Abstract
BACKGROUND: Premenopausal women undergoing chemotherapy are at risk for amenorrhea and impaired fertility. The objective of the current study was to assess levels of mullerian inhibitory substance (MIS), estradiol (E2), follicle-stimulating hormone (FSH), and menstrual status, in women undergoing chemotherapy. METHODS: A nested prospective cohort study was conducted in women aged <40 years with breast cancer (BC) who were undergoing adjuvant chemotherapy (n = 26). Serum MIS, FSH, and E2 were measured before chemotherapy (baseline) and at Weeks 6, 12, 36, and 52. Controls were 134 age-matched women with known fertility. Hormone levels were compared between the cases and controls at baseline. Differences between amenorrhea and age subgroups were tested using the nonparametric Wilcoxon 2-sample test using a 2-sided alpha of 0.05. RESULTS: Subjects with BC and age-matched controls had similar baseline MIS levels (median, 0.94 ng/mL vs 0.86 ng/mL;, P > .05). Serum MIS decreased significantly at 6 weeks and remained suppressed for 52 weeks. E2 levels decreased, and FSH levels increased during chemotherapy; however, at 52 weeks, the levels returned to baseline. At 52 weeks, only 1 patient had MIS above the lower normal range, 15 had return of menstrual function, 11 had premenopausal levels of FSH, and 13 had follicular phase levels of E2. In women aged <35 years, 25% remained amenorrheic, whereas in women aged >35 years, 50% were amenorrheic. Amenorrheic and menstruating women were found to have similar MIS values at baseline and follow-up. CONCLUSIONS: In young women with BC, chemotherapy decreases MIS rapidly and dramatically. Rapid reductions in MIS do not appear to be predictive of subsequent menstrual function. Ovarian reserve and endocrine function may be affected differently by chemotherapy.