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. 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, 2 and 5

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... s thereafter. Data at 5 years after GH-cessation, at age 21 years, were also compared to 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 DXA scans. In the GnRHa/GH and GH-only group, 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 AGA controls, a higher BMD-lumbar spine and lower lean body mass than AGA controls. This study during 5 years after GH cessation shows that addition of 2 years of GnRHa treatment to long-term GH treatment of short children born SGA has no unfavorable effects on metabolic and bone health in early adulthood.