Does the Anti-Mullerian Hormone Decline Rate Improve the Prediction of Age at Menopause?

Abstract

ObjectivesThere are controversial studies investigating whether multiple anti-Mullerian hormone (AMH) measurements can improve the individualized prediction of age at menopause in the general population. This study aimed to reexplore the additive role of the AMH decline rate in single AMH measurement for improving the prediction of age at physiological menopause, based on two common statistical models for analysis of time-to-event data, including time-dependent Cox regression and Cox proportional-hazards regression models.MethodsA total of 901 eligible women, aged 18–50 years, were recruited from the Tehran Lipid and Glucose Study (TLGS) population and followed up every 3 years for 18 years. The serum AMH level was measured at the time of recruitment and twice after recruitment within 6-year intervals using the Gen II AMH assay. The added value of repeated AMH measurements for the prediction of age at menopause was explored using two different statistical approaches. In the first approach, a time-dependent Cox model was plotted, with all three AMH measurements as time-varying predictors and the baseline age and logarithm of annual AMH decline as time-invariant predictors. In the second approach, a Cox proportional-hazards model was fitted to the baseline data, and improvement of the complex model, which included repeated AMH measurements and the logarithm of the AMH annual decline rate, was assessed using the C-statistic.ResultsThe time-dependent Cox model showed that each unit increase in the AMH level could reduce the risk of menopause by 87%. The Cox proportional-hazards model also improved the prediction of age at menopause by 3%, according to the C-statistic. The subgroup analysis for the prediction of early menopause revealed that the risk of early menopause increased by 10.8 with each unit increase in the AMH annual decline rate.ConclusionThis study confirmed that multiple AMH measurements could improve the individual predictions of the risk of at physiological menopause compared to single AMH measurements. Different alternative statistical approaches can also offer the same interpretations if the essential assumptions are met.

Anti-Müllerian hormone for the diagnosis and prediction of menopause: a systematic review

“…Similarly, in the TLGS cohort, the serum AMH trajectory was a strong predictor for age at menopause ( Gohari et al , 2016 ), with subsequent analyses demonstrating that the addition of the AMH annual decline within models significantly improved the prediction of age at menopause over AMH and age alone ( Ramezani Tehrani et al , 2020 ). Analysis of that study using Cox proportional hazards showed that repeated measurement of AMH only slightly improved prediction of age at menopause; the best model for predicting menopause only generated a 3% improvement in prediction, with the C -statistic increasing from 0.71 (95% CI: 0.69–0.73) at baseline to 0.74 (95% CI: 0.71–0.76) when a second measurement and calculation of the annual decline were included ( Ramezani Tehrani et al , 2021 ). These contradictory results may be partly due to the different modelling used, the variation in time to menopause, the different time periods between repeat AMH measures, and/or the heterogeneity in populations.…”

“…Several studies assessed the utility of repeat AMH measures, incorporating a variety of different mathematical approaches to try to model the menopausal transition or improve the prediction of time to menopause compared with single measurements. These included differences in absolute values ( Iino et al , 2013 ), Weibull accelerated failure time models ( Tehrani et al , 2013 ), flexible parametric survival models ( Tehrani et al , 2013 ; Ramezani Tehrani et al , 2016 ), mixed models ( de Kat et al , 2016 ), Kaplan–Meier estimations ( Freeman et al , 2012a ), and Cox proportional hazards models with time-varying covariates ( de Kat et al , 2019 ; Ramezani Tehrani et al , 2021 ). The findings are inconsistent.…”

Anti‐Müllerian hormone for screening, diagnosis, evaluation, and prediction: A systematic review and expert opinions

“…To address this issue, ultrasensitive assays and longitudinal measurements over time may be helpful. Tehrani et al demonstrated better predictive potential using the log annual AMH levels decline rate than using AMH levels at a fixed point (C‐static:0.64 in AMH levels and 0.84 in log annual AMH levels decline rate) 24 . The sensitivity and positive predictive value for predicting the final menstrual period were higher using a cut‐off of AMH levels as <10 pg/mL than <100 pg/mL 25 …”

Antimüllerian Hormone as a Tool to Predict the Age at Menopause

“…They described that the rate of AMH decline has a low discriminative ability to estimate the risk of early menopause [ 42 ]. Conversely, an analysis of the Tehran Lipid and Glucose Study population showed that the rate of AMH decline is the most effective predictor of early menopause [ 43 ]. They demonstrated that a 1-unit increase in the yearly AMH decline rate was associated with a 10.8-times higher risk of early menopause [ 43 ].…”