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Observations over the past decade using longitudinal data reveal a gender-specific shift in adrenal steroid production. This shift is represented by an increase in the circulating concentrations of delta 5 steroids in 85% of all women and is initiated only after the menopausal transition has begun. While the associated rise in the major adrenal androgen, dehydroepiandrosterone sulfate (DHEAS), is modest, the parallel rises in dehydroepiandrosteone (DHEA) and androstenediol (Adiol) are much more robust. These increases in circulating steroid concentrations are qualitatively similar on average between ethnicities but quantitatively different between individual women. Both circulating testosterone (T) and androstenedione (Adione) also rise concomitantly but modestly by comparison. This phenomenon presents a new and provocative aspect to the endocrine foundations of the menopausal transition and may provide important clues to understanding the fundamentals of mid-aged women's healthy aging, particularly an explanation for the wide diversity in phenotypes observed during the MT as well as their different responses to hormone replacement therapies. Experimental studies using the nonhuman primate animal model show an acute adrenal response to human chorionic gonadotropin (hCG) challenge as well as the presence of luteinizing hormone receptors (LHR) in their adrenal cortices. These experimental results support the concept that LHRs are recruited to the adrenal cortices of mid-aged women that subsequently function to respond to increasing circulating LH to shunt pregnenolone metabolites towards the delta 5 pathway. Future investigations are required to determine the relationship of these changes in adrenal function to symptoms and health outcomes of mid-aged women.

A letter to the editor is presented in response to the article "Comparing clean intermittent catheterization and transurethral indwelling catheterization for incomplete voiding after vaginal prolapse surgery: a multicentre randomized trial," published in a previous issue.

Introduction: Prehospital teamwork occurs in dynamic environments where paramedics work together using technologies to care for patients. Despite increasing interest in using head-worn displays (HWDs) to support prehospital workers, little is known about how HWDs affect teamwork., Methods: We tested the effect of HWDs on the team processes and patient care of paramedic trainee teams in a laboratory study using an online prehospital simulation environment, SPECTRa. In a randomized crossover design, 20 two-person teams worked in the SPECTRa laptop environment from separate physical rooms to assess and treat 2 simulated patients in 3 prehospital patient care scenarios. In each scenario, each trainee used either an HWD, a tablet computer (TAB), or no mobile device (CON) to help them monitor the vital signs of both patients. We measured team processes based around 3 themes of mutual understanding, team performance, and administered an 18-item questionnaire about teamwork and use of the devices., Results: The mean number (HWD = 11; TAB = 7; P = 0.061) and duration (HWD = 1746 milliseconds; TAB = 1563 milliseconds; P = 0.504) of attention switches that teams made toward the mobile device did not differ with HWDs or TABs. However, teams switched attention between patients less with HWDs than with TABs ( P = 0.026) or CON ( P = 0.007) (medians: HWD = 5; TAB = 8; CON = 8). Teams communicated less when using HWDs than TABs ( P = 0.017) (medians: HWD = 76; TAB = 96; CON = 83), but there were other mixed effects on communication. Team performance did not differ across device conditions on the timeliness to notice critical patient changes ( P = 0.387) (medians: HWD = 244 seconds; TAB = 246 seconds; CON = 168 seconds) or to complete the scenarios ( P = 0.212) (medians: HWD = 800 seconds; TAB = 913 seconds; CON = 835 seconds). Questionnaire results revealed some perceived benefits of the HWD., Conclusions: Head-worn displays may let prehospital teams monitor each other's performance more efficiently than TABs or CON, requiring less communication to maintain patient care performance with lower workload than with TABs. However, improvements in mutual understanding with HWDs compared with CON were more evident in teams' preferences than in actual behavior. Further research is needed to confirm and extend these results., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Society for Simulation in Healthcare.)

