, testosterone deficiency was found to affect about 1 in 18 men aged 30–79 years, but in men aged 60–79 this increased to about 1 in 8. Significantly, there is also a strong association between testosterone deficiency and diabetes. A study in the United Kingdom found that 42% of men with type 2 diabetes also had low or borderline levels of testosterone.

For more information about testosterone deficiency, see Male Hypogonadism (Primary Hypogonadism and Secondary/Hypogonadotrophic Hypogonadism).

Testosterone deficiency, diabetes and the metabolic syndrome

The association between low levels of testosterone (a condition known as hypogonadism) and type 2 diabetes mellitus are well recognised, but it also appears that testosterone deficiency is common in men with diabetes regardless of type. Metabolic syndrome is a condition characterised by several co-occurring metabolic imbalances (e.g. impaired insulin metabolism, obesity, high blood pressure); it often precedes type 2 diabetes mellitus, and is also associated with testosterone deficiency. There is considerable evidence that men with metabolic syndrome are more likely to develop hypogonadism and vice versa.

There is also a link between low testosterone levels and insulin resistance in men with type 1 diabetes. Testosterone replacement therapy has been shown to improve insulin metabolism.

Testosterone and testosterone metabolism

In men, testosterone is primarily produced by the Leydig cells of the testes. Testosterone production in the testes is stimulated when a man’s pituitary gland produces a hormone called luteinising hormone (LH). If either the pituitary gland or the testes are dysfunctional, testosterone production may decline or stop, leading to testosterone deficiency or hypogonadism.

For more information, see Testosterone.

Insulin and insulin metabolism

Insulin is a hormone produced by the pancreas and functions to lower levels of glucose in the blood. If the body does not produce enough insulin, or if the insulin produced does not function properly to reduce blood glucose, levels of blood glucose rise and lead to health conditions such as metabolic syndrome and type 1 and type 2 diabetes mellitus.

How does insulin resistance affect testosterone levels?

Testosterone production is affected in diabetic men because they have higher than normal concentrations of glucose in their blood. When blood glucose levels are high, the pituitary gland produces less LH than it normally would. As testosterone is only produced when LH is secreted from the pituitary, thisreduces the amount of testosterone produced by a man’s body.

The association between diabetes and hypogonadism are interdependent – that is, they work both ways. Low testosterone is a risk factor for diabetes and the metabolic syndrome because testosterone levels affect body fat composition, glucose transport and the ways in which the body’s cells use testosterone. Diabetes is also a risk factor for hypogonadism because it is associated with increased body mass and altered hormone profiles (e.g. reduced LH as a result of high blood glucose levels, which in turn reduces testosterone levels).

Evidence of the associations between diabetes, metabolic syndrome and testosterone deficiency

Studies have reported that 20–64% of men with testosterone deficiency/hypogonadism also have type 2 diabetes. The proportion of men who have both type 2 diabetes mellitus and hypogonadism increases in older groups of men.

Men who have slightly reduced testosterone concentrations (but not low enough to be considered testosterone deficient) are also more likely to have low insulin (and high blood glucose) levels. Therapies that reduce testosterone levels (e.g. androgen deprivation therapy, which is used by men with prostate cancer because testosterone stimulates the growth of prostate cancer) have also been shown to lower insulin levels.

Men with low testosterone concentrations, in addition to having lower insulin levels, are more likely to develop the metabolic syndrome or one of the metabolic imbalances that characterise it (e.g. impaired insulin metabolism, obesity, high blood pressure). Scientists have even suggested that hypogonadism should be considered one of the imbalances that characterise metabolic syndrome.

Evidence shows that approximately one third of type 2 diabetics are testosterone deficient. An even greater proportion of men who are both diabetic and obese experience testosterone deficiency, and the likelihood of testosterone deficiency increases as type 2 diabetes progresses or worsens.

There is also evidence of an association between insulin resistance, glucose levels, abdominal obesity and free testosterone levels in type 1 diabetic men. Abdominal obesity appears to play a particularly important role in these relationships. Abdominal obesity causes insulin resistance, which in turn reduces testosterone levels because it increases the amount of testosterone converted to oestradiol.

Increasing knowledge about the associations between testosterone deficiency and diabetes have lead to trialling testosterone replacement therapy (TRT) as a treatment for insulin resistance in diabetic men. Evidence to date shows that TRT improves insulin metabolism in hypogonadal diabetic men.

For more information on TRT, see Testosterone Replacement Therapy.

