Fatigue is a common complaint and considered a very challenging symptom to cope with in many different medical diseases. The assessment of fatigue is bound up with the problems of both conceptualization and definition. In addition, few studies have investigated suitable neuropsychological tests to examine fatigue and its consequences. This thesis evaluates whether neuropsychological tests can elicit cognitive fatigue. It also investigates whether specific hormones and hormone replacement therapy influence fatigue as well as cognitive performance. Study I examined and compared neuropsychological measures of cognitive fatigue with self-rated fatigue in patients with mild traumatic brain injury (mTBI). These patients scored significantly higher than controls on both self-rated and on test- derived measures of cognitive fatigue. Cognitive fatigue was best captured with a score derived from the WAIS Digit Symbol. From our findings we concluded that cognitive fatigue was independent of depression and sleep disorder. Self-rated fatigue, on the other hand, was highly correlated to depression. Study II compared the effect of combined testosterone and estrogen replacement with estrogen treatment alone on subjective and objective measures of memory in oophorectomized women. Treatment with testosterone undecanoate 40 mg and estradiol 2 mg was associated with lower performance on immediate verbal memory compared to treatment with estrogen plus placebo. All other memory functions were unaffected. Study III explored cognitive fatigue in oophorectomized women, and whether hormonal treatment regimens, as described in study II, were related to self perceived well-being, estrogen or testosterone serum levels. We found that cognitive fatigue was frequent in oophorectomized women and negatively associated to self-perceived health and positively associated to BMI. However, treatment with testosterone + estrogen or estrogen alone had no significant effect on cognitive fatigue. Study IV investigated fatigue and cognitive performance in ...