Objective: High-density lipoprotein cholesterol (HDL-C) is one of 5 components [high blood pressure, glucose, triglycerides, waist circumference, low HDL-C], 3 of which, needed to diagnose metabolic syndrome (MetS). Evolving research shows that higher HDL-C is not necessarily cardioprotective in midlife women, supporting a need to re-evaluate HDL-C's contribution to risks related to MetS. We tested whether risk of future diabetes and higher carotid intima-media thickness (cIMT) differ by HDL-C status in midlife women diagnosed with MetS based on the other 4 components., Methods Midlife Women Were Classified Into 3 Groups: 1) no MetS, 2) MetS with HDL-C ≥ 50 mg/dL (MetS hiHDL), and 3) MetS with HDL-C < 50 mg/dL (MetS loHDL). cIMT was measured 13.8 ± 0.6 years post baseline. Incident diabetes was assessed yearly., Results: Among 2773 women (1350 (48 %) of them had cIMT), 2383 (86 %) had no MetS, 117 (4 %) had MetS hiHDL, 273 (10 %) had MetS loHDL. Compared with no MetS, both MetS- hiHDL and loHDL groups had higher cIMT and diabetes risk. Risk of having high cIMT did not differ between MetS loHDL vs. hiHDL groups. Adjusting for levels of MetS criteria other than HDL-C at baseline explained the associations of each of the two MetS groups with cIMT. Conversely, after adjustment, associations of MetS hiHDL and MetS loHDL with incident diabetes persisted., Conclusions: In midlife women, HDL-C status matters for predicting risk of incident diabetes but not higher cIMT beyond other MetS components., Competing Interests: We wish to draw the attention of the Editor to the following facts which may be considered as potential conflicts of interest and to significant financial contributions to this work. Dr. Rebecca Thurston is a consultant and advisor for Astellas Pharma, consultant and received travel support from Bayer, and on the medical advisory board for Hello Therapeutics. All other coauthors have nothing to disclose., (© 2024 The Author(s).)

Purpose: Previous work has focused on the role of diabetes in peripheral neuropathy (PN), but PN often occurs before, and independently from, diabetes. This study measures the association of cardiometabolic and inflammatory factor with PN, independent of diabetes., Methods: Study of Women's Health Across the Nation participants (n = 1910), ages 60 to 73 (mean 65.6) were assessed for PN by symptom questionnaire and monofilament testing at the 15th follow-up visit (V15). Anthropometric measures and biomarkers were measured at study baseline approximately 20 years prior, and C-reactive protein (CRP) and fibrinogen were measured longitudinally. Log-binomial regression was used to model the association between metabolic syndrome (MetS), obesity (≥35 body mass index), CRP, and fibrinogen with PN, adjusting for sociodemographic and health behavior measures., Results: Baseline MetS [prevalence ratio (PR) 1.79, 95% CI (1.45, 2.20)], obesity [PR 2.08 (1.65, 2.61)], median CRP [PR 1.32 per log(mg/dL), (1.20, 1.45)], and mean fibrinogen (PR 1.28 per 100 mg/dL, (1.09, 1.50)] were associated with PN symptoms at V15. After excluding participants with baseline diabetes or obesity, MetS [PR 1.59 (1.17, 2.14)] and CRP [PR 1.19 per log(mg/dL), (1.06, 1.35)] remained statistically significantly associated with PN. There was a negative interaction between MetS and obesity, and the association between these conditions and PN was mediated by CRP., Conclusions: Cardiometabolic factors and inflammation are significantly associated with PN, independent of diabetes and obesity. CRP mediates the relationship of both obesity and MetS with PN, suggesting an etiological role of inflammation in PN in this sample., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Palliative care is an emerging scope of practice for paramedicine. The COVID-19 pandemic has highlighted the opportunity for emergency settings to deliver palliative and end-of-life care to patients wishing to avoid intensive life-sustaining treatment. However, a gap remains in understanding the scope and limitations of current ambulance services' approach to palliative and end-of-life care., Aim: To examine the quality and content of existing Australian palliative paramedicine guidelines with a sample of guidelines from comparable Anglo-American ambulance services., Design: We appraised guideline quality using the AGREE II instrument and employed a collaborative qualitative approach to analyse the content of the guidelines., Data Sources: Eight palliative care ambulance service clinical practice guidelines (five Australian; one New Zealand; one Canadian; one United Kingdom)., Results: None of the guidelines were recommended by both appraisers for use based on the outcomes of all AGREE II evaluations. Scaled individual domain percentage scores varied across the guidelines: scope and purpose (8%-92%), stakeholder involvement (14%-53%), rigour of development (0%-20%), clarity of presentation (39%-92%), applicability (2%-38%) and editorial independence (0%-38%). Six themes were developed from the content analysis: (1) audience and approach; (2) communication is key; (3) assessing and managing symptoms; (4) looking beyond pharmaceuticals; (5) seeking support; and (6) care after death., Conclusions: It is important that ambulance services' palliative and end-of-life care guidelines are evidence-based and fit for purpose. Future research should explore the experiences and perspectives of key palliative paramedicine stakeholders. Future guidelines should consider emerging evidence and be methodologically guided by AGREE II criteria.

