0277-5379/&393.00+0.00 0 1988 Pergalnon Press plc The Permanent Effect of Reproductive Events on Blood Prolactin Levels and its Relation to Breast Cancer Risk: a Population Study of Postmenopausal Women D.Y. WANG,* B.L. DE STAVOLA,* R.D. BULBROOK,* D.S. ALLEN,* H.G. KWA,t AA. VERSTRAETEN,? J.W. MOORE,* I.S. FENTIMAN,: J.L. HAYWARD: and I.H. GRAVELLEg *Imperial Cancer Research Fund, P.O. Box 123, Lincoln’s Inn Fields, London WC2R 3PX, C’.K., TAntoni van Leeuwenhoekhuis, Plesmanlaan 12 1, 1066 CX Amsterdam, The Netherlands , +,Clinical Oncology Unit, Guy’s Hospital, London SE1 9RT, L1.K. and SDepartment of Radiology, University Hospital of Wales, CardifJ L:.K. Abstract-In each of two population-based studies conducted on the Island of Guernsey between 1967-1976 and 1977-1984, respectively, single specimens of blood were taken from over 5000 normal women. From these two studies there were 1173 and 946 postmenopausal women in whom blood prolactin was determined and multivariate analysis was used to establish the association between blood prolactin concentration and possible determinants of risk of breast cancer. Since prolactin levels were log-normally distributed these analyses ioere done on log- transformed data. The age at menarche or menopause, age at first or last childbirth, length of reproductive life (i.e. time ,from menarche to menopause) or post-menopausal life (i.e. time from menopause to time of blood sampling), contraceptive use and history of breast cancer were not significantly associated with blood prolactin concentration. Of sign$cance were age, par+, time of blood sampling and assay drift. Ponderosity (Quetelet’s Index) was positively associated with prolactin concentration and this was signtfiant using a one-tail criterion. Women with a mammographic pattern designated DY by Wolfe had signijcantb higher prolactin levels than those wlith N1 patterns. However, the main Jinding to emerge was that after standardizing for all the other variables increasing parity was related to a step-wise reduction in blood prolactin levels. Since this had occurred in women who had had their last child up to 35 years previously it implies this effect is permanent. It could therefore be that the protective effect on breast cancer risk of multiparity and earlq’,first pregnancy could be mediated by such a life-long reduction in blood prolactin levels. INTRODUCTION IT IS difficult to relate breast cancer risk factors with blood prolactin concentration because of the number of confounding factors which also influence prolactin levels [I]. However, this difficulty can be overcome by the use of multivariate analysis provided that prolactin measurements have been made on a sufficiently large population of women. An opportunity for such an analysis has been pre- sented by two prospective studies on the Island of Guernsey in which over 5000 women enrolled in each study and donated a sample of blood. A multivariate analysis on premenopausal women from these studies showed that the breast Acccptrd 29 February 1988. 1225 cancer risk factors of parity, ponderosity and DY mammographic pattern were significantly associ- ated with changes in prolactin levels giving support to the hypothesis that prolactin levels are positively associated with risk [ 11. In particular, multiparity, which is claimed to be protective [2-41, was signifi- cantly related with low levels of blood prolactin [ 11. The intention of this paper is to apply multivari- ate analysis to the prolactin data from the postmeno- pausal women who participated in the two Guernsey studies in order to explore further the association between determinants of breast cancer risk and prolactin levels and to establish whether the relationships found previously in premenopausal women [l] are of long duration and persist in postmenopausal women.