M Depmann1, M J C Eijkemans2, S L Broer1, F Ramezani Tehrani3, M Solaymani-Dodaran4, F Azizi5, C B Lambalk6, J F Randolph7, S D Harlow8, E W Freeman9, M D Sammel10, W M M Verschuren2, Y T van der Schouw2, B W Mol11, F J M Broekmans1. 1. University Medical Center Utrecht, Department of Reproductive Medicine & Gynecology, Utrecht, The Netherlands. 2. Julius Center for Health Sciences and Primary Care, Department of Biostatistics and Research Support, Utrecht, The Netherlands. 3. Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 4. Minimally Invasive Surgery Research Center, Iran University of Medical Sciences, Tehran, Iran. 5. Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 6. VU University Medical Center, Department of Obstetrics and Gynecology, IVF Center, Amsterdam, The Netherlands. 7. University of Michigan Medical Center, Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Ann Arbor, Michigan. 8. University of Michigan, Department of Epidemiology, School of Public Health, Ann Arbor, MI, USA. 9. Perelman School of Medicine, Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA, USA. 10. Perelman School of Medicine, Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, PA, USA. 11. Monash Medical Center, Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia.
Abstract
CONTEXT: Anti-Müllerian hormone based (AMH) age at menopause predictions remain cumbersome due to predictive inaccuracy. OBJECTIVE: To perform an Individual Patient Data (IPD) meta-analysis, regarding AMH based menopause prediction. DATA SOURCES: A systematic literature search was performed using PubMed, Embase and Cochrane databases. STUDY SELECTION: Prospective cohort studies regarding menopause prediction using serum AMH levels were selected by consensus discussion. DATA SELECTION: Individual cases were included if experiencing a regular cycle at baseline. Exclusion criteria were hormone use and gynecological surgery. DATA SYNTHESIS: 2596 women were included, 1077 experienced menopause. A multivariable Cox regression analysis assessed time to menopause (TTM) using age and AMH. AMH predicted TTM, however, added value on top of age was poor (age alone C-statistic 84%; age + AMH HR 0.66 95% CI 0.61-0.71, C-statistic 86%). Moreover, the capacity of AMH to predict early (≤45 years) and late menopause (≥55 years) was assessed. An added effect of AMH was demonstrated for early menopause (age alone C-statistic 52%; age + AMH HR 0.33, 95% CI 0.24-0.45, C-statistic 80%). A Weibull regression model calculating individual age at menopause revealed that predictive inaccuracy remained present and increased with decreasing age at menopause. Lastly, a check of non-proportionality of the predictive effect of AMH demonstrated a reduced predictive effect with increasing age. CONCLUSION: AMH was a significant predictor of TTM and especially of time to early menopause. However, individual predictions of age at menopause demonstrated a limited precision, particularly when concerning early age at menopause, making clinical application troublesome.
CONTEXT: Anti-Müllerian hormone based (AMH) age at menopause predictions remain cumbersome due to predictive inaccuracy. OBJECTIVE: To perform an Individual Patient Data (IPD) meta-analysis, regarding AMH based menopause prediction. DATA SOURCES: A systematic literature search was performed using PubMed, Embase and Cochrane databases. STUDY SELECTION: Prospective cohort studies regarding menopause prediction using serum AMH levels were selected by consensus discussion. DATA SELECTION: Individual cases were included if experiencing a regular cycle at baseline. Exclusion criteria were hormone use and gynecological surgery. DATA SYNTHESIS: 2596 women were included, 1077 experienced menopause. A multivariable Cox regression analysis assessed time to menopause (TTM) using age and AMH. AMH predicted TTM, however, added value on top of age was poor (age alone C-statistic 84%; age + AMH HR 0.66 95% CI 0.61-0.71, C-statistic 86%). Moreover, the capacity of AMH to predict early (≤45 years) and late menopause (≥55 years) was assessed. An added effect of AMH was demonstrated for early menopause (age alone C-statistic 52%; age + AMH HR 0.33, 95% CI 0.24-0.45, C-statistic 80%). A Weibull regression model calculating individual age at menopause revealed that predictive inaccuracy remained present and increased with decreasing age at menopause. Lastly, a check of non-proportionality of the predictive effect of AMH demonstrated a reduced predictive effect with increasing age. CONCLUSION: AMH was a significant predictor of TTM and especially of time to early menopause. However, individual predictions of age at menopause demonstrated a limited precision, particularly when concerning early age at menopause, making clinical application troublesome.
Authors: H Irene Su; Brian Kwan; Brian W Whitcomb; Ksenya Shliakhsitsava; Andrew C Dietz; Shaylyn S Stark; Elena Martinez; Patrick M Sluss; Mary D Sammel; Loki Natarajan Journal: J Clin Endocrinol Metab Date: 2020-08-01 Impact factor: 5.958