Effects of growth hormone substitution therapy on cognitive functioning in growth hormone deficient patients: a functional MRI study

Patients with childhood-onset growth hormone (GH) deficiency (GHD) show impairments in mood and cognitive functioning which may resolve following GH substitution. Brain functional magnetic resonance imaging (fMRI) during performance of a memory task was used to assess the cerebral activity of such patients. Thirteen childhood-onset GHD patients (mean age 27.3 ± 6.9 years) were included in a double-blind, placebo-controlled study. The effects of 6 months of GH replacement or placebo therapy were studied using neuropsychological tests and fMRI. One patient was excluded from the study due to noncompliance with the protocol. Six months of GH substitution in these GHD patients resulted in improved memory functioning, both for long-term and working memory. fMRI showed activations during the working memory task in prefrontal, parietal, motor, and occipital cortices, as well as in the right thalamus and anterior cingulate cortex. Decreased activation in the ventrolateral prefrontal cortex was observed after GH treatment as compared with placebo treatment, indicating decreased effort and more efficient recruitment of the neural system involved. It can be concluded that GH treatment for 6 months improved the long-term as well as the working memory in patients with GHD, and this was associated with decreased brain activation in the ventrolateral prefrontal cortex. GH substitution in GHD patients is beneficial for cognitive functioning, the effects of which can be visualized by means of neuroimaging. Copyright © 2006 S. Karger AG

Impaired quality of life in hypopituitary adults with growth hormone deficiency: can somatropin replacement therapy help?

It is generally known that growth hormone (GH)-deficient patients experience emotional instability, reduced energy, sleep disturbances, and problems with (sexual) relationships. GH and insulin-like growth factor-1 (IGF-I) may affect mood parameters by their actions at binding sites in specific brain areas and/or by their effects on dopamine turnover in the brain. Indeed, there is substantial evidence that somatropin (growth hormone) treatment improves the quality of life (QOL) of GH-deficient patients. However, the variety of instruments used makes it questionable whether QOL in particular is affected by somatropin therapy. The measurement of QOL is subject to methodologic difficulties and is frequently not properly distinguished from health status and well-being. QOL ratings are characterized by an emphasis on mental health and health status by an emphasis on physical function, while well-being is concerned with depression, anxiety, and energy levels. Examples of instruments used to measure QOL, health status, and well-being in GH-deficient patients are the Quality of Life-Assessment of Growth Hormone Deficiency in Adults, the Short-Form Health Survey, and the Psychological General Well-Being Schedule, respectively. One additional problem in establishing the effects of somatropin treatment on QOL is that the QOL effects of somatropin treatment may be different for patients with isolated GH deficiency (GHD) and those with multiple pituitary hormone deficiencies. Previously, in order to answer the question of whether somatropin therapy improves mood status in GH-deficient patients, we conducted a meta-analysis comparing somatropin treatment effects relative to baseline and placebo. At 3, 6, and 12 months of somatropin replacement the mood status of GH-deficient patients improved with decreasing effect sizes over time (d = 0.81, 0.55, and 0.29, respectively) from baseline. However, the median somatropin treatment period of 6 months did not improve mood status more than placebo. In a second analysis we classified the questionnaires into those on QOL, those on health status, and those on well-being, respectively, and analyzed the separate effects of pooled treatment durations of about 9 months. Somatropin replacement improved QOL with a small effect size (d = 0.18), well-being with a medium effect size (d = 0.47), and health status with a small effect size (d = 0.26). Although the separate effects of somatropin on QOL, health status, and well-being could not be compared to placebo, we concluded that somatropin treatment most likely plays a role in improving the well-being of patients with GHD. This conclusion is based on correlations that have been found between IGF-I levels and parameters of well-being, such as anxiety and depression

The relation between insulin-like growth factor I levels and cognition in healthy elderly: a meta-analysis

OBJECTIVE: Insulin-like growth factor I (IGF-I) levels and cognitive functioning decrease with aging. Several studies report positive correlations between IGF-I levels and cognitive functioning in healthy elderly. However, because of controversial data no definitive conclusions can be drawn concerning the relation between IGF-I and cognition. Therefore, we carried out a meta-analysis on studies that report on the relation between IGF-I and cognition in healthy elderly. DESIGN: We searched the electronic databases for articles about IGF-I and cognition. Studies from 1985 to January 2005 are included. Two reviewers independently extracted data on study design and cognitive outcomes. Thirteen studies on IGF-I and cognition in elderly, with a total number of 1981 subjects, met the inclusion criteria. On the data from these studies meta-analyses were carried out by means of the program Comprehensive Meta-analysis using a random effects model. RESULTS: Pooled effects show that IGF-I levels in healthy elderly have a positive correlation with cognitive functioning, which appeared to be mainly measured with the mini mental state examination (MMSE). The effect size is 0.6, which indicates the presence of a large positive relationship between IGF and cognition in healthy elderly. CONCLUSION: These meta-analyses showed an overall relationship between IGF-I levels and cognitive functioning in healthy elderly. Further studies should be performed to clarify the role of IGF-I substitution in preserving cognitive functions with agin

