Staging Reproductive Aging in Four Cohorts: Issues of Hormone Use Spotting Bias

描述（由申请人提供）：更年期标志着妇女的生物学和健康的关键变化时期。建立生殖老化分期系统将使提供者能够更好地为妇女提供更年期症状和预防性治疗方面的咨询，并使研究人员能够准确地对妇女的生殖状况进行分类。生殖衰老阶段研讨会（Stages of Reproductive Aging Workshop）提出了这样一个分期系统。虽然ESTA的建议是基于正在进行的队列研究的新结果，但不是数据驱动的，并且包括与临床和研究实践的重要偏离。ReSTAGE是四项关于绝经过渡期的大型队列研究（TREMIN，墨尔本妇女中年健康项目，西雅图中年妇女健康研究，全国妇女健康研究）的合作项目。我们的目标是根据月经日历、激素和症状数据，对绝经过渡期的出血标准进行经验性评估，这些标准是ESTA建议的基础。最初的资助只集中在更年期过渡的自然史上。这种竞争性的更新解决了三个关键的方法问题，以指定广泛适用于一个异质性的妇女人口的包容性分期标准。它将扩展分期标准，以包括在中年期间使用激素（HT）的女性，解决与经间期出血/点状出血（1 MB）相关的错误分类，并描述绝经过渡研究中的左截断和左删失偏倚问题。我们的目标首先是开发和比较两种方法来修改绝经过渡期出血标准，以解释妇女使用HT的情况，并评估在四项队列研究中包括HT使用者对绝经过渡期年龄和持续时间估计的影响。其次，由于1 MB使得出血标准的评估变得困难，我们的目标是开发一种算法，用于区分1 MB和月经日历中的月经事件，并评估IMB对四个队列中过渡期的年龄和持续时间的估计的影响。第三，我们的目标是开发可能性的方法，以纠正左删失和左截断偏倚与中年妇女队列研究中的不同年龄的进入标准，并评估这些偏倚对估计年龄和绝经过渡期的影响。这项研究将扩展生殖老化的分期系统，包括HT使用者，并提供关于HT使用者和1 MB女性生殖老化分期标准的明确指导。结果将有助于妇女和提供者有关避孕，对症治疗和预防治疗的临床决策。

DESCRIPTION (provided by applicant): The menopause marks a period of critical change in women's biology and health. Establishing a staging system for reproductive aging would enable providers to better counsel women about menopausal symptoms and preventive therapy and permit researchers to accurately classify women's reproductive status. The Stages of Reproductive Aging Workshop (STRAW) proposed such a staging system. STRAW'S recommendations, although based on emerging results of ongoing cohort studies, were not data driven and included important departures from clinical and research practice. ReSTAGE is a collaboration among four large cohort studies of the menopausal transition (TREMIN, Melbourne Women's Midlife Health Project, Seattle Midlife Women's Health Study, Study of Women's Health Across the Nation). Our goal has been to empirically evaluate bleeding criteria for the menopausal transition that were the basis for STRAW'S recommendations using menstrual calendars, hormones and symptom data. The original grant focused only on the natural history of the menopausal transition. This competitive renewal addresses three methodological issues critical to specifying inclusive staging criteria broadly applicable to a heterogeneous population of women. It will extend staging criteria to include women who use hormones (HT) during the midlife, address misclassification associated with intermenstrual bleeding/spotting (1MB), and characterize the problem of left truncation and left censoring biases in studies of the menopausal transition. We aim first to develop and compare two approaches for modifying bleeding criteria for the menopausal transition to account for the case where women use HT and assess the effect of including HT users on estimates of age and duration of the menopausal transition in the four cohort studies. Second, as 1MB makes assessment of bleeding criteria difficult, we aim to develop an algorithm for distinguishing 1MB from menstrual episodes in menstrual calendars and to assess IMB's impact on estimates of age at and duration of the transition in the four cohorts. Third, we aim to develop likelihood methods to correct for left censoring and left truncation biases associated with the differential age at entry criteria in cohort studies of midlife women and assess the impact of these biases on estimates of age at and duration of the menopausal transition. This research will extend staging systems for reproductive aging to include HT users and provide definitive guidance regarding criteria for staging reproductive aging in HT users and women with 1MB. Results will facilitate clinical decision making for women and providers relevant to contraception, symptomatic treatment and preventive therapy.