Alternatives to Testosterone Replacement: Testosterone Restoration
The European Male Aging Study has demonstrated that the hypogonadism of male aging is predominantly secondary. Theoretically with appropriate stimulation from the pituitary, the aging testis should be able to produce eugonadal levels of testosterone. The strategies for the treatment of late onset hypogonadism (LOH) have focused on replacement with exogenous testosterone versus restoration of endogenous production. The purpose of this article is to review existing peer-reviewed literature supporting the concept of restoration of endogenous testosterone in the treatment of LOH.
In view of the EMAS studies, secondary hypogonadism accounts for over 85% of LOH. Ample evidence exists for a deficiency in GTP stimulation with the older men and the ability of the testes to respond to increased GTP production. We currently have several generic medications that accomplish an increase in GTP and normalization of serum testosterone with a favorable side-effect profile. Though shown to be efficacious and well-tolerated in a number of trials, none of the restorative strategies are FDA approved and caution must be advised in their off-label use. Hopefully, future trials will be undertaken to establish a long-term efficacy and safety restorative therapies. Early clinical trials of the compound enclomiphene are encouraging and hopefully will lead to a change in paradigm from TREP to TRES.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4650464/
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