1. TD is a well-established, significant medical condition that negatively affects male sexuality, reproduction, general health and quality of life. TD may predict increased risk of developing diabetes, metabolic syndrome, contributes to decreased bone mineral density, is associated with increased all-cause and cardiovascular mortality and negatively impacts general health and quality of life.

There is no scientific basis for any age-specific recommendations against the use of testosterone therapy in men.

2.TD is a global public health concern. Prevalence rates in men range from 2% to 38% in studies from Asia, Europe, North America and South America. Variation in prevalence rates can be explained by differences in the operative definition of TD and biochemical thresholds.

3. The symptoms and signs of TD occur as a result of low levels of testosterone and may benefit from treatment regardless of whether there is an identified underlying aetiology. Symptoms and signs of TD occur in healthy volunteers or patients who undergo androgen deprivation, these symptoms and signs resolve with testosterone normalisation. Historically recognised causes of TD are rare (eg anorchia, craniopharyngioma, pituitary tumour), recently termed classical hypogonadism. These conditions account for only a tiny fraction of men with TD. TD occurs frequently with conditions other than ‘classical’ causes. No evidence exists to support restriction of testosterone therapy only to men with known underlying aetiology.

4. Testosterone therapy for men with TD is effective, rational and evidence based. High-level evidence shows testosterone therapy effectively:

  • Increases sexual desire (libido) and erectile and orgasmic function
  • Increases lean body mass
  • Decreases fat mass
  • Improves bone mineral density
  • Strongly suggestive evidence for improvement in mood and energy.

5. There is no testosterone concentration threshold that reliably distinguishes those who will respond to treatment from those who will not. No study has revealed a single testosterone threshold that reliably separates those who experience signs and symptoms of TD from those who do not, nor who will likely respond to treatment. Interpretation of total testosterone concentrations is confounded by:

  • Inter-individual variation
  • Variation in serum SHBG (binds tightly to testosterone, removing it from the bioavailable pool)
  • Genetic variation in androgen sensitivity due to AR gene polymorphisms (number of CAG repeats)
  • Free testosterone can be a useful indicator of androgen status.

6. There is no scientific basis for any age-specific recommendations against the use of testosterone therapy in men. The term age-related hypogonadism is of questionable validity since the decline in mean serum testosterone level with age is minor and primarily attributable to comorbidities, especially obesity. Older men respond well to testosterone therapy, as do younger men. Increased risk of erythrocytosis in older men requires monitoring but does not merit withholding testosterone therapy if indicated. It is illogical to single out TD as the one medical condition among many (eg diabetes, hypertension, heart disease, cancer, arthritis) that does not merit treatment because it becomes more prevalent with age.

7. The evidence does not support increased risks of CV events with testosterone therapy. Two observational studies received intense media attention after reporting increased CV risks. Both had major flaws/limitations. One misreported result. The other had no control group. Low serum T is associated with increased atherosclerosis, coronary artery disease, obesity, diabetes and mortality. Several RCTs in men with known heart disease (angina, heart failure) showed greater benefits with testosterone versus placebo (greater time to ischaemia, greater exercise capacity). The largest meta-analysis showed no increased risk with testosterone therapy, reduced risk was noted in men with metabolic conditions. No increased risk of venothrombotic events with testosterone therapy.

8. The evidence does not support increased risk of prostate cancer (PCa) with testosterone therapy. Serum androgen concentrations are not associated with increased risk of PCa, nor aggressive disease. Testosterone therapy has no greater risk of PCa than placebo. Aggressive/high-grade PCa is associated with low serum testosterone levels. Early data suggest no increased risk of recurrence/progression with testosterone therapy in men previously treated for PCa.

9. The evidence supports a major research initiative to explore possible benefits of testosterone therapy for cardiometabolic disease, including diabetes. A large body of evidence suggests lower serum testosterone concentrations are associated with increased CV risk, higher levels are protective. Testosterone therapy reliably increases lean mass; decreases fat mass, and may improve glycaemic control. Mortality rates are reduced by half in men with TD who received T therapy compared with untreated men in observational studies. Among men who received T therapy, those with normalised testosterone levels had a reduced rate of CV events/ mortality versus men with persistently low testosterone.