School of Medicine, University of Glasgow, Glasgow, UK.
NIHR Bristol Biomedical Research Centre, University of Bristol, Oakfield House, Oakfield Grove, Bristol, UK.
Hum Reprod Update. 2023 May 2;29(3):327-346. doi: 10.1093/humupd/dmac045.
The early onset of menopause is associated with increased risks of cardiovascular disease and osteoporosis. As a woman's circulating anti-Müllerian hormone (AMH) concentration reflects the number of follicles remaining in the ovary and declines towards the menopause, serum AMH may be of value in the early diagnosis and prediction of age at menopause.
This systematic review was undertaken to determine whether there is evidence to support the use of AMH alone, or in conjunction with other markers, to diagnose menopause, to predict menopause, or to predict and/or diagnose premature ovarian insufficiency (POI).
A systematic literature search for publications reporting on AMH in relation to menopause or POI was conducted in PubMed®, Embase®, and the Cochrane Central Register of Controlled Trials up to 31 May 2022. Data were extracted and synthesized using the Synthesis Without Meta-analysis for diagnosis of menopause, prediction of menopause, prediction of menopause with a single/repeat measurement of AMH, validation of prediction models, short-term prediction in perimenopausal women, and diagnosis and prediction of POI. Risk-of-bias was evaluated using the Tool to Assess Risk of Bias in Cohort Studies protocol and studies at high risk of bias were excluded.
A total of 3207 studies were identified, and 41, including 28 858 women, were deemed relevant and included. Of the three studies that assessed AMH for the diagnosis of menopause, one showed that undetectable AMH had equivalent diagnostic accuracy to elevated FSH (>22.3 mIU/ml). No study assessed whether AMH could be used to shorten the 12 months of amenorrhoea required for a formal diagnosis of menopause. Studies assessing AMH with the onset of menopause (27 publications [n = 23 835 women]) generally indicated that lower age-specific AMH concentrations are associated with an earlier age at menopause. However, AMH alone could not be used to predict age at menopause with precision (with estimates and CIs ranging from 2 to 12 years for women aged <40 years). The predictive value of AMH increased with age, as the interval of prediction (time to menopause) shortened. There was evidence that undetectable, or extremely low AMH, may aid early diagnosis of POI in young women with a family history of POI, and women presenting with primary or secondary amenorrhoea (11 studies [n = 4537]).
The findings of this systematic review support the use of serum AMH to study the age of menopause in population studies. The increased sensitivity of current AMH assays provides improved accuracy for the prediction of imminent menopause, but diagnostic use for individual patients has not been rigorously examined. Prediction of age at menopause remains imprecise when it is not imminent, although the finding of very low AMH values in young women is both of clinical value in indicating an increased risk of developing POI and may facilitate timely diagnosis.
绝经前期与心血管疾病和骨质疏松症风险增加有关。由于女性循环中的抗苗勒管激素（AMH）浓度反映了卵巢中剩余卵泡的数量，并随着绝经而下降，因此血清 AMH 可能有助于早期诊断和预测绝经年龄。
本系统评价旨在确定是否有证据支持单独使用 AMH 或与其他标志物结合使用来诊断绝经、预测绝经、预测和/或诊断卵巢早衰（POI）。
在 PubMed®、Embase®和 Cochrane 中央对照试验注册库中进行了系统的文献检索，以查找截至 2022 年 5 月 31 日有关 AMH 与绝经或 POI 关系的出版物。使用诊断绝经的无荟萃分析综合法、预测绝经、使用 AMH 单次/重复测量预测绝经、预测模型验证、围绝经期妇女短期预测和 POI 的诊断和预测，提取和综合数据。使用队列研究方案的风险偏倚评估工具评估风险偏倚，并排除风险偏倚高的研究。
共确定了 3207 项研究，其中 41 项（包括 28858 名女性）被认为是相关的，并纳入其中。在三项评估 AMH 用于诊断绝经的研究中，有一项研究表明，无法检测到的 AMH 与升高的 FSH（>22.3 mIU/ml）具有同等的诊断准确性。没有研究评估 AMH 是否可用于缩短正式诊断绝经所需的 12 个月的闭经时间。评估绝经时 AMH 的研究（27 篇文献[n=23835 名女性]）通常表明，较低的年龄特异性 AMH 浓度与更早的绝经年龄相关。然而，AMH 本身无法准确预测绝经年龄（对于年龄<40 岁的女性，估计值和 CI 范围为 2 至 12 年）。随着预测时间（绝经时间）的缩短，AMH 的预测价值随着年龄的增长而增加。有证据表明，对于有 POI 家族史的年轻女性和原发性或继发性闭经的女性，无法检测到或极低的 AMH 可能有助于早期诊断 POI（11 项研究[n=4537]）。
本系统评价的结果支持使用血清 AMH 来研究人群研究中的绝经年龄。目前 AMH 检测方法的敏感性提高，提高了对即将发生的绝经的预测准确性，但对个体患者的诊断用途尚未经过严格检查。当绝经时间不临近时，预测绝经年龄仍然不够精确，尽管在年轻女性中发现非常低的 AMH 值具有临床价值，表明发生 POI 的风险增加，并且可能有助于及时诊断。
