Abstract:Objective To investigate influencing factors of Chemotherapy-Induced Amenorrhea(CIA)and identify their ovarian function and actual menstrual status. Methods Patients with premenopausal breast cancer undergoing at least 4 cycles of chemotherapy were recruited. The patient's age, pathological type, tumor stage, the number of axillary lymph node metastasis, the hormone receptor, HER-2, chemotherapy, radiotherapy, endocrine therapy, targeted therapy, the changes of menstruation, and serum sex hormone levels(FSH, LH, E2)were analyzed. ROC curve, Fisher's exact probability test, and chi-square test were used to determine the relationship between the factors and CIA. Meanwhile, Kaplan Meier-survival was applied to analyze the interval between CIA and menopause. Results The CIA was observed in 204 patients. Age exhibited apparent correlation with the CIA, AUC 0.899(P<0.001,95% CI: 0.863~0.935)and the CIA's best threshold was 43. The occurrence of CIA was not significantly associated with tumor stage, pathological type, the number of axillary lymph node metastasis, the status of ER, PR, and HER-2, chemotherapy regimens, whether received radiotherapy,targeted therapy or endocrine therapy(P>0.05). Among the individuals with CIA, age less than or equal to 45 years old were more likely to restore menstruation(91.4% vs 35.8%, P<0.001), the median time of menstrual recovery was 6.7 months(3.0~11.3 months). Menopause generally occurred in cases over 45 years old(1.4% vs 50.0%, P<0.001). Through Kaplan Meier-analysis, the time of CIA occurred evidently earlier than menopause(2.6 months vs 13.6 months, P<0.001); in the group of 46~50 years old and over 50 years old, the time interval was significantly(2.6 months vs 17.2 months, P<0.001; 1.9 months vs 12.1 months, P<0.001). Conclusions Age is an independent and major predictor for the occurrence of CIA, menstrual resumption, and menopause. Menopause generally occurs in patients over 45 years old, while menstruation recovery is found in patients less than or equal to 45. The occurrence of CIA is earlier than menopausal, which is critical in judging actual menopause status and for optimizing endocrine regimen.