NEUROPHYSIOLOGIC DYSFUNCTION, LEAD MOBILIZATION, AND MENOPAUSE

这项提案的主要目标是在未来确定 重复干预的城市妇女纵向流行病学研究。 1)绝经期间铅是否从骨骼进入血液，以及 2)铅量之间是否存在剂量-反应关系 发布神经心理功能障碍指数。 为了验证绝经期间铅从骨骼中转移的假说 这种释放与亚临床神经心理学有关 功能障碍，我们计划评估血液和血浆铅水平，骨铅 浓度，骨密度，血清铁蛋白和激素水平， 标准化问卷数据、更年期症状、情绪和 200名居住在纽约的女性的神经心理功能调查 计划接受手术诱导的更年期(双侧 卵巢切除术)。激素替代治疗对血铅水平的影响 神经心理功能也将得到评估。血与骨 手术前和术后6个月和18个月分别测得血糖值。 手术后几个月。骨密度将在基线时进行评估 术前及术后18个月随访。神经心理学评价 分别于术前和术后18个月进行功能测试。 铅暴露的指标将包括全血和血浆铅。 水平，骨铅浓度的非侵入性测定方法 109CdK X射线荧光(XRF)分析。骨量将通过以下方式测量 双能X射线吸收法(DXA)。总的骨铅含量将是 按骨铅浓度与骨矿物质的乘积计算 内容。全骨切除手术前后的差异 铅将提供绝经后铅暴露总量的估计 骨骼来源。 亚临床神经心理效应的衡量标准将包括这两个方面 计算机管理和手动管理的神经心理测试 评估一系列功能，包括记忆、认知、精神运动 能力、注意力、执行功能和情绪。更年期 症状将通过更年期指数进行评估。 观察期内神经心理功能的变化 将与血液和骨铅水平的变化进行比较。在……里面 具体地说，神经心理功能的变化将与 从骨骼中释放出的铅的总量。潜在的混杂因素 并将在所有分析中评估效果修饰剂。 预计这项研究将为研究 绝经期骨质脱矿对血铅和骨铅水平的影响 骨量与铅水平之间的关系以及可能的 内源性铅在亚临床疾病发展中的作用 成年女性的神经心理障碍。它的力量在于它的 纵向研究设计，它使用了最先进的身体指标 铅负担，以及对经过充分验证、基础广泛和 神经心理功能的客观测量。

The primary objectives of this proposal are to determine in a prospective longitudinal epidemiologic study in urban women with repeated measures. 1) whether lead is mobilized from bone into blood during menopause and whether 2) a dose-response relationship exists between the amount of lead released and indices of neuropsychological dysfunction. To test the hypotheses that lead is mobilized from bone during menopause and that this release is associated with subclinical neuropsychological dysfunction, we plan to assess blood and plasma lead levels, bone lead concentration, bone density, serum ferritin and hormone levels, standardized questionnaire data, menopausal symptoms, mood, and neuropsychological function in 200 women residing in New York City who are scheduled to undergo a surgically induced menopause (bilateral oophorectomy). The effect of hormone replacement therapy on lead levels and neuropsychologic functioning will also be assessed. Blood and bone levels will be obtained preoperatively and again at 6 months and 18 months after surgery. Bone mineral density will be evaluated at baseline preoperatively and the 18 month visit. Evaluation of neuropsychological function will be performed preoperatively and 18 months after surgery. Indicators of lead exposure will include whole blood and plasma lead levels, bone lead concentration determined non-invasively by means of 109CdK X-ray fluorescence (XRF) analysis. Bone mass will be measured by dual energy X-ray absorptiometry (DXA). Total bone lead content will be calculated as the product of bone lead concentration and bone mineral content. The difference between the pre and postoophorectomy total bone lead will provide an estimate of total postmenopausal lead exposure from skeletal sources. Measures of subclinical neuropsychological effects will include both computer-administered and manually-administered neuropsychological tests that assess a range of functions including memory, cognition, psychomotor abilities, attention, executive functioning, and mood. Menopausal symptoms will be evaluated by the menopausal index. Changes in neuropsychological function over the interval of observation will be compared with changes in blood and bone lead levels. In particular, changes in neuropsychological function will be correlated with the total quantity of lead release from bone. Potential confounders and effect modifiers will be assessed in all analysis. This study is expected to provide important insights into the effects of bone demineralization during menopause on blood and bone lead levels, on the relationship between bone mass and lead levels, and on the possible contribution of endogenous lead to the development of subclinical neuropsychological impairment in adult women. Its strength lies in its longitudinal study design, its use of state-of-the-art indicators of body lead burden, and its employment of well validated, broad based, and objective measures of neuropsychological function.