生长激素（GH）替代治疗对心血管危险因素、心脏形态与功能以及动脉粥样硬化是否存在性别相关效应？一项针对严重生长激素缺乏的青年男性和女性进行的为期两年的开放性前瞻性研究结果。
Does a gender-related effect of growth hormone (GH) replacement exist on cardiovascular risk factors, cardiac morphology, and performance and atherosclerosis? Results of a two-year open, prospective study in young adult men and women with severe GH deficiency.
作者信息
Colao Annamaria, Di Somma Carolina, Cuocolo Alberto, Spinelli Letizia, Acampa Wanda, Spiezia Stefano, Rota Francesca, Savanelli Maria Cristina, Lombardi Gaetano
机构信息
Department of Molecular and Clinical Endocrinology and Oncology, "Federico II" University of Naples, via S. Pansini 5, 80131 Naples, Italy.
出版信息
J Clin Endocrinol Metab. 2005 Sep;90(9):5146-55. doi: 10.1210/jc.2005-0597. Epub 2005 Jun 28.
CONTEXT
GH secretion and response to GH replacement are gender-related.
OBJECTIVE
The objective of this study was to investigate the effects of GH deficiency (GHD) and replacement on the cardiovascular system according to gender.
DESIGN
The design was open and prospective.
SETTING
The study was conducted at a university hospital.
SUBJECTS
Subjects included 36 severe adult-onset GHD patients (18 men, 20 women, aged < 45 yr); 36 gender-, age-, and body mass index-matched healthy subjects served as controls.
INTERVENTIONS
Subjects received GH replacement at a median dose of 6.5 microg/kg.d in men and 7.7 microg/kg.d in women for 2 yr.
MAIN OUTCOME MEASURES
Homeostasis model assessment index, total to HDL cholesterol ratio, fibrinogen and C-reactive protein levels, left ventricular mass index, blood pressure, heart rate, diastolic filling, and systolic function at rest and at peak exercise and intima-media thickness (IMT) at common carotid arteries were measured.
RESULTS
Basal prevalence and/or degree of insulin resistance, lipid alterations, compromised cardiac function, and IMT were similar in women and men. Diastolic dysfunction was more prevalent in men (61 vs. 25%, P = 0.036). After GH replacement, IGF-I levels normalized in all patients. Lipid profile, fibrinogen, and C-reactive protein levels normalized in all cases. The total to HDL ratio (P = 0.04) was higher in women than men. The homeostasis model assessment index persisted higher in GHD patients than controls and decreased only in GHD men (P = 0.017). Left ventricular mass index normalized during treatment in both women and men, abnormal diastolic function persisted in three women (P = 0.031), and abnormal systolic performance persisted in six women and one man (P = 0.13). IMT decreased similarly in women and men, persisting higher than in controls. Exercise performance normalized in all.
CONCLUSIONS
Two-year GH replacement has similar beneficial effects on cardiac and exercise performance and atherosclerosis in women and men with severe GHD.
背景
生长激素（GH）分泌及对GH替代治疗的反应存在性别差异。
目的
本研究旨在根据性别探讨生长激素缺乏（GHD）及其替代治疗对心血管系统的影响。
设计
开放性前瞻性研究。
地点
在一家大学医院进行研究。
研究对象
研究对象包括36例严重成年起病的GHD患者（18例男性，20例女性，年龄<45岁）；36例性别、年龄和体重指数匹配的健康受试者作为对照。
干预措施
受试者接受GH替代治疗，男性中位剂量为6.5μg/kg·d，女性为7.7μg/kg·d，持续2年。
主要观察指标
测量稳态模型评估指数、总胆固醇与高密度脂蛋白胆固醇比值、纤维蛋白原和C反应蛋白水平、左心室质量指数、血压、心率、静息和运动峰值时的舒张充盈及收缩功能，以及颈总动脉内膜中层厚度（IMT）。
结果
女性和男性的基础胰岛素抵抗患病率和/或程度、血脂改变、心脏功能受损及IMT相似。男性舒张功能障碍更为常见（61%对25%，P = 0.036）。GH替代治疗后，所有患者的胰岛素样生长因子-I（IGF-I）水平恢复正常。所有病例的血脂谱、纤维蛋白原和C反应蛋白水平均恢复正常。女性的总胆固醇与高密度脂蛋白比值（P = 0.04）高于男性。GHD患者的稳态模型评估指数持续高于对照组，仅GHD男性有所下降（P = 0.017）。治疗期间，女性和男性的左心室质量指数均恢复正常，3例女性舒张功能异常持续存在（P = 0.031），6例女性和1例男性收缩功能异常持续存在（P = 0.13）。女性和男性的IMT均有相似程度下降，但仍高于对照组。所有患者的运动能力均恢复正常。
结论
为期两年的GH替代治疗对严重GHD的女性和男性的心脏功能、运动能力及动脉粥样硬化具有相似的有益作用。
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