Early pregnancy sex steroids and maternal risk of epithelial ovarian cancer.

Well-established associations between reproductive characteristics and epithelial ovarian cancer (EOC) support an involvement of sex steroid hormones in the etiology of EOC. Limited previous studies have evaluated circulating androgens and the risk of EOC, and estrogens and progesterone have been investigated in only one of the previous studies. Furthermore, there is little data on potential heterogeneity in the association between circulating hormones and EOC by histological subgroup. Therefore, we conducted a nested case-control study within the Finnish Maternity Cohort and the Northern Sweden Maternity Cohort to investigate the associations between circulating pre-diagnostic sex steroid concentrations and the histological subtypes of EOC. We identified 1052 EOC cases among cohort members diagnosed after recruitment (1975-2008) and before March 2011. Up to three controls were individually matched to each case (n=2694). Testosterone, androstenedione, 17-hydroxyprogesterone (17-OHP), progesterone, estradiol (E2), and sex hormone-binding globulin levels were measured in serum samples collected during the last pregnancy before EOC diagnosis. We used conditional logistic regression to estimate odds ratios (ORs) and 95% CIs. Associations between hormones and EOC differed with respect to tumor histology and invasiveness. Sex steroid concentrations were not associated with invasive serous tumors; however, doubling of testosterone and 17-OHP concentration was associated with approximately 40% increased risk of borderline serous tumors. A doubling of androgen concentrations was associated with a 50% increased risk of mucinous tumors. The risk of endometrioid tumors increased with higher E2 concentrations (OR: 1.89 (1.20-2.98)). This large prospective study in pregnant women supports a role of sex steroid hormones in the etiology of EOC arising in the ovaries

Plasma metabolite markers of parkinson’s disease and atypical parkinsonism

Differentiating between Parkinson’s disease (PD) and the atypical Parkinsonian disorders of multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) is difficult clinically due to overlapping symptomatology, especially at early disease stages. Consequently, there is a need to identify metabolic markers for these diseases and to develop them into viable biomarkers. In the present investigation, solution nuclear magnetic resonance and mass spectrometry metabolomics were used to quantitatively characterize the plasma metabolomes (a total of 167 metabolites) of a cohort of 94 individuals comprising 34 PD, 12 MSA, and 17 PSP patients, as well as 31 control subjects. The distinct and statistically significant differences observed in the metabolite concentrations of the different disease and control groups enabled the identification of potential plasma metabolite markers of each disorder and enabled the differentiation between the disorders. These group-specific differences further implicate disturbances in specific metabolic pathways. The two metabolites, formic acid and succinate, were altered similarly in all three disease groups when compared to the control group, where a reduced level of formic acid suggested an effect on pyruvate metabolism, methane metabolism, and/or the kynurenine pathway, and an increased succinate level suggested an effect on the citric acid cycle and mitochondrial dysfunction

Hormone concentrations throughout uncomplicated pregnancies : a longitudinal study

Background: Evidence suggests that the hormonal milieu of pregnancy is an important determinant of subsequent cancer and other chronic diseases in both the mother and the offspring. Many of the existing maternity and birth cohorts include specimens drawn only once during pregnancy. How well a single blood specimen collected during a pregnancy characterizes exposure to these hormones throughout gestation, and also in subsequent pregnancies, is not well understood. Methods: We used serial serum samples from 71 pregnant women (25 primiparous, 25 multiparous, and 21 with two consecutive pregnancies) with natural, complication-free pregnancies and a healthy offspring at term who participated in a population-based screening trial for congenital infections in Finland between January 1st, 1988 and June 30, 1989 and provided a blood sample in each trimester. Results: Hormone levels were more strongly correlated between consecutive trimesters of a pregnancy than between the 1st and 3rd trimester (e.g., estradiol, r(T1 vs. T2) = 0.51 and r(T2 vs. T3) = 0.60, p < 0.01; r(T1 vs. T3) = 0.32, p < 0.05). Concentrations of sRANKL remained stable throughout gestation, whereas estradiol, estrone, progesterone, testosterone, prolactin, and osteoprotegerin increased throughout pregnancy. First trimester hormone concentrations explained less of the variation in the third trimester on their own than second trimester hormone levels (e.g. estradiol R-T1(2) = 16 % and R-T2(2) = 42 %). Addition of maternal (e.g., smoking) and/or child characteristics (e.g., sex) improved the accuracy of the 3rd trimester estimates for some of the hormones. Conclusions: One hormone measurement in early pregnancy, in conjunction with maternal and fetal characteristics, permits estimation of 3rd trimester hormone concentrations. Therefore, single hormone measurements available from maternity cohorts are suitable to quantify hormone exposure during pregnancy. To our knowledge, we provide the first data on correlations between hormone concentrations both across trimesters of a single pregnancy, as well as between two subsequent pregnancies

Early pregnancy sex steroids during primiparous pregnancies and maternal breast cancer : a nested case-control study in the Northern Sweden Maternity Cohort

Background: Pregnancy and parity are associated with subsequent breast cancer risk. Experimental and epidemiologic data suggest a role for pregnancy sex steroid hormones. Methods: We conducted a nested case–control study in the Northern Sweden Maternity Cohort (1975–2007). Eligible women had provided a blood sample in the first 20 weeks of gestation during a primiparous pregnancy leading to a term delivery. The current study includes 223 cases and 417 matched controls (matching factors: age at and date of blood collection). Estrogen receptor (ER) and progesterone receptor (PR) status was available for all cases; androgen receptor (AR) data were available for 41% of cases (n = 92). Sex steroids were quantified by high-performance liquid chromatography tandem mass spectrometry. Odds ratios (ORs) and 95% confidence intervals were estimated using conditional logistic regression. Results: Higher concentrations of circulating progesterone in early pregnancy were inversely associated with ER+/PR+ breast cancer risk (ORlog2: 0.64 (0.41–1.00)). Higher testosterone was positively associated with ER+/PR+ disease risk (ORlog2: 1.57 (1.13–2.18)). Early pregnancy estrogens were not associated with risk, except for relatively high estradiol in the context of low progesterone (split at median, relative to low concentrations of both; OR: 1.87 (1.11–3.16)). None of the investigated hormones were associated with ER–/PR– disease, or with AR+ or AR+/ER+/PR+ disease. Conclusions: Consistent with experimental models, high progesterone in early pregnancy was associated with lower risk of ER+/PR+ breast cancer in the mother. High circulating testosterone in early pregnancy, which likely reflects nonpregnant premenopausal exposure, was associated with higher risk of ER+/PR+ disease