Background: The present study aimed to investigate the rate and time of ovarian function restoration in breast cancer patients between 40 and 60 years of age who were in menopause (biochemically documented) and received letrozole after chemotherapy. We intended to further clarify the management strategy for breast cancer patients with different menopausal status.Methods: We prospectively measured the effects of replacing tamoxifen with letrozole on ovarian function recovery in 90 women from two age groups (40-50 and 51-60 years). All had breast cancer and were treated by chemotherapy. Patients had laboratory documentation of menopause (FSH >40 mIU/ml and estradiol <20 pg/mL). Patients did not have menstruation for at least one year. Study patients received letrozole. At three month intervals, we checked their FSH and estradiol levels.Results: At three months after beginning letrozole, 12 patients in the younger age group had laboratory ovarian function restoration, among which three had vaginal bleeding. In the older group, 8 patients had increased estradiol levels; however, there was no evidence of vaginal bleeding in this group. At 6, 9 and 12 months, no ovarian function restoration was seen in the older group. However in younger patients, 4 had laboratory evidence of ovarian function restoration at 6 months, 2 at 9 months and 1 patient showed laboratory ovarian function restoration at 12 months of follow-up. Totally, there was a significant difference in the occurrence of ovarian function restoration between the two groups (P=0.03).Conclusion: A remarkable portion of women with chemotherapy-induced amenorrhea may develop ovarian function restoration. Therefore, endocrine therapy using aromatase inhibitors in patients with chemotherapy-induced amenorrhea should be followed by a regular hormonal study.