The interplay between hormones, lipids, and dietary intake: the BioCycle study

Background: Exogenous estrogens (i.e. hormone therapy and oral contraceptives) have been shown to affect the lipid profile, leading to the hypothesis that endogenous estrogens may have similar effects. However, the relationship between estrogens and lipoproteins is complex, especially given that cholesterol is the initial precursor for steroid biosynthesis and dyslipidemia has been associated with altered hormone levels and anovulation. The effects of baseline cholesterol levels on anovulation are also not well understood. As fiber intake lowers both estrogen and lipoproteins, it is unknown whether estrogen may mediate the effect of fiber among premenopausal women. Methods: The BioCycle study was a prospective cohort of 250 self-reported regularly menstruating women aged 18 to 44, followed for two menstrual cycles. Lipoprotein cholesterol and hormones were measured in serum collected at up to 16 visits timed using fertility monitors. Marginal structural models with inverse probability of exposure weights were used to model the associations of interest. Results: Estradiol was positively associated with HDL cholesterol in acute effects models, and inversely associated with total and LDL cholesterol and triglycerides in persistent effects models. Total cholesterol levels preceding the predicted time of ovulation were weakly associated with an increased risk of anovulation, and luteinizing hormone:follicle-stimulating hormone ratio, sex hormone binding-globulin, insulin, and acne were identified as significant predictors of anovulation. Fiber consumption at or above 22 g/day was associated with lower total and LDL cholesterol, independent of estrogen, however the controlled direct effect was reduced at high levels of estrogen. Conclusions: Our results support the hypothesis that estrogen exerts beneficial effects on lipoprotein cholesterol levels and sheds light into the timing of these effects. The more atherogenic lipid profile and endocrine characteristics indicative of hyperandrogenism among anovulatory women are indicative of a mild undiagnosed phenotype of polycystic ovary syndrome, however further research is needed to elucidate the biological mechanisms. The reduced controlled direct effects of fiber on cholesterol at higher estrogen levels suggest that estrogen decreases fiber's effect among premenopausal women. Cycle phase should be considered in the design and interpretation of studies in women of reproductive age due to estrogen's influence on many biological processes

Preconception care: it’s never too early

The preconception window has been recognized as one of the earliest sensitive windows of human development, and interventions that focus on this period have the potential to affect not only pregnancy but long term outcomes as well. The journal Reproductive Health has published a supplement entitled ‘Preconception Interventions’ which includes a series of systematic reviews regarding the impact of public health interventions during the preconception period on maternal and child health. These articles describe the role that poor preconception health plays in creating health disparities across the globe. The reviews highlight our current understanding (or lack thereof) regarding how both maternal and paternal preconception health and knowledge shapes the long-term health of not only children, but of families, communities, and nations. Researchers and healthcare workers should take particular note of these interventions, as the preconception time period may be as important as the pregnancy and post-pregnancy periods, and is critical in terms of bridging the gap in the continuum of care, particularly for adolescents.Fil: Mumford, Sunni L.. National Institutes of Health; Estados UnidosFil: Michels, Kara A.. National Institutes of Health; Estados UnidosFil: Salaria, Natasha. BioMed Central; Reino UnidoFil: Valanzasca, Pilar. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Belizan, Jose. Instituto de Efectividad Clínica y Sanitaria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Dietary Restraint and Gestational Weight Gain

To determine whether a history of preconceptional dieting and restrained eating was related to higher weight gains in pregnancy

Adherence to the Mediterranean diet and body fat distribution in reproductive aged women

Background/Objectives Adherence to the Mediterranean Diet (MD) high in fruits, vegetables and monounsaturated fats, has been associated with lower body mass index. Associations with measured body fat, including regional adiposity, have not been previously investigated. We examined the associations between the alternate Mediterranean Diet Score (aMED), anthropometry and measured adiposity by dual energy x-ray absorptiometry. Subjects/Methods This study included 248 healthy females, aged 18–44 years from the BioCycle Study. Each woman’s aMED (range 0–9) was calculated from up to eight 24-hr dietary recalls over 1–2 menstrual cycles (>97% had ≥7 recalls). Multiple linear regression was used to determine whether aMED and its specific components were associated with total and regional adiposity after adjusting for age, race, education, physical activity and energy intake. Results: Participants had an average (SD) aMED of 4.2 (1.7) and percent body fat of 29.5 (6.0)%. Significant inverse associations were found between aMED and all the examined adiposity measures except waist to hip ratio. Among the DXA measures, a 1-unit increment in aMED was associated with a 0.06 (95% CI:−0.09,−0.02) lower trunk-to-leg fat ratio (T/L), a measure of upper to lower body fat. In an analysis examining T/L as an outcome with the separate components of the aMED, T/L was lower with increased legume consumption (β=−0.280, 95% CI:−0.550,−0.010) but was higher with increased consumption of red and processed meat (β=0.060, 95% CI:0.002,0.117). Conclusions: Adherence to the aMED was associated with lower total and regional adiposity, adding to the mounting evidence of the health benefits of the MD

