Table of Contents 22-1

Motivations for GH/GnRHa Treatment and Psychosocial Functioning

Visser-van Balen et al reported (in the first paper) on the psychological consequences of combined growth hormone (GH)/gonadotropin-releasing hormone agonist (GnGHa) treatment in a multicenter, randomized-controlled study conducted in early pubertal youths (ages 11 to 13 years; Tanner breast stage 2 or 3 for girls, Tanner genital stage 2 or 3 for boys) with a diagnosis of either idiopathic short stature (ISS; 17 girls, 9 boys) or born small for gestational age (SGA; 8 girls, 4 boys). The authors explained the unusual predominance of girls as reflective of the combination of SS and relatively early puberty is more common in girls that boys. Participants had a height SDS below –2, or between –1 and –2 with a predicted adult height SDS below –2. In the second paper, the authors examined patients’ and parents’ motivations in choosing to participate in this study.

Adolescents in the treatment group were administered GH (4 IU [1.33mg]/m² BSA, SQ, daily) and GnRHa (3.75 mg, IM depot, every 4 weeks). At baseline, 1, 2, and 3 years after beginning treatment, adolescents and their parents (mostly mothers) in both groups completed questionnaires to assess the psychosocial functioning of the adolescents by completing a standardized assessment evaluating adolescents’ health-related development, current height-related stressors, and parental concerns about their child’s future behavioral and emotional functioning; perceived current and expected adult height; global intelligence; perceived competence, psychological distress, and personality characteristics.

At baseline, a minority of parents (28%) reported their child experienced teasing or juvenilization by peers; however, a higher proportion (44.5%) anticipated their child would face challenges in the labor market as an adult (39% of boys, 48% of girls) and 39% expected their child to have lower prospects of finding a spouse (77% of boys, 17% of girls, p<0.01). Parent reports of behavioral and emotional functioning suggested a statistically significant excess of problems. In contrast, adolescents’ self-reports of emotional distress and self-concept did not systematically differ from normative values. Differences in psychosocial variables at baseline were not detected between the treatment and control groups, ISS and SGA subgroups, or children whose parents reported stature-related psychosocial stressors. With regard to motivation to participate, patients were categorized into 4 subgroups based on the presences of height-related psychosocial stressors, parental worries about their child’s current behavior and about future prospects, and patients’ self-reported problems in psychosocial functioning.

During treatment, parent reports of current stigmatization and worries over future challenges did not change, and did not differ between the treatment and control groups. The same was not true for perceptions of the child’s behavioral and emotional functioning. In contrast, self-perceived scholastic and athletic competence in the treatment group significantly decreased over time (ie, became more negative), while that of the adolescents in the control group increased (moderate effect size). Trait anxiety decreased for adolescents in the control group, but remained at approximately the same level for adolescents in the treatment group. The authors noted that, despite these statistically significant effects, there was considerable overlap of scores between the 2 groups and one apparent outlier in the treatment group.

As noted above, parents perceived an excess of psychological adjustment problems in their children, however this difference was not matched by the children’s self-reports. As such, the investigators concluded that it is primarily the parents’ perceptions of problems (current or anticipated) that drive the process in search of a medical intervention. The adolescents wanted to gain height, but their underlying motivation remains unclear.

Visser-van Balen H, Geenen R, Moerbeek M, J et al. Psychosocial functioning of adolescents with idiopathic short stature or persistent short stature born small for gestational age during three years of combined growth hormone and gonadotropin-releasing hormone agonist treatment. Horm Res. 2005;64:77 - 87.

Visser-van Balen H, Geenen R, Kamp GA, Huisman J, Wit JM, Sinnema G. Motives for choosing growth-enhancing hormone treatment in adolescents with idiopathic short stature: a questionnaire and structured interview study. BMC Pediatr . 2005;5:15.

