Age-specific anti-Müllerian hormone reference values using an ultrasensitive assay: Associations with ovarian aging and menopausal transition symptoms

BACKGROUND: Accurately assessing ovarian aging remains a critical challenge in women's health, particularly during the late reproductive stage and menopausal transition. Anti-Müllerian hormone (AMH) is widely used to reflect ovarian reserve, but its application in midlife women is limited by the lack of standardized age-specific reference values and poor sensitivity of conventional assays at low AMH levels. This study aimed to establish age-specific AMH reference percentiles in midlife Chinese women using an ultrasensitive assay and to evaluate their clinical relevance for assessing ovarian aging during the menopausal transition. METHODS: We analyzed serum AMH levels in 10,543 Chinese women aged 34-56 years from a nationally representative cohort using a highly sensitive assay (limit of detection: 0.003 ng/mL). Generalized additive models for location, scale, and shape were used to construct age-specific AMH percentiles. Associations with longitudinal AMH decline (n = 2521), perimenopausal symptoms (PMSs) (via modified Kupperman index), and menopausal status (n = 422 postmenopausal women) were evaluated. RESULTS: The ultrasensitive assay enabled detection of AMH levels in most women aged 44-49 years and distinguished postmenopausal from premenopausal women (median 0.043 vs. 0.187 ng/mL, P < 0.001). Area under the curve for menopause diagnosis was 0.72 (cutoff = 0.0055 ng/mL). Age-specific AMH percentiles were established based on a nationwide cross-sectional cohort of 10,543 women, providing the first standardized reference for late reproductive stages. In the longitudinal cohort, women with baseline AMH below the 10th percentile experienced faster decline before age 40. Among women aged 35-55 years, lower AMH percentiles were associated with more severe PMSs (β = 0.12), particularly vasomotor symptoms (VMSs). CONCLUSIONS: Ultrasensitive AMH profiling enables the construction of age-specific reference percentiles applicable to women in late reproductive stages. This framework enhances the clinical utility of AMH for individualized fertility counseling, PMS management, and menopausal status assessment.