Span J P, Pieters G F, Sweep F G, Hermus A R, Smals A G
Department of Internal Medicine, University Medical Centre Nijmegen, Geert Grooteplein 8, The Netherlands.
J Clin Endocrinol Metab. 2001 Sep;86(9):4161-5. doi: 10.1210/jcem.86.9.7815.
In GH-deficient adults, rhGH has pronounced effects on total body water, fat free mass, and fat mass. Recently, we observed a gender difference in IGF-I responsivity to rhGH that was sex steroid dependent. The aim of the present study was to assess the effect of rhGH therapy on body composition parameters with due attention to the gender differences in biological responsiveness to rhGH. Forty-four women [36.9 +/- 11.9 yr (mean +/- SD)] and 33 men (37.2 +/- 13.8 yr) with GH deficiency were studied every 6 months during 2 yr. The treatment goal was to achieve IGF-I levels within the age-adjusted normal range. Total body water, fat free mass, and fat mass were measured by bioimpedantiometry. To reach the treatment goal, the daily rhGH dose (IU/kg/d) had to be significantly higher in women than in men at all time intervals. During rhGH therapy, total body water and fat free mass increased significantly in both men and women (P < or = 0.01 by ANOVA), but changes were more pronounced in men. Fat mass decreased during rhGH treatment and reached its nadir at 6 months, which was more pronounced in men than in women (P = 0.02 by ANOVA). After the initial decrease, fat mass increased again and reached baseline values after 2 yr of treatment. In both men and women, the total body water and fat free mass increases were closely related to the IGF-I increments (P < 0.001 by Pearson's correlation test). The decrease in fat mass correlated significantly with the increase in IGF-I in men (r = -0.89, P < 0.001), not in women. Confirming our earlier data, IGF-I responsivity to rhGH was significantly higher in men than in women at all time intervals (P < 0.01 by ANOVA). Total body water and fat free mass responsivities were also higher in men than in women (P < 0.01 by ANOVA). In conclusion, gender differences in IGF-I responsivities to rhGH are accompanied by gender differences in the extent of body composition changes to rhGH. Probably because of these gender differences in IGF-I responsivity, the increases of total body water and fat free mass to rhGH replacement were greater in men than in women. Remarkably, however, in men, only total body water and fat free mass responses relative to changes in IGF-I increased during the 2 yr of rhGH therapy (P = 0.02 and 0.01, respectively, by ANOVA). In our opinion, this phenomenon might be explained by the increasing target organ sensitivity to IGF-I over time.
在生长激素缺乏的成年人中，重组人生长激素（rhGH）对总体水、去脂体重和脂肪量有显著影响。最近，我们观察到胰岛素样生长因子-I（IGF-I）对rhGH的反应存在性别差异，且这种差异依赖于性类固醇。本研究的目的是评估rhGH治疗对身体成分参数的影响，并充分关注rhGH生物学反应中的性别差异。44名患有生长激素缺乏的女性[36.9±11.9岁（平均值±标准差）]和33名男性（37.2±13.8岁）在2年期间每6个月接受一次研究。治疗目标是使IGF-I水平达到年龄校正后的正常范围。通过生物电阻抗分析法测量总体水、去脂体重和脂肪量。为了达到治疗目标，在所有时间间隔内，女性的每日rhGH剂量（国际单位/千克/天）都必须显著高于男性。在rhGH治疗期间，男性和女性的总体水和去脂体重均显著增加（方差分析，P≤0.01），但男性的变化更为明显。脂肪量在rhGH治疗期间减少，并在6个月时达到最低点，男性比女性更明显（方差分析，P = 0.02）。在最初下降之后，脂肪量再次增加，并在治疗2年后达到基线值。在男性和女性中，总体水和去脂体重的增加与IGF-I的增加密切相关（Pearson相关检验，P < 0.001）。男性脂肪量的减少与IGF-I的增加显著相关（r = -0.89，P < 0.001），而女性则不然。与我们早期的数据一致，在所有时间间隔内，男性对rhGH的IGF-I反应均显著高于女性（方差分析，P < 0.01）。男性的总体水和去脂体重反应也高于女性（方差分析，P < 0.01）。总之，IGF-I对rhGH反应的性别差异伴随着rhGH治疗后身体成分变化程度的性别差异。可能由于IGF-I反应的这些性别差异，rhGH替代治疗后男性总体水和去脂体重的增加大于女性。然而，值得注意的是，在男性中，在rhGH治疗的2年期间，相对于IGF-I变化的总体水和去脂体重反应仅增加（方差分析，分别为P = 0.02和0.01）。我们认为，这种现象可能是由于随着时间推移靶器官对IGF-I的敏感性增加所致。
