NEUROPHYSIOLOGIC DYSFUNCTION, LEAD MOBILIZATION, AND MENOPAUSE

本提案的主要目标是确定未来 城市妇女重复测量的纵向流行病学研究。 1)在绝经期铅是否从骨骼进入血液， 2）铅的量是否存在剂量-反应关系 释放和神经心理功能障碍的指数。 为了验证绝经期铅从骨中动员的假设， 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， 200名居住在纽约市的妇女， 计划进行手术诱导绝经（双侧 卵巢切除术）。 激素替代治疗对铅水平的影响 和神经心理功能也将被评估。 血与骨 将在术前以及术后6个月和18个月时再次获得水平 手术后几个月 将在基线时评价骨密度 术前和18个月访视。 神经心理学评价 将在术前和术后18个月进行功能检查。 铅暴露的指标将包括全血和血浆铅 水平，骨铅浓度测定非侵入性的手段， 109 CdK X射线荧光（XRF）分析。 将通过以下方法测量骨量： 双能X线吸收法（DXA）。 总骨铅含量将是 计算为骨铅浓度和骨矿物质的乘积 内容 全骨切除术前后的差异 铅将提供绝经后总铅暴露估计值， 骨骼来源 亚临床神经心理学效应的测量将包括 计算机和人工神经心理测验 评估一系列的功能包括记忆，认知，心理 能力、注意力、执行功能和情绪。 更年期 将通过绝经指数来评估症状。 观察期间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 特别是神经心理功能的变化 与骨中铅释放总量的关系。 潜在混杂因素 和效果调节剂将在所有分析中进行评估。 这项研究预计将提供重要的见解， 绝经期骨脱矿对血铅和骨铅水平的影响， 骨量和铅水平之间的关系，以及可能的 内源性铅对亚临床发展的贡献 成年女性的神经心理障碍。 它的力量在于 纵向研究设计，其使用最先进的指标体 铅的负担，以及它的就业情况良好的验证，广泛的基础上， 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.