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ABSTRACT: The immune activation that occurs with infection diverts energy from growth and can contribute to poor nutritional outcomes in developing infants and children. This study investigates the association between salivary immunoglobulin A (IgA) levels and growth outcomes among Ariaal infants of northern Kenya. The Ariaal are a group of settled northern Kenyan pastoralists who are under considerable nutritional stress. Two hundred and thirty-nine breastfeeding Ariaal infants were recruited into the study and underwent anthropometric measurement and saliva collection, with mothers providing individual and household characteristics for them via questionnaire. Infant saliva samples were analyzed with an ELISA for IgA in the United States. Infant anthropometric measurements were converted to height-for-age z-scores (HAZ) using the WHO Child Growth Standards. Based on multivariate models performed in SAS 9.2 two main results emerge: 1) low HAZ, an indicator of chronic undernutrition, was significantly associated with higher IgA concentration (β = -0.12, P = 0.050) and 2) boys had significantly higher IgA levels than girls (β = 0.25, P = 0.039). Although there was not a significant interactive effect between HAZ and sex, the two variables confound each other, with boys having significantly lower HAZ values than girls do. In addition, maternal breastmilk IgA was significantly associated with infant salivary IgA, indicating that maternal effects play a role in infant IgA development. Future research will unravel the three-way association between sex, stunting, and immune function in the Ariaal community.
American Journal of Physical Anthropology 06/2012; 149(1):136-41. · 2.82 Impact Factor
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ABSTRACT: Variability in the pattern of change in estradiol (E2) and FSH levels over the menopause transition has not been well defined.
The current study aimed to determine whether different trajectories of E2 and FSH could be identified and whether race/ethnicity and body mass index were related to the different trajectories.
The Study of Women's Health Across the Nation is a longitudinal observational study of the menopausal transition.
Women aged 42-52 yr from seven participating sites were recruited and underwent up to 11 annual visits.
Postmenopausal women with 12 or more months of amenorrhea that was not due to hysterectomy/oophorectomy and who were not using hormone therapy before the final menstrual period participated in the study.
Annual serum E2 and FSH levels anchored to final menstrual period were measured.
Four distinct E2 trajectories and three distinct FSH trajectories were identified. The E2 trajectories were: slow decline (26.9%), flat (28.6%), rise/slow decline (13.1%), and rise/steep decline (31.5%). The FSH trajectories were: low (10.6%), medium (48.7%), and high (41.7%) rising patterns. Obesity increased the likelihood of a flat E2 and low FSH trajectory for all race/ethnic groups. Normal-weight Caucasian and African-American women tended to follow the rise/steep decline E2 and high FSH trajectories. Normal-weight Chinese/Japanese women tended to follow the slow decline E2 and the high/medium FSH trajectories.
E2 and FSH trajectories over the menopausal transition are not uniform across the population of women. Race/ethnicity and body mass index affect the trajectory of both E2 and FSH change over the menopausal transition.
The Journal of clinical endocrinology and metabolism 06/2012; 97(8):2872-80. · 6.50 Impact Factor
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ABSTRACT: It is now recognized that mean circulating dehydroepiandrosterone sulfate (DHEAS) concentrations in most midlife women exhibit a positive inflection starting in early perimenopause, continuing through early postmenopause and returning to early perimenopausal levels by late postmenopause. This rise in mean DHEAS is accompanied by concomitant rises in testosterone (T), dehydroepiandrosteone (DHEA), and androstenedione (Adione) and an equal rise in androstenediol (Adiol). These observations suggest that there is a specific relationship between the circulating levels of steroids emanating from the adrenal glands, declining ovarian function, and the stages of the menopausal transition. This study was designed to test the hypothesis that the menopausal stage-specific change in circulating DHEAS is associated with concomitant changes in the circulating pattern of adrenal steroids and that some of these adrenal androgens could influence the circulating estrogen/androgen balance.
Stored annual serum samples (N = 120) were first selected to represent four longitudinal DHEAS profiles of individual women to assess and compare changes in the adrenal contribution to circulating steroids.
Changes in mean circulating DHEAS levels in midlife women during the menopausal transition is associated with changes in mean circulating T, Adione, and Adiol. Mean Adione and T concentrations changed the least, whereas mean DHEAS and Adiol changed the most.
