Introduction: The dystrophic features in hindlimb skeletal muscles of female mdx mice are unclear. Methods: We analyzed force-generating capacity and force decline after lengthening contraction-induced damage (fragility). Results: Young (6-month-old) female mdx mice displayed reduced force-generating capacity (-18%) and higher fragility (23% force decline) compared with female age-matched wild-type mice. These 2 dystrophic features were less accentuated in young female than in young male mdx mice (-32% and 42% force drop). With advancing age, force-generating capacity decreased and fragility increased in old (20 month) female mdx mice (-21% and 57% force decline), but they were unchanged in old male mdx mice. Moreover, estradiol treatment had no effect in old female mdx mice. Conclusions: Female gender-related factors mitigate dystrophic features in young but not old mdx mice. Further studies are warranted to identify the beneficial gender-related factor in dystrophic muscle. Muscle Nerve, 2013