Time-dependent anti-Müllerian hormone dynamics during GnRHa-based endocrine therapy in young breast cancer survivors: a longitudinal real-world cohort study

Background Anti-Müllerian hormone (AMH) is widely used to assess ovarian reserve in young women with breast cancer. However, its interpretation during gonadotropin-releasing hormone agonist (GnRHa)-based endocrine therapy remains challenging because pharmacologic ovarian suppression may alter AMH levels over time. We aimed to characterize longitudinal AMH dynamics according to chemotherapy exposure and subsequent GnRHa-based endocrine therapy. Methods We conducted a retrospective longitudinal cohort study of women diagnosed with early breast cancer before age 40 at Sun Yat-sen University Cancer Center between August 2019 and December 2024. Patients were categorized into four groups according to chemotherapy exposure and GnRHa-based endocrine therapy. Longitudinal trajectories of log-transformed AMH were modeled using linear mixed-effects models with restricted cubic splines, adjusting for prespecified clinical covariates. Sensitivity analyses included baseline-AMH adjustment and exclusion of observations with extreme standardized residuals. Results The full cohort included 685 women contributing 1758 AMH measurements. The adjusted complete-case model included 613 women contributing 1602 measurements. The group-by-time interaction was significant (likelihood ratio χ 2 = 249.33, df = 9, P < 0.001), demonstrating distinct AMH trajectories across treatment groups. Among women without chemotherapy, predicted AMH did not differ significantly between those with and without GnRHa-based endocrine therapy. Among chemotherapy-treated patients, the GnRHa-based endocrine therapy group was associated with lower predicted AMH at 12 and 36 months, but the differences attenuated at later follow-up. Similar trajectory patterns were observed in sensitivity analyses. Conclusions AMH trajectories during GnRHa-based endocrine therapy are time-dependent and influenced by treatment context. AMH measurements during GnRHa exposure should be interpreted in relation to treatment timing and longitudinal changes rather than as isolated indicators of ovarian reserve.