Changes in circulating steroid hormone emanating from the adrenal during the menopausal transition may be more important than the decline in ovarian function in terms of altering the estrogen/androgen balance.
Menopause (New York, N.Y.) 03/2012; 19(6):658-63. · 3.08 Impact Factor
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ABSTRACT: The perimenopausal increase in circulating dehydroepiandrosterone sulfate (DHEAS) levels during the menopausal transition (MT) is accompanied by other adrenal steroids that have the potential to alter estrogen/androgen balance and explain the wide interwoman range of estrogen-related symptoms experienced during the MT.
Annual serum samples from the Study of Women's Health Across the Nation, which had previously been analyzed for immunoreactive estradiol (E2), testosterone, DHEAS, and sex hormone-binding globulin, were selected based on DHEAS concentration and analyzed for immunoreactive and bioactive estrogens and androgens, including immunoreactive androstenedione, dehydroepiandrosterone, and 5-androstene-3β,17β-diol (androstenediol [Adiol]).
A two-fold increase in circulating androstenedione and testosterone was found to rise in parallel with the rise in circulating DHEAS, whereas dehydroepiandrosterone and Adiol concentrations rose seven- to eight-fold. Circulating Adiol, which has both androgenic and estrogenic biological activity, was significantly associated (P < 0.02) with circulating estrogen bioactivity only when E2 concentrations were low and Adiol levels were high.
The wide range of circulating levels of Adiol and its contribution to total circulating estrogenicity during the MT is consistent with the observed interwoman difference in symptoms at this time. Therefore, we conclude that Adiol contributes to circulating estrogenicity when E2 production falls at menopause and may contribute significantly to the endocrine changes experienced by midlife women.
Menopause (New York, N.Y.) 03/2012; 19(6):650-7. · 3.08 Impact Factor
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ABSTRACT: Covariate measurement error is common in epidemiologic studies. Current methods for correcting measurement error with information from external calibration samples are insufficient to provide valid adjusted inferences. We consider the problem of estimating the regression of an outcome Y on covariates X and Z, where Y and Z are observed, X is unobserved, but a variable W that measures X with error is observed. Information about measurement error is provided in an external calibration sample where data on X and W (but not Y and Z) are recorded.
We describe a method that uses summary statistics from the calibration sample to create multiple imputations of the missing values of X in the regression sample, so that the regression coefficients of Y on X and Z and associated standard errors can be estimated using simple multiple imputation combining rules, yielding valid statistical inferences under the assumption of a multivariate normal distribution.
The proposed method is shown by simulation to provide better inferences than existing methods, namely the naive method, classical calibration, and regression calibration, particularly for correction for bias and achieving nominal confidence levels. We also illustrate our method with an example using linear regression to examine the relation between serum reproductive hormone concentrations and bone mineral density loss in midlife women in the Michigan Bone Health and Metabolism Study.
Existing methods fail to adjust appropriately for bias due to measurement error in the regression setting, particularly when measurement error is substantial. The proposed method corrects this deficiency.
Epidemiology (Cambridge, Mass.) 01/2012; 23(1):165-74. · 5.51 Impact Factor
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ABSTRACT: Immunoglobulin A dominates mucosal surfaces and is a biomarker of interest in populations with a high disease burden. The objectives of this work are to describe an ELISA for IgA and test the stability of storage on filter paper for human milk and saliva collection to be used in remote field locations.
A two-site sandwich ELISA for IgA was developed. To test filter paper storage capabilities under field conditions, 248 matched whole and dried human milk filter paper samples and 251 matched whole and dried saliva samples were collected from northern Kenyan women. Whole samples were frozen in liquid nitrogen while dried samples were stored at ambient temperature for up to 8 weeks. Recovered dried IgA levels were compared to whole IgA levels and adjusted for time stored at ambient temperature.
The lower limit of quantification for this assay is 10.1 ng/ml. Linearity of dilution for human milk and saliva samples was excellent. High and low-control coefficient of variation values across plates were 9.1 (341.8 ng/ml) and 9.4% (132.5 ng/ml). IgA was detected in all whole and dried samples. There is a moderate concordance between dried and whole samples (R(2) = 0.62). There is a small but significant effect of time stored, with a loss of ∼1 μg/ml per day (P = 0.0052).