Editor’s Comment: My initial reading of this study left me somewhat confused: why would researchers look for effects of combined GH/GnRHa treatment on psychological outcomes when the long-term benefits of GnRHa on adult height had not yet been realized? In fact, the addition of GnRHa could have slowed growth. The answer to this puzzle is that this study was not about psychological effects of changes in height, but rather was examining the influence of arrested pubertal development on adolescents’ psychosocial adaptation. An implicit assumption justifying GnRHa as an adjunct to GH treatment is that the benefits of taller adult height outweigh the potential psychosocial liabilities of delayed or arrested pubertal development. The findings of a more negative self-concept in the treatment group give reason for pause. There are many reasons for viewing these findings as tentative, not the least of which is the high rate of missing data by the third year of treatment, confounding interpretation of the findings.

It was not so long ago that delayed puberty (in males, at least) was considered a significant threat to the individual’s psychosocial development.^1,2 Perhaps the time has come to consider a head-to-head comparison of the short- and long-term psychological benefits of on-time puberty versus taller adult stature.

Few studies directly examine parents’ motivations in seeking care for their child,^3,4 and no studies of the children themselves. This study begins the process of filling an important gap in knowledge. It has long been known that there is limited concordance in the reports of parents and their children when a description of the child’s psychosocial adaptation is in question,⁵ a clear limitation in employing “parent-proxy only” assessments. Another methodological cautionary note derives from the likelihood of overestimating the incidence of emotional/behavioral problems when comparing clinical samples to population norms. The authors correctly pointed out that norms for a commonly used behavior problem checklist, the Child Behavior Checklist, are biased towards mental health and not representative of the general population.⁶

This study documented that future (even more than current) worries about the short child, are on the minds of parents when they seek treatment for their child. To the extent that this finding is replicated in independent and larger studies, it suggests that parents’ decisions may hinge predominantly upon the negative stereotypes of foreclosed life options for adults with short stature. The empirical basis for these stereotypes are shaky.^7,8  Accordingly, it is the clinician’s responsibility to check for, and to correct these faulty assumptions when present, lest they engender self-fulfilling prophecies.

David E. Sandberg, PhD

References - (linked to )

1. Rosenfeld RG, Northcraft GB, Hintz RL. A prospective, randomized study of testosterone treatment of constitutional delay of growth and development in male adolescents. Pediatrics. 1982;69:681 - 687.
2. Wilson DM, Kei J, Hintz RL, Rosenfeld RG. Effects of testosterone therapy for pubertal delay. Am J Dis Child 1988;142:96 - 99.
3. Singh J, Cuttler L, Shin M, Silvers JB, Neuhauser D. Medical decision-making and the patient: understanding preference patterns for growth hormone therapy using conjoint analysis. Med Care. 1998;36(Suppl):AS31 - AS45.
4. Finkelstein BS, Singh J, Silvers JB, Marrero U, Neuhauser D, Cuttler L. Patient attitudes and preferences regarding treatment: GH therapy for childhood short stature. Horm Res. 1999;51(Suppl):67 - 72.
5. Achenbach TM, McConaughy SH, Howell CT. Child/adolescent behavioral and emotional problems: Implications of cross-informant correlations for situational specificity. Psychol Bull. 1987;101:213 - 232.
6. Sandberg DE, Meyer-Bahlburg HF, Yager TJ. The Child Behavior Checklist nonclinical standardization samples: should they be utilized as norms? J Am Acad Child Adolesc Psychiatry. 1991;30:124 - 134.
7. Sandberg DE, Colsman M. Assessment of psychosocial aspects of short stature. Growth Genet Horm. 2005;21:18 - 25.
8. Sandberg DE, Colsman M, Voss LD. Short stature and quality of life: A review of assumptions and evidence. In: Pescovitz OH, Eugster E, eds. Pediatric Endocrinology: Mechanisms, Manifestations, and Management. Philadelphia: Lippincourt, Williams & Wilkins, 2004:191-202.