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Anti-Mullerian hormone levels and incidence of early natural menopause in a prospective study.

ABSTRACT: STUDY QUESTION:Are anti-Müllerian hormone (AMH) levels assessed in women aged 32-44 associated with risk of incident early natural menopause? SUMMARY ANSWER:We observed strong, significant associations between lower AMH levels and higher risk of early menopause. WHAT IS KNOWN ALREADY:The ability to predict risk early menopause, defined as menopause before age 45, prior to fertility decline would improve options for family planning and cardiovascular disease prevention. Though AMH is an established marker of menopause timing in older reproductive-aged women, whether AMH is associated with risk of early menopause has not been evaluated. STUDY DESIGN, SIZE, DURATION:We assessed these relations in a nested case-control study within the prospective Nurses' Health Study II cohort. Premenopausal blood samples were collected in 1996-1999. Participants were followed until 2011 for early natural menopause, with follow-up rates >94%. PARTICIPANTS/MATERIALS, SETTING, METHODS:Early menopause cases (n = 327) were women reporting natural menopause between blood collection and age 45. Controls (n = 491) experienced menopause after age 45 and included 327 cases matched to controls on the basis of age at blood draw (±4 months) and other factors. AMH levels up to 12 years before early menopause were assayed in 2016. MAIN RESULTS AND THE ROLE OF CHANCE:In multivariable conditional logistic regression models adjusting for matching factors, body mass index, smoking, parity, oral contraceptive use, and other factors, each 0.10 ng/ml decrease in AMH was associated with a 14% higher risk of early menopause (95% confidence interval (CI) 1.10 to 1.18; P < 0.001). In polynomial regression models including linear and quadratic terms for AMH, odds ratios for early menopause for women with AMH levels of 1.5, 1.0 and 0.5 ng/ml compared to 2.0 ng/ml were 2.6, 7.5 and 23 (all P < 0.001). Significant associations were observed irrespective of smoking status, adiposity, infertility history and menstrual cycle characteristics. Furthermore, models assessing the predictive ability of AMH showed high concordance, and C-statistics were high, ranging from 0.68 (age ?35) to 0.93 (age 42). LIMITATIONS, REASONS FOR CAUTION:Our population was relatively homogenous with respect to race/ethnicity. Further work in more ethnically diverse populations is needed. WIDE IMPLICATION OF THE FINDINGS:To our knowledge, this is the first prospective study to evaluate whether AMH levels are associated with early menopause. These findings support the utility of AMH as a clinical marker of early menopause in otherwise healthy women. STUDY FUNDING/COMPETING INTEREST(S):This project was supported by UM1CA176726, R01CA67262, and R01HD078517 from the U.S. Department of Health and Human Services, National Institutes of Health. No competing interests declared.

SUBMITTER: Bertone-Johnson ER

PROVIDER: S-EPMC6366539 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Anti-Müllerian hormone levels and incidence of early natural menopause in a prospective study.

Bertone-Johnson Elizabeth R ER Manson JoAnn E JE Purdue-Smithe Alexandra C AC Steiner Anne Z AZ Eliassen A Heather AH Hankinson Susan E SE Rosner Bernard A BA Whitcomb Brian W BW

Human reproduction (Oxford, England) 20180601 6

<h4>Study question</h4>Are anti-Müllerian hormone (AMH) levels assessed in women aged 32-44 associated with risk of incident early natural menopause?<h4>Summary answer</h4>We observed strong, significant associations between lower AMH levels and higher risk of early menopause.<h4>What is known already</h4>The ability to predict risk early menopause, defined as menopause before age 45, prior to fertility decline would improve options for family planning and cardiovascular disease prevention. Thou ...[more]

PMID: 29659835

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Project description: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.