Objectives: To (1) develop a simulation software environment to conduct prehospital research during the COVID-19 pandemic on paramedics' teamwork and use of mobile computing devices, and (2) establish its feasibility for use as a research and training tool., Background: Simulation-based research and training for prehospital environments has typically used live simulation, with highly realistic equipment and technology-enhanced manikins. However, such simulations are expensive, difficult to replicate, and require facilitators and participants to be at the same location. Although virtual simulation tools exist for prehospital care, it is unclear how best to use them for research and training., Methods: We present SPECTRa-Simulated Prehospital Emergency Care for Team Research-an online simulated prehospital environment that lets participants care concurrently for single or multiple patients remotely. Patient scenarios are designed using Laerdal's SimDesigner. SPECTRa records data about scenario states and participants' virtual interaction with the simulated patients. SPECTRa's supporting environment records participants' verbal communication and their visual and physical interactions with their interface and devices using Zoom conferencing and audiovisual recording. We discuss a pilot research implementation to assess SPECTRa's feasibility., Results: SPECTRa allows researchers to systematically test small-team interaction in single- or multipatient care scenarios and assess the impact of mobile devices on participants' assessment and care of patients. SPECTRa also supports pedagogical features that could allow prehospital educators to provide individual trainees or teams with online simulation training and evaluation., Conclusions: SPECTRa, an online tool for simulating prehospital patient care, shows potential for remote healthcare research and training.

Background: Mammographic density (MD) phenotypes, including percent density (PMD), area of dense tissue (DA), and area of non-dense tissue (NDA), are associated with breast cancer risk. Twin studies suggest that MD phenotypes are highly heritable. However, only a small proportion of their variance is explained by identified genetic variants., Methods: We conducted a genome-wide association study, as well as a transcriptome-wide association study (TWAS), of age- and BMI-adjusted DA, NDA, and PMD in up to 27,900 European-ancestry women from the MODE/BCAC consortia., Results: We identified 28 genome-wide significant loci for MD phenotypes, including nine novel signals (5q11.2, 5q14.1, 5q31.1, 5q33.3, 5q35.1, 7p11.2, 8q24.13, 12p11.2, 16q12.2). Further, 45% of all known breast cancer SNPs were associated with at least one MD phenotype at p < 0.05. TWAS further identified two novel genes (SHOX2 and CRISPLD2) whose genetically predicted expression was significantly associated with MD phenotypes., Conclusions: Our findings provided novel insight into the genetic background of MD phenotypes, and further demonstrated their shared genetic basis with breast cancer., (© 2022. The Author(s).)

