Pregnancy weight gain is not associated with maternal or mixed umbilical cord estrogen and androgen concentrations

The association of maternal weight gain with serum hormone concentrations was explored in 75 women who had healthy, singleton pregnancies. Estradiol, estriol, estrone, androstenedione, testosterone, dehydroepiandrosterone (DHEA), and DHEA sulfate concentrations were measured both in maternal and mixed umbilical cord serum to assess hormone levels in both the maternal and fetal circulation at delivery. Our data show no association of maternal or cord steroid hormone concentrations with pregnancy weight gain. Increased exposure to steroid hormones, especially estrogens, during pregnancy has been hypothesized to play a role in subsequent breast cancer risk for both mother and female offspring. Our results are not consistent with an effect of pregnancy weight gain being mediated by this pathway as reflected by hormone concentrations at the end of pregnancy. The US Government’s right to retain a non-exclusive, royalty free license in and to any copyright is acknowledged.     

Associations of maternal and umbilical cord hormone concentrations with maternal,gestational and neonatal factors (United States)

Objective: Risks of some cancers in adults have been associated with several pregnancy factors, including greater maternal age and birth weight. For hormone-related cancers, these effects are hypothesized to be mediated through higher in utero estrogen concentrations. In addition, racial differences in pregnancy hormone levels have been suggested as being responsible for differences in testicular and prostate cancer risk by race. However, data on hormonal levels related to these characteristics of pregnancy are sparse, particularly those from studies of the fetal circulation. Methods: Estrogen and androgen concentrations were measured in maternal and umbilical cord sera from 86 normal, singleton pregnancies. Results: Birth size measures (weight, length and head circumference) were positively correlated with maternal estriol (r = 0.25–0.36) and with cord DHEAS concentrations (r = 0.24–0.41), but not with estrogens in cord sera. Maternal age was inversely correlated with maternal DHEAS, androstenedione and testosterone concentrations (r = –0.30, –0.25 and –0.30, respectively), but uncorrelated with estrogens in either the maternal or cord circulation. Black mothers had higher androstenedione and testosterone concentrations than white mothers, however, there were no racial differences in any of the androgens in cord sera. Cord testosterone concentrations were higher in mothers of male fetuses, while both maternal and cord concentrations of estriol were lower in these pregnancies. Conclusions: These data demonstrate associations between hormone concentrations and pregnancy factors associated with offspring's cancer risk, however, the hormones involved and their patterns of association differ by whether the maternal or fetal circulation was sampled. Hormone concentrations in the fetal circulation in this study are not consistent with the hypothesis that greater estrogen concentrations in high birth weight babies mediate the positive association with breast cancer risk observed in epidemiologic studies, or with the hypothesis that higher testosterone exposure in the in utero environment of black males explains their higher subsequent prostate cancer risk.     

Associations among maternal soy intake, isoflavone levels in urine and blood samples, and maternal and umbilical hormone concentrations (Japan)

Absract Objectives In utero exposure to high levels of endogenous estrogens has been hypothesized to increase breast cancer risk in later life. A high intake of soy has been suggested to protect against breast cancer. We examined the hypothesis that maternal soy intake may be inversely associated with pregnancy hormone levels. Methods The concentrations of hormones (estradiol, estriol, and testosterone) and isoflavones (genistein, deidzein, and equol) were measured in the maternal urine and serum, and umbilical cord blood of 194 women during pregnancy and at delivery. Soy intake during pregnancy was assessed by 5-day diet records at approximately the 29th week of pregnancy. Results High correlations were observed for isoflavone levels between maternal samples and umbilical cord blood, indicating that isoflavone can be transferred from the maternal to the fetal compartment. None of the hormones measured in umbilical cord blood was significantly associated with any of the isoflavones measured. There were a few significant associations between maternal hormone levels and isoflavone measures during pregnancy, but their patterns of associations varied by gestational week and differed depending on whether isoflavone exposure was measured by diet records, urine or serum. Conclusion Our data contain no strong evidence showing that soy intake affects hormone levels during pregnancy.     

