Madeleine Dólleman1, W M Monique Verschuren2, Marinus J C Eijkemans3, Frank J M Broekmans4, Yvonne T van der Schouw5. 1. Department of Reproductive Medicine and Gynaecology, University Medical Center Utrecht, Utrecht, The Netherlands Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. 2. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands National Institute for Public Health and the Environment, Bilthoven, The Netherlands. 3. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. 4. Department of Reproductive Medicine and Gynaecology, University Medical Center Utrecht, Utrecht, The Netherlands. 5. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands y.t.vanderschouw@umcutrecht.nl.
Abstract
STUDY QUESTION: What is the added value of anti-Müllerian hormone (AMH) on top of patient characteristics for predicting the risk to enter menopause within 10 years? SUMMARY ANSWER: For women who did enter menopause, the risk of entering menopause within 10 years assigned by the model with AMH was on average 3% higher than that assigned by the model without AMH, and in the subgroup of young women with regular cycles, this increase was 14%. WHAT IS KNOWN ALREADY: Prediction of age at menopause may be useful in predicting the end of female fertility. AMH may be useful for this, but the current evidence is based on small studies or specific subgroups, and does not take into account predictors other than age. STUDY DESIGN, SIZE, DURATION: This was a retrospective cohort study among 1163 premenopausal women participating in the second follow-up round of the Doetinchem Cohort Study with follow-up assessments of menopausal status and age after 5 and 10 years of follow-up. PARTICIPANTS/MATERIALS, SETTING, METHODS: This study included premenopausal women from the general population with a mean age of 41 (SD 7) years. A Cox proportional hazards' model without AMH was fitted using variables selected based on Akaike's information criterion. Performance of the prediction rule was assessed with C-statistics and compared with a model additionally including AMH and to a model with age only. The added value of AMH was assessed with Net Reclassification Index and change in absolute predicted risk. Performance of these three models was compared in subgroups based on age and reproductive characteristics. MAIN RESULTS AND THE ROLE OF CHANCE: The final model included age, BMI, packyears of smoking and menstrual cycle status (regular, irregular, pregnant or taking oral contraceptives). This model had a C-statistic of 0.89 (0.01 SD), compared with 0.88 (0.01 SD) for the model including age only. Addition of AMH increased it to 0.91 (0.03 SD). In a subgroup of 25-43 year olds with regular menstrual cycles, the model with age only had a C-statistic of 0.79 (0.04 SD) and for the models without and with AMH the C-stastic was 0.79 (0.04 SD) and 0.87 (0.03 SD), respectively. The risk of entering menopause within 10 years assigned by the model with AMH was on average 3% higher than that assigned by the model without AMH, for women who did enter menopause. In the subgroup of young women with regular cycles, this increase was 14%. LIMITATIONS, REASONS FOR CAUTION: Longer follow-up would have resulted in more of the young women becoming menopausal, improving the precision of the predictions for these women. WIDER IMPLICATIONS OF THE FINDINGS: This study clearly shows the added value of AMH in predicting time to menopause on top of clinical predictors, in particular for younger women. New studies in specific target populations in clinical practice are needed to develop a prediction model for use in that target population. STUDY FUNDING/COMPETING INTERESTS: The Doetinchem Cohort Study is carried out by the National Institute for Public Health and the Environment which works under the authority of the Ministry of Health, Welfare and Sport of The Netherlands. F.J.M.B. declares to have received fees and grant support from the following companies (in alphabetical order); Ferring, Gedeon Richter, Merck Serono, MSD and Roche. The remaining authors declare no conflict of interest.
STUDY QUESTION: What is the added value of anti-Müllerian hormone (AMH) on top of patient characteristics for predicting the risk to enter menopause within 10 years? SUMMARY ANSWER: For women who did enter menopause, the risk of entering menopause within 10 years assigned by the model with AMH was on average 3% higher than that assigned by the model without AMH, and in the subgroup of young women with regular cycles, this increase was 14%. WHAT IS KNOWN ALREADY: Prediction of age at menopause may be useful in predicting the end of female fertility. AMH may be useful for this, but the current evidence is based on small studies or specific subgroups, and does not take into account predictors other than age. STUDY DESIGN, SIZE, DURATION: This was a retrospective cohort study among 1163 premenopausal women participating in the second follow-up round of the Doetinchem Cohort Study with follow-up assessments of menopausal status and age after 5 and 10 years of follow-up. PARTICIPANTS/MATERIALS, SETTING, METHODS: This study included premenopausal women from the general population with a mean age of 41 (SD 7) years. A Cox proportional hazards' model without AMH was fitted using variables selected based on Akaike's information criterion. Performance of the prediction rule was assessed with C-statistics and compared with a model additionally including AMH and to a model with age only. The added value of AMH was assessed with Net Reclassification Index and change in absolute predicted risk. Performance of these three models was compared in subgroups based on age and reproductive characteristics. MAIN RESULTS AND THE ROLE OF CHANCE: The final model included age, BMI, packyears of smoking and menstrual cycle status (regular, irregular, pregnant or taking oral contraceptives). This model had a C-statistic of 0.89 (0.01 SD), compared with 0.88 (0.01 SD) for the model including age only. Addition of AMH increased it to 0.91 (0.03 SD). In a subgroup of 25-43 year olds with regular menstrual cycles, the model with age only had a C-statistic of 0.79 (0.04 SD) and for the models without and with AMH the C-stastic was 0.79 (0.04 SD) and 0.87 (0.03 SD), respectively. The risk of entering menopause within 10 years assigned by the model with AMH was on average 3% higher than that assigned by the model without AMH, for women who did enter menopause. In the subgroup of young women with regular cycles, this increase was 14%. LIMITATIONS, REASONS FOR CAUTION: Longer follow-up would have resulted in more of the young women becoming menopausal, improving the precision of the predictions for these women. WIDER IMPLICATIONS OF THE FINDINGS: This study clearly shows the added value of AMH in predicting time to menopause on top of clinical predictors, in particular for younger women. New studies in specific target populations in clinical practice are needed to develop a prediction model for use in that target population. STUDY FUNDING/COMPETING INTERESTS: The Doetinchem Cohort Study is carried out by the National Institute for Public Health and the Environment which works under the authority of the Ministry of Health, Welfare and Sport of The Netherlands. F.J.M.B. declares to have received fees and grant support from the following companies (in alphabetical order); Ferring, Gedeon Richter, Merck Serono, MSD and Roche. The remaining authors declare no conflict of interest.
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