Project description:BackgroundEndometrial proliferative lesions (EPL) usually refer to endometrial hyperplasia (EH) and endometrial cancer (EC). Among patients with premenopausal EPL who wish to preserve their fertility, only those with EH and early-stage EC have the possibility to undergo fertility preservation therapy. However, there is currently a lack of specific and reliable screening criteria and models for identifying these patients.MethodsThis study utilized a retrospective diagnostic study design. The training set included medical record information that met the criteria between August 2017 and October 2022, while the validation set consisted of medical record information that met the criteria from November 2022 to May 2023. The endometrial pathological test served as the gold standard. The serum anti-Mullerian hormone (AMH) level before endometrial sampling and a regression model were employed to predict EPL.ResultsThe study included a total of 1209 patients with PCOS (1119 in the control group and 90 in the endometrial proliferative lesion group) and 5366 women without PCOS (5249 in the control group and 117 in the proliferative lesion group). In the case of PCOS patients aged 20-39 years, the most effective screening threshold for AMH was found to be a serum AMH level of ≤5.39 ng/mL. The model used for this group was logit(p) = -2.562 - 0.430 × AMH + 0.127 × BMI + 1.512 × hypertension + 0.956 × diabetes -1.145 × regular menstruation. On the other hand, for non-PCOS women aged 20-39 years, the optimal screening threshold for AMH was determined to be a serum AMH value of ≤2.18 ng/mL. The model used for this group was logit(p) = -3.778 - 0.823 × AMH + 0.176 × BMI + 2.660 × diabetes -1.527 × regular menstruation -1.117 × dysmenorrhea. It is important to note that all of these findings have successfully passed internal verification.ConclusionFor PCOS and non-PCOS women aged 20-39 years, the serum AMH test and related multiple regression models were obtained for the warning of EPL.

Project description:BackgroundPreviously, we reported a model for assessing ovarian reserves using 4 predictors: anti-Müllerian hormone (AMH) level, antral follicle count (AFC), follicle-stimulating hormone (FSH) level, and female age. This model is referred as the AAFA (anti-Müllerian hormone level-antral follicle count-follicle-stimulating hormone level-age) model.ObjectiveThis study aims to explore the possibility of establishing a model for predicting ovarian reserves using only 3 factors: AMH level, FSH level, and age. The proposed model is referred to as the AFA (anti-Müllerian hormone level-follicle-stimulating hormone level-age) model.MethodsOocytes from ovarian cycles stimulated by gonadotropin-releasing hormone antagonist were collected retrospectively at our reproductive center. Poor ovarian response (<5 oocytes retrieved) was defined as an outcome variable. The AFA model was built using a multivariable logistic regression analysis on data from 2017; data from 2018 were used to validate the performance of AFA model. Measurements of the area under the curve (AUC), sensitivity, specificity, positive predictive value, and negative predicative value were used to evaluate the performance of the model. To rank the ovarian reserves of the whole population, we ranked the subgroups according to the predicted probability of poor ovarian response and further divided the 60 subgroups into 4 clusters, A-D, according to cut-off values consistent with the AAFA model.ResultsThe AUCs of the AFA and AAFA models were similar for the same validation set, with values of 0.853 (95% CI 0.841-0.865) and 0.850 (95% CI 0.838-0.862), respectively. We further ranked the ovarian reserves according to their predicted probability of poor ovarian response, which was calculated using our AFA model. The actual incidences of poor ovarian response in groups from A-D in the AFA model were 0.037 (95% CI 0.029-0.046), 0.128 (95% CI 0.099-0.165), 0.294 (95% CI 0.250-0.341), and 0.624 (95% CI 0.577-0.669), respectively. The order of ovarian reserve from adequate to poor followed the order from A to D. The clinical pregnancy rate, live-birth rate, and specific differences in groups A-D were similar when predicted using the AFA and AAFA models.ConclusionsThis AFA model for assessing the true ovarian reserve was more convenient, cost-effective, and objective than our original AAFA model.

Dataset Information

Anti-Mullerian hormone levels and incidence of early natural menopause in a prospective study.

Publications

Anti-Müllerian hormone levels and incidence of early natural menopause in a prospective study.

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