Association of maternal fat and alcohol intake with maternal and umbilical hormone levels and birth weight

High levels of estrogen during pregnancy have been hypothesized to increase the risk of breast cancer in offspring. Some studies have reported a positive association of estrogen level during pregnancy with fetal size, which has been linked to the subsequent risk of breast cancer in offspring. We examined whether maternal diet, including fat and alcohol intake, was associated with hormone levels during pregnancy, as well as with birth weight. The concentrations of estradiol, estriol, and testosterone were measured in the maternal serum and umbilical cord blood of 189 women during pregnancy and at delivery. Intakes of fat, alcohol, and other nutrients were assessed by 5-day diet records at approximately the 29th week of pregnancy before blood sampling. Intake of polyunsaturated fatty acids was moderately but significantly positively correlated with the umbilical cord estriol level (r = 0.17, P = 0.03) after controlling for covariates. The positive association between intake of polyunsaturated fatty acids and birth weight was of borderline significance (r = 0.14, P = 0.06). Intake of long-chain n-3 fatty acids was significantly inversely correlated with the umbilical cord estradiol and testosterone levels (r = -0.18, P = 0.02 and r = -0.24, P = 0.002, respectively). Alcohol intake was significantly positively correlated with the maternal estradiol level in the 29th week of pregnancy (r = 0.19, P = 0.01), but was unrelated to birth weight. Estrogen level during pregnancy may be regulated by dietary polyunsaturated fatty acids and mediate their effects on fetal growth.     

Maternal androgen and estrogen concentrations are not associated with blood pressure changes in uncomplicated pregnancies.

Systolic blood pressure increase between the second and third trimester of pregnancy has been associated with a substantially reduced maternal breast cancer risk, and it has been suggested that elevated androgens mediate the association. Androgen and estrogen concentrations were measured in maternal serum collected in 86 uncomplicated, singleton pregnancies. Overall, there were no consistent or statistically significant patterns of association between the hormones and systolic, diastolic, or mean arterial blood pressure or blood pressure change between trimesters. Results were similar with adjustment for factors related to the hormones. These data are not consistent with the hypothesis that elevated androgen concentrations mediate the observed reduction in maternal breast cancer risk associated with increases in blood pressure over the pregnancy.     

Mechanisms by which high maternal fat intake during pregnancy increases breast cancer risk in female rodent offspring

Emerging evidence indicates that a high in utero estrogenic environment increases breast cancer risk in women. We have proposed that a maternal intake of a high-fat diet is a source for high pregnancy estrogen levels and increases breast cancer risk among female offspring. In this review, the role of dietary fat in breast cancer, particularly during fetal life, is discussed. In addition, we provide possible mechanisms of action of the effects of a high-fat diet on the breast. These mechanisms include protein kinase C, estrogens and estrogen receptor, and alterations in mammary parenchymal structures.     

Preeclampsia and maternal breast cancer risk by offspring gender: do elevated androgen concentrations play a role?

Among older mothers, preeclampsia in the first pregnancy was associated with a reduction in maternal breast cancer risk that was significantly more pronounced in women bearing male than female infants. Androgen concentrations in male, preeclamptic pregnancies were consistent with the hypothesis that elevated pregnancy androgens might mediate this apparent modifying effect of fetal gender.     

