BACKGROUND: In children born small for gestational age (SGA) with persistent short stature, 2 years of gonadotropin-releasing hormone analogue (GnRHa), in addition to long-term growth hormone (GH) treatment, can improve adult height. We assessed safety on metabolic and bone health of GnRHa/GH treatment during 5 years after cessation of GH. METHODS: A total of 363 young adults born SGA, previously treated with combined GnRHa/GH or GH-only, were followed for 5 years after attainment of adult height at GH cessation and 2 and 5 years thereafter. Data at 5 years after GH cessation, at age 21 years, were also compared with 145 age-matched adults born appropriate for gestational age (AGA). Frequently sampled intravenous glucose tolerance (FSIGT) tests were used to assess insulin sensitivity, acute insulin response, and β-cell function. Body composition and bone mineral density (BMD) was determined by dual-energy x-ray absorptiometry (DXA) scans. FINDINGS: In the GnRHa/GH and GH-only groups, fat mass increased during the 5 years after GH cessation, but the changes in FSIGT results, body composition, blood pressure, serum lipid levels, and BMD were similar in both groups. At age 21 years, the GnRHa/GH group had similar fat mass, FSIGT results, blood pressure, serum lipid levels and BMD-total body as the GH-only group and the AGA control group, a higher BMD-lumbar spine and lower lean body mass than the AGA control group. INTERPRETATION: This study during 5 years after GH cessation shows that addition of 2 years of GnRHa treatment to long-term GH treatment of children short in stature born SGA has no unfavorable effects on metabolic and bone health in early adulthood. CLINICAL TRIAL REGISTRATION: ISRCTN96883876, ISRCTN65230311 and ISRCTN18062389.

GnRHa treatment, growth hormone, insulin sensitivity, metabolic health, pubertal suppression, SGA,
Journal of Clinical Endocrinology and Metabolism
Department of Pediatrics

Goedegebuure, W.J. (Wesley J.), van der Steen, M, Kerkhof, G.F, & Hokken-Koelega, A.C.S. (2020). Longitudinal Study on Metabolic Health in Adults SGA During 5 Years After GH With or Without 2 Years of GnRHa Treatment. Journal of Clinical Endocrinology and Metabolism, 105(8). doi:10.1210/clinem/dgaa287