BALTIMORE LONGITUDINAL STUDY OF AGING (BLSA)--PERIMENOPAUSAL INITIATIVE

巴尔的摩老龄化纵向研究 (BLSA)——围绝经期倡议

• 批准号: 6281933
• 负责人: MICHELE F BELLANTONI
• 金额: $ 5.69万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-10 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6281933
• 关键词: aging; blood chemistry; body composition; bone density; clinical research; female; hormone metabolism; human subject; longitudinal human study; menopause; osteoporosis; photon absorptiometry; sex hormones; somatotropin; women's health

Cross-sectional studies suggest that the menopause is associated with changes in endocrine-metabolic function and body composition that may accelerate the development of osteoporosis and cardiovascular disease. The hypotheses of this longitudinal study are that the menopausal transition is associated with change before the cessation of menses as described: 1) decreases in nocturnal secretory profile of growth hormone, that in combination with the decreases in ovarian sex hormones, contribute to changes in body composition, specifically decreases in bone mass and increases in fat mass, 2) increases in biochemical markers of bone turnover that are measured in blood and urine that predict decreases in bone mass, and 3) increases in body fat mass and fat distribution to the intra-abdominal area that are associated with adverse changes in lipid and lipoprotein profiles. The women are 110 healthy, nonsmoking female participants of the Baltimore Longitudinal Study of Aging (BLSA), ages 45-55 years who are experiencing monthly menses at enrollment. They receive quarterly GCRC outpatient visits until menses have ceased for 2 years. The visits include a menopausal symptom questionnaire, endocrine and blood lipid profiles, anthropometry, dual energy x-ray absorptiometry (DEXA), bone biochemistries, and dietary assessments. As of November 30, 1997, 104 women have completed 956 outpatient visits. We have performed preliminary analyses of longitudinal data of bone mineral density (BMD) at the lumbar spine and hip. As of April 1997, 27 women who remain premenopausal (PRE), defined as midfollicular phase plasma FSH levels all <30mU/ml, were followed >1 year (mean 2.5 years), and had a mean age of 48.7 +/-0.3 years. They were compared to 21 women classified as perimenopausal (PERI), defined as at least one plasma FSH >30mU/ml with at least one visit >0.3 years before (mean 0.84 years) and at least one visit >1 year after (mean 1.90 years) the initial high FSH value. They were followed an average of 2.7 years, with a mean age of 50.3+/- 0.6 years. The PRE group had a significant increase in BMD in the spine (1.7+/- 0.7%, *p<.05 vs baseline), while the PERI group had a sifnificant decrease (-2.7+/- 1.1%, p<.05 vs baseline), and was significantly different than the PRE group (p<.002). Both the PRE and the PERI groups were significantly losing bone at the femoral neck (-4.3+/- 1.2%, -6.5+/- 1.4% respectively) and trochanteric region (-4.0+/- 1.1%, -6.9+/- 1.6%, p<.002 vs baseline). There was no significant difference between PRE and PERI in any hip site. These data reveal the expected accelerated vertebral bone loss during the perimenopausal transition, whereas the similar losses of hip BMD in pre- and perimenopausal women appear not to be distinguishable by the reproductive hormone milieu. Data analyses are underway to determine if serial changes in biochemical markers of bone turnover correlate with changes in bone density. Body composition is measured by DEXA and anthropometrics. As of April 1997, complete body composition data are available for 21 women who remain premenopausal and 24 who are classified as perimenopausal, as defined above. None of the parameters of body composition measured (weight, body mass index, (BMI), waist circumference, waist-hip ratio (WHR), total fat mass by DEXA scan, or % fat) differed by ANOVA comparing premenopausal and perimenoapusal groups at baseline. Perimenopausal women, in contrast to the premenopausal group, exhibit significant increases in the estimates of fatness (total fat and % fat by DEXA, p<0.03 by ANOVA comparing premenopausal and perimenopausal deltas), in fat distribution (waist circumference and WHR, p<0.05), and in serum leptin levels (p<0.03), but not in weight or BMI. These data suggest that changes in body composition may occur early in the menopausal transition as defined by a serum FSH level >/- 30 mU/mL. As of November 30, 1997, 14 premenopausal women have compeletd the first of three pairs of overnight visits for study of growth hormone by frequent blood sampling. Two of these 14 women have begun the menopausal transition based on elevation of plasma FSH level and irregularity of menses and have completed the second set of overnight visits. A preliminary analysis of the longitudinal data will be performed when plasma FSH levels are greater than 30 mU/mL in 6 of the women. In January 1998, we recrutied an additional premenopausal woman for the overnight visits, thus completing the study cohort of 15 women. Future plans include the continued characterization of the biological antecedents and sequelae of the menopausal transition. Biochemical markers of bone and cardiovascular disease risk will be studied so as to target hormone replacement therapy to those women who are most likely to benefit. Moreover, the continued longitudinal assessment of the BLSA cohort beyond that provided in this proposal will permit an evaluation of the effects of the menopausal transition on age-related disease in women.

