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

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

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 A...

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Published in:Human reproduction (Oxford) Vol. 29; no. 3; pp. 584 - 591
Main Authors: Dólleman, M., Depmann, M., Eijkemans, M.J.C., Heimensem, J., Broer, S.L., van der Stroom, E.M., Laven, J.S.E., Van Rooij, I.A.J., Scheffer, G.J., Peeters, P.H.M., van der Schouw, Y.T., Lambalk, C.B., Broekmans, F.J.M.
Format: Journal Article
Language:English
Published: England Oxford University Press 01-03-2014
Subjects:
Adult
Age Factors
Anti-Mullerian Hormone - blood
Anti-Mullerian Hormone - genetics
Female
Forecasting
Humans
Menopause
Middle Aged
Mothers
Quantitative Trait, Heritable
menopause
ovarian reserve
anti-Müllerian hormone
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Summary: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.
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ISSN:0268-1161
1460-2350
DOI:10.1093/humrep/det446