Coming Up Short: Risks of Bias in Assessing Psychological Outcomes in Growth Hormone Therapy for Short Stature

Context: Two often cited assumptions for treating children with GH are that short stature (SS), as an isolated physical characteristic, is associated with psychosocial morbidity and that GH treatment may increase height and improve psychological adjustment. Findings across studies regarding the psychological consequences associated with GH management of children with SS are variable and frequently contradictory. The purpose of this systematic review is to evaluate the degree to which any conclusions about the relative risks or benefits of GH treatment on psychological outcomes can be made based on the published literature. Evidence Acquisition: Electronic databases were searched for randomized clinical trials and non-randomized studies, published between 1958-2014, in which GH was administered for management of children with SS and psychosocial, cognitive, academic, or health-related quality of life outcomes were assessed. Methodological quality of each study was assessed using the Cochrane Collaboration's tool for assessing risk of bias. Evidence Synthesis: Eighty studies were evaluated. No studies were rated as having a low risk of bias, the risk of bias was unclear in seven study outcome areas, and the remaining studies were judged as having a high risk of bias. Conclusions: The high risk of bias present in the majority of the literature on GH treatment effects on psychological outcomes (in particular, lack of blinding) substantially weakens confidence in their results. This may serve to explain the variability of findings for these outcomes across studies.