Objective: The menopausal transition is characterized by progressive changes in ovarian function and increasing circulating levels of gonadotropins, with some women having irregular menstrual cycles well before their final menstrual period. These observations indicate a progressive breakdown of the hypothalamic-pituitary-ovarian axis often associated with an increase in menopausal symptoms. Relationships between vasomotor symptoms (VMS) and depressed mood and sleep as well as a bidirectional association between VMS and depressed mood in mid-life women have been reported, but the endocrine foundations and hormone profiles associated with these symptoms have not been well described. Our objective was to determine the relationship between daily urinary hormone profiles and daily logs of affect and VMS during the early perimenopausal transition., Study Design: SWAN, the Study of Women's Health Across the Nation, is a large, mutli-ethnic, multisite cohort study of 3302 women aged 42-52 at baseline, designed to examine predictors of health and disease in women as they traversed the menopause. Inclusion criteria were: an intact uterus and at least one ovary present, at least one menstrual period in the previous three months, no use of sex steroid hormones in the previous three months, and not pregnant or lactating. A subset (n = 849) of women aged 43-53 years from all study sites in the first Daily Hormone Study collection were evaluated for this substudy., Outcome Measures: We measured daily VMS, and urinary hormones: follicle stimulating hormone (FSH), luteinizing hormone (LH), pregnanediol glucuronide (PdG) and estradiol (estrone conjugate, E1C)., Results: A variable pattern of LH and negative LH feedback were the hormone patterns most strongly associated with increased VMS. In contrast, no hormone pattern was significantly related to negative mood., Conclusion: Fluctuations of LH associated with low progesterone production were associated with VMS but not negative mood, suggesting different endocrine patterns may be related to increased negative mood than to the occurrence of VMS., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: A greater frequency of vasomotor symptoms (VMSs) has been associated with higher low-density lipoprotein cholesterol (LDL-C), but the association with high-density lipoprotein cholesterol (HDL-C) remains unclear. Endogenous estradiol (E2) levels are associated with both VMS and lipid levels and thus may confound such associations., Objectives: To assess the relationship of VMS frequency with HDL-C, LDL-C, and lipoprotein concentrations (HDL and LDL particles [HDL-P; LDL-P]) and lipoprotein sizes in midlife women and to evaluate whether these associations are explained by E2., Methods: Participants were from the Study of Women's Health Across the Nation (SWAN) HDL ancillary study who had both nuclear magnetic resonance (NMR) spectroscopy lipoprotein subclass metrics and self-reported frequency of VMS measured 2-5 times over the menopause transition. VMS frequency was categorized into none, 1-5 days (infrequent), or ≥6 days (frequent) within the past 2 weeks., Results: We evaluated 522 women [at baseline: mean age 50.3 (SD: 2.8) years; infrequent VMS: 29.8%, frequent VMS: 16.5%]. Adjusting for potential confounders except E2, frequent VMS was associated with smaller HDL size [β(SE): -0.06 (0.03); P = .04] and higher concentrations of LDL-C [β(SE): 3.58 (1.77); P = .04] and intermediate LDL-P [β(SE): 0.09 (0.05); P = .04] than no VMS. These associations were largely explained by E2, all P's > .05., Conclusions: Frequent VMSs were associated with smaller HDL size and higher concentrations of LDL-C and intermediate LDL-P. These associations were explained by endogenous E2. Whether treating frequent VMS with exogenous E2 could simultaneously improve lipids/lipoproteins profile should be assessed in future studies., (Copyright © 2020 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Hotel housekeepers are exposed to stressors at work and outside of work. A minimal amount is known about these workers' pathophysiological responses to those stressors. Allostatic load is a concept increasingly used to understand pathophysiologic manifestations of individuals' bodily response to stress. The purpose of this study was to examine the associations between work and nonwork stressors, allostatic load, and health outcomes among hotel housekeepers. Work and nonwork stressors (e.g., the number of traumatic events, everyday discrimination, and job strain) and health outcomes (e.g., general health status, physical and mental health, and chronic diseases) were measured. Biometric and anthropometric measures and fasting blood specimens were collected. Blood biomarkers included CRP, HbA1c, HDL, and cortisol. Descriptive analyses, correlations, regressions, and t-tests were conducted. Forty-nine women hotel housekeepers participated, with a mean age of 40 years. One-fifth reported high job strain and more than 40% had at least one traumatic event. Chronic conditions were commonly reported, with about 78%, 55%, and 35% reporting one, two, and three chronic conditions, respectively. Correlation analyses showed that reports of high job strain and everyday discrimination were significantly associated with high ALI quartile score (r = 0.39, p = 0.011; r = 0.41, p = 0.004). Job strain and everyday discrimination had medium to large effect sizes on ALI quartile scores. High ALI quartile score was significantly associated with having at least one chronic disease (r = 0.40, p = 0.005), and it had a large effect size on chronic diseases. To our knowledge, this is the first study to explore allostatic load among hotel housekeepers. Hotel housekeepers have high exposure to stressors within and outside of their work and experience poor chronic conditions. Allostatic load had strong associations with both stressors and health outcomes. Despite this worker group being a hard-to-reach worker group to participate in research studies, this study demonstrates the feasibility of accessing, recruiting and collecting survey data and blood samples among them to determine health risks and guide future targeted interventions.

