Growth Hormone Therapy and Short Stature-Related Distress

A Randomized Placebo-Controlled Trial

Moran Shemesh-Iron; Liora Lazar; Yael Lebenthal; Nessia Nagelberg; Ariel Tenenbaum; Revital Ezra; Nir Leffler; Michal Yackobovitch-Gavan; Michal Schoenberg-Taz; Moshe Phillip


Clin Endocrinol. 2019;90(5):690-701. 

In This Article

Abstract and Introduction


Context: Growth hormone (GH) treatment of short healthy children is based on the belief that short stature is associated with psychosocial problems and a diminished quality of life.

Objective: To determine the impact of GH therapy on psychosocial well-being and the ability of psychological metrics to define short stature-related distress.

Methods: Sixty prepubertal boys with idiopathic short stature (age: 10.0 ± 1.4 years, height-SDS: −2.38 ± 0.3) were enrolled in this 4-year intervention study (1-year double-blinded, randomized, placebo-controlled [GH/placebo-2:1] and 3-year open-labelled GH therapy). Explicit (conscious/voluntary) psychological metrics (Pediatric Quality of Life Inventory [PedsQL], Silhouette Apperception Test [SAT], Rosenberg Self-Esteem Scale [RSES], Child Behavior Checklist [CBCL]) and implicit (unconscious/involuntary) psychological metrics (Single-Category Implicit Association Test for height [SC-IAT-H], Height Perception Picture Test [HPPT]). Psychosocial evaluations were performed at study entry, after 1 and 4 years.

Results: At study entry, PedsQL of boys with idiopathic short stature was lower than Israeli norms (P = 0.001). After 1-year blinded intervention, only the GH-treated boys improved their actual and anticipated adult height perception (SAT, P < 0.001 and P = 0.022) with reduced short stature-related distress (SC-IAT-H, P < 0.001). At study end, RSES and SC-IAT-H improved significantly (P < 0.001), with no change in PedsQL and CBCL.

Conclusions: Our finding of improved psychosocial functioning only in the GH-treated boys after 1-year blinded intervention suggests that it was the GH therapy, rather than being enrolled in a clinical trial, which contributed to the outcome. Long-term open-labelled GH treatment significantly improved height perception and self-esteem. Future studies are needed to fully assess the relevance of complementing the routinely used explicit self-report measures with the implicit measures.


Growth hormone (GH) treatment of short healthy children is based on the belief that short stature is associated with psychosocial problems and a diminished quality of life (QoL).[1,2] In 2003, the FDA approved GH therapy for children with idiopathic short stature (ISS).[3] It has been assumed that the GH-induced height gain would improve their QoL but the validity of this claim has evoked considerable debate. Some researchers found that children with short stature had lower self-esteem,[4,5] were more prone to verbal and physical harassment,[1,2,6,7] and that their parents perceived them as having more social problems,[8,9] while other studies failed to identify any psychopathology or diminished self-esteem in short children as compared with normal height controls matched for age, sex and social class.[10–15] Similarly, the effect of GH therapy in GH-sufficient short children on their well-being during childhood and in improving their QoL in adulthood is still inconclusive. Several studies reported improved emotional and social functioning of GH-treated children,[16–18] while others found no change following GH therapy.[19,20] In their systematic review, Gardner et al[21] proposed that the inconsistency of the psychosocial outcomes may stem from methodologic flaws: referral bias, small numbers of participants, absent/inadequate control groups, lack of blinding[8] and the relatively poor sensitivity of the explicit tools used to evaluate psychological functioning.[22]

Explicit attitudes are attitudes that are at the conscious level, are deliberately formed and are easy to self-report.[23] On the other hand, implicit attitudes are attitudes that are at the unconscious level, formed involuntarily, of which the subject is typically unaware.[23] In this study, we used both explicit and implicit psychological measures as complementary tools. We hypothesized that GH treatment in short boys would improve their psychosocial adaptation and self-esteem.

The aims of this prospective double-blind placebo-controlled study were as follows: (a) to determine the impact of 1 year of blinded intervention (GH vs placebo treatment) on the child's psychosocial adjustment and self-esteem; (b) to evaluate the long-term effect of GH therapy on the well-being of ISS children; and (c) to assess the ability of implicit psychological metrics to expose the child's unconscious perception of and affective response to short stature.