The risk of premature menopause induced by chemotherapy for early breast cancer

J Womens Health Gend Based Med. 1999 Sep;8(7):949-54. doi: 10.1089/jwh.1.1999.8.949.


The objectives of this retrospective case series were to determine the prevalence and timing of menstrual abnormalities in early-stage breast cancer patients undergoing adjuvant methotrexate or anthracycline-based chemotherapy and to more fully assess the possible mechanism of the amenorrhea reported after chemotherapy. One hundred forty-two premenopausal patients undergoing adjuvant chemotherapy were analyzed for patient age, breast cancer stage, type of chemotherapy, and menstrual abnormalities before, during, and after chemotherapy completion. A 24-month minimum follow-up after chemotherapy completion was available for all patients. One hundred nine of 142 patients were evaluable. Sixty-nine patients (46 node negative, 23 node positive) received methotrexate-based chemotherapy, 33 patients (3 node negative, 30 node positive) received anthracycline-based chemotherapy, and 7 patients received both treatments (all node positive). Amenorrhea occurred in about a third of patients during chemotherapy (methotrexate groups 31%, anthracycline group 33%), and a higher proportion were amenorrheic 1 year after chemotherapy was completed (methotrexate group 45%, anthracycline group 46%). Abnormalities were more likely to occur in older premenopausal patients (Chi square = 6.18, p < 0.05), although 28% of patients under age 35 developed persistent abnormal menses. In some amenorrheic patients, follicle-stimulating hormone (FSH) levels were decreased within 6 months of chemotherapy (24.4 IU). The levels tended to be higher after chemotherapy (59.1 IU), suggesting ovarian failure. Menstrual abnormalities and menopause will frequently occur in premenopausal early-stage breast cancer patients, with 30% of all patients amenorrheic 1 year after chemotherapy.

MeSH terms

  • Adult
  • Amenorrhea / chemically induced*
  • Antibiotics, Antineoplastic / adverse effects
  • Antibiotics, Antineoplastic / therapeutic use
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Breast Neoplasms / drug therapy*
  • Estradiol / blood
  • Female
  • Follicle Stimulating Hormone / blood
  • Follow-Up Studies
  • Humans
  • Menopause, Premature*
  • Methotrexate / adverse effects
  • Methotrexate / therapeutic use
  • Primary Ovarian Insufficiency / chemically induced
  • Retrospective Studies
  • Risk Factors
  • Time Factors


  • Antibiotics, Antineoplastic
  • Antineoplastic Agents
  • Estradiol
  • Follicle Stimulating Hormone
  • Methotrexate