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对绝经后女性进行为期一年的胰岛素样生长因子I治疗,不会影响其骨密度、身体成分或心理指标。

One year of insulin-like growth factor I treatment does not affect bone density, body composition, or psychological measures in postmenopausal women.

作者信息

Friedlander A L, Butterfield G E, Moynihan S, Grillo J, Pollack M, Holloway L, Friedman L, Yesavage J, Matthias D, Lee S, Marcus R, Hoffman A R

机构信息

Medical Service, Geriatric Research Education Clinical Center, Palo Alto Veterans Administration Health Care System, California 94304, USA.

出版信息

J Clin Endocrinol Metab. 2001 Apr;86(4):1496-503. doi: 10.1210/jcem.86.4.7377.

Abstract

The activity of the hypothalamic-GH-insulin-like growth factor I (hypothalamic-GH-IGF-I) axis declines with age, and some of the catabolic changes of aging have been attributed to the somatopause. The purpose of this investigation was to determine the impact of 1 yr of IGF-I hormone replacement therapy on body composition, bone density, and psychological parameters in healthy, nonobese, postmenopausal women over 60 yr of age. Subjects (n = 16, 70.6 +/- 2.0 yr, 71.8 +/- 2.8 kg) were randomly assigned to either the self-injection IGF-I (15 microg/kg twice daily) or placebo group and were studied at baseline, at 6 months, and at 1 yr of treatment. There were no significant differences between the IGF-I and placebo groups in any of the measured variables at baseline. Fasting blood IGF-I levels were significantly elevated above baseline values (65.6 +/- 11.9 ng/mL) at 6 months (330.0 +/- 52.8) and 12 months (297.7 +/- 40.8) in the IGF-I treated group but did not change in the placebo subjects. Circulating levels of IGF-binding protein-1 and -3 were unaffected by the IGF-I treatment. Bone mineral density of the forearm, lumbar spine, hip, and whole body [as measured by dual-energy x-ray absorptiometry (DXA)] did not change in either group. Similarly, there was no difference in DXA-measured lean mass, fat mass, or percent body fat throughout the treatment intervention. Muscle strength values (grip, bench press, leg press), blood lipid parameters (cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides), and measures of postmeal glucose disposal were not altered by IGF-I treatment, although postmeal insulin levels were lower in the IGF-I subjects at 12 months. IGF-I did not affect bone turnover markers (osteocalcin and type I collagen N-teleopeptide), but subjects who were taking estrogen had significantly lower turnover markers than subjects who were not on estrogen at baseline, 6 months, and 12 months. Finally, the psychological measures of mood and memory were also not altered by the intervention. Despite the initial intent to recruit additional subjects, the study was discontinued after 16 subjects completed the protocol, because the preliminary analyses above indicated that no changes were occurring in any outcome variables, regardless of treatment regimen. Therefore, we conclude that 1 yr of IGF-I treatment, at a dose sufficient to elevate circulating IGF-I to young normal values, is not an effective means to alter body composition or blood parameters nor improve bone density, strength, mood, or memory in older women.

摘要

下丘脑 - 生长激素 - 胰岛素样生长因子I(下丘脑 - 生长激素 - 胰岛素样生长因子I)轴的活性随年龄增长而下降,衰老过程中的一些分解代谢变化被归因于生长激素缺乏症。本研究的目的是确定1年的胰岛素样生长因子I激素替代疗法对60岁以上健康、非肥胖绝经后女性的身体成分、骨密度和心理参数的影响。受试者(n = 16,年龄70.6±2.0岁,体重71.8±2.8 kg)被随机分为自我注射胰岛素样生长因子I组(每日两次,每次15μg/kg)或安慰剂组,并在基线、治疗6个月和1年时进行研究。在基线时,胰岛素样生长因子I组和安慰剂组在任何测量变量上均无显著差异。在胰岛素样生长因子I治疗组中,空腹血胰岛素样生长因子I水平在6个月(330.0±52.8)和12个月(297.7±40.8)时显著高于基线值(65.6±11.9 ng/mL),而安慰剂组受试者的该水平未发生变化。胰岛素样生长因子结合蛋白 -1和 -3的循环水平不受胰岛素样生长因子I治疗的影响。两组中,前臂、腰椎、髋部和全身的骨矿物质密度[通过双能X线吸收法(DXA)测量]均未改变。同样,在整个治疗干预过程中,通过DXA测量的瘦体重、脂肪量或体脂百分比也没有差异。尽管在12个月时胰岛素样生长因子I组受试者的餐后胰岛素水平较低,但胰岛素样生长因子I治疗并未改变肌肉力量值(握力、卧推、腿举)、血脂参数(胆固醇、高密度脂蛋白、低密度脂蛋白、甘油三酯)以及餐后葡萄糖处置指标。胰岛素样生长因子I不影响骨转换标志物(骨钙素和I型胶原N - 端肽),但在基线、6个月和12个月时,服用雌激素的受试者的转换标志物显著低于未服用雌激素的受试者。最后,干预也未改变情绪和记忆的心理指标。尽管最初打算招募更多受试者,但在16名受试者完成方案后,该研究停止,因为上述初步分析表明,无论治疗方案如何,任何结局变量均未发生变化。因此,我们得出结论,1年的胰岛素样生长因子I治疗,剂量足以将循环胰岛素样生长因子I水平提高到年轻正常水平,并非改变老年女性身体成分或血液参数、改善骨密度、力量、情绪或记忆的有效方法。

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