Growth Hormone Stimulation Testing Patterns Contribute to Sex Differences in Pediatric Growth Hormone Treatment

Abstract

Introduction: Males are twice as likely as females to receive pediatric growth hormone (GH) treatment in the United States, despite similar distributions of height z-scores in both sexes. Male predominance in evaluation and subspecialty referral for short stature contributes to this observation. This study investigates whether sex differences in GH stimulation testing and subsequent GH prescription further contribute to male predominance in GH treatment. Methods: Retrospective chart review was conducted of all individuals, age 2-16 years, evaluated for short stature or poor growth at a single large tertiary referral center between 2012-2019. Multiple logistic regression models were constructed to analyze sex differences. Results: Of 10,125 children referred for evaluation, a smaller proportion were female (35%). More males (13.1%) than females (10.6%) underwent GH stimulation testing (p<0.001) and did so at heights closer to average (median height z-score -2.2 [interquartile range (IQR) -2.6, -1.8] vs. -2.5 [IQR -3.0,-2.0], respectively; p<0.001). The proportion of GH prescriptions by sex was similar by stimulated peak GH level. Predictor variables in regression modeling differed by sex: commercial insurance predicted GH stimulation testing and GH prescription for males only, whereas lower height z-score predicted GH prescription for females only. Conclusions: Sex differences in rates of GH stimulation testing, but not subsequent GH prescription based on response to GH stimulation testing, seem to contribute to male predominance in pediatric GH treatment. That height z-score predicted GH prescription in females but not males raises questions about the extent to which sex bias—from children, parents and/or physicians—, as opposed to objective growth data, influence medical decision-making in the evaluation and treatment of short stature.

Identifying and addressing disparities in the evaluation and treatment of children with growth hormone deficiency

“…Disparities are seen with GHST, with more White males proceeding with the test than minority groups and females ( 37 ). These studies also highlight the high proportion of females not being assessed for SS; this is distressing as SS can be the only physical examination finding in patients with Turner Syndrome ( 38 , 39 , 42 , 44 , 45 ). Grimberg et al.…”

Beyond the bias! Sex distribution in paediatric growth hormone deficiency reexamined

“…5 Additionally, it has been shown that a male predominance exists among those who undergo growth hormone provocative testing (GH PT), the primary test in many centres to exclude GHD; and this appears to be related to the male predominance in paediatric GHD treatment in the United States. 6 Moreover, more boys than girls worldwide also receive growth hormone (GH) therapy for various indications which include both GHD and non-GH deficient states. 7,8 Societal bias and parental willingness to accept short stature more in girls could also be responsible for the sex disparity in GH therapy.…”

Adherence to Growth Hormone-Determined by a Consensual, Center-Based Supply-Associates with Height Outcomes in Youth

“…Patients born small for gestational age (SGA) nearly reached their target height SDS after 8 years of rhGH therapy as shown in Figure 2 [31][32][33]. There was a male preponderance in our study cohort of 61%, which may be a consequence of factors previously identified to contribute to sex disparity in rhGH treatment such as: screening bias by primary care physician, referal bias to pediatric endocrionologists for evaluation, bias of acceptable height cutoffs and interpretation of GH testing results, as well as bias related to prescribing and starting GH treatment [34]. Strengths of this study include duration, completeness and comprehensiveness of individual follow-up data.…”