Effects of cytotoxic chemotherapy on ovarian and adrenal steroidogenesis in pre-menopausal breast cancer patients.

Many patients on cytotoxic chemotherapy show reduced frequency of menstrual bleeding due to a reduction in ovarian follicular activity. The endocrine perturbations related to these changed menstrual patterns were studied in detail. Nineteen regularly menstruating patients with primary breast cancer were given either cyclophosphamide or chlorambucil in combination with methotrexate and fluorouracil as adjuvant therapy. Some patients continued to menstruate normally, while others became amenorrhoeic. However, the majority showed reduced menstrual activity, and, in these, the reproductive endocrinology was highly variable. Increased gonadotrophin levels brought about episodes of follicular activity but not ovulation. During these episodes, oestradiol levels reached normal follicular values. Adrenal function appeared to be unaffected. Although an endocrine response by the tumour might be expected to cytotoxic-induced ovarian ablation, the clinical significance of the disrupted, but incompletely suppressed ovarian function, is unknown.