Maternal and cord blood hormone levels in the United States and China and the intrauterine origin of breast cancer

BackgroundBreast cancer is less common in China than in the United States and perinatal characteristics predict breast cancer risk in the offspring. We determined levels of pregnancy hormones in Boston and Shanghai to identify those possibly involved in the intrauterine origin of breast cancer.Participants and methodsWe compared maternal and cord blood levels of estradiol, estriol, testosterone, progesterone, prolactin, insulin-like growth factors (IGF) 1 and 2, insulin-like growth factor-binding protein 3, adiponectin and sex hormone-binding globulin (SHBG) in 241 Caucasian and 295 Chinese women.ResultsIn both centers, hormone levels at the 16th were predictive of those at the 27th gestational week, but there was little correlation between maternal and cord blood levels. In cord blood, we found significantly (P < 0.01) higher levels of estradiol (44.2%), testosterone (54.5%), IGF-2 (22.7%) and strikingly SHBG (104.6%) in Shanghai women, whereas the opposite was true for IGF-1 (-36.8%).ConclusionsTaking into account the current understanding of the plausible biological role of the examined endocrine factors, those likely to be involved in the intrauterine origin of breast cancer are SHBG and IGF-2, with higher cord blood levels among Chinese, and IGF-1, with higher cord blood levels among Caucasian women.     

Pregnancy characteristics and maternal breast cancer risk: a review of the epidemiologic literature

The short- and long-term effects of pregnancy on breast cancer risk are well documented. Insight into potential biological mechanisms for these associations may be gained by studying breast cancer risk and pregnancy characteristics (e.g., preeclampsia, twining), which may reflect hormone levels during pregnancy. To date, no review has synthesized the published literature for pregnancy characteristics and maternal breast cancer using systematic search methods. We conducted a systematic search to identify all published studies. Using PUBMED (to 31 July 2009), 42 relevant articles were identified. Several studies suggest that multiple births may be associated with a lowered breast cancer risk of about 10–30%, but results were inconsistent across 18 studies. The majority of 13 studies suggest about a 20–30% reduction in risk with preeclampsia and/or gestational hypertension. Six of seven studies reported no association for infant sex and breast cancer risk. Data are sparse and conflicting for other pregnancy characteristics such as gestational age, fetal growth, pregnancy weight gain, gestational diabetes, and placental abnormalities. The most consistent findings in a generally sparse literature are that multiple births and preeclampsia may modestly reduce breast cancer risk. Additional research is needed to elucidate associations between pregnancy characteristics, related hormonal profiles, and breast cancer risk.     

The relationship between twin births and maternal risk of breast cancer: a meta-analysis

Women who undergo a greater number of menstrual cycles may be at increased risk of breast cancer, possibly due to cumulative exposure to ovarian hormones. Pregnancy reduces the lifetime number of menstrual cycles and also influences the levels of ovarian hormones. Twin pregnancies differ from singleton pregnancies in both hormone levels and perinatal changes. To date, a meta-analysis on the effects of twin birth on the risk of maternal breast cancer has not been conducted. Among 17 relevant publications identified in a systematic search, some suggest that twin births may be associated with lower breast cancer risk but others do not; therefore, the results are inconclusive. Although our pooled results of all 17 published studies did not show a reduced maternal risk of breast cancer for twin births (HR 0.94; 95% CI = 0.87-1.02; P = 0.127), a trend toward reduced maternal risk of breast cancer was identified in a subgroup analysis of cohort studies (HR 0.91; 95% CI = 0.83-1.01; P = 0.068). The results of this meta-analysis suggest that twin pregnancy does not significantly decrease the maternal risk of breast cancer.     

Aromatase, 17β-hydroxysteroid dehydrogenase and intratissular sex hormone concentrations in cancerous and normal glandular breast tissue in postmenopausal women

