FORMS OF GONADOTROPINS AS MARKERS OF MENOPAUSE

随着人类寿命的延长，女性花费三分之一的时间 他们的寿命超过了生育年限。过渡到 更年期与生理风险和心理风险有关 调整。目前正在进行重大研究活动，以 提高对这些变化的理解，但这些努力是 因缺乏诊断工具而受阻 决定一个女人离更年期有多近。如果一项可靠的测试 存在的目的是区分绝经前女性和早期女性 在更年期，新的研究计划将是可能的，因为 更年期的变化可以放在与 更年期过渡。这样的测试也将有助于诊断患者 其症状与目前的FSH水平无关， 没有子宫，因此没有月经来衡量的女性 更年期，并可能作为雌激素替代剂量的指南。 我们提出了一种新的尿液分析方法来 根据排泄物判断女性接近更年期的程度 人促黄体生成素和促卵泡刺激素β亚基的代谢。异二聚体 促性腺激素在尿液中不稳定，但这些代谢物高度 稳定性好，不含任何添加剂，便于储存和冻融。基于 尿代谢物在尿毒症诊断中的应用 人绒毛膜促性腺激素和新发现(在本申请中报告)的代谢产物 我们建议开发检测FSH尿代谢物的工具 并使用这些免疫学工具，以及那些HLH，来测试 假设对FSH排泄代谢产物的测量可能 提供了更好的进入更年期的标志 目前不可靠的血清FSH水平标志物。我们建议 TO：1.FSHβ亚基片段的分离和鉴定 来自绝经后妇女的尿液。2.制定具体的 抗FSH代谢物的单抗及两种部位免疫分析 用于检测尿液中的FSH代谢物。3.测试的适用性 测定促黄体生成素和卵泡刺激素片段作为急性早幼粒细胞白血病发病的标志 更年期和雌激素替代疗法的反应标记物。

With the extension of the human life span, women spend a third of their lives beyond the reproductive years. The transition into menopause is associated with physical risks and psychological adjustments. Major research initiatives are currently under way to improve understanding of these of these changes but these efforts are hampered by the hampered by the lack of diagnostic tools for determining how close a woman is to menopause. If a reliable test existed to differentiate a premenopausal woman from a woman early in menopause, new research initiatives would be posible since menopausal changes could be placed in relation to the stage of the menopusal transition. Such a test would also help diagnose patients whose symptoms are dissociated from current critria as FSH levels, women who have no uterus and thus no menses by which to gauge menopause, and as a possible guide to estrogen replacement dosing. We propose a novel approach of developing urinary assays to determine how close a woman is to menopause based on the excreted metabolities of the beta subunits of hLH and hFSH. Heterodimeric gonadotropins are not stable in urine but these metabolites are highly stable, without any additives, to storage and freeze-thaws. Based on our experiences with the diagnostic utility of urinary metabolites of hCG and new findings (reported in this application) on metabolites of hLH, we propose to develop tools to measure FSH urinary metabolites and use these immunogical tools, along with those hLH, to test the hypothesis that measurement of excreted metabolites of FSH may provide better markers of the entry into menopause than does the current unreliable marker of serum FSH concentration. We propose to: 1. Isolate and characterize the beta subunit fragments of FSH from the urine of postmenopausal women. 2. Develop specific monoclonal antibodies to FSH metabolites and two site immunoassays for measuring the FSH metabolites in urine. 3. Test applicability of measurement of LH and FSH fragments as markers of the onset of menopause and as response markers to estrogen replacement therapy.