This IgA assay is a cost-effective alternative to commercial secretory IgA kits. Human milk and saliva can be stored on filter paper for up to 8 weeks.
American Journal of Human Biology 09/2011; 23(6):823-5. · 2.27 Impact Factor
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ABSTRACT: The concept that adrenal androgen production gradually declines with age has changed after analysis of longitudinal data from the Study of Women's Health Across the Nation (SWAN). It is now recognized that 4 adrenal androgens rise during the menopausal transition in most women. Ethnic and individual differences in sex steroids are more apparent in circulating adrenal steroids than in either estradiol or cyclic ovarian steroid hormone profiles, particularly during the early and late perimenopause. Thus, adrenal steroid production may play a larger role in the occurrence of symptoms and the potential for healthier aging than previously recognized.
Obstetrics and Gynecology Clinics of North America 09/2011; 38(3):467-75. · 1.70 Impact Factor
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ABSTRACT: This study examined the relationship between endogenous hormones and cognitive function in nondemented, ethnically-diverse community-dwelling older men enrolled in the Einstein Aging Study (EAS). All eligible participants (185 men, mean age=81 years) received neuropsychological assessment (Free and Cued Selective Reminding Test (FCSRT), Logical Memory (LM), Trail Making Test B (TMTB), block design (BD)) and provided blood samples for hormonal assays (total estradiol, total testosterone, calculated free testosterone index). Linear regression analysis adjusted for age, education, body mass index, and cardiovascular comorbidities indicated that men with high levels of total estradiol demonstrated better FCSRT verbal memory performance (β=0.17, p<0.02) compared to men with lower levels of total estradiol. The results remained unchanged when the model was further adjusted for ethnicity. We did not detect an association between testosterone and cognitive performance. These findings indicate that high levels of total estradiol in older men are associated with better performance on a cue-based, controlled learning test of verbal memory that is a sensitive predictor of dementia.
Brain and Cognition 02/2011; 76(1):158-65. · 3.17 Impact Factor
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ABSTRACT: Cortisol is frequently used as a marker of physiologic stress levels. Using cortisol for that purpose, however, requires a thorough understanding of its normal longitudinal variability. The current understanding of longitudinal variability of basal cortisol secretion in women is very limited. It is often assumed, for example, that basal cortisol profiles do not vary across the menstrual cycle. This is a critical assumption: if cortisol were to follow a time dependent pattern during the menstrual cycle, then ignoring this cyclic variation could lead to erroneous imputation of physiologic stress. Yet, the assumption that basal cortisol levels are stable across the menstrual cycle rests on partial and contradictory evidence. Here we conduct a thorough test of that assumption using data collected for up to a year from 25 women living in rural Guatemala.
We apply a linear mixed model to describe longitudinal first morning urinary cortisol profiles, accounting for differences in both mean and standard deviation of cortisol among women. To that aim we evaluate the fit of two alternative models. The first model assumes that cortisol does not vary with menstrual cycle day. The second assumes that cortisol mean varies across the menstrual cycle. Menstrual cycles are aligned on ovulation day (day 0). Follicular days are assigned negative numbers and luteal days positive numbers. When we compared Models 1 and 2 restricting our analysis to days between -14 (follicular) and day 14 (luteal) then day of the menstrual cycle did not emerge as a predictor of urinary cortisol levels (p-value>0.05). Yet, when we extended our analyses beyond that central 28-day-period then day of the menstrual cycle become a statistically significant predictor of cortisol levels.
The observed trend suggests that studies including cycling women should account for day dependent variation in cortisol in cycles with long follicular and luteal phases.
PLoS ONE 01/2011; 6(3):e18242. · 4.09 Impact Factor
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ABSTRACT: A rise in circulating dehydroepiandrosterone sulfate (DHEAS) concentration occurs during the menopausal transition (MT) that is ovarian stage related but not age related. The objective of this study was to determine the source of the rise in circulating DHEAS.