In a study of the origin of estrogens in patients with breast cancer, the concentrations of estrogens and their androgen precursors, and aromatase and 17β-hydroxysteroid dehydrogenase (E₂DH) activities were determined in normal glandular and cancerous breast tissue. The correlation between tissue estrogens, precursor concentrations, enzyme activities and plasma levels and/or receptor status were calculated. In both normal glandular and carcinomatous breast tissue, the concentrations of androstenedione (A), dehydroepiandrosterone (DHEA), 5 androstene-3β, 17β-diol (5-Adiol), estrone (E₁), estradiol (E₂) and progesterone (P) were significantly higher than plasma concentrations. While testosterone (T) concentrations were similar, dehydroepiandrosterone (DHCA) and estrone sulphate (E₁S) concentrations were lower in tissue than in plasma. In carcinomatous tissue androgen concentrations were lower, but estrogen concentrations were higher than in glandular breast tissue. Estradiol (E₂) concentration was positively correlated with the receptor concentration with the mean E₂ concentration corresponding to an estimated receptor occupancy of about 25%, probably sufficient for a submaximal biological response. Aromatase and E₂DH (E₂ → E₁) activities were observed in all breast cancer and glandular breast tissues, activities being higher in carcinoma than in glandular breast tissues; nevertheless, aromatase activity accounts probably only for a small fraction of tissue estrogen concentration. E₂DH, but not aromatase activity, was significantly higher in estrogen receptor positive than in estrogen receptor negative tissues and was negatively correlated with tissue dehydroepiandrosterone (DHEA) and its sulphate (DHEAS) concentration; the latter two steroids are non competitive inhibitors of E₂DH which inactivates E₂ to E₁. This effect of DHEA (S) may constitute a mechanism by which these androgens stimulate cancer growth and a rationale (besides suppression of estrogen precursors) for medical or surgical adrenalectomy in hormone sensitive metastatic mammary cancer. E₂DH activity might constitute an additional marker of hormone dependency of mammary cancer.     

Cord serum estrogens, androgens, insulin-like growth factor-I, and insulin-like growth factor binding protein-3 in Chinese and U.S. Caucasian neonates

Markedly lower breast cancer incidence rates in Asians than Caucasians are not explained by established adult risk factors. Migration studies suggest the importance of early-life exposures, including perhaps the in utero period. Concentrations of steroid hormones and insulin-like growth factors (IGF) were measured in umbilical cord sera from pregnancies in Shanghai, China (n = 121) and Boston, MA (n = 111). Pregnancy characteristics were ascertained by interview and medical records. Means and percent differences in hormone concentrations comparing Chinese with Caucasians and 95% confidence intervals were estimated from linear regression models. Cord concentrations of androstenedione (91.9%), testosterone (257%), estriol (48.6%), and IGF binding protein-3 (21.1%) were significantly higher in the Chinese than U.S. samples, and cord prolactin was lower (-14.9%). Cord estradiol and IGF-I concentrations did not differ by race/ethnicity. With adjustment for gestational length, maternal age, pre-pregnancy weight, and weight gain, androstenedione (60.5%), testosterone (185%), and IGF binding protein-3 (40.4%) remained significantly higher in the Chinese, whereas the higher estriol and lower prolactin concentrations were attenuated. In addition, estradiol levels became lower in the Chinese (-29.8%) but did not reach statistical significance. Results were generally similar when restricted to first full-term pregnancies, with reduced estradiol concentrations in the Chinese reaching statistical significance after adjustment. These data are consistent with the hypothesis that elevated prenatal androgen exposure could mediate reductions in breast cancer risk. The meaning of the change in findings for estrogens after controlling for factors related to the pregnancy is unclear with regard to explaining international breast cancer differences.     

Effects of parity on pregnancy hormonal profiles across ethnic groups with a diverse incidence of breast cancer.

