No lasting metabolic health costs from combined GH and GnRH analogue therapy

By Eleanor McDermid, Senior medwireNews Reporter

Gonadotropin-releasing hormone analogue (GnRHa) given alongside growth hormone (GH) during puberty in order to increase adult height does not have long-term metabolic health consequences in children born small for gestational age (SGA), research shows.

At final adult height, children’s fat mass percentage, blood pressure and lipid profiles were similar regardless of whether or not they had received 2 years of treatment with GnRHa in addition to GH, report Manouk van der Steen (Dutch Growth Research Foundation, Rotterdam, the Netherlands) and co-researchers.

The findings arise from an analysis of the Dutch SGA study, which previously showed that pubertal SGA children, aged at least 8 years, receiving GH treatment achieved a taller adult height if they were also given GnRHa.

“GnRHa treatment is, however, known to increase [fat mass] in children with precocious puberty”, write the researchers in The Journal of Clinical Endocrinology & Metabolism.

But in this analysis, the fat mass percentage standard deviation score (SDS) at adult height was 0.4 both in the 64 children who received GnRHa plus GH and the 43 given GH alone.

Systolic blood pressure SDS was 0.4 and 0.6 in children who did and did not receive GnRHa, respectively, and lipid levels, including total cholesterol, low-density lipoprotein cholesterol and triglycerides, were nearly identical between the groups.

The team previously showed that a GH dose of 2 mg/m² per day resulted in a taller adult height than a daily dose of 1 mg/m². In a subgroup of 47 children who were pubertal at the time of treatment, fat mass percentage increased during treatment in those given the lower GH dose, but not those given the higher dose, resulting in a significant difference after 2 years of treatment, and when the children reached their adult height.

This led the researchers to speculate that the higher GH dose offsets the adverse metabolic effects of GnRHa, although they note that the increased fat mass percentage in the lower-dose group may not be clinically relevant, as it remained below 1 SDS in all children.

Systolic blood pressure declined during treatment irrespective of GH dose, while lipid levels changed only marginally and were unaffected by the GH dose.

“Started in early puberty, a GH dose of 2 mg/m²/d results in a similar metabolic health at [adult height] and a more favorable [fat mass percentage] than the standard 1 mg/m²/d and can therefore be considered in children who start GH treatment in early puberty with a poor [adult height] expectation”, concludes the team.

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