Diagnosing hypogonadism in men with diabetes and metabolic syndrome

Despite mounting evidence of the associations between diabetes, metabolic syndrome and hypogonadism, testosterone deficiency in diabetic men may not always be diagnosed at routine visits to the doctors. There are a number of challenges doctors face when attempting to make such a diagnosis, including:

• Communication: For example, the man may be embarrassed to discuss symptoms of testosterone deficiency (which include reduced sex drive and loss of masculine characteristics such as a large penis and thick body hair) at a doctor’s consultation for diabetes;
• Focus on treating erectile dysfunction: For example, men who experience testosterone deficiency may confuse its symptoms (in particular reduced libido) with erectile dysfunction, and seek treatment for erectile dysfunction. However, the causes of testosterone deficiency and erectile dysfunction are very different and treatment for erectile dysfunction is unlikely to improve symptoms of testosterone deficiency;
• Education: Men with diabetes are often unaware of the associations between hypogonadism and low testosterone levels and metabolic conditions;
• Focus on treating diabetes: Doctors may focus on treating diabetes and assessing and managing direct symptoms of diabetes (e.g. blood glucose levels). As consultations are often very short, this may not leave time for testosterone deficiency symptoms to be discussed;
• Lack of resources: There are few questionnaires available to help doctors assess testosterone deficiency in men with diabetes or metabolic syndrome; and
• No recommendation for universal screening of testosterone levels in diabetic men. This may mean that low testosterone is not perceived to be as important as other conditions that co-occur with diabetes (e.g. eye diseases) for which universal screening is recommended.

Accurate diagnosis is further complicated because many of the symptoms of diabetes are also symptoms of testosterone deficiency. These include:

• Erectile dysfunction;
• Reduced libido;
• Depression;
• Decreased bone mineral density; and
• Reduced sense of wellbeing.

Screening for testosterone deficiency in men with diabetes and metabolic syndrome

Men with diabetes or metabolic syndrome should therefore openly discuss any symptoms that may reflect testosterone deficiency with their doctor. They should not be surprised if their doctor provides them with information about the associations between testosterone levels and metabolic conditions. When providing such information, the doctor is not implying that a man has testosterone deficiency or a problem with his sexual functioning. Men should not feel like their doctor is judging them or their manliness if they receive such information.

Men with diabetes should also be prepared for the doctor to ask them questions about their sexual functioning. This may include asking if the man has experienced:

• Reduced libido;
• Depression;
• Decreased bone mineral density;
• Headaches and visual problems;
• Galactorrhoea (secretion of milk from the breasts);
• Intolerance of cold;
• Weight changes, including anorexia and weight loss;
• Malaise and fatigue;
• Severe hypoglycaemia (low blood sugar) with rapid onset;
• Papilloedema (swelling of the optic disk);
• Reduced sense of wellbeing.

A doctor may also ask him to complete a questionnaire about testosterone deficiency symptoms to help them assess whether or not the man has testosterone deficiency. If a doctor considers testosterone deficiency to be likely, they will do a blood test to measure testosterone levels.

Making such enquiries helps doctors to diagnose testosterone deficiency in a greater number of men with diabetes. This in turn enables the doctor to consider using TRT, which may improve both diabetes and testosterone deficiency.

Diagnosing diabetes and metabolic syndrome in men with symptoms of testosterone deficiency

It is also important for men with testosterone deficiency to be aware that this condition often co-occurs with diabetes and metabolic syndrome. Doctors may enquire about metabolic disorders such as diabetes when men present with sexual dysfunctions which may be symptoms of testosterone deficiency. This does not mean that the doctor is not taking the sexual dysfunctions seriously. On the contrary, the doctor recognises that sexual dysfunctions may not improve in men with diabetes, unless their diabetes is also treated.

Testosterone replacement therapy for men with diabetes and metabolic syndrome

Testosterone is one of the oldest marketed drugs. It has been used in TRT to resolve sexual dysfunctions and other symptoms of hypogonadism in men since the 1930s. While the key goal of TRT is to restore concentrations of testosterone in the blood, there exists considerable evidence that, in addition to resolving symptoms of testosterone deficiency, TRT improves insulin metabolism and other markers of metabolic syndrome.

For example, 83% of hypogonadal men with metabolic syndrome who received combined TRT and diet and exercise intervention reversed symptoms of the condition after one year of treatment, compared to 30% of men who received a diet and exercise intervention alone.Other studies conducted amongst men with metabolic syndrome and testosterone treatment have reported reduced body mass and body fat mass, reduced body mass index (BMI), weight and waist circumference, reduced insulin sensitivity and/or improved glucose control.