Circulating DHEAS concentrations in women who had undergone bilateral salpingo-oophorectomy (BSO) were compared with the pattern of circulating DHEAS in women who progressed through the MT naturally. Annual serum samples from the Study of Women's Health Across the Nation (SWAN) over a 10-year study period were used. From 1,272 women in the SWAN cohort who were eligible for longitudinal evaluation of DHEAS annual samples, 81 underwent BSO during the premenopausal or early perimenopausal stage of the MT and were potentially available for study. Of these 81 BSO participants, 20 had sufficient annual samples for evaluation of the post-BSO trajectory of circulating DHEAS. SWAN women not having used hormone therapy previously and those with intact ovaries were compared with women who underwent a BSO immediately after a premenopausal or early perimenopausal annual visit. There were no interventions, and circulating concentration of DHEAS was the main outcome.
A detectable rise in DHEAS was observed in 14 (70%) of the 20 BSO women, which is similar to the proportion (85%) of women with intact ovaries who had a detectable DHEAS rise. The mean rise in DHEAS (5%-8%) was similar in both BSO and non-BSO women.
The MT rise in DHEAS (5%-8%) occurring in the absence of ovaries is largely of adrenal origin.
Menopause (New York, N.Y.) 12/2010; 18(5):494-8. · 3.08 Impact Factor
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ABSTRACT: The present study resolves some of the discrepancies in the literature by correlating the effects of tobacco smoking on hormone release with venous plasma nicotine levels. Cortisol, prolactin, and beta-endorphin concentrations were measured. Habitual male tobacco users smoked denicotinized (very low nicotine) and average nicotine cigarettes in the morning after overnight tobacco abstinence. Several venous blood samples were withdrawn before and during the smoking sessions for subsequent analyses. The increases in plasma nicotine correlated well with plasma cortisol and prolactin levels (correlation coefficients r=0.66 and 0.53, respectively, p<0.05). This study quantifies the well known increase in plasma cortisol and prolactin after nicotine postsmoking for about 1h with peak plasma levels up to 35 ng/ml. Contrary to most abused drugs which release dopamine and decrease prolactin, nicotine concentration correlated with increased prolactin release. Increases in maximal plasma beta-endorphin levels following tobacco smoking were barely statistically significant with insufficient data to obtain a correlation coefficient.
Pharmacology Biochemistry and Behavior 04/2010; 95(2):209-15. · 2.53 Impact Factor
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ABSTRACT: Smoking, diet, and physical activity may impact chronic diseases in part by promoting or attenuating oxidative stress. We evaluated associations between lifestyle factors and urine F(2a)-isoprostanes, a marker of oxidative stress in 1610 participants of the Study of Women's Health Across the Nation (SWAN). Dietary intake and physical activity were assessed at baseline and the 5th year 05 (Y05). These data were related to Y05 urinary F(2a)-isoprostane concentration with regression analyses. Median urine F(2a)-isoprostane concentration was 433 ng/L overall, 917 ng/L in smokers [inter-quartile range (IQR): 467, 1832 ng/L], and 403 ng/L in nonsmokers (IQR: 228, 709 ng/L; P < 0.0001 for difference). Higher trans fat intake was associated with higher urine F(2a)-isoprostane concentration; partial Spearman correlations (rho(x|y)) between Y05 urine F(2a)-isoprostane concentration and trans fatty acids was 0.19 (P = 0.03) in smokers and 0.13 (P < 0.0001) in nonsmokers. Increased log trans fat intake from baseline to Y05 was associated with higher concentration of log urine F(2a)-isoprostanes in nonsmokers (beta = 0.131, SE = 0.04, P = 0.0003). In nonsmokers, the partial correlation (rho(x|y)) between lutein and urine F(2a)-isoprostane concentration was -0.13 (P < 0.0001). Increased intake of log lutein from baseline to Y05 was also associated with lower log urine F(2a)-isoprostane concentration (beta = -0.096, SE = 0.03, P = 0.0005) in nonsmokers. Increased zinc intake from baseline to Y05 was associated with lower log urine F(2a)-isoprostane concentration in smokers and nonsmokers (beta = -0.346, SE = 0.14, P = 0.01), and -0.117, 0.04 (P = 0.001), respectively]. In conclusion, diet (fat subtypes, zinc, and vegetable components) and smoking were associated with urine F(2a)-isoprostanes, a marker of oxidative stress.