横断面研究表明，更年期与 内分泌代谢功能和身体成分的变化， 加速骨质疏松和心血管疾病的发展。的 这项纵向研究的假设是， 与月经停止前的变化有关，如所述：1） 生长激素的夜间分泌减少， 结合卵巢性激素的减少，有助于 身体组成的变化，特别是骨量减少， 脂肪量增加，2）骨生化标志物增加 在血液和尿液中测量的周转率， 骨量，和3）增加体脂肪量和脂肪分布到 腹腔内区域与脂质的不利变化相关， 脂蛋白谱。这些妇女是110名健康、不吸烟的女性 巴尔的摩老龄化纵向研究（BLSA）的参与者，年龄 45-55岁，入组时每月月经。他们 每季度接受GCRC门诊访视，直至月经停止2 年访问包括更年期症状问卷，内分泌 和血脂谱，人体测量，双能X线吸收测定法 （DEXA）、骨生物化学和膳食评估。 截至1997年11月30日，104名妇女完成了956次门诊。 我们对骨的纵向数据进行了初步分析， 腰椎和髋部的矿物质密度（BMD）。截至1997年4月，27 处于绝经前（PRE）的女性，定义为卵泡中期 血浆FSH水平均<30 mU/ml，随访时间>1年（平均2.5年）， 平均年龄为48.7 ± 0.3岁。他们与21名女性进行了比较 分类为围绝经期（PERI），定义为至少一种血浆FSH > 30 mU/ml，至少有一次访视>0.3年（平均0.84年）， 初始高FSH后>1年（平均1.90年）至少有一次访视 值他们平均随访2.7年，平均年龄为 50.3+/- 0.6年。 PRE组脊柱BMD显著增加（1.7+/-0.7%， *p<0.05 vs基线），而PERI组显著降低 (-2.7+/-1.1%，p<0.05 vs基线），并且与 PRE组（p<0.002）。PRE和PERI组均为 股骨颈明显骨质丢失（-4.3+/-1.2%，-6.5+/- 1.4% 和转子区（-4.0+/-1.1%，-6.9+/-1.6%，p<0.002 相对于基线）。PRE和PERI之间在 任何髋关节部位。这些数据揭示了预期的加速脊椎骨 在围月过渡期的损失，而类似的损失， 绝经前和围绝经期妇女髋部BMD似乎无法区分 生殖激素环境的影响。数据分析正在进行中， 确定骨转换生化标志物的系列变化 与骨密度的变化有关。 身体成分通过DEXA和人体测量学测量。截至四月 1997年，21名妇女的完整身体组成数据可用， 绝经前和24名被归类为围绝经期，如定义 以上未测量任何身体组成参数（体重、身体 体重指数（BMI）、腰围、腰臀比（WHR）、总脂肪 通过方差分析比较绝经前和绝经后妇女， 基线时的月经周期组。围绝经期妇女，与 绝经前组，表现出显著增加的估计， 肥胖（DEXA测定的总脂肪和%脂肪，ANOVA测定的p<0.03， 绝经前和围绝经期三角洲），脂肪分布（腰部 围度和腰臀比，p<0.05），血清瘦素水平（p<0.03），但 而不是体重或BMI。这些数据表明身体成分的变化 可能发生在绝经过渡早期，如血清FSH所定义 水平>/- 30 mU/mL。 截至1997年11月30日，14名绝经前妇女完成了第一次 三对过夜访问的研究生长激素的频繁 血样采集这14名妇女中有两名已经开始更年期过渡 基于血浆FSH水平升高和月经不规则， 完成了第二次夜间访问。的初步分析 当血浆FSH水平高于 其中6名女性的血细胞浓度超过30 mU/mL。1998年1月，我们招募了一名 额外的绝经前女性进行过夜访视，从而完成 15名女性的研究队列。 未来的计划包括继续表征生物 绝经过渡期的前因和后遗症。生化标志物 骨和心血管疾病的风险将进行研究， 激素替代疗法对那些最有可能受益的妇女。 此外，对BLSA队列的持续纵向评估 本提案中规定的内容将允许评估 绝经过渡期对女性年龄相关疾病的影响。