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Pregnancy Hormones, Pre-eclampsia, and Implications for Breast Cancer Risk in the Offspring¹

Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts [R. T., P. L., L. M., D. T., A. E., H-O. A., C-C. H.]; Department of Hygiene and Epidemiology, School of Medicine, University of Athens, Athens, Goudi, Greece [P. L., D. T.]; Department of Community Medicine and General Practice, School of Medicine, Norwegian University of Science and Technology, Trondheim, Norway [L. J. V.]; Department of Obstetrics and Gynecology, Beth Israel Hospital, Boston, Massachusetts [S. H.]; Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden [A. E., H-O. A.]; and University of Massachusetts Cancer Research Center, Worcester, Massachusetts 01605 [C-C. H.]

The aim of this study is to prospectively assess pregnancy hormone levels as correlates of subsequent development of pre-eclampsia, a condition that has been shown to be inversely associated with breast cancer risk in the offspring. A cohort of 260 Caucasian women in Boston, Massachusetts, was followed through pregnancy. Maternal blood was collected at the 16th and 27th weeks of gestation, and 18 women were diagnosed with pre-eclampsia after blood collection. Information on sociodemographic variables and risk factors of pre-eclampsia was collected through an interviewer-administered questionnaire and review of medical records. At the 16th week, there was a nonsignificant positive association between progesterone levels and pre-eclampsia [relative risk (RR) = 1.63, 95% confidence interval (CI), 0.97–2.74, per 1 SD increase]. By the 27th week, the association between progesterone and pre-eclampsia was strengthened (RR = 2.65, 95% CI, 1.46–4.81, per SD), and sex hormone-binding globulin levels were somewhat inversely related to pre-eclampsia (RR = 0.61, 95% CI, 0.31–1.20, per SD). No difference was found with respect to prolactin, estradiol, and estriol levels. Our findings indicate that progesterone may have a role in the late manifestation of pre-eclampsia pathology but are also compatible with the hypothesis that increases in progesterone represent an early compensatory mechanism.

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