A Secular Change in Menstrual Characteristicis of Adult and Midlife Women?

描述（由申请人提供）：月经初潮年龄的长期下降已被充分证明，一些研究表明绝经年龄的长期增加。月经初潮或绝经年龄的变化具有科学意义，因为它们的时间与妇女的生育能力、慢性病风险和死亡率有关。一个同样重要，但很少涉及的问题是，是否长期的变化发生在月经功能的主要生殖年或绝经过渡期。成年女性的月经特征是卵巢功能的重要标志，并与生育能力、绝经年龄和女性慢性疾病的长期风险相关。考虑到影响月经功能的危险因素的长期变化，包括体型、吸烟、产次和激素使用，评估它们对月经功能的影响是必要的。历史性的TREMIN数据集为解决美国女性月经特征长期变化的问题提供了一个独特的机会。它是世界上唯一一个具有前瞻性记录的月经周期信息的数据集，这些信息来自于从可比参考人群中抽样的两代不同女性，并与生殖、人体测量和生活方式特征相关。就读于明尼苏达大学的学生分别于1936-39年（队列1）和1961-64年（队列II）入学。我们建议分析1151名队列I妇女和905名队列II妇女参与5至35年的前瞻性记录的月经日历和健康记录数据。我们的目标是评估成年女性的月经模式或绝经过渡期的时间是否发生了长期变化，如果是这样，这些差异是否可以通过胎次、体重指数、吸烟或激素使用的长期差异来解释。我们将使用线性混合模型和边际模型估计整个生命周期的月经特征，并使用广义估计方程分别对月经周期长度与年龄的平均值、方差和相关性进行建模。我们将使用考克斯比例风险和变系数考克斯模型沿着以及均值和方差的变点模型来估计队列对绝经过渡开始时的年龄和过渡持续时间的影响。我们提出了多重插补技术来解释间歇性缺失数据和解决激素使用掩盖生殖老化时间的新方法。对这些真正独特的数据的分析将对我们理解整个生殖生命中月经特征的长期变化的本质做出重大贡献。了解生育高峰期月经功能受人口风险因素长期变化影响的程度，将使我们能够预测这种变化对生育力、月经发病率和生殖老化的潜在影响。最终，监测年轻妇女的月经特征可能有助于预测与年龄相关的生育动力学变化、绝经过渡期的时间以及与生殖老化相关的慢性疾病风险。该项目利用了历史性的TREMIN数据集-全球唯一的数据集，前瞻性地记录了从可比参考人群中抽样的两代不同女性的月经周期信息-以评估年轻成年人和中年女性的月经经历是否发生了长期变化。月经特征是卵巢功能的重要标志，与生育能力、绝经年龄和女性慢性疾病的长期风险有关。了解妇女的月经经历受人口风险因素（如体型、吸烟、产次和激素使用）长期变化的影响程度，将有助于预测这些人口变化对生育率、月经发病率和生殖老化的潜在影响。

DESCRIPTION (provided by applicant): Secular declines in age at menarche have been well documented and a secular increase in age at menopause has been suggested by some studies. Change in age at menarche or menopause are of scientific interest because their timing is related to women's fertility, risk of chronic diseases, and mortality. An equally important, but rarely addressed question is whether secular change has occurred in menstrual function during the prime reproductive years or the menopausal transition. Menstrual characteristics of adult women are important markers of ovarian function and have been associated with fertility, age at menopause, and women's long term risk of chronic disease. Given the secular change in risk factors that influence menstrual function, including body size, smoking, parity and hormone use, evaluation of their impact on menstrual function is warranted. The historic TREMIN dataset presents a unique opportunity to address the question of secular change in menstrual characteristics of US women. It is the only dataset in existence worldwide with prospectively recorded menstrual cycle information across two distinct generations of women sampled from a comparable referent population and linked to information on reproductive, anthropometric and lifestyle characteristics. Students attending the University of Minnesota were enrolled in 1936-39 (Cohort 1) and in 1961-64 (Cohort II). We propose to analyze the prospectively recorded menstrual calendar and health record data from the 1151 Cohort I women and 905 Cohort II women who participated for 5 to 35 years. Our goal is to evaluate whether secular change has occurred in menstrual patterns of adult women or in the timing of the menopausal transition and, if so, whether these differences are explained by secular differences in parity, body mass index, smoking, or hormone use. We will estimate menstrual characteristics across the lifespan using linear mixed models and marginal models fit with generalized estimating equations to separately model mean, variance and correlation of menstrual cycle length by age. We will estimate the effect of cohort on age at onset of the menopausal transition and on duration of the transition using Cox proportional hazards and the varying coefficient Cox model along with a change-point model for mean and variance. We propose multiple imputation techniques to account for intermittent missing data and new methods for addressing the problem of hormone use masking the timing of reproductive aging. Analyses of these truly unique data will make a substantial contribution to our understanding of the nature of secular change in menstrual characteristics throughout reproductive life. Understanding of the extent to which menstrual function during the prime of reproductive life is influenced by secular change in population risk factors would allow us to predict the potential impact of such changes on fertility, menstrual morbidity and reproductive aging. Ultimately, surveillance of menstrual characteristics young women might facilitate prediction of changes in age-related fertility dynamics, timing of the menopausal transition and chronic disease risk associated with reproductive aging. This project takes advantage of the historic TREMIN dataset -- the only dataset in existence worldwide with prospectively recorded menstrual cycle information across two distinct generations of women sampled from a comparable referent population -- to assess whether secular change has occurred in the menstrual experience of young adult and midlife women. Menstrual characteristics are important markers of ovarian function and are associated with fertility, age at menopause, and women's long term risk of chronic disease. Understanding of the extent to women's menstrual experience is influenced by secular change in population risk factors such as body size, smoking, parity and hormone use will facilitate prediction of the potential impact of these population changes on fertility, menstrual morbidity and reproductive aging.