Effect of oxandrolone therapy on adult height in Turner syndrome patients treated with growth hormone: a meta-analysis

Abstract

Turner syndrome is a chromosomal abnormality in which there is complete or partial absence of the X chromosome. Turner syndrome effects 1 in every 2000 live births. Short stature is a cardinal feature of Turner Syndrome and the standard treatment is recombinant human growth hormone. When growth hormone is started at an early age a normal adult height can be achieved. With delayed diagnosis young women with Turner Syndrome may not reach a normal height. Adjuvant therapy with oxandrolone is used but there is no consensus on the optimal timing of treatment, the duration of treatment and the long term adverse effects of treatment. The objective of this review and meta-analysis is to examine the effect of oxandrolone on adult height in growth hormone treated Turner syndrome patients. Eligible trials were identified by a literature search using the terms: Turner syndrome, oxandrolone. The search was limited to English language randomized-controlled trials after 1980. Twenty-six articles were reviewed and four were included in the meta-analysis. A random effects model was used to calculate an effect size and confidence interval. The pooled effect size of 2.0759 (95 % CI 0.0988 to 4.0529) indicates that oxandrolone has a positive effect on adult height in Turner syndrome when combined with growth hormone therapy. In conclusion, the addition of oxandrolone to growth hormone therapy for treatment of short stature in Turner syndrome improves adult height. Further studies are warranted to investigate if there is a subset of Turner syndrome patients that would benefit most from growth hormone plus oxandrolone therapy, and to determine the optimal timing and duration of such therapy.

Keywords: Growth hormone; Height; Oxandrolone; Turner syndrome.

Fig. 1

Flow diagram of article selection. The initial literature search identified 26 articles. Nine articles were excluded because they were not evaluating adult height. An additional 13 articles were excluded because adult height data was not available, not all subjects were treated with growth hormone, or the study included the same cohort as a selected study. ^a = other sources included asking authors in the field if they were working on any current studies in this area and footnote chasing (looking at references of the 26 articles to identify more articles). ^b = 9 studies were excluded because the primary aim was not evaluating final height/near final height, ex. Effect of oxandrolone on glucose metabolism, on voice frequency, on psychological and behavioral characteristics, on body proportions, gonadotropin pulsatility, lipoprotein a, arithmetic learning disability, cognition, and thyroid hormone parameters (reference # 15–23). ^c = 13 studies total were excluded for the following reasons: 3 studies did not have final height or near final height data (ref #12,13,31), in 2 studies not all subjects were treated with GH (ref #7, 11), 7 of the studies involved the same cohort/population as the 4 chosen studies (ref #24-30), and 1 study had no control group on GH only (ref#32)

Fig. 2

a Adult height: effect size and 95 % confidence interval. Forest Plot of effect size for each article and mean effect size for adult height. b Height gain: effect size and 95 % confidence interval. Forest Plot of effect size for each article and mean effect size for height gain