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.