OR11-1 Effect of Childhood Low-Dose Androgen Treatment on Self Image and Quality of Life in Boys with Klinefelter Syndrome (KS): Results of a Two-Year, Placebo-Controlled Clinical Trial

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: OR11-Pediatric Endocrinology
Clinical
Saturday, June 15, 2013: 11:30 AM-1:00 PM
Presentation Start Time: 11:30 AM
Room 104 (Moscone Center)
Judith L Ross*1, Martha D Bardsley1, Harvey Kushner2, Karen Kowal3 and David Roeltgen4
1duPont Hospital for Children, 2Biomedical Research Company, Philadelphia, PA, 3Thomas Jefferson University, Philadelphia, PA, 4University of Pennsylvania, South Seaville, NJ
Background: KS is a common genetic disorder (1/700 males) defined by the karyotype 47,XXY. The behavioral/social phenotype in KS includes increased social problems, anxiety, and somatic symptoms and may result in part from testicular failure and androgen deficiency in childhood. Androgen replacement is standard in adolescent and adult KS males but has not been used in childhood. The effects of treatment with prepubertal androgen replacement in KS are unknown.  In this study, we examined the effects of early low-dose androgen on self-image and quality of life in prepubertal boys with KS ages 5-12 years.
Objective: To determine the effects of Oxandrolone (Ox) versus Placebo (Pl) treatment for two years on self-image and quality of life in boys with KS.
Design/Methods: In this 2-year, double-blind, placebo-controlled clinical trial (2005-2011, NCT00348946), 93 boys with KS (95% 47,XXY), ages 4-12 y, were randomized to two groups: Ox (0.06 mg/kg (N=46)) and Pl (N=47). The evaluation at baseline (BL), one, and two years included two child self-report questionnaires: the Revised Childrens’ Manifest Anxiety Scale (RCMAS, ages 6-19 y), and the Children’s Depression Inventory (CDI, ages 6-17 y), and one Parent questionnaire: the Child Behavior Checklist (CBCL, ages 2-18 y). Statistical analysis included ANCOVA for change at 2-years from BL, adjusting for baseline differences in age.
Results: 80 (86%) subjects completed the 2-year study. Mean ages at study completion were (Ox) 9.1±2.1 years (n=39) vs. (Pl) 10.2 ±2.6 years (n=41), indicating the Ox group was slightly younger (P=0.03). At 2-years, on the RCMAS, the Ox group had significantly more positive Total (P=0.01) and Worry (P=0.02) scale scores and on the CDI, better outcomes on the Interpersonal Problems (P=0.003) and negative self esteem (P=0.0003) scales vs no significant changes from baseline in the Pl group. On the CBCL, at 2-years vs baseline, the Ox group had significantly better self-image scores for Problem Behaviors (P=0.02), Internalizing (P=0.02), Withdrawn (P=0.002), Anxious (P=0.04), and Somatic Problems (P=0.003) scales vs no significant changes from baseline in the Pl group. In contrast, neither the Ox nor the Pl groups had any significant changes at two years in CBCL hyperactive or aggressive behavior scales.  No major safety issues were identified.
Conclusions: This unique double-blind, randomized clinical trial demonstrates that childhood low-dose androgen treatment for two years in boys with KS had a positive impact on children’s self-esteem and social function and on parental perception of their children’s symptoms of anxiety, depression, and somatic problems. In contrast, there were no group differences in delinquent or aggressive problem behaviors. Treatment was well tolerated. Therefore, low-dose, childhood androgen replacement appears to have a positive impact on self-image in boys with KS.


Nothing to Disclose: JLR, MDB, HK, KK, DR

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: NIH NS050597
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