The effects of playing action video games have been investigated across a wide range of attentional and cognitive abilities. However, few studies have examined the association between motor control and action gaming experience. We report data from two discrete pointing tasks, manipulating the index of difficulty (ID) by movement distance and target size, respectively. Participants' gaming experience ranged from non-players to individuals who played several hours a night. Our results indicated greater experience playing action games, but not video games in general, was associated with shorter movement times (MT), higher velocities, and shallower ID-MT slopes when difficulty was manipulated across increasingly further distances and smaller target sizes. Additionally casual players, those who only play action games a couple times a week, were able to achieve a similar level of performance as more experienced players., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Lack of physical activity is a severe health concern in the United States with fewer than half of all Americans meeting the recommended weekly physical activity guidelines. Although wearable fitness devices can be effective in motivating people to be active, consumers are abandoning this technology soon after purchase. We examined the impact of several user (i.e. personality, age, computer self-efficacy, physical activity level) and device characteristics (trust, usability, and motivational affordances) on the behavioral intentions to use a wearable fitness device. Novice users completed a brief interaction with a fitness device similar to a first purchase experience before completing questionnaires about their interaction. We found computer self-efficacy, physical activity level, as well as personality traits indirectly increased the desire to use a fitness device and influenced the saliency of perceived motivational affordances. Additionally, trust, usability, and perceived motivational affordances were associated with increased intentions to use fitness devices., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: We investigated the effects of a passive break, relaxation activity, and casual video game on affect, stress, engagement, and cognitive performance., Background: Reducing stress and improving cognitive performance is critical across many domains. Previous studies investigated taking a break, relaxation techniques, or playing a game; however, these methods have not been compared within a single experiment., Method: Participants completed a baseline affective and cognitive assessment (ACA), which included the Positive and Negative Affect Schedule, shortened version of the Dundee Stress State Questionnaire, and backward digit-span. Next, participants completed a vigilance task, followed by another ACA. Participants were then assigned at random to complete a break or relaxation activity or play a casual video game, followed by a final ACA., Results: Participants who played the casual video game exhibited greater engagement and affective restoration than the relaxation condition. The break condition slightly decreased affect and prevented cognitive restoration., Conclusion: Playing a casual video game even briefly can restore individuals' affective abilities, making it a suitable activity to restore mood in response to stress. However, future research is needed to find activities capable of cognitive restoration., Application: Many activities in life require sustained cognitive demand, which are stressful and decrease performance, especially for workers in performance-critical domains. Our research suggests some leisure activities are better than others for restoring fatigued affective processes.

Background: Previous reports have noted that dehydroepiandrosterone-sulfate (DHEAS) increases prior to the final menstrual period (FMP) and remains stable beyond the FMP. How DHEAS concentrations correspond with other sex hormones across the menopausal transition (MT) including androstenedione (A4), testosterone (T), estrone (E1), and estradiol (E2) is not known. Our objective was to examine how DHEAS, A4, T, E1, and E2 changed across the MT by White vs. African-American (AA) race/ethnicity., Methods: We conducted a longitudinal observational analysis of a subgroup of women from the Study of Women's Health Across the Nation observed over 4 visits prior to and 4 visits after the FMP ( n = 110 women over 9 years for 990 observations). The main outcome measures were DHEAS, A4, T, E1, and E2., Results: Compared to the decline in E2 concentrations, androgen concentrations declined minimally over the MT. T (β 9.180, p < 0.0001) and E1 (β 11.365, p < 0.0001) were higher in Whites than in AAs, while elevations in DHEAS (β 28.80, p = 0.061) and A4 (β 0.2556, p = 0.052) were borderline. Log-transformed E2 was similar between Whites and AAs (β 0.0764, p = 0.272). Body mass index (BMI) was not significantly associated with concentrations of androgens or E1 over time., Conclusion: This report suggests that the declines in E2 during the 4 years before and after the FMP are accompanied by minimal changes in DHEAS, A4, T, and E1. There are modest differences between Whites and AAs and minimal differences by BMI., Competing Interests: Competing interests The authors declare that they have no competing interests.