Epidemiologic evidence suggests that a full-term pregnancy may affect maternal risk of breast cancer later in life. The objective of this cross-sectional study was to compare circulating levels of maternal hormones affecting breast differentiation (human chorionic gonadotropin and prolactin) and proliferation [alpha-fetoprotein, insulin-like growth factor I (IGF-I), and estradiol] between women at a low to moderate risk (Asians and Hispanics), as compared with women at a high risk for breast cancer (Caucasians and African-Americans). Between May 2002 and December 2004, a total of 586 pregnant women were approached during a routine prenatal visit. Among them, 450 women (206 Caucasian, 126 Asian, 88 Hispanic, and 30 African-American) met the inclusion criteria and signed the informed consent. Only singleton pregnancies were considered. Blood samples were drawn during the second trimester of pregnancy. Laboratory analyses were done using the IMMULITE 2000 immunoassay system. Gestational age standardized mean levels of estradiol, IGF-I, and prolactin were significantly higher in Hispanic women compared with Caucasian women. Mean concentration of IGF-I was significantly higher in African-American women compared with Caucasian and Asian women. No significant differences in pregnancy hormone levels were observed between Caucasian and Asian (predominantly second-generation Chinese) women in this study. Irrespective of ethnicity, women who had their first pregnancy had substantially higher mean levels of alpha-fetoprotein, human chorionic gonadotropin, estradiol, and prolactin compared with women who previously had at least one full-term pregnancy. These data suggest that circulating pregnancy hormone levels may explain some of the ethnic differences in breast cancer risk.     

Maternal hormones during early pregnancy: a cross-sectional study

Background

Little is known about correlates of first-trimester pregnancy hormones as in most studies maternal hormones have been measured later in gestation. We examined the associations of maternal characteristics and child sex with first-trimester maternal concentrations of four hormones implicated in breast cancer: human chorionic gonadotropin (hCG), α-fetoprotein (AFP), insulin-like growth factor (IGF)-I, and IGF-II.

Methods

About 338 serum samples donated to the Northern Sweden Maternity Cohort (NSMC), 1975–2001, during the first trimester of uncomplicated pregnancies, were analyzed for the hormones of interest as a part of a case–control study. The associations of maternal characteristics and child sex with hormone concentrations were investigated by correlation, general linear regression, and multivariate regression models.

Results

In the first trimester, greater maternal age was inversely correlated with IGF-I and IGF-II. In comparison with women carrying their first child, already parous women had higher IGF-I but lower hCG. Greater maternal weight and smoking were inversely correlated with hCG. No differences in hormone levels by child sex were observed.

Conclusions

Our analyses indicated that potentially modifiable maternal characteristics (maternal weight and smoking) influence first-trimester pregnancy maternal hormone concentrations.     

Maternal height, pregnancy estriol and birth weight in reference to breast cancer risk in Boston and Shanghai

Birth weight has been positively associated with breast cancer risk in adult life and is positively associated with the principal pregnancy estrogen estriol. Birth weight is lower among Chinese women than among Caucasian women, but paradoxically, pregnancy estriol levels are higher among the former than the latter. We studied a cohort of 317 Caucasian pregnant women in Boston, MA, and 339 Chinese pregnant women in Shanghai, China. We investigated whether maternal height, which is inversely associated with pregnancy estriol levels, interacts with this hormone in relation to birth weight, thus accommodating the apparently contradictory ecologic and analytic evidence concerning the role of pregnancy estrogens on breast cancer risk in the offspring. In both Boston and Shanghai, there was a positive association of pregnancy estriol with birth weight among taller women, whereas among shorter women the association was essentially null. The relevant interaction terms were highly significant in Boston (p approximately 0.006), whereas in Shanghai, where pregnant women were generally shorter, the interaction term was suggestive (p approximately 0.14). We conclude that maternal height should be considered an important risk factor for breast cancer in the offspring since it is a crucial determinant of birth weight, both directly and through positive interaction with the principal pregnancy estrogen estriol.     

Plasma volume expansion in pregnancy: implications for biomarkers in population studies.