Journal of Nutrition 11/2007; 137(11):2412-9. · 3.92 Impact Factor
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ABSTRACT: Hepatitis C virus (HCV) and environmental hepatotoxins may have an indirect influence on health by altering the synthesis and function of hormones, particularly reproductive hormones. We aimed to evaluate liver diseases and sex steroid hormones in Egypt, which has the highest prevalence of HCV worldwide.
We measured markers of hepatitis B virus (HBV), HCV and schistosomiasis infection as well as liver function in 159 apparently healthy subjects. We measured total testosterone (T), sex-hormone binding globulin (SHBG) and albumin, and calculated the free androgen index.
Anti-HCV antibodies were detected in 51% of men and 42% of women. Based on HCV reverse transcription PCR (RT-PCR) of 44 men and 33 women, 11% of men and 21% of women showed HCV viremia. There was schistosomiasis in 25% of men and 9% of women, and mixed HCV viremia and schistosomiasis in 57% of men and 52% of women. Compared with men with schistosomiasis only (mean 593.3 +/- 73.4 ng/dL), T was higher in men with mixed HCV viremia and schistosomiasis (mean 854.5 +/- 47.9 ng/dL; P = 0.006) and men with mixed chronic HCV and schistosomiasis (mean 812.1 +/- 43.3 ng/dL; P = 0.001). Men with mixed chronic HCV and schistosomiasis had also significantly higher SHBG (mean 57.7 +/- 3.9 ng/dL) than males with schistosomiasis only (mean 34.8 +/- SE 4.5 ng/dL; P = 0.0003).
Future investigations should consider that a high prevalence of asymptomatic liver disease may alter associations between hormone concentrations and chronic disease etiology.
Journal of Gastroenterology and Hepatology 06/2007; 23(7 Pt 2):e137-45. · 2.87 Impact Factor
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ABSTRACT: The availability of daily hormone values for entire menstrual cycles offers an opportunity to apply new analytic techniques that confirm current knowledge and provide new insights into patterns of changing hormone profiles in women as they transition to the menopause. The Study of Women's Health Across the Nation (SWAN) collected urine samples during 1997-1999 from one menstrual cycle or up to 50 days from 848 women who live in seven cities across the United States. These samples were assayed for the urinary forms of estrogen, progesterone, follicle-stimulating hormone, and luteinizing hormone. The authors used functional data analysis to study variability in the hormone patterns of 572 of the 848 pre- and early-perimenopausal women with evidence of a luteal transition. Functional data analysis enabled the authors to identify asymmetries in women's hormone patterns related to cycle length that are not captured with single hormone value comparisons. Longer cycles were characterized by increasing dyssynchrony between follicle-stimulating hormone and luteinizing hormone in the luteal phase.
American Journal of Epidemiology 05/2007; 165(8):936-45. · 5.22 Impact Factor
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ABSTRACT: It is important to characterize the biological activity of circulating androgenic steroid hormones during the menopausal transition because these appear to impact the metabolic and cardiovascular health risk factors of women.
The objective of the study was to develop and characterize a cell-based bioassay that measures the androgen receptor-mediated signal transduction in serum.
This was a clinically relevant experimental study nested in a sample population of a longitudinal cohort study.
The study was conducted at a university laboratory.
A receptor-mediated luciferase expression bioassay based on HEK 293 cells that were stably cotransfected with plasmids containing the human androgen receptor and luciferase gene was developed. In 49 samples from menstruating women aged 42-52 yr, total testosterone (T) and SHBG concentrations were measured by immunoassay; free T concentrations were calculated from the total T and SHBG concentrations.
Mean total T concentration of the sample was 1.15 nm (sd 0.46, range 0.57-3.86 nm). The mean bioactive androgen detected was 1.00 nm (sd 0.24, range 0.53-1.60 nm). Calculated free T (mean 0.0156 nm) was significantly lower than the levels of bioactive androgens measured by receptor-mediated bioassay. There was significant positive correlation between bioactive androgen levels and total T values in young women and polycystic ovarian disorder patients, whereas no correlation was found between the two values in middle-aged women.