Objective: To compare concentrations of antimüllerian hormone (AMH) in women with and without type 1 diabetes., Design: Cross-sectional analysis of longitudinal studies, adjusting for repeated measures., Setting: Not applicable., Patient(s): Women aged 30-45 years who had not undergone oophorectomy, hysterectomy, or natural menopause at the time of AMH measurement were included (n = 376 in the Michigan Bone Health and Metabolism Study and n = 321 in the Epidemiology of Interventions and Complications Study). Linear mixed regression was used to evaluate whether AMH concentrations differed by diabetes status, adjusting for repeated measurements of AMH within individual women, body mass index, smoking status, and oral contraceptive use., Intervention(s): None., Main Outcome Measure(s): Concentrations of AMH., Result(s): In unadjusted comparisons, women with and without diabetes had similar median AMH values before 35 years of age, although women with type 1 diabetes had a lower proportion of women with elevated AMH concentrations (≥5.0 ng/dL). After adjustment for covariates and multiple observations per woman, log AMH concentrations were significantly lower among women with type 1 diabetes compared with women without diabetes (β-coefficient -1.27, 95% confidence interval [-2.18, -0.36] in fully adjusted models) before 35 years of age., Conclusion(s): Before 35 years of age, women with type 1 diabetes have lower AMH levels than women without diabetes. Further investigation is needed to determine the etiologies of this difference and how it may contribute to reproductive disorders among women with type 1 diabetes., Competing Interests: There are no conflicts of interest relevant to this article. Assay kits for the measurement of AMH in the Michigan Bone Health and Metabolism Study were provided at no charge by Beckman Coulter. Dr. Kong was an employee at Purdue University during the completion of the manuscript. The DCCT/EDIC has been supported by U01 Cooperative Agreement grants (1982–93, 2011–2016), and contracts (1982–2011) with the Division of Diabetes Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Disease (current grant numbers U01 DK094176 and U01 DK094157), and through support by the National Eye Institute, the National Institute of Neurologic Disorders and Stroke, the Genetic Clinical Research Centers Program (1993–2007), and Clinical Translational Science Center Program (2006-present), Bethesda, Maryland, USA. Additional support for this work was provided by DP3 DK098129. The Michigan Bone Health and Metabolism Study received support from the National Institute of Arthritis and Muscular Skeletal and Skin Diseases (AG051384). SDH gratefully acknowledges use of the services and facilities of the Population Studies Center at the University of Michigan, funded by NICHD Center Grant R24 HD041028.CKG is partially supported by a Claude Pepper Career Development Award., (Copyright © 2016. Published by Elsevier Inc.)

Objective: The aim of the study was to investigate the heterogeneity of temporal patterns of vasomotor symptoms (VMS) over the menopausal transition and identify factors associated with these patterns in a diverse sample of women., Methods: The Study of Women's Health Across the Nation is a multisite longitudinal study of women from five racial/ethnic groups transitioning through the menopause. The analytic sample included 1,455 women with nonsurgical menopause and a median follow-up of 15.4 years. Temporal patterns of VMS and associations with serum estradiol and follicle-stimulating hormone, race/ethnicity, body mass index, and demographic and psychosocial factors were examined using group-based trajectory modeling., Results: Four distinct trajectories of VMS were found: onset early (11 years before the final menstrual period) with decline after menopause (early onset, 18.4%), onset near the final menstrual period with later decline (late onset, 29.0%), onset early with persistently high frequency (high, 25.6%), and persistently low frequency (low, 27.0%). Relative to women with persistently low frequency of VMS, women with persistently high and early onset VMS had a more adverse psychosocial and health profile. Black women were overrepresented in the late onset and high VMS subgroups relative to white women. Obese women were underrepresented in the late onset subgroup. In multivariable models, the pattern of estradiol over the menopause was significantly associated with the VMS trajectory., Conclusions: These data distinctly demonstrate heterogeneous patterns of menopausal symptoms that are associated with race/ethnicity, reproductive hormones, premenopause body mass index, and psychosocial characteristics. Early targeted intervention may have a meaningful impact on long-term VMS.

In this paper we suggest that differing approaches to the science of social cognition mirror the arguments between radical embodied and traditional approaches to cognition. We contrast the use in social cognition of theoretical inference and mental simulation mechanisms with approaches emphasizing a direct perception of others' mental states. We build from a recent integrative framework unifying these divergent perspectives through the use of dual-process theory and supporting social neuroscience research. Our elaboration considers two complementary notions of direct perception: one primarily stemming from ecological psychology and the other from enactive cognition theory. We use this as the foundation from which to offer an account of the informational basis for social information and assert a set of research propositions to further the science of social cognition. In doing so, we point out how perception of the minds of others can be supported in some cases by lawful information, supporting direct perception of social affordances and perhaps, mental states, and in other cases by cues that support indirect perceptual inference. Our goal is to extend accounts of social cognition by integrating advances across disciplines to provide a multi-level and multi-theoretic description that can advance this field and offer a means through which to reconcile radical embodied and traditional approaches to cognitive neuroscience.

