Ovarian function and adjuvant chemotherapy for early breast cancer.

The effect of cyclophosphamide, methotrexate and fluorouracil (CMF) on ovarian function has been studied in 74 pre-menopausal patients with operable breast cancer. After median follow-up of 47 months, 50, 70 and 80% of 35 patients receiving CMF became permanently amenorrhoeic within 3, 6 and 12 months respectively; in contrast, only 5 in the no treatment (control) group of 39 patients became permanently amenorrhoeic within 12 months. Younger patients (less than 35 years) were more likely to retain or regain menstrual function while on or after CMF treatment. Estimation of ovarian and pituitary hormones in a subset of these women showed that CMF treatment was associated with a decrease in serum oestradiol and progesterone and an increase in serum follicle stimulating hormone and luteinizing hormone to post-menopausal levels. These hormonal changes are consistent with the induction of amenorrhoea during CMF treatment and the absence of resumption of menstrual function after completion of treatment suggests that CMF causes permanent ovarian ablation in a majority of these patients.