Effects of an oral mixture containing glycine, glutamine and niacin on memory, GH and IGF-I secretion in middle-aged and elderly subjects

Aging is associated with declining activity of the growth hormone-insulin-like growth factor-I (GH-IGF-I) axis and with a decrease in cognitive function. The stimulatory effect of an orally administered nutritional supplement, mainly containing glycine, glutamine and niacin on the GH-IGF-I axis and on mood and cognition was investigated. Forty-two healthy subjects (14 men and 28 women, aged 40-76 years) were enrolled in a randomised, double blind, placebo-controlled trial. They received 5 g of a nutritional supplement or placebo, twice daily orally for a period of 3 weeks. At baseline and after 3 weeks, blood was collected for measurement of serum GH and IGF-I levels and mood and cognitive function were tested. The nutritional supplement ingestion for 3 weeks was found to increase serum GH levels with 70% relatively to placebo, whereas circulating IGF-I levels did not change. Mean GH (± SD) increased in this group from 3.23 (± 4.78) to 4.67 mU/l (± 5.27) (p = 0.03). GH increase was not associated with improvement in mood or memory. Correlation analyses, however, revealed that individual increases in IGF-I, but not GH, were associated with improved memory and vigour. It is concluded that an oral mixture of glycine, glutamine and niacin can enhance GH secretion in healthy middle-aged and elderly subjects

The influence of growth hormone (GH) substitution on patient-reported outcomes and cognitive functions in GH-deficient patients: a meta-analysis

OBJECTIVE: The influence of growth hormone (GH) replacement on patient-reported outcomes (i.e., quality of life, health status and well-being) and cognitive functioning in GH-deficient adults is controversial. DESIGN: We carried out a meta-analysis of clinical trials concerning the influence of GH substitution on patient-reported outcomes and cognitive functions (studies were selected from 1985 to 2004). The results of individual studies were combined in a series of meta-analyses using a random effects model. Effects of GH replacement in GH-deficient adults were compared to baseline and/or placebo. RESULTS: Fifteen studies on GH and patient-reported outcomes were included (830 patients, follow-up 3-50 months). Four of these studies also provided data on cognitive functions (85 patients, follow-up 6-12 months). Relative to baseline, GH treatment is found to have a large effect on patient-reported outcomes at 3 months, a medium effect at 6 months and a small effect at 12 months. With respect to the median treatment duration of 6 months placebo appears to be as effective as GH substitution. Cognitive functioning does not improve after 6 months of GH substitution, relative to baseline. CONCLUSION: This meta-analysis provides no evidence that GH improves patient-reported outcomes in GH-deficient patients. As the amount of cognitive data was too limited to allow for comparisons with placebo, from the present meta-analysis no conclusions can be drawn with respect to the impact of GH treatment on cognitio

Long-term growth hormone treatment preserves GH-induced memory and mood improvements: a 10-year follow-up study in GH-deficient adult men

Growth hormone (GH) replacement therapy with duration of several years is known to be safe and beneficial in GH-deficient adult patients. However, long-term follow-up data on GH substitution, cognition, and well-being are scarce. The purpose of this study was to investigate whether the benefits of GH replacement in psychological functioning found in previous studies lasting up to 2 years are preserved over a 10-year follow-up period. Twenty-three men (mean age at baseline 28.6 years) with childhood-onset GH deficiency were studied during a 10-year period of GH substitution. Memory tasks, mood questionnaires, and IGF-I values were obtained at baseline and after 0.5, 1, 2, 3, 5, and 10 years of GH substitution. Both mood and memory improved during GH therapy. After 6 months of treatment, anxiety and tension were reduced and vigor had improved. Memory improved after 1 year of substitution. These improvements were maintained during the 10-year follow-up period. Higher intra-subject IGF-I levels were associated with better mood (anxiety, tension, vigor). This study shows that 10 years of GH therapy is beneficial in terms of well-being and cognitive functioning in childhood-onset GH-deficient men. It may be concluded that once the decision to start GH treatment has been taken, this may imply that GH therapy has to be continued for a long period to maintain the psychological improvements and to prevent a relaps