Unlabelled: Abstract Background: The immune factors in human milk protect infants from infection and promote immune development. Evidence suggests that the production of milk-specific immunoproteins is energetically costly, making them a form of maternal investment in offspring health that is subject to life history trade-offs., Aim: This research tests the relationship between measures of reproductive effort and the production of milk immunoglobulin A (IgA) among Ariaal women, a settled northern Kenyan pastoralist population that experiences nutritional and disease stress., Subjects and Methods: Two hundred and forty-three lactating Ariaal women participated in a questionnaire, anthropometric measurement and milk collection. Milk IgA was analysed using ELISA., Results: There was a significant U-shaped relationship between post-partum months and milk IgA, reflecting decreasing investment in the current offspring over the early post-partum period and subsequent recovery of maternal energy status near the end. There was also a significant inverse U-shaped relationship between milk IgA and parity, with high parity women showing a drop in milk IgA. In contrast, anthropometric measures of energy status were not associated with the production of milk IgA., Conclusion: This research shows that patterns of reproductive investment can be demonstrated in milk IgA in the absence of measured energy changes.

Game controllers are emerging as a preferred choice for the manual control of unmanned vehicles, but an understanding of their usability characteristics has yet to emerge. We compared the usability of an Xbox 360 game controller in a dual task situation using MATB II to the traditional joystick and keyboard interface in two experiments. In the first experiment, performance with the game controller was associated with fewer tracking errors. In a second experiment, we trained users on the devices, and found that even after training the game controller was still associated with fewer tracking errors as well as higher usability and lower workload ratings. These results are consistent with the idea that game controllers are highly usable input devices and do not require high mental workload to operate, thus making them suitable for complex control tasks.

Study Question: What is the daily variation in serum inhibin B (InhB) and anti-Müllerian hormone (AMH) in relation to the LH surge in women of reproductive age., Summary Answer: AMH is secreted in a biphasic follicular/luteal pattern in women with higher AMH secretion, while InhB secretion is episodic in the early to mid-follicular phase and immediately after the LH surge but not in the luteal phase., What Is Known Already: In women of reproductive age with a mean serum AMH >1 ng/ml, levels are highest in Days 2-7 of the cycle. InhB concentrations are highest in the follicular phase of the cycle., Study Design, Size, Duration: In this cohort study conducted in an academic center, blood samples were collected daily from 20 women during one normal menstrual cycle., Participants/materials, Setting, Methods: Regularly menstruating 30- to 40-year-old women had daily serum InhB, AMH, LH and FSH levels measured. Intracycle variability of InhB and AMH were assessed after aligning to the LH surge., Main Results and the Role of Chance: When classified into quartiles of AMH concentration, the lowest AMH levels did not vary across the cycle; the highest AMH levels showed a mid-follicular increase, mid-cycle decrease and mid-luteal increase. A surge of InhB was noted following the LH surge in 16/20 cycles. Episodic increases in InhB occurred in 17/20 cycles prior to the LH surge. In the luteal phase, InhB decreased or became undetectable and did not demonstrate episodic secretion. Old and new assays for AMH and InhB were compared in all samples, with the AMH assays demonstrating good correlation (Rsq = 0.9625) but the InhB assays showing less correlation (Rsq = 0.4903)., Limitations, Reasons for Caution: The study population is small and in the mid-to-late reproductive age group. Single daily sampling may not detect more frequent variability (i.e. pulses) in hormone levels., Wider Implications of the Findings: These data suggest different regulatory mechanisms for InhB and AMH secretion, and confirm an 'aging ovary' pattern of AMH and InhB secretion, which is consistent with decreased ovarian reserve. We also demonstrated comparability of the AMH Gen II assay with the previous version in standard usage but our data raised concerns about comparability of the InhB Gen II assay., Study Funding/competing Interest(s): General Clinical Research Center for phlebotomy work has been supported in part by NIH grant UL1RR024986. Recruitment and data analyses were supported by the Center for Integrated Approaches to Complex Diseases (SD Harlow, Director). The authors report no conflicts of interest., Trial Registration Number: N/A.

