Cognitive, Emotional, and Psychosocial Functioning of Girls Treated with Pharmacological Puberty Blockage for Idiopathic Central Precocious Puberty

Abstract

Central precocious puberty (CPP) develops due to premature activation of the hypothalamic-pituitary-gonadal (HPG) axis, resulting in early pubertal changes and rapid bone maturation. CPP is associated with lower adult height and increased risk for development of psychological problems. Standard treatment of CPP is based on postponement of pubertal development by blockade of the HPG axis with gonadotropin releasing hormone analogs (GnRHa) leading to abolition of gonadal sex hormones synthesis. Whereas the hormonal and auxological effects of GnRHa are well-researched, there is a lack of knowledge whether GnRHa treatment influences psychological functioning of treated children, despite the fact that prevention of psychological problems is used as one of the main reasons for treatment initiation. In the present study we seek to address this issue by exploring differences in cognitive function, behavior, emotional reactivity, and psychosocial problems between GnRHa treated CPP girls and age-matched controls. Fifteen girls with idiopathic CPP; median age 10.4 years, treated with slow-release GnRHa (triptorelin acetate—Decapeptyl SR® 11.25) and 15 age-matched controls, were assessed with a comprehensive test battery consisting of paper and pencil tests, computerized tasks, behavioral paradigms, heart rate variability, and questionnaires filled in by the children's parents. Both groups showed very similar scores with regard to cognitive performance, behavioral and psychosocial problems. Compared to controls, treated girls displayed significantly higher emotional reactivity (p = 0.016; Cohen's d = 1.04) on one of the two emotional reactivity task conditions. Unexpectedly, the CPP group showed significantly lower resting heart rates than the controls (p = 0.004; Cohen's d = 1.03); lower heart rate was associated with longer treatment duration (r = −0.582, p = 0.037). The results suggest that GnRHa treated CPP girls do not differ in their cognitive or psychosocial functioning from age matched controls. However, they might process emotional stimuli differently. The unexpected finding of lower heart rate that was associated with longer duration of the treatment should be further explored by methods appropriate for assessment of cardiac health.

Toward More Targeted and Cost-Effective Gonadotropin-Releasing Hormone Analog Treatment in Girls with Central Precocious Puberty

“…A study of 15 girls with CPP and 15 age-matched controls reported the only detectable difference in a large battery of tests was that treated girls showed higher emotional reactivity on 1 of 2 tests. Overall, these authors concluded that treated CPP girls did not differ in their cognitive or psychological functioning from control girls [26]. In summary, with few studies, utilizing different patient selection criteria and reporting disparate prevalence of behavioral problems in CPP girls, it remains unclear if psychosocial stress should be considered a predictable consequence of early puberty supporting a decision to start GnRHa therapy, and if so, whether treatment relieves such stress.…”

Commentary: Cognitive, Emotional, and Psychosocial Functioning of Girls Treated with Pharmacological Puberty Blockage for Idiopathic Central Precocious Puberty

“…Gonadotropin releasing hormone agonists (GnRHas) have been found to impair memory in adults, so the study by Wojniusz et al (2016) on the possible cognitive effects of these drugs on children treated for idiopathic central precocious puberty (CPP) represents an important contribution to research in this area. Recent findings that GnRHas increase depression symptoms (Macoveanu et al, 2016) and slow reaction time (Stenbæk et al, 2016) in healthy women, and reduce long-term spatial memory in sheep (Hough et al, 2017) underline the importance of the research that Wojniusz et al (2016) have undertaken.…”

“…Recent findings that GnRHas increase depression symptoms (Macoveanu et al, 2016) and slow reaction time (Stenbæk et al, 2016) in healthy women, and reduce long-term spatial memory in sheep (Hough et al, 2017) underline the importance of the research that Wojniusz et al (2016) have undertaken. However, their reassuring statement in the abstract that girls undergoing GnRHa treatment for CPP and controls “showed very similar scores with regard to cognitive performance” and their conclusion that “GnRHa treated girls do not differ in their cognitive functioning … from the same age peers” (Wojniusz et al, 2016) may be overly optimistic. These statements minimize the fairly substantial difference found in IQ scores and may also overemphasize its lack of statistical significance, as given the small number of participants in the study statistical significance has a high threshold.…”

“…It was found that the girls had a mean IQ of 94, as against a mean IQ of 102 for the matched control group (Wojniusz et al, 2016). These IQ estimations are presented as standardized IQ scores, which places a girl scoring 102 at the 55th percentile, and a girl scoring of 94 at the 34th percentile.…”

“…The authors contend that despite the small number of participants the results can—probably—be relied on to indicate that if GnRHas do cause a decline in IQ, this decline will be under 1 standard deviation ( SD ), which “represents a boundary of what is a clinically interesting difference” (Wojniusz et al, 2016). The contention that a decline only becomes clinically interesting if it is of at least 1 standard deviation is unconvincing.…”