Testosterone replacement therapy is widespread. Davis and Wahlin-Jacobsen reviewed in the Lancet Diabetes Endocrinology in December 2015 (3(12):980-92) the physiology of testosterone and its aromatised metabolite oestradiol, present in smaller quantities in the body. The primary indication for prescription of testosterone for women, and perhaps for men also, outside of the purely medical indications, is loss of sexual desire. Eventhough no formulation has been approved, widespread use takes place, off-label or as compounded therapy. Observation indicates favourable cardiovascular effects but  the risk of cardiovascular disease and total mortality, particularly in older people is yet to be established.

The athletic use is banned, of course, although it is well known to be attempted repeatedly in varying fashions. Medical indications of testosterone replacement therapy are very few, when men have their testicles totally inactivated surgicallly, chemically or by radiotherapy. Other use is considered off-label, not to say illegal, and it is not usually carried out in the USA or countries in the European Community. Canada, Brazil, Russia, and many other countries have more lax legislations. In Brazil, Dr Rodrigo M Greco prescribed Vitor Belfort a testosterone derivative before a fight in Las Vegas, but he was condemned anyhow, as in the USA and internationally, these hormones are always banned.

Clinical trials of testosterone replacement therapy suggest that exogenous testosterone enhances cognitive performance and improves musculoskeletal health in postmenopausal women, but there are no approved formulations for women with regard to cardiovascular, cognitive, and musculoskeletal health and the risk of cancer.

A systematic review and meta-analysis of testosterone replacement therapy by Zhao et al in Prev Med in April 2016 85:1-10 warned that the Canadian FDA issued a cardiovascular risk alert for exogenous testosterone in smokers because cotinine, a tobacco metabolite, inhibits testosterone breakdown, raising the serum concentrations of testosterone and its metabolites in smokers. The authors looked at the association of smoking and testosterone treatment in 13000 men and 6000 women, aged 20-60 years. The statistical analysis comparing serum concentrations of testosterone in smokers and non-smokers showed higher serum testosterone in males and a trend towards higher concentrations in females. It remains to be investigated whether this is true for e-cigarettes and passive smoking.

In general, there are very few studies of androgen hormones in any situation, because they are not used in situations controlled by the FDA or organs in any way similar. The lack of information is used by proponents of their use in a positive manner, as if there were no problems. But every one has seen athletes die of cardiac arrythmia in soccer fields, due to a well known cardiac muscle complication. The muscle hypertrophy so easy to see in all these athletes has obvious musculo-skeletal consequences, increased lesions, as happened to Anderson Silva. There is a mental syndrome, people become bipolar, agitated, and physicians and physical educators untrained in psychiatry are unlikely to catch these mental signs and symptoms.

Prof. Dr Paulo Bittencourt, PhD, FAAN

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