Menstrual cycle and exposure to oestrogens unopposed by progesterone: relevance to studies on breast cancer incidence.

It is claimed that the exposure of women to oestrogens unopposed by progesterone increases the risk of breast cancer. Despite indirect evidence in support of this claim, the impracticability of monitoring oestrogen and progesterone levels in large numbers of women for prolonged periods of time has meant that no direct demonstration of the effect has been made. A possible technique is suggested. The ratio (R) of oestrogens to pregnanediol in urine has been used as an index of oestrogen exposure relative to progesterone. Samples were collected at weekly intervals on 700 occasions from 30 perimenopausal women, and on 519 occasions from 66 women with a history of regular menstrual cyclicity. Unusually prolonged episodes of unopposed high oestrogen excretion (R greater than or equal to 100 for greater than or equal to 2 successive weeks) were observed on 30 occasions in 15 of the perimenopausal women and on four occasions in the other women. In the perimenopausal group, these episodes occurred in 46.9% of the 32 menstrual cycles which were longer than 50 days compared with 6.9% of the 72 cycles which were shorter than 35 days (P less than 0.001). The association of prolonged episodes of unopposed high oestrogen excretion with long menstrual cycles suggests the possibility of using menstrual cycle length as an index of oestrogen exposure during the menopausal transition.