Testosterone / Epitestosterone Ratio: How is it Significant?

Testosterone is an anabolic steroid & a potent androgenic hormone which is produced naturally in the body by the male testes as well as female ovaries, although the proportional production in males and females vary significantly. It is known to be responsible for the development of male reproductive organs and secondary sexual characteristics & its use may lead to a significant increase in the muscle mass, mood changes, hair loss, deepened voice, acne and infertility although such effects are case, context & dose dependent.

A range of testosterone-like anabolic steroids have ceremoniously been abused to enhance muscle development, strength, and endurance in various sports & athletic competitions. Such sort of exogenous performance enhancement is considered to be a form of doping by most of the sports regulatory authorities.

Epitestosterone is an inactive stereoisomer of testosterone & has a different configuration at only one of several stereogenic centers. It is, thus, a chemically similar, natural steroid that is produced independently of testosterone through a different bio-synthetic pathway.

Usually, the amount of Testosterone (T) & Epitestosterone (E) are in similar proportions and their normal presence in urine has been found, on an average to be roughly equal to 1:1, although it varies on a case specific basis. In case any anabolic steroids or any related preparation is taken or if some pathological condition exists the testosterone level may increase while the epitestosterone levels tend to remain unaffected. Thus the overall T/E ratio is skewed from the normal values and as a result, T/E ratio tends to vary significantly from the normal in such cases. However, if an additional amount of epitestosterone is administered to such individuals, theoretically, it is capable to bring the skewed T/E ratio back to normal. As a result, epitestosterone is banned by many sporting authorities for being a potent masking agent for testosterone use, or rather steroid abuse!

A T/E ratio higher than 6:1 was used to be considered as proof of abuse in the past; however, cases of naturally occurring higher T/E ratios have been described. Since the introduction of the T/E ratio in doping analysis, the parameters that may or may not influence the T/E ratio, possibly leading to false-positive results, have been debated.

Other than Steroids, various antimycotics, NSAIDs, & opioid analgesics used in sports medicine are all known to effect prostaglandin E2 synthesis and thus, they are capable of changing effective T/E ratios in various prostaglandin-mediated processes. Given the devastating personal and career consequences that may result from false positive results, the T/E ratio should be considered more of an indicator of the alterations in steroid metabolism, & should not be considered as a standalone specific marker for exogenous Testosterone administration.