Impaired ovulation and breast cancer risk.

Conflicting results have been reported on the association between breast cancer risk and symptoms of luteal insufficiency, such as irregular or prolonged menstrual cycles and difficulty in becoming pregnant. Studies on the association between breast cancer risk and hormonal markers of impaired ovulation have also yielded conflicting results. Inadequate allowance for body mass and fat distribution may lead to inconsistent results when assessing the association between luteal insufficiency in premenopausal women and breast cancer risk. Ovulatory function is impaired by obesity, especially if it is predominantly abdominal in distribution. The Western diet and lifestyle favour early manifestation of hyperinsulinaemic insulin resistance in genetically-predisposed women. It is commonly associated with obesity which is predominantly abdominal in distribution. In a subset of premenopausal women, the concomitants of hyperinsulinaemia may impair maturation of ovarian follicles by a direct effect of insulin or insulin-like growth factors on ovarian tissue. Even when women are ovulating regularly, obesity may be associated with luteal insufficiency as shown by decreased levels of progestins or other changes in the sex steroid profile. Insulin resistance is likely to be involved and might explain the weak reduction in breast cancer risk associated with overweight in premenopausal Western women, in contrast with the increased risk widely reported in obese post menopausal women.