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

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可能 加快发展骨质疏松症和心血管疾病。这个 这项纵向研究的假设是更年期转变 与月经停止前的变化有关，如下所述：1) 夜间生长激素分泌减少，即 再加上卵巢性激素的减少，有助于 身体成分的变化，特别是骨量的减少和 脂肪质量增加，2)骨生化标记物增加 以血液和尿液衡量的周转率，预测 骨量，以及3)增加身体脂肪质量和脂肪分布到 腹内区域与血脂和营养不良变化有关 脂蛋白图谱。这些女性是110名健康的、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，注册时每月有月经。他们 每季度接受GCRC门诊就诊，直到月经停止2次 好几年了。这些访问包括更年期症状问卷、内分泌 和血脂，人体测量，双能x射线吸收测量仪 (地塞米松)、骨生化和膳食评估。 截至1997年11月30日，104名妇女完成了956次门诊。 我们对骨骼的纵向数据进行了初步分析。 腰椎和臀部的骨密度(BMD)。截至1997年4月，27 绝经前(Pre)妇女，定义为卵泡中期 血浆FSH水平均为30mU/ml，随访1年(平均2.5年)， 平均年龄48.7±0.3岁。她们与21名女性进行了比较 被归类为围绝经期(Peri)，定义为至少一种血浆FSH -gt；30mU/ml，0.3年前至少一次(平均0.84年)和 至少一次FSH过高后一年(平均1.90年)就诊 价值。他们的平均跟踪时间为2.7年，平均年龄为 50.3+/-0.6年。 Pre组脊柱骨密度显著增加(1.7+/-0.7%， *P&lt；.05与基线相比)，而Peri组显著下降 (-2.7+/-1.1%，与基线相比p&lt；0.05)，与 Pre集团(P&lt；.002)。Pre和Peri组都是 股骨颈显著骨质丢失(-4.3+/-1.2%，-6.5+/-1.4% 粗隆区(-4.0+/-1.1%，-6.9+/-1.6%，p&lt；0.002 VS基线)。Pre和PERI之间无显著差异。 任何臀部部位。这些数据揭示了预期的椎骨加速 在围绝经期过渡期间的损失，而类似的损失 绝经前和围绝经期妇女的髋部骨密度似乎无法区分 由生殖荷尔蒙环境决定。数据分析正在进行中，以 确定骨转换生化标记物的系列变化 与骨密度的变化有关。 身体成分是由DEXA和人体测量学测量的。截至4月 1997年，21名留下来的女性有完整的身体成分数据 绝经前24人，定义为围绝经期 上面。没有测量的身体成分参数(体重、身体 体重指数(BMI)、腰围、腰臀比(WHR)、总脂肪 经方差分析比较绝经前和绝经前的质量 基线为围绝经组。围绝经期妇女，与 绝经前组，表现出显著增加的估计 肥胖度(DEXA的总脂肪和脂肪百分比，用方差分析比较0.03 绝经前和围绝经期增量)，脂肪分布(腰围 周长和腰臀比(p&lt；0.05)，以及血清瘦素水平(p&lt；0.03)，但 不是体重或体重指数。这些数据表明，身体成分的变化 可能发生在绝经期的早期，根据血清FSH的定义 水平/-30亩/毫升。 截至1997年11月30日，已有14名绝经前妇女完成了第一个 三对研究生长激素的过夜探访 采血。这14名妇女中有两名已进入绝经期 根据血浆FSH水平升高和月经不规律 完成了第二套过夜访问。浅谈我国农村社会保障体系建设 当血浆FSH水平较高时，将进行纵向数据 有6名妇女的血药浓度超过30 mU/m L。1998年1月，我们招募了一名 额外为绝经前妇女过夜就诊，从而完成 这项由15名女性参与的研究队列。 未来的计划包括继续表征生物 绝经过渡期的前驱因素和后遗症。生化标记物 将研究骨骼和心血管疾病的风险，以便针对 激素替代疗法对那些最有可能受益的女性。 此外，对BLSA队列的持续纵向评估 本提案中规定的将允许对以下方面的影响进行评估 绝经过渡期对女性年龄相关性疾病的影响。

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.