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Gender of Growth Hormone Recipients in the US and Globally« Back to Volume 24, Issue 2, November 2008 - Table of Contents The investigators examined gender-based patterns of recombinant human growth hormone (rhGH) use in the US and how it compares to that of other countries, in the context of findings of previously reported gender disparities and the fact that rhGH has entered its third decade of clinical use. Data from all patients enrolled in the International Growth Study (KIGS) registry were included in the analysis. Patients were categorized into 4 geopolitical regions: US; Europe/Australia/New Zealand; Asia; and Rest of the World (ROW; Argentina, Brazil, Colombia, Egypt, El Salvador, Guatemala, México, South Africa, and Venezuela). The US portion of the database was further divided into 10 geographic regions, according to US Postal Service zip code. To minimize the diagnostic inconsistencies across investigators, geographic regions and time, over 100 KIGS diagnoses were collapsed into 8 categories: (1) congenital GH deficiency; (2) organic acquired GH deficiency; (3) renal insufficiency; (4) Turner syndrome; (5) Prader Willi syndrome (PWS); (6) small for gestational age (SGA), intrauterine growth retardation (IUGR); (7) familial short stature/constitutional growth delay/idiopathic short stature (FSS/CGD/ISS); and (8) idiopathic, neurosecretory, and transient GH deficiencies (IGHD). Analyses depicted a consistent male predominance among US pediatric rhGH recipients, at almost 2:1. The gender ratio did not change significantly across the 3 time periods defined by the sequence of FDA-approved indications: 1992 and before comprised the classic GH-deficiency era; 1993-2000 the non-GH deficiency pathophysiology era; and 2001 onwards, the height-based era. All indications except PWS (and Turner syndrome because it is female-limited) significantly exceeded 50% males. The male predominance for all non-organic indications combined (72%) exceeded that for the organic indications, with or without Turner syndrome (38% and 59% male, respectively; P<0.0001 for both). Males outnumbered females at all ages, but with increased disparity during the second decade. With regard to male predominance across US regions, the areas with maximal and minimal percentages differed for each indication and the predominance did not correlate with either the number of children in each geographic area or the ratio of pediatric endocrinologists to children in each area. Comparing the US with global patterns demonstrated the US to have the second greatest male predominance, exceeded by Asia (mostly Japan), but greater than Europe/Australia/New Zealand. Recipients of rhGH in the ROW region were only 47% male. The authors concluded that male predominance among US pediatric rhGH recipients, described at the introduction of rhGH, persisted into this third decade of use. The factor that most consistently affected the gender distribution was the diagnostic indication, with the greatest disparity appearing in indications without clear organic etiologies, ie, ISS. The absence of male predominance in the ROW region raises the question of cultural influences on rhGH use. The authors also noted that of the 10 greatest rhGH users, the US is the only country with a commercial third-party payer health system as well as being the only country in which ISS became a government-approved indication for pediatric rhGH therapy. The investigators concluded that medical care providers need to be aware of the reported practice bias, and carefully consider girls with growth failure to ensure timely diagnosis and treatment of underlying health problems. Editor’s CommentThe persistent trend in the disproportionate number of males treated with rhGH should raise a number of concerns as well as provoke questions regarding the likely cosmetic (rather than medical necessity) rationale for rhGH treatment. Grimberg and colleagues previously reported that girls were referred for short stature half as often as boys and were more likely to have an identifiable underlying condition.1 It could be concluded that in the shift from monitoring growth, as a general indicator of physical health to measuring height and treating short stature, that girls, in general, are placed at higher risk of having serious medical conditions diagnosed later than boys. Given the incremental cost-effectiveness of rhGH therapy for ISS is approximately $52,000 per inch,2 it is well worth pondering why the US is the only country in which ISS became a government-approved indication for pediatric rhGH therapy. As Grimberg and colleagues noted, the data from this study suggest that social and cultural differences, in conjunction with perceived acceptability of rhGH expenditures, foster greater gender disparities in pediatric rhGH use in Japan and the US compared with other world regions. One of the largest gender disparities was found to be within the category of rhGH initiation starting at 15-20 years of age. Multiple studies have demonstrated that age of rhGH initiation is one of the best predictors of growth response, with the younger the age at initiation, the better the response.3,4 Initiating rhGH treatment in boys significantly more than girls between the ages of 15-20 years, with the knowledge that replicated clinical findings predict minimal growth response outcomes for this age range, lends support to the interpretation of over-treatment of boys. David E. Sandberg, PhD References - (linked to
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Volume 26 Number 1
September 2010
www.GGHjournal.com
ISSN 1932-9032
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