However, it is not clear whether there is a gender difference in the clinical outcomes of SCI. What are the challenges of translating 17β-estradiol therapy into a clinical setting for the treatment of SCI? First, it is difficult to compare the pre-clinical investigations performed in different laboratories because of the diversity of SCI paradigms and rodent species/strains used, and the distinct 17β-estradiol treatment regimens implemented (Table 1). Continuous administration of 17β-estradiol by means of subcutaneously implanted pellets or Silastic capsules, a single injection of 17β-estradiol following SCI or repeated injections over hours or days are dissimilar treatment strategies that can impact in different ways the injury-provoked mechanisms and outcomes. Another major challenge is the timewindow of 17β-estradiol administration. In the majority of animal studies, treatment was initiated prior to or immediately after SCI, a time frame that is not applicable to human SCI. Even a 4 to 6 hour delay in the initiation of treatment could be difficult to implement in clinics.