What is Epitestosterone?
Epitestosterone is a naturally occurring endogenous steroid hormone that acts as an antiandrogen by competitively binding to androgen receptors, inhibiting testosterone biosynthesis and its conversion to dihydrotestosterone, and exerting antigonadotropic activity. 1, 2
Biochemical Characteristics
Epitestosterone is the 17α-epimer of testosterone, meaning it differs from testosterone only in the spatial orientation at the C-17 position 3, 1. It is found as a natural component of biological fluids in several mammals, including humans 1, 2.
Biosynthesis and Regulation
- The exact biosynthetic pathway and site of formation in humans remain incompletely understood 1, 2
- Epitestosterone formation apparently parallels testosterone production, but its concentration is not influenced by exogenous testosterone administration 1, 2
- This independence from exogenous testosterone forms the basis for anti-doping control, where the testosterone/epitestosterone (T/E) ratio is used to detect testosterone abuse 1, 2
Age and Sex-Related Variations
Plasma epitestosterone levels show distinct age-dependent patterns that differ between males and females 3, 4:
In Males:
- Before puberty, epitestosterone levels actually exceed testosterone levels, resulting in a high epitestosterone:testosterone ratio 3
- Peak epitestosterone concentrations occur around age 35 years 4
- After the peak, levels decline continuously with advancing age 4
- A sharp decrease in the epitestosterone/testosterone ratio occurs around puberty 4
In Females:
- Maximum epitestosterone levels occur around age 20 years 4
- Levels decline continuously until menopause 4
- A further increase occurs in the postmenopausal period 4
- The epitestosterone/testosterone ratio also decreases sharply around puberty 4
Biological Activity and Antiandrogenic Effects
Epitestosterone exerts complex antiandrogenic actions through multiple mechanisms 1, 2:
- Competitive binding to androgen receptors, blocking testosterone's effects 1, 2
- Inhibition of testosterone biosynthesis 1, 2
- Inhibition of testosterone reduction to dihydrotestosterone (DHT) 1, 2
- Antigonadotropic activity demonstrated in rat, mouse, and human tissues 1, 2
Physiological Significance
The concentrations of epitestosterone, particularly in prepubertal children where it reaches or exceeds testosterone levels, are sufficient to exert meaningful antiandrogenic actions 4. This suggests epitestosterone functions as an endogenous antiandrogen that may regulate androgen-dependent processes including:
- Control of prostate growth 1, 2
- Body hair distribution 1, 2
- Other androgen-dependent developmental events 1, 2
Clinical Relevance
The high epitestosterone:testosterone ratio in prepubertal boys and girls supports its role as a natural counterbalance to androgenic effects during development 3, 4. The sharp decline in this ratio at puberty allows for the normal androgenic effects necessary for sexual maturation 4.