Longitudinal trajectory of menopausal symptoms in premenopausal women throughout adjuvant chemotherapy: a two-stage analytical approach

Abstract

Purpose Breast cancer incidence in Asian women peaks in the mid-40 s, when many remain premenopausal. The progression of chemotherapy-induced menopausal symptoms in this population remains underexplored. This study examined their temporal trajectory and clinical significance during adjuvant chemotherapy. Method This prospective study assessed breast cancer patients undergoing adjuvant chemotherapy at a tertiary hospital. Participants were classified by menopausal status and treated with AC-D (Adriamycin, Cyclophosphamide, and Docetaxel) or FAC (5-Fluorouracil, Adriamycin, and Cyclophosphamide) regimens. Menopausal symptoms were evaluated using the Menopausal Rating Scale (MRS) at four time points: before chemotherapy (T0), after the first (T1) and fourth (T2) cycles, and one month post-chemotherapy (T3). Symptom trajectories were analyzed using a linear mixed-effects model (LMM) and Generalized Estimating Equations (GEE). Results Menopausal symptoms significantly worsened in premenopausal women (AC-D: p < 0.001, FAC: p < 0.001), particularly from T2 onward. Psychological symptoms showed the greatest increase (AC-D: p < 0.001, FAC: p < 0.001), followed by significant worsening of urogenital symptoms (AC-D: p = 0.002, FAC: p = 0.004). Somatic symptoms showed a non-significant increasing trend (AC-D: p = 0.120, FAC: p = 0.101). At T3, 67.9% of AC-D and 59.4% of FAC patients experienced moderate-to-severe symptoms, with severe cases doubling in AC-D (from 16.1% at T0 to 37.5%) and tripling in FAC (6.8% at T0 to 18.9%). Conclusion Chemotherapy-induced menopausal symptoms progressively worsened, particularly psychological symptoms. By treatment completion, approximately two-thirds required clinical intervention, underscoring the need for early assessment and proactive management to improve patient outcomes.