There is a growing body of literature focused on endogenous hormone exposures during pregnancy and subsequent cancer risk for both mother and offspring. Examples of these studies include those focused on the biological mechanism for the association of preeclampsia with reduced risk of breast cancer for mother and female offspring or studies that have examined hormone concentrations during pregnancy between different ethnic groups who vary in their rates of breast cancer incidence. Although these studies seem relatively straightforward in conception and analysis, measurement of the concentration of hormones and other biomarkers in pregnant subjects is influenced by plasma volume expansion (PVE). During pregnancy, the maternal plasma volume expands 45% on average to provide for the greater circulatory needs of the maternal organs. Consequently, serum protein and hormone concentrations are greatly altered when comparing the pregnant with nonpregnant state. Assessing PVE also is complicated by the vast individual variation in PVE, ranging from minimal to a 2-fold increase. We propose that PVE needs to be evaluated when comparing biomarker concentrations during pregnancy in two populations that may differ with respect to PVE. Small body size is associated with lower PVE compared with higher body size. Therefore, we hypothesize that variation in PVE will influence the interpretation of differences in biomarker concentrations across population groups with respect to the etiologic significance of the biomarker to the disease under study (e.g., breast cancer). It is possible that some observations may be due only to differences in dilution between the two groups. We present PVE as a topic for consideration in population-based studies, examples of the types of studies where PVE may be relevant, and our own analysis of one such study in the text below.     

Prenatal and perinatal risk factors and testicular cancer: a hospital-based case-control study

Some evidence exists to support the hypothesis that elevated levels of circulating maternal estrogens during early pregnancy may increase risk of testicular germ cell cancer. However, the results from studies evaluating maternal factors have been mixed. We evaluated maternal factors, particularly those associated with excess estrogen levels, as risk factors for testicular cancer. We conducted a hospital-based case-control study at The University of Texas M. D. Anderson Cancer Center in Houston, Texas of 144 testicular cancer patients diagnosed between 1990 and 1996 and 86 friend controls matched to cases on age, race, and state of residence. Risk factor data about the mother, the son, and the pregnancy were obtained from the mothers by telephone interviews and from the sons by self-administered questionnaires. Extreme nausea during the first trimester of pregnancy was associated with an elevated risk of testicular cancer [odds ratio (OR) = 2.0; 95% confidence interval (CI) = 1.0-3.9]. Adjustment for potential confounders slightly lowered this risk (OR = 1.8; 95% CI = 0.9-3.8). Risks were modestly increased for other factors that are proxy measures for maternal estrogens, including preterm delivery (OR = 2.2; 95% CI = 0.4-12.9), birth weight <3000 g (OR = 2.4: 95% CI = 0.7-8.1), and birth weight >4000 g (OR = 1.7; 95% CI = 0.9-3.2), albeit nonsignificantly so. Our finding that severe nausea was associated with increased testicular cancer risk adds evidence to support the in utero estrogen exposure hypothesis because nausea early in pregnancy is related to rising levels of circulating estrogens. For other factors, which are less direct measures of maternal estrogens, the modest associations found indicate a suggestive pattern in support of the excess estrogen hypothesis.     

Dietary modulation of pregnancy estrogen levels and breast cancer risk among female rat offspring.

PURPOSE: Against the hypothesis that high estrogen levels in utero increase the risk of developing breast cancer in later life are data showing that pregnancy estrogen levels are significantly higher in Asian women who have low breast cancer risk than in Caucasian women. We investigated whether maternal dietary intake of genistein or n-3 polyunsaturated fatty acids (PUFAs), which are typical to Asian but not Caucasian diet, affect pregnancy estrogen levels and susceptibility to mammary tumorigenesis among offspring. EXPERIMENTAL DESIGN: For that purpose, pregnant female Sprague Dawley rats were fed isocaloric AIN-93-based diets containing either at 15 mg (low), 150 mg (medium), or 300 mg (high)/kg genistein/diet or low- or high-fat (16 versus 39% energy from fat) diet composed either of n-3 PUFA menhaden oil or n-6 PUFA corn oil. All diets were switched to regular AIN-93 diet when pups were born. RESULTS: Maternal intake of n-3 PUFA diets significantly increased pregnancy 17 beta-estradiol (E2) levels (48% increase when compared with high n-6 PUFA diet; P < 0.0045). High genistein exposure also increased pregnancy estrogen levels, but the increase did not reach statistical significance (P < 0.14). The offspring of high-fat n-3 PUFA-consuming dams were significantly less likely to develop 7,12-dimethylbenz-[a]anthracene-induced mammary tumors (38% of these rats developed tumors during week 17 versus 64% of high n-6 PUFA offspring; P < 0.003). Maternal genistein intake did not affect offspring's tumor incidence. The mammary glands of high fat n-3 PUFA offspring contained more lobules (P < 0.07) and were thus more differentiated, whereas the glands of high genistein offspring contained more terminal end buds (P < 0.0015), which are the sites of malignant transformation. CONCLUSIONS: Our findings indicate that the elevated estrogen levels in the n-3 PUFA mothers were linked to reduced rather than increased breast cancer risk among their offspring, suggesting that other effects of n-3 PUFA may counteract the effects of high fetal estrogenicity on the mammary gland. High maternal genistein intake did not reduce offspring's breast cancer risk, and therefore high maternal soy intake in Asian women may not be associated with daughters' low breast cancer risk.     

