Götherström G, Svensson J, Koranyi J, Alpsten M, Bosaeus I, Bengtsson B, Johannsson G
Research Centre for Endocrinology and Metabolism, Gröna Stråket 8, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden.
J Clin Endocrinol Metab. 2001 Oct;86(10):4657-65. doi: 10.1210/jcem.86.10.7887.
GH replacement therapy has proved its efficacy and safety in short-term trials and in a few long-term trials with limited number of subjects. In this 1-center study, including 118 consecutive adults (70 men and 48 women; mean age, 49.3 yr; range, 22-74 yr) with adult-onset GH deficiency, the effects of 5 yr of GH replacement on body composition, bone mass, and metabolic indices were determined. The mean initial GH dose was 0.98 mg/d. The dose was gradually lowered, and after 5 yr the mean dose was 0.48 mg/d. The mean IGF-I SD score increased from -1.73 at baseline to 1.66 at study end. A sustained increase in lean body mass and a decrease in body fat were observed. The GH treatment increased total body bone mineral content as well as lumbar (L2-L4) and femur neck bone mineral contents. BMD in lumbar spine (L2-L4) and femur neck were increased and normalized at study end. Total cholesterol and low density lipoprotein cholesterol decreased, and high density lipoprotein cholesterol increased. At 5 yr, serum concentrations of triglycerides and hemoglobin A(1c) were reduced compared with baseline values. The treatment responses in IGF-I SD score, body fat as estimated by four- and five-compartment body composition models, total body protein and nitrogen, and lumbar bone mineral content and BMD were more marked in men than in women. One patient died during the period, four patients discontinued the study due to adverse events, and one dropped out due to lack of compliance. Four patients were lost to follow-up. However, all patients were retained in the statistical analysis according to the intention to treat approach used. In conclusion, 5 yr of GH substitution in GH-deficient adults is safe and well tolerated. The effects on body composition, bone mass, and metabolic indices were sustained. The effects on body composition and low density lipoprotein cholesterol were seen after 1 yr, whereas the effects on bone mass, triglycerides, and hemoglobin A(1c) were first observed after years of treatment.
生长激素替代疗法已在短期试验以及少数受试者数量有限的长期试验中证明了其有效性和安全性。在这项单中心研究中，纳入了118例连续的成年起病的生长激素缺乏患者（70例男性和48例女性；平均年龄49.3岁；范围22 - 74岁），确定了5年生长激素替代治疗对身体成分、骨量和代谢指标的影响。初始生长激素平均剂量为0.98mg/d。剂量逐渐降低，5年后平均剂量为0.48mg/d。平均胰岛素样生长因子-I标准差评分从基线时的-1.73增加到研究结束时的1.66。观察到瘦体重持续增加且体脂减少。生长激素治疗增加了全身骨矿物质含量以及腰椎（L2 - L4）和股骨颈骨矿物质含量。腰椎（L2 - L4）和股骨颈的骨密度增加，并在研究结束时恢复正常。总胆固醇和低密度脂蛋白胆固醇降低，高密度脂蛋白胆固醇增加。在5年时，与基线值相比，甘油三酯和糖化血红蛋白A1c的血清浓度降低。胰岛素样生长因子-I标准差评分、通过四室和五室身体成分模型估计的体脂、全身蛋白质和氮以及腰椎骨矿物质含量和骨密度的治疗反应在男性中比在女性中更明显。在此期间有1例患者死亡，4例患者因不良事件中断研究，1例因依从性差退出。4例患者失访。然而，根据所采用的意向性治疗方法，所有患者均保留在统计分析中。总之，对生长激素缺乏的成年人进行5年的生长激素替代治疗是安全且耐受性良好的。对身体成分、骨量和代谢指标的影响是持续的。对身体成分和低密度脂蛋白胆固醇的影响在1年后出现，而对骨量、甘油三酯和糖化血红蛋白A1c的影响在治疗数年之后才首次观察到。