TRT has also been demonstrated effective in improving characteristics of type 2 diabetes.One study of TRT in hypogonadal men with type 2 diabetes showed significant reductions in fasting blood glucose and insulin sensitivity in the group treated with testosterone. These men also experienced reductions in waist circumference and waist-to-hip ratio and improvements in cholesterol levels.

TRT is therefore an effective treatment option for some men with metabolic disorders and testosterone deficiency. It may be an important new avenue for improving insulin resistance and the overall cardiovascular health of these men. However, your doctor will be able to advise if it is a suitable treatment option for you.

Starting testosterone replacement therapy

Some men may be reluctant to start TRT because they are afraid the treatment will negatively affect their cardiovascular health, though there is no evidence that TRT induces negative cardiovascular effects.

It it is important that men with type 2 diabetes or metabolic syndrome and testosterone deficiency do not treat their testosterone deficiency in isolation. These men should also treat their metabolic disorders, and it is particularly important that they adopt a healthy lifestyle, as both type 2 diabetes and metabolic syndrome are associated with lifestyle factors such as lack of exercise and too much fat in the diet. In some cases, medicine may also be prescribed.

Men with type 1 diabetes, a genetic condition which is not associated with lifestyle factors, can also use testosterone replacement therapy.

Administering testosterone

There are many ways by which testosterone can be administered, including orally (swallowing tablets), intramuscularly (injection into the muscle) and subdermally (absorption through the skin). Each method has its own benefits and limitations; for example, some are easier to administer than others, and some cost less.

The most appropriate form of testosterone will depend on the man being treated. Your doctor can discuss suitable options with you if this treatment is applicable.

How will sexual performance change while undergoing testosterone replacement therapy?

Most men experience low testosterone in mid or late life (past 40 or 50 years of age). At this point, some may not have been sexually active for a considerable time. Their bodies may have changed markedly in that period (particularly if their blood vessels have become damaged due to diabetes and other metabolic conditions), and their sexual response may also differ. For example, achieving erection or orgasm may be more difficult than at a younger age. As such, it is important for men who commence TRT to have realistic expectations, or they may feel that their treatment is ineffective and stop TRT.

It is also important for men to realise that even if rapid improvements to libido and other symptoms of testosterone deficiency are experienced, it is common for men to experience a plateau effect as treatment continues. This means that the improvements will level off soon after starting.

Assessing and managing lifestyle risk factors

In addition to starting TRT, it is important for hypogonadal men with metabolic conditions to manage modifiable lifestyle factors, as an unhealthy lifestyle may make their metabolic conditions worse and also reduce the effectiveness of their treatment. Lifestyle factors play an important role in the development of type 2 diabetes mellitus, metabolic syndrome and testosterone deficiency. In particular, low levels of physical activity, unhealthy eating habits (e.g. eating too much, consuming too much fat and sugar), smoking and obesity increase the risk of each of these conditions. The risk of testosterone deficiency in men with diabetes increases further if they are also obese. Men with diabetes who maintain a healthy lifestyle may prevent the onset of testosterone deficiency.

Diet and exercise

Increasing body mass index (BMI) is associated with an increased risk of hypogonadism, and is also an important risk factor for metabolic syndrome. Thus maintaining a healthy BMI is an important component of managing testosterone deficiency. Men should:

• Consume a healthy balanced diet; and
• Be physically active.

Alcohol, smoking and other recreational drug use

Alcohol, smoking and recreational drug use also increase the risk of testosterone deficiency and metabolic disorders. Men should therefore:

• Reduce alcohol consumption: Both short and long term alcohol consumption has been shown in experiments performed on animals to reduce testosterone levels. This is because it affects the function of the hypothalamus and pituitary glands, which produce hormones that regulate testosterone production;
• Quit smoking: Some studies have shown that smoking increases the risk of hypogonadism.

Stress

Work-related stress was shown in one study to be associated with an increased risk of hypogonadism, and reducing work-related stress (e.g. by finding a healthy balance between work and life) may therefore reduce the risk of testosterone deficiency.

More information

For more information on testosterone deficiency in men, including testosterone tests and testosterone replacement therapy, see Testosterone Deficiency.

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Related diseases

• Male Hypogonadism (Primary Hypogonadism and Secondary/Hypogonadotrophic Hypogonadism)
• Diabetes Mellitus Type 2 (non-insulin dependent, mature age onset)
• Metabolic Syndrome