Nipple Aspirate Fluid Hormone Concentrations and Breast Cancer Risk

Prior reports identify higher serum concentrations of estrogens and androgens as risk factors for breast cancer, but steroids in nipple aspirate fluid (NAF) may be more related to risk. Incident breast cancer cases and mammography controls were recruited. Sex steroids were measured in NAF from the unaffected breasts of cases and one breast of controls. Menopausal status and menstrual cycle phase were determined. NAF steroids were purified by HPLC and quantified by immunoassays. Conditional logistic regression models were used to examine associations between NAF hormones and case-control status. NAF samples from 160 cases and 157 controls were evaluable for hormones. Except for progesterone and dehydroepiandrosterone (DHEA), the NAF and serum concentrations were not significantly correlated. NAF estradiol and estrone were not different between cases and controls. Higher NAF (but not serum) DHEA concentrations were associated with cases, particularly among estrogen receptor (ER)-positive cases (NAF odds ratio (OR)?=?1.18, 95 % confidence interval (CI) 1.02, 1.36). NAF DHEA was highly correlated with NAF estradiol and estrone but not with androstenedione or testosterone. Higher progesterone concentrations in both NAF and serum were associated with a lower risk of ER-negative cancer (NAF OR?=?0.69, 95 % CI 0.51, 0.92). However, this finding may be explained by case-control imbalance in the number of luteal phase subjects (2 cases and 19 controls). The significantly higher concentration of DHEA in NAF of cases and its correlation with NAF estradiol indicates a potentially important role of this steroid in breast cancer risk; however, the negative association of progesterone with risk is tentative.     

Light exposure at night, urinary 6-sulfatoxymelatonin, and serum estrogens and androgens in postmenopausal Japanese women.

It has been hypothesized that exposure to light at night increases the risk of breast cancer by suppressing the normal nocturnal increase in melatonin production and release, thereby resulting in increased levels of circulating estrogen. We assessed associations among concentrations of serum estrogen and androgen and the principal metabolite of melatonin in urine, 6-sulfatoxymelatonin, and exposure to light at night based on information regarding the sleeping habits and history of graveyard-shift work of 206 postmenopausal Japanese women. Serum estradiol level was significantly higher in women who were not asleep at or after 1:00 a.m. (the approximate time of the melatonin peak) than those who were asleep after controlling for covariates. Significantly increased estrone levels were observed in women who had worked graveyard shift. Serum testosterone and DHEA sulfate were unrelated to sleeping habits and history of graveyard-shift work. Urinary 6-sulfatoxymelatonin was lower in women who were not asleep at or after 1:00 a.m. on weekends than those who were asleep at this time, but the difference was of borderline significance (P = 0.08). There was no significant association between urinary 6-sulfatoxymelatonin and any serum hormone levels. These data suggest that exposure to light at night has implications for the risk of breast cancer in postmenopausal women. However, the potential role of melatonin as an intervening factor between light exposure at night and the serum concentrations of estrogen was equivocal.