回归卵巢衰老的基础：一项基于人群的抗苗勒管激素纵向下降研究。
Back to the basics of ovarian aging: a population-based study on longitudinal anti-Müllerian hormone decline.
作者信息
de Kat A C, van der Schouw Y T, Eijkemans M J C, Herber-Gast G C, Visser J A, Verschuren W M M, Broekmans F J M
机构信息
Department of Reproductive Medicine and Gynecology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
出版信息
BMC Med. 2016 Oct 3;14(1):151. doi: 10.1186/s12916-016-0699-y.
BACKGROUND
Anti-Müllerian hormone (AMH) is currently used as an ovarian reserve marker for individualized fertility counseling, but very little is known of individual AMH decline in women. This study assessed whether the decline trajectory of AMH is uniform for all women, and whether baseline age-specific AMH levels remain consistently high or low during this trajectory.
METHODS
A total of 3326 female participants from the population-based Doetinchem Cohort Study were followed with five visits over a 20-year period. Baseline age was 40 ± 10 years with a range of 20-59 years. AMH was measured in 12,929 stored plasma samples using the picoAMH assay (AnshLabs). Decline trajectories of AMH were studied with both chronological age and reproductive age, i.e., time to menopause. Multivariable linear mixed effects models characterized the individual AMH decline trajectories.
RESULTS
The overall rate of AMH decline accelerated after 40 years of age. Mixed models with varying age-specific AMH levels and decline rates provided the significantly best fit to the data, indicating that the fall in AMH levels over time does not follow a fixed pattern for individual women. AMH levels remained consistent along individual trajectories of age, with an intraclass correlation coefficient (ICC) of 0.87. The ICC of 0.32 for AMH trajectories with time to menopause expressed the large variation in AMH levels at a given time before the menopause. The differences between low and high age-specific AMH levels remained distinguishable, but became increasingly smaller with increasing chronological and reproductive age.
CONCLUSIONS
This is the first study to characterize individual AMH decline over a long time period and broad age range. The varying AMH decline rates do not support the premise of a uniform AMH decline trajectory. Although age-specific AMH levels remain consistently high or low with increasing age, the converging trajectories and variance of AMH levels at a given time before menopause shed doubt on the added value of AMH to represent individualized reproductive age.
背景
抗苗勒管激素（AMH）目前被用作卵巢储备指标，用于个体化生育咨询，但对于女性个体AMH的下降情况知之甚少。本研究评估了AMH的下降轨迹是否对所有女性都是一致的，以及在这个轨迹中特定年龄的基线AMH水平是否始终保持高或低。
方法
基于人群的多廷赫姆队列研究中的3326名女性参与者在20年期间进行了5次随访。基线年龄为40±10岁，范围为20至59岁。使用picoAMH检测法（AnshLabs）在12929份储存的血浆样本中测量AMH。采用实际年龄和生殖年龄（即绝经时间）研究AMH的下降轨迹。多变量线性混合效应模型描述了个体AMH的下降轨迹。
结果
40岁以后AMH的总体下降速度加快。具有不同特定年龄AMH水平和下降率的混合模型对数据的拟合效果显著最佳，表明随着时间推移，个体女性AMH水平的下降并非遵循固定模式。AMH水平在个体年龄轨迹上保持一致，组内相关系数（ICC）为0.87。AMH轨迹与绝经时间的ICC为0.32，表明在绝经前给定时间AMH水平存在较大差异。特定年龄的低AMH水平和高AMH水平之间的差异仍然可区分，但随着实际年龄和生殖年龄的增加，差异越来越小。
结论
这是第一项在长时间和广泛年龄范围内描述个体AMH下降情况的研究。AMH下降率的差异不支持AMH下降轨迹一致的前提。尽管随着年龄增长，特定年龄的AMH水平始终保持高或低，但在绝经前给定时间AMH水平的趋同轨迹和差异对AMH代表个体化生殖年龄的附加价值提出了质疑。
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