SCREENING FOR GROWTH HORMONE AND SEX STEROID EFFECTS

人类衰老通常伴随着各种生理功能的逐渐衰退，这在某些人中会导致身体损伤，最终可能导致残疾，从而恶化生活质量，限制独立。正常衰老还经常与循环中生长激素(GH)、胰岛素样生长因子-I(IGF-I)和性类固醇激素水平降低有关；肌肉质量和力量减少；总脂肪和腹内脂肪增加。重组人生长激素(RhGH)或性激素治疗可以改善一些老年人的身体成分，但这种激素治疗(单独或联合使用)对各种生理功能的影响仍有待确定。我们假设，与年龄相关的生长激素、胰岛素样生长因子-I和性类固醇激素的减少分别并相互作用地导致老年女性和男性骨骼肌质量和力量减少、体脂增加和有氧能力降低；通过联合激素治疗恢复正常的生长激素、胰岛素样生长因子-I和性类固醇状态将产生相加或协同作用，增加肌肉质量和力量，减少体脂，增加有氧能力。因此，我们现在正在进行一项安慰剂对照的双盲研究，对象是65岁以上、IGF-I和性类固醇水平较低的健康、非卧床、社区居住的女性和男性，以确定单独使用rhGH 6个月、单独使用性类固醇激素(女性使用雌激素/孕激素，男性使用睾丸素)，或者联合使用rhGH和性类固醇可以增加或改善骨骼肌质量、力量和全身蛋白质合成；减少总脂肪和腹内脂肪；改善有氧能力和心血管功能，以及选定的内分泌、代谢、免疫、皮肤和精神行为功能。在本研究的筛查/招募部分，我们通过健康筛查访谈、提供两个小时的研究信息和知情同意、筛查男性血清中的睾酮、IGF-I和PSA来评估感兴趣的志愿者，而女性则通过常规CBC、血液化学、肝肾功能测试、甲状腺功能测试、胆固醇、IGF-I和尿液分析进行筛查。结果进行了评估，符合条件的受试者接受了完整的病史和身体、简易心理检查和运动压力测试。在体检时对男性进行血液检查，以完成评估。如果女性在一年内没有做过乳房X光检查，则安排她们接受检查，并进行妇科评估和子宫内膜活检。这一筛选过程为研究团队提供了有关自愿患者适合性的关键信息，使潜在参与者对研究团队有了个人的熟悉，并对所有人都促进了降低可能风险的努力。生长激素和性激素研究的招募和筛选于1998年6月中旬结束。在最后一年，200多名男子和妇女因健康问题和/或药物使用而被排除在外；10名男子和7名妇女接受了筛查，其中4名男子和5名妇女参加了登记。积极的筛查过程没有导致不良事件，尽管一些人被新发现有与健康有关的问题，被排除在研究之外，并被转介到私人医生进行进一步评估。如果目前的研究揭示了激素替代的有益效果，那么我们计划进行某些有针对性的、更长期的调查，以检查类似的激素治疗与其他干预措施(例如，运动调节)的相互作用，以及它们对选定的老年人群功能状况测量的影响。

Human aging is generally accompanied by a gradual decline in various physiological functions, which in some people results in physical impairments, and ultimately may cause disabilities which worsen the quality of life and limit independence. Normal aging is also frequently associated with reduced circulating levels of growth hormone (GH), insulin-like growth factor-I (IGF-I), and sex steroid hormones; decreased muscle mass and strength; and increased total and intra-abdominal fat. Treatment with recombinant human GH (rhGH) or sex steroids can improve body composition in some older persons, yet the effects of such hormonal treatment (singly or in combination) on various physiological functions remain to be defined. We hypothesize that age-related decreases in GH, IGF-I and sex steroids separately and interactively contribute to diminished skeletal muscle mass and strength, increased body fat, and reduced aerobic capacity in elderly women and men; and that restitution of normal GH, IGF-I and sex steroid status by combined hormone therapy wil exert additive or synergistic effects to increase muscle mass and strength, decrease body fat, and increase aerobic capacity. Thus, we are now conducting a placebo-controlled, double-masked study in a group of healthy, ambulatory, community- dwelling women and men beyond 65 years of age, with low IGF-I and sex steroid levels, to determine whether 6-months of administration of rhGH alone, sex steroid hormones alone (estrogen/progestin in women and testosterone in men), or combined rhGH plus sex steroids will increase or improve skeletal muscle mass, strength, and total body protein synthesis; decrease total and intra-abdominal fat; and improve aerobic capacity and cardiovascular function, as well as selected endocrine, metabolic, immunological, dermatological, and psychobehavioral functions. In the screening/recruitment portion of this study, we have evaluated interested volunteers by way of health screening interviews, providing a two-hour study information and informed consent, screening serum for testosterone, IGF-I, and PSA in men, while women are screened by a routine CBC, blood chemistries, liver and kidney function tests, thyroid function test, cholesterol, IGF-I, and urinalysis. Results were evaluated and eligible subjects underwent a complete history and physical, mini-mental exam and an exercise stress test. Blood work was collected on men at the time of their physical in order to complete their evaluation. Women were scheduled for a mammogram if they had not had one within one year, and gynecological evaluation and endometrial biopsy. This screening process afforded the researcher team key information regarding the suitability of volunteer patients, afforded potential participants personal familiarity with the study team, and, for all, promoted efforts to reduce possible risks. Recruitment and screening for the Growth Hormone and Sex Steroid Study ended in mid-June, 1998. In the final year, more than 200 men and women were excluded due to health problems and/or medication use; 10 men and 7 women were screened of whom 4 men and 5 women were enrolled. There were no adverse events resulting from the active screening process, although a number of individuals were newly found to have health-related issues to exclusion from the study and referral to private physicians for further evaluation. Should the current study reveal beneficial effects of hormone replacement then we plan to conduct certain targeted, longer-term investigations to examine the interactions of similar hormone treatments with other interventions (e.g., exercise conditioning), and their effects on functional status measurements in selected elderly populations.