Tampon use, environmental chemicals and oxidative stress in the BioCycle study

Background Tampons are used by up to 86% of US women and are a rarely considered potential source of pesticide and metal exposure. Tampons may be of particular concern given the likely higher absorption that occurs in the vagina. Our objective was to examine the potential associations between tampon use and metal concentrations, and biomarkers of inflammation and oxidative stress among healthy women. Methods We used information from a prospective cohort of 259 regularly menstruating women, aged 18–44, followed for two menstrual cycles. Tampon use was assessed using information provided in participant study diaries. Metal concentrations were measured from a blood sample collected at enrollment. Oxidative stress and inflammation biomarker concentrations were determined from blood samples collected at up to 8 clinic visits for each cycle. Linear regression models were used to estimate associations of tampon use with metal exposure, and linear mixed models to estimate associations of tampon use with inflammation and oxidative stress biomarkers at different times during the menstrual cycle. Results We observed non-significantly higher mean levels of mercury for tampon users compared to non-tampon users (exp(β) = 1.25, 95% CI = 0.93, 1.68). We found no evidence of an association between tampon use and inflammation biomarkers. We observed consistently higher isoprostane levels, an oxidative stress biomarker, among tampon users compared to non-tampon users (e.g. exp.(β) = 1.05, 95%CI = 0.96, 1.16, for the average isoprostane during the menstruating week); however, these results were not statistically significant. Conclusions While our results are not statistically significant, we observed suggestive associations between tampon use and elevated levels of mercury and oxidative stress biomarkers. Although our finding should be interpreted in light of our limitations, they indicate that tampons may be a source of exposure to metals and chemicals that have been largely ignored, and any related health effects are an important public health concern

The Impact of Dietary Folate Intake on Reproductive Function in Premenopausal Women: A Prospective Cohort Study

Background: Folic acid is recommended to reproductive-aged women to prevent birth defects, though little is known about the effects of dietary intake on other reproductive outcomes. Improved pregnancy rates have been documented after folic acid supplement use, suggesting a possible link with ovulation, however research is limited. Our objective was to evaluate the association between dietary folate intake, hormone levels, and sporadic anovulation in healthy, regularly menstruating women. Methodology/Principal Findings: The BioCycle study (2005–2007) prospectively followed 259 healthy women aged 18–44 years from the western New York region for up to 2 menstrual cycles. Total folate and specific sources of folate were assessed up to 4 times per cycle by 24-hour recall. Estradiol, progesterone, luteinizing hormone, and follicle-stimulating hormone were measured in serum up to 8 times per cycle, timed using fertility monitors. Anovulation was defined as a cycle with peak progesterone concentration ≤5 ng/mL and no LH peak in the mid/late luteal phase. Higher intake of dietary folate (in dietary equivalents) across tertiles had a marginally significant association with greater luteal progesterone levels (P trend 0.08). Higher intake of synthetic folate was significantly associated with higher luteal progesterone levels (P trend 0.05). Specifically, women in the 3rd tertile of synthetic folate intake had, on average, 16.0% (95% CI, 0.5–33.8%) higher luteal progesterone levels compared to women in the 1st tertile. Moreover, consumption of synthetic folate was significantly and inversely associated with anovulation such that women in the 3rd tertile had a 64% (95% CI, 8–86%) decreased odds of anovulation compared to the women in the 1st tertile (P trend 0.03). Conclusions/Significance: These findings suggest that a diet high in synthetic folate may be associated with increased progesterone levels and lower risk of sporadic anovulation. Further study of the effect of dietary folate and folic acid supplement use on reproductive health is warranted

The Association between a Medical History of Depression and Gestational Diabetes in a Large Multi-ethnic Cohort in the United States

Background: Both major depression and gestational diabetes mellitus (GDM) are prevalent among women of reproductive age. Our objective was to determine whether a medical history of depression is related to subsequent development of GDM. Methods: The Consortium on Safe Labor was a US retrospective cohort study of 228 562 births between 2002 and 2008. Exclusion criteria for the present analysis included multiple gestation pregnancies (n = 5059), pre-existing diabetes (n = 12 771), deliveries(n = 395), site GDM prevalence ( Results: The final analytic population included 121 260 women contributing 128 295 pregnancies, of which 5606 were affected by GDM. A history of depression was significantly associated with an increased risk of developing GDM (multivariate odds ratio [aOR] = 1.42 [95% confidence interval (CI) 1.26, 1.60]). Adjusting for pre-pregnancy BMI and weight gain during pregnancy attenuated the association, although it remained statistically significant (aOR = 1.17 [95% CI 1.03, 1.33]). Conclusions: A history of depression was significantly associated with an increased GDM risk among a large multi-ethnic US cohort of women. If the association is confirmed, depression presents a potentially modifiable risk factor of GDM and provides additional clues to the underlying pathophysiology of GDM

Imputation approaches for potential outcomes in causal inference

Background: The fundamental problem of causal inference is one of missing data, and specifically of missing potential outcomes: if potential outcomes were fully observed, then causal inference could be made trivially. Though often not discussed explicitly in the epidemiological literature, the connections between causal inference and missing data can provide additional intuition

Effect of Dietary Fiber Intake on Lipoprotein Cholesterol Levels Independent of Estradiol in Healthy Premenopausal Women

High-fiber diets are associated with improved lipid profiles. However, pre- and postmenopausal women respond differently to fiber intake, suggesting that endogenous estradiol mediates the effect. The authors' objective was to determine the direct effect of fiber intake on lipoprotein cholesterol levels independent of estradiol among premenopausal women. The BioCycle Study, a prospective cohort study conducted at the State University of New York at Buffalo from 2005 to 2007, followed 259 healthy women for up to 2 complete menstrual cycles. Serum lipoprotein and hormone levels were measured at 16 visits timed using fertility monitors. Fiber intake was assessed by 8 24-hour recalls. Marginal structural models with inverse probability weights for both lipoprotein and estradiol levels were used to estimate controlled direct effects of the highest category of fiber intake (≥22 g/day vs. <22 g/day) while accounting for age, body mass index, total energy, vitamin E intake, physical activity, luteinizing hormone, follicle-stimulating hormone, and progesterone. Reductions were observed in total and low density lipoprotein cholesterol in women with higher fiber intakes. Direct effects were greater than total effects. These analyses suggested that estradiol mediates at least part of the association between fiber and cholesterol among premenopausal women. More research is needed to elucidate the biologic mechanisms driving these associations