Physiologic effects of androgen and estrogen deficiency in young and old men

雄激素和雌激素缺乏对年轻和老年男性的生理影响

基本信息

批准号：
7907613
负责人：
JOEL S FINKELSTEIN
金额：
$ 62.46万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-15 至 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7907613
关键词：
Adult Affect Age Aging Agonist Androgens Aromatase Inhibitors Biochemical Markers Biological Assay Body Composition Body fat Bone Density Bone Development Bone Resorption Castration Chronic Disease Clinical Clinical Trials Data Decreased Libido Detection Development Disease Doctor of Medicine Dose Dual-Energy X-Ray Absorptiometry Epidemiology Estradiol Estrogens Fatty acid glycerol esters Future Gel Goals Gonadal Steroid Hormones Gonadotropin Hormone Releasing Hormone Hematocrit procedure Homeostasis Hypogonadism Libido Lipids Lipoproteins Measures Monitor Muscle Osteoblasts Osteoporosis Patients Peripheral Physical activity Physiological Pituitary Gland Play Production Quality of life Randomized Recruitment Activity Research Personnel Risk Role Serum Sex Functioning Symptoms Syndrome Testicular Diseases Testosterone Tissues age effect analog bone loss bone metabolism bone turnover falls hormone deficiency male men men&apos s group muscle strength older men prepuberty prevent programs research study response skeletal virtual wasting young adult

项目摘要

DESCRIPTION (provided by applicant): The role of gonadal steroid deficiency in many of the physiologic changes of aging in men remains unclear. Serum testosterone (T) levels decline as men age and are below the normal adult male range in 20% of men over age 60. Many of the changes that accompany aging, including bone loss, muscle wasting, fat accumulation, decreased strength, and decreased sexual function may be related to the gradual decline in serum T levels with age. Thus, many millions of men may be at risk for consequences of the normal decline in sex steroids that occurs with aging. The degree of gonadal steroid deficiency at which these undesirable changes begins is unknown, however. Thus we do not know which men are at risk for these consequences of aging, or which men might benefit from T administration. The over-arching goals of the study are 1) to determine the dose-response relationships between T and bone turnover, body composition, and other factors in young and old men, 2) to determine whether inhibition of estrogen production alters these dose-response relationships, and 3) to determine whether these relationships change with aging. To accomplish these aims we will recruit 3 groups of men (ages 20-50 in Aim 1 and 2 or > 60 in Aim 3). Men will be treated with a GnRH agonist (to suppress endogenous T and E2 production) and: 1) various doses of a T gel alone (to create serum T levels that range from prepubertal to high-normal) for 16 weeks (Aims 1 and 3) or 2) various doses of a T gel plus a potent aromatase inhibitor (to create a similar range of T levels with very low Ej levels) for 16 weeks (Aim 2). Changes in bone resorption markers and body composition (by DXA and CT) will be the key end points. Changes in strength, muscle size, BMD, sexual function, lipids, PSA, hematocrit, and symptoms will also be assessed. These studies will delineate the degree to which T levels must fall before young and old men are at risk for undesirable physiologic changes and the minimum dose of T gel needed to prevent those changes. By comparing dose-response relationships from aims 1 and 2 or 1 and 3, these studies will demonstrate the extent to which T dose-response relationships are modified by aromatization to estrogens and by aging. These studies will provide fundamental physiologic information related to effects of gonadal steroids in men. Moreover, results from these studies will help define the syndrome of male hypogonadism, assist clinicians in deciding when to treat young and old men with testosterone, and provide essential information for the rational selection of men for future clinical trials of androgen replacement in aging men

描述（由申请人提供）：性腺类固醇缺乏在男性衰老的许多生理变化中的作用尚不清楚。血清睾丸激素（T）水平随着男性年龄的年龄而下降，在60岁以上的男性中的成年男性范围低于正常的成年男性范围。伴随衰老的许多变化，包括骨质流失，肌肉浪费，脂肪积累，降低强度和性功能降低可能与年龄伴随年龄的血清T水平逐渐下降有关。因此，数百万男性可能有可能导致衰老发生性类固醇正常下降的后果。但是，这些不良变化开始的性腺类固醇缺乏程度尚不清楚。因此，我们不知道哪些男人有衰老后果的风险，或者哪些男人可能会受益于T管理。研究的总体目标是1）确定T和骨转换，身体组成和其他年轻人中其他因素之间的剂量反应关系，2）确定雌激素产生的抑制是否会改变这些剂量反应关系，以及3）是否会随着年龄的变化而确定这些关系是否会改变。为了实现这些目标，我们将招募3组男性（AIM 3中的AIM 1和2或> 60岁的20-50岁）。男性将接受GNRH激动剂（以抑制内源性T和E2的产生）和：）：1）单独使用各种剂量的T凝胶（创建血清T水平，从青春期前到高正常的水平范围为16周（目标1和2）或2个或2个剂量的剂量，以使T凝胶加上有效的芳香族酶降低范围（目的是非常低的水平）（目的是非常低的范围）。骨吸收标记和身体成分的变化（由DXA和CT）将是关键终点。还将评估强度，肌肉大小，BMD，性功能，脂质，PSA，血细胞比容和症状的变化。这些研究将描述在年轻人和老年男性面临不良生理变化的风险和防止这些变化所需的T凝胶的最低剂量之前必须降低T水平的程度。通过比较目标1和2或1和3的剂量反应关系，这些研究将证明T剂量反应关系通过芳香化与雌激素和衰老来改变了T剂量反应关系。这些研究将提供与性腺类固醇对男性作用有关的基本生理信息。此外，这些研究的结果将有助于定义雄性性疾病的综合征，协助临床医生决定何时治疗睾丸激素的年轻人和老年男性，并为男性的合理选择提供必要的信息，以供未来的雄激素替代者临床试验