ABSTRACT
Given that the decline in testosterone and sperm production is slower in men than in mice, the duration of treatment in humans should probably be at least double that used in animal models. Animal data suggest a potential benefit of treatment given before, during and after cytotoxic insult. Starting hormonal treatment before chemotherapy is unlikely to be practical, so treatment during and for at least 20 weeks after chemotherapy is likely to be the optimum achievable protocol. Selection of the appropriate study population is one of the most important factors in determining the success of any hormonal treatment protocol in men. To adequately assess the impact of hormonal therapy, the patients must have received a cytotoxic insult which is sufficiently gonadotoxic to result in temporary or permanent azoospermia in a significant proportion of patients. This insult must also, however, be associated with spontaneous recovery of spermatogenesis in a significant proportion of men, which would imply preservation of spermatogonial stem cells in at least some patients. Proof of a positive effect of hormonal manipulation may be derived from an increase in the proportion of men recovering normal spermatogenesis or from an increase in the speed of recovery. In practice, it is likely that if benefit is derived from this approach it will be in men who already have a reasonable chance of a spontaneous return of spermatogenesis. Thus, paradoxically, the group who have the greatest need for a new method of preserving fertility during cancer treatment, i.e. those in whom recovery of spermatogenesis is very unlikely, are the least likely to benefit from this technique. Nonetheless, hormonal treatment may significantly improve the chances of retaining fertility following successful treatment for cancer in a proportion of men, and such research in humans would lead to a greater understanding of the basic process of spermatogenesis.
