Longitudinal Trajectories of Menopausal Symptoms in Women Receiving Endocrine Therapy for Breast Cancer Compared with Natural Menopause

BackgroundEndocrine therapy (ETx) for hormone receptor–positive breast cancer frequently induces menopausal symptoms that may compromise treatment adherence. However, longitudinal symptom trajectories compared with natural menopausal progression remain unclear.MethodsThis longitudinal cohort study included 5,734 women from two prospective cohorts. Menopausal symptoms were assessed using the Menopause Rating Scale (MRS). Women with breast cancer (n=2,583) were recruited from the Breast Cancer Information Grand Round for Survivorship cohort, and women without breast cancer (n=3,151) from the Kangbuk Samsung Health Study. Linear mixed-effects models estimated longitudinal changes in MRS scores according to breast cancer status, menopausal status, and ETx use. Difference-in-differences (DiD) analyses used premenopausal women without breast cancer as the reference group.ResultsAmong premenopausal women, ETx was associated with greater increases in total MRS scores compared with women without breast cancer (DiD 3.30; 95% CI, 2.04–4.58 at 1 year). Premenopausal women receiving ETx experienced sustained symptom increases over 3 years, particularly those receiving ovarian function suppression. Regimens including gonadotropin-releasing hormone agonists were associated with the greatest increases in symptom burden. Among postmenopausal women, ETx was associated with modest changes in total MRS scores but a significant increase in urogenital symptoms (DiD 0.71; 95% CI, 0.26–1.16).ConclusionsETx for breast cancer is associated with sustained increases in menopausal symptoms beyond those observed during natural menopause. The excess symptom burden is most pronounced among premenopausal women receiving ovarian function suppression. These findings highlight the importance of proactive symptom monitoring and supportive care strategies to improve long-term adherence to endocrine therapy.