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: 6121393
• 负责人: MICHELE F BELLANTONI
• 金额: $ 6.52万
• 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: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6121393
• 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. To date, 1092 outpatient visits have been compeleted. We have performed preliminary analyses of longitudinal data of bone mineral density (BMD) at the lumbar spine and hip. We found that in women who remained premenopausal, without elevations in plasma FSH levels measured during the midfollicular phase of the menstrual cycle, the group has a significant increase in BMD in the spine (1.7+/- 0.7%, *p<.05 vs baseline), while the group who became perimenopausal with plasma FSH >30mU/mL had a significant decrease (-2.7+/- 1.1%, p<.05 vs baseline). The two groups were significantly different in their rates of change in BMD (p<.002). Both the premenopausal women and the perimenopausal women 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 the premeonpausal and perimenopausal women 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. The preliminary data also suggest that the serial changes in biochemical markers of bone turnover correlate with changes in bone density. Body composition is measured by DEXA and anthropometrics. 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 perimenopausal 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 >+/- 30mU/mL. Of the 15 women who have compeleted the first of three pairs of overnight vists for study of growth hormone by frequent blood sampling, two have begun the menopausal transition based on elevation of plasma FSH level and irregularity of menses, and one has been two years without menstrual periods. These three women have completed the second set of overnight visits, and the postmenopausal woman has compeletd a final overnight visit. 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. 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有关，这可能会加速骨质疏松症和心血管疾病的发展。这项纵向研究的假设是，更年期过渡与月经停止前的变化有关，如下所述：1)夜间生长激素分泌谱的减少，与卵巢性激素的减少结合，导致身体成分的变化，特别是骨量的减少和脂肪量的增加；2)在血液和尿液中测量的骨转换生化标志物增加，预测骨量减少；3)体脂量增加和脂肪分布到腹腔内区域，这与脂质和脂蛋白谱的不利变化有关。这些女性是巴尔的摩老龄化纵向研究（BLSA）的110名健康、不吸烟的女性参与者，年龄在45-55岁之间，在登记时每月都有月经。他们每季度接受GCRC门诊检查，直到月经停止2年。检查内容包括更年期症状问卷、内分泌和血脂、人体测量、双能x线吸收测量（DEXA）、骨骼生化和饮食评估。迄今为止，已完成1092次门诊。我们对腰椎和髋部骨密度（BMD）的纵向数据进行了初步分析。我们发现，在绝经前的女性中，在月经周期中卵泡期测量的血浆FSH水平没有升高，该组脊柱骨密度显著增加（1.7+/- 0.7%，与基线相比，*p< 0.05），而围绝经期血浆FSH bbb30mu /mL的组骨密度显著降低（-2.7+/- 1.1%，与基线相比，p< 0.05）。两组骨密度变化率差异有统计学意义（p< 0.002）。绝经前妇女和围绝经期妇女在股骨颈（分别为-4.3+/- 1.2%,-6.5+/- 1.4%）和股骨粗隆区（-4.0+/- 1.1%,-6.9+/- 1.6%，与基线相比p< 0.002）骨质明显丢失。绝经前和围绝经期妇女在任何髋关节部位没有显著差异。这些数据揭示了围绝经期过渡期间预期的加速椎体骨质流失，而在绝经前和围绝经期妇女中，髋部骨密度的类似损失似乎不能通过生殖激素环境来区分。初步数据还表明，骨转换生化指标的一系列变化与骨密度的变化相关。身体成分由DEXA和人体测量学测量。通过方差分析比较绝经前和围绝经期组在基线时测量的身体组成参数（体重、身体质量指数（BMI）、腰围、腰臀比（WHR）、DEXA扫描的总脂肪量或脂肪百分比）均无差异。与绝经前组相比，围绝经期妇女的脂肪估计（DEXA计算的总脂肪和百分比脂肪，比较绝经前和围绝经期δ，方差分析得出的p<0.03）、脂肪分布（腰围和腰宽比，p<0.05）和血清瘦素水平（p<0.03）显著增加，但体重或BMI没有增加。这些数据表明，根据血清FSH水平>+/- 30mU/mL的定义，身体成分的变化可能发生在更年期过渡的早期。15名妇女通过频繁的血液取样完成了三对夜间生长激素研究的第一次访问，其中两人已经开始了基于血浆FSH水平升高和月经不规律的更年期过渡，还有一人已经两年没有月经了。这三名妇女已经完成了第二组夜间访问，绝经后妇女已经完成了最后一次夜间访问。当6名妇女的血浆FSH水平大于30 mU/mL时，将对纵向数据进行初步分析。未来的计划包括继续描述绝经期过渡的生物学前因和后遗症。将研究骨骼和心血管疾病风险的生化标志物，以便针对最有可能受益的妇女进行激素替代疗法。此外，对BLSA队列的持续纵向评估超出了本提案所提供的范围，将允许评估绝经过渡对妇女年龄相关疾病的影响。