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抗苗勒管激素是预测个体绝经时间比母亲绝经年龄更准确的指标。

Anti-Mullerian hormone is a more accurate predictor of individual time to menopause than mother's age at menopause.

机构信息

Department of Reproductive Medicine and Gynaecology, University Medical Center Utrecht, Utrecht, The Netherlands.

出版信息

Hum Reprod. 2014 Mar;29(3):584-91. doi: 10.1093/humrep/det446. Epub 2014 Jan 15.

Abstract

STUDY QUESTION

In the prediction of time to menopause (TTM), what is the added value of anti-Müllerian hormone (AMH) when mother's age at natural menopause (ANM) is also known?

SUMMARY ANSWER

AMH is a more accurate predictor of individual TTM than mother's age at menopause.

WHAT IS KNOWN ALREADY

Mother's ANM is considered a proxy for daughter's ANM although studies on its predictive accuracy are non-existent. AMH is a biomarker with a known capacity to predict ANM. However, its added value on top of known predictors, like mother's ANM, is unknown.

STUDY DESIGN, SIZE, DURATION: Population-based cohort studies were used. To assess any additive predictive value of mother's ANM, 164 mother-daughter pairs were used (Group 1). To assess the added value of AMH, a second group of 150 women in whom AMH and mother's ANM were recorded prior to a 12-year follow-up period during which daughter's ANM was assessed was used (Group 2).

PARTICIPANTS/MATERIALS, SETTING, METHODS: Group 1 consisted of participants of the DOM cohort (an ongoing breast cancer study). Group 2 was a pooled cohort of women with regular menstrual cycles from two independent published studies. Cox proportional hazards analysis estimated uni- and multivariate regression coefficients for female age at study entry, mother's ANM and AMH in the prediction of TTM. Discrimination of models was assessed with C-statistics. Clinical added value of AMH was quantified with a net reclassification index (NRI).

MAIN RESULTS AND THE ROLE OF CHANCE

A model with female age and mother's ANM had a c-statistic of 79 and 85% in groups 1 and 2, respectively. Both age and mother's ANM were significantly associated with TTM (HR 1.54 and HR 0.93 for age and mother's ANM in Cohort 1 and HR 1.59 and HR 0.89 in Group 2, respectively. P-value for all <0.001). In Group 2, the multivariate model with age, mother's ANM and AMH had a c-statistic of 92%, and only female age and AMH remained significantly associated with TTM (HR 1.41 P < 0.0001; HR 0.93 P = 0.08 and HR 0.06 P < 0.0001 for age, mother's ANM and AMH, respectively). The mean weighted NRI suggests that a 47% improvement in predictive accuracy is offered by adding AMH to the model of age and mother's ANM. In conclusion, AMH and mother's ANM both have added value in forecasting TTM for the daughter based on her age. In comparison, AMH is a more accurate added predictor of TTM than mother's ANM.

LIMITATIONS, REASONS FOR CAUTION: The cohort of women is relatively small and different cohorts of women were pooled.

WIDER IMPLICATIONS OF THE FINDINGS

This study shows that AMH is a more accurate predictor of ANM than mother's ANM. However, before achieving clinical applicability, the certainty with which a woman's prediction is made must improve. The association between mother's ANM and TTM in daughters did not appear to be influenced by whether ANM was recorded by mothers or daughters--an important finding because in the clinical setting daughters usually provide this information.

STUDY FUNDING/COMPETING INTEREST(S): No funding was received and there were no competing interests in direct relation to this study.

摘要

研究问题

在预测绝经时间(TTM)时,当已知母亲的自然绝经年龄(ANM)时,抗苗勒管激素(AMH)的增值是什么?

总结答案

AMH 是预测个体 TTM 比母亲绝经年龄更准确的指标。

已知情况

尽管关于其预测准确性的研究尚未存在,但母亲的 ANM 被认为是女儿 ANM 的代表。AMH 是一种具有已知预测 ANM 能力的生物标志物。然而,它在已知预测因子(如母亲的 ANM)之上的附加值是未知的。

研究设计、大小和持续时间:使用了基于人群的队列研究。为了评估母亲 ANM 的任何附加预测价值,使用了 164 对母女(第 1 组)。为了评估 AMH 的附加值,使用了第二个组,其中在 12 年随访期间记录了 AMH 和母亲的 ANM,在此期间评估了女儿的 ANM,共纳入了 150 名女性(第 2 组)。

参与者/材料、设置、方法:第 1 组由 DOM 队列(一项正在进行的乳腺癌研究)的参与者组成。第 2 组是来自两项独立发表的研究中具有规律月经周期的女性的合并队列。Cox 比例风险分析估计了女性研究入组时的年龄、母亲的 ANM 和 AMH 在预测 TTM 中的单变量和多变量回归系数。使用 C 统计量评估模型的区分度。使用净重新分类指数(NRI)量化 AMH 的临床附加值。

主要结果和机会的作用

在第 1 组和第 2 组中,具有女性年龄和母亲 ANM 的模型的 C 统计量分别为 79%和 85%。年龄和母亲的 ANM 均与 TTM 显著相关(第 1 组中的 HR 分别为 1.54 和 HR 0.93,第 2 组中的 HR 分别为 1.59 和 HR 0.89,P 值均 <0.001)。在第 2 组中,具有年龄、母亲的 ANM 和 AMH 的多变量模型的 C 统计量为 92%,只有女性年龄和 AMH 与 TTM 仍显著相关(HR 1.41,P <0.0001;HR 0.93,P = 0.08;HR 0.06,P <0.0001,分别为年龄、母亲的 ANM 和 AMH)。平均加权 NRI 表明,通过将 AMH 添加到年龄和母亲的 ANM 模型中,可以提高预测准确性 47%。总之,AMH 和母亲的 ANM 都在基于女儿年龄预测 TTM 方面具有增值。相比之下,AMH 是比母亲的 ANM 更准确的 TTM 附加预测指标。

局限性、谨慎的原因:女性队列相对较小,并且不同的女性队列被合并。

研究结果的更广泛影响

这项研究表明,AMH 是预测 ANM 的比母亲的 ANM 更准确的指标。然而,在实现临床适用性之前,必须提高女性预测的确定性。母亲的 ANM 与女儿 TTM 之间的关联似乎不受 ANM 是由母亲还是女儿记录的影响——这是一个重要的发现,因为在临床环境中,女儿通常提供此信息。

研究资金/利益冲突:没有收到资金,与这项研究没有直接相关的利益冲突。

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