An androgen receptor-mediated bioassay can provide additional information in the evaluation of total bioactive androgens in midlife women. Our data suggest that levels of circulating SHBG may have a significant impact on the levels of total circulating bioavailable androgens.
Journal of Clinical Endocrinology & Metabolism 12/2006; 91(11):4387-94. · 6.50 Impact Factor
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ABSTRACT: The purpose of this study was to relate measured concentrations of estradiol (E2) and the urinary estrogen metabolites 2-hydroxyestrone (2-OHE1) and 16alpha-hydroxyestrone (16alpha-OHE1) to single nucleotide polymorphisms (SNPs) from CYP1A1 and CYP1B1, the primary genes involved in estrogen catabolism. We investigated the association of 4 CYP1A1 SNPs (CYP1A1 rs4646903, CYP1A1 rs1531163, CYP1A1 rs2606345, and CYP1A1 rs1048943) and 2 CYP1B1 SNPs (CYP1B1 rs162555 and CYP1B1 rs1056836) to circulating serum E2 concentrations and the urinary estrogen metabolites 2-OHE1 and 16alpha-OHE1. The associations were evaluated in 1,340 participants of 4 racial/ethnic groups from the Study of Women's Health Across the Nation (SWAN) who were premenopausal and perimenopausal. There was substantial variation in the allele frequencies of the SNPs for African American and Caucasian women. There was, however, remarkable comparability between Chinese and Japanese women; their CYP1A1 and CYP1B1 allele frequencies differed by only < or =11%. There was significant variation in E2 concentrations by genotype within racial/ethnic group for CYP1A1 rs2606345. In particular, Japanese women with the CC genotype had lower E2 concentrations than did Japanese women with the AC genotype. Chinese women with the CC genotype had higher 2-OHE1 concentrations than did Chinese women with the AC genotype. Further, African American women with the CC genotype had higher 16alpha-OHE1 concentrations than did those with other genotypes. CYP1A1 rs2606345 may play an important role in estrogen metabolism in women who are premenopausal and perimenopausal.
The American journal of medicine 09/2006; 119(9 Suppl 1):S44-51. · 4.47 Impact Factor
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ABSTRACT: We evaluated potential associations between single nucleotide polymorphism (SNP) variants of the estrogen receptor genes ESR1 and ESR2 and circulating estradiol (E2) concentrations in women of 4 races/ethnicities. The study population was drawn from participants in the Study of Women's Health Across the Nation (SWAN). A total of 1,538 African American, Caucasian, Chinese, and Japanese women from SWAN participated in the Sex Steroid Hormone Genetics Protocol by providing blood for sex steroid hormone analyses and consenting to lymphocyte transformation from which DNA was extracted and genotyped. We evaluated 4 ESR1 SNPs (ESR1 rs9340799, ESR1 rs2234693, ESR1 rs728524, and ESR1 rs3798577), and 3 ESR2 SNPs (ESR2 rs1255998, ESR2 rs1256030, and ESR2 rs1256065). Mean E2 level was 196.0 +/- 4.0 pmol/L in women who were premenopausal and perimenopausal (with blood drawn on days 2 through 5 of the menstrual cycle follicular phase); however, mean E2 levels in Chinese and Japanese women were lower (155.7 +/- 10.6 pmol/L and 170.0 +/- 10.3 pmol/L, respectively) than in African American (196.4 +/- 8.1 pmol/L, P <0.05) or Caucasian women (210.7 +/- 5.9 pmol/L, P <0.002). The ESR1 rs3798577 CC genotype was associated with lower circulating E2 concentrations in African American women (P <0.07) and explained about 1% of the variation in circulating E2 concentrations. In Japanese women, the GC genotype of ESR2 rs1255998 was associated with significantly lower circulating E2 concentrations that explained about 4% of the variation. Circulating E2 concentrations were not strongly or consistently associated with selected polymorphisms for the estrogen receptor genes. The 2 strongest associations explained <4% of the total variation in the circulating E2 concentrations.
