Longevity and Reproductive Aging · Reproductive Aging

Can Menopause Prediction Be Improved With Multiple AMH Measurements? Results From the Prospective Doetinchem Cohort Study

de Kat AC, van der Schouw YT, Eijkemans MJC, Broer SL, Verschuren WMM, Broekmans FJM

Published November 2019 The Journal of Clinical Endocrinology and Metabolism, 104(11), 5024-5031
DOI 10.1210/jc.2018-02607 PMID 31006802

RRM Academy Synopsis

Multiple AMH Tests Do Not Improve Menopause Age Prediction

A 20-year cohort study of 2,434 Dutch women found that repeat AMH tests did not predict menopause better than one test. The team checked AMH about every five years and tracked age at menopause by survey.

Key Findings

  • Of the 2,434 premenopausal women followed, 1,298 (53%) reached natural menopause during the study, and 96 of them (7.4%) did so before age 45.
  • Adding a long-term AMH decline rate, measured from each woman's first and last sample, to a single baseline AMH level did not improve the model's prediction of time to menopause.
  • At age 25, adding the prior five-year AMH decline rate raised the model's C-statistic for predicting menopause from 0.64 (95% CI, 0.62-0.66) to 0.69 (95% CI, 0.67-0.70).
  • Beyond age 25, adding the AMH decline rate gave no further benefit for predicting menopause or early menopause at older ages.
  • At age 20, prediction accuracy was near chance (C-statistic 0.62 for menopause, 0.47 for early menopause); below age 30, models underestimated the actual risk of early menopause.

Interpretation

This cohort study followed women from the general Dutch population for up to 21.9 years, covering 96 women who reached menopause before age 45. A single AMH level carried nearly all the predictive value found here. The findings support larger studies of AMH decline patterns alongside other measures of reproductive aging.

RRM Context

Fertility awareness based methods track several body signs each cycle. This gives more than one data point over time. The study adds to evidence that AMH screening has limited use for menopause-age advice, whether run once or many times. The authors note another study found no link between AMH and time to pregnancy in women ages 30 to 44.

Abstract

Context

Anti-Müllerian hormone (AMH) levels are used worldwide as a screening tool for the duration of the female reproductive lifespan. Although AMH levels are associated with age at menopause, individual predictions of menopause with a single AMH measurement are unreliable.

Objective

This study investigated whether individual AMH decline patterns can improve the prediction of menopause compared with a single measurement.

Design

The study population comprised 2434 premenopausal women from the population-based Doetinchem Cohort Study. Participants were followed up every 5 years for a total of 20 years, and AMH was measured in 6699 plasma samples with the picoAMH assay. Longitudinal statistical modeling was combined with time varying Cox modeling, to integrate multiple AMH measurements per woman.

Results

The mean age at menopause was 50 years, and 7.4% of the women who reached menopause during follow-up did so before age 45 years. For a 25-year-old, the AMH decline rate between ages 20 and 25 years increased the C-statistic of menopause prediction from 0.64 to 0.69. Beyond that age, the AMH decline rate did not improve predictions of menopause or early menopause. For women younger than age 30 years, for whom menopause prediction is arguably most relevant, the models underestimated the risk of early menopause.

Conclusion

These results suggest that knowledge of the AMH decline rate does not improve the prediction of menopause. Based on the low discriminative ability and underestimation of the risk of early menopause, the use of AMH as a screening method for the timing of menopause cannot currently be advocated.

Topics

By this author

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Longevity and Reproductive Aging › Reproductive Aging › Ovarian Aging · Reproductive Endocrinology › Ovarian Hormones › Estrogen · Perimenopause and Menopause › Early and Premature Transition › Premature Ovarian Insufficiency
Annelien C de Kat, Yvonne T van der Schouw, Marinus J C Eijkemans, Simone L Broer, W M Monique Verschuren, Frank J M Broekmans
A Kat, Y Schouw, M Eijkemans, S Broer, F Broekmans
PMID 31006802 31006802 DOI 10.1210/jc.2018-02607 10.1210/jc.2018-02607 de Kat et al. 2019, de Kat 2019