Effect of low-normal and high-normal IGF-1 levels on memory and wellbeing during growth hormone replacement therapy: a randomized clinical trial in adult growth hormone deficiency

Background: The aim of the present study was to investigate the effect of low-normal and high-normal levels of IGF-1 in growth hormone (GH) deficient adults on cognition and wellbeing during GH treatment. Methods: A randomized, open-label, clinical trial including 32 subjects receiving GH therapy for at least 1 year. Subjects were randomized to receive either a decrease (IGF-1 target level of -2 to -1 SDS) or an increase of their daily GH dose (IGF-1 target level of 1 to 2 SDS) for a period of 24 weeks. Memory was measured by the Cambridge Neuropsychological Test Automated Battery, selecting the Pattern Recognition Memory task and the Spatial Working Memory. Wellbeing was measured as mood by the Profile of Moods States questionnaire, and quality of life by the Nottingham Health Profile and QoL Assessment in GH Deficiency in Adults questionnaires. Results: Data from 30 subjects (65.6% male, mean age 46.6 (9.9 SD) years), who fulfilled the target levels, were analyzed. Females in the low dose treatment arm were found to have a better working memory and a better strategic memory control after 24 weeks as opposed to the females in the high treatment arm. With respect to mood, the decrease in IGF-1 levels in females within the low treatment arm was associated with more fatigue and less vigor. Conclusions: The adjustment of GH dose in female patients seems to have a narrow window. A dose too high may impair prefrontal cognitive functioning, while a dose too low may result in decreased vigor.