The American journal of medicine 09/2006; 119(9 Suppl 1):S16-22. · 4.47 Impact Factor
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ABSTRACT: We related variation in 4 sex steroid genes to 3 phenotypic indicators of ovarian aging, including no evidence of luteal activity as a marker of anovulatory cycles, shorter or longer menstrual cycle lengths, and the profiles of metabolites of estrogens, progesterone, follicle-stimulating hormone, and luteinizing hormone measured in urine samples collected daily across a menstrual cycle in women aged 43 to 53 years. The study sample included 485 menstruating women without hormone therapy who had collected daily urine hormone samples across 1 menstrual cycle or 50 days, whichever occurred first. There were 14 single nucleotide polymorphisms from 4 genes, including estrogen receptor-alpha (ESR1), estrogen receptor-beta, aromatase, and 17beta hydroxysteroid dehydrogenase type 1, related to ovarian aging phenotypes that include the presence or absence of luteal activity, menstrual cycle lengths < or > 24 to 31 days, and profiles of urinary hormone metabolites. Women with the TT genotype of ESR1 rs3798577 have evidence of advanced ovarian aging compared with women with the CT or CC genotypes, after adjustment for race/ethnicity, chronologic age, and race/ethnicity-specific body mass index. Further, women with the TC and CC genotypes of ESR1 rs2234693 may have a greater likelihood of more advanced ovarian aging than do women with the TT genotype, adjusting for covariates. Using a candidate gene approach, 2 ESR1 polymorphisms are related to 3 phenotypic markers of ovarian aging, suggesting a possible role for the ESR1 gene in the timing of the menopausal transition.
The American journal of medicine 09/2006; 119(9 Suppl 1):S31-43. · 4.47 Impact Factor
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ABSTRACT: Diet and lifestyle factors, body size, and smoking behavior may influence estrogen metabolism, but the nature of these relations may vary according to race/ethnic groups. We evaluated the association of lifestyle factors with estrogen metabolites 2-hydroxyestrone (2-OHE1) and 16alpha-hydroxyestrone (16alpha-OHE1) in a racially diverse population. With a cross-sectional study design, urine samples from 1881 African-American, Caucasian, Chinese, Japanese, and Hispanic women, aged 42-52 y, from the Study of Women's Health Across the Nation (SWAN) were assayed by EIA for 2-OHE1 and 16alpha-OHE1. Dietary factors and beverages were measured using a modified Block FFQ. Dietary fiber, vegetable and fruit servings, Brassica vegetables, polyphenols, coffee, caffeine, green and black tea, and total alcohol and wine were related to metabolite values using multiple variable regression analyses. In adjusted analyses, 2-OHE1 concentrations were significantly associated with race/ethnicity, weight, smoking, and consumption of hydroxybenzoic acid, anthocyanidins, wine, and caffeine (P < 0.05). Regression models incorporating these variables explained 19-20% of the variation in 2-OHE1 concentrations. Regression models for 16alpha-OHE1, which explained 16-17% of the variability, included race/ethnicity, smoking, caffeine, total dietary fiber, and fiber from fruits and vegetables as variables. These associations may reflect why increased consumption of polyphenol-containing foods and fruit as well as decreased smoking, caffeine intake, and body size would be consistent with hypothesized benefits and risks for selected health outcomes.
Journal of Nutrition 07/2006; 136(6):1588-95. · 3.92 Impact Factor
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ABSTRACT: Maternal stress is commonly cited as an important risk factor for spontaneous abortion. For humans, however, there is little physiological evidence linking miscarriage to stress. This lack of evidence may be attributable to a paucity of research on maternal stress during the earliest gestational stages. Most human studies have focused on "clinical" pregnancy (>6 weeks after the last menstrual period). The majority of miscarriages, however, occur earlier, within the first 3 weeks after conception (approximately 5 weeks after the last menstrual period). Studies focused on clinical pregnancy thus miss the most critical period for pregnancy continuance. We examined the association between miscarriage and levels of maternal urinary cortisol during the first 3 weeks after conception. Pregnancies characterized by increased maternal cortisol during this period (within participant analyses) were more likely to result in spontaneous abortion (P < 0.05). This evidence links increased levels in this stress marker with a higher risk of early pregnancy loss in humans.
Proceedings of the National Academy of Sciences 04/2006; 103(10):3938-42. · 9.68 Impact Factor