Observations over the past decade using longitudinal data reveal a gender-specific shift in adrenal steroid production. This shift is represented by an increase in the circulating concentrations of delta 5 steroids in 85% of all women and is initiated only after the menopausal transition has begun. While the associated rise in the major adrenal androgen, dehydroepiandrosterone sulfate (DHEAS), is modest, the parallel rises in dehydroepiandrosteone (DHEA) and androstenediol (Adiol) are much more robust. These increases in circulating steroid concentrations are qualitatively similar on average between ethnicities but quantitatively different between individual women. Both circulating testosterone (T) and androstenedione (Adione) also rise concomitantly but modestly by comparison. This phenomenon presents a new and provocative aspect to the endocrine foundations of the menopausal transition and may provide important clues to understanding the fundamentals of mid-aged women's healthy aging, particularly an explanation for the wide diversity in phenotypes observed during the MT as well as their different responses to hormone replacement therapies. Experimental studies using the nonhuman primate animal model show an acute adrenal response to human chorionic gonadotropin (hCG) challenge as well as the presence of luteinizing hormone receptors (LHR) in their adrenal cortices. These experimental results support the concept that LHRs are recruited to the adrenal cortices of mid-aged women that subsequently function to respond to increasing circulating LH to shunt pregnenolone metabolites towards the delta 5 pathway. Future investigations are required to determine the relationship of these changes in adrenal function to symptoms and health outcomes of mid-aged women.

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., (Copyright © 2012 Wiley Periodicals, Inc.)

Context: Variability in the pattern of change in estradiol (E2) and FSH levels over the menopause transition has not been well defined., Objective: 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., Design: The Study of Women's Health Across the Nation is a longitudinal observational study of the menopausal transition., Setting: Women aged 42-52 yr from seven participating sites were recruited and underwent up to 11 annual visits., Participants: 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., Main Outcome Measures: Annual serum E2 and FSH levels anchored to final menstrual period were measured., Results: 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., Conclusions: 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.

Background: We measured antimullerian hormone (AMH), a marker of ovarian reserve, in women with lupus treated with cyclophosphamide (CYC) (group I), CYC plus gonadotropin-releasing hormone agonist (GnRH-a) (group II) or neither (group III). We hypothesized that AMH would be diminished in women exposed to CYC versus women receiving adjunctive GnRH-a treatment or no CYC exposure., Methods: Forty-eight premenopausal lupus patients were retrospectively divided into three treatment groups: CYC alone (group I, n = 11), CYC + GnRH-a (group II, n = 10) and neither (group III, n = 27). Serum AMH levels between groups were compared using a nonparametric test (Wilcoxon rank-sum). Multiple linear regression adjusting for age was performed., Results: AMH (ng/mL) levels at the last collection were significantly lower in group I versus group III (mean ± SD: 0.18 ± 0.20 group I vs 1.33 ± 1.59 group III; p = 0.015), and versus group II (mean ± SD: 0.86 ± 1.06; p = 0.018). When centered on age 30 years, average AMH levels for group I, group II and group III were 0.20, 0.44 and 1.00, respectively. When adjusted for age, AMH between all groups was significantly different (p<0.0001)., Conclusion: Posttreatment AMH levels were significantly higher among patients receiving CYC + GnRH-a compared to CYC alone, suggesting that GnRH-a coadministration mitigates CYC-induced ovarian injury.

Individuals who have Attention Deficit/Hyperactivity Disorder (ADHD) experience adverse effects relating to driving; additionally, they experience deficits in scanning ability. The present study examined the effects of ADHD on eye tracking while driving. This study consisted of ten participants, of which, five have ADHD. It was hypothesized that individuals who have ADHD will make more saccadic eye movements and thus shorter fixations than individuals without ADHD (Control). Furthermore, it was hypothesized that despite the fact that individuals who have ADHD will make more saccadic eye movements than individuals without ADHD, those individuals with ADHD will commit more traffic violations including collisions compared to the control group. Findings indicated that hypothesis one was not supported by the data, whereas hypothesis two was supported in that ADHD individuals' had more collisions and committed more traffic violations than the control group. Additionally, a significant difference was found in the spatial distributions of the fixations between the ADHD and Control groups. The findings of this study could help better understand the factors involved in ADHD driving and could be used to train individuals with ADHD to become more aware of their surroundings and driving habits and thus become safer drivers.

Distracted driving has been shown to be a safety issue in numerous studies. To combat this problem, in-vehicle technology, legislation, media interventions, and other methods have been proposed and attempted. However research indicates that the drivers themselves may circumvent, ignore, or not be able to react in time for these interventions to be effective. Therefore research into training programs for drivers may improve reaction time under distraction. Research indicates that action game players have faster reaction times and more attentional resources than non-players on paper-based tests. However, transferability to driving has not been studied yet. This paper outlines a study to determine if action game players perform better at a driving task based on frequency of game-play. Participants will be placed into two groups of play (high vs. low) and tested against two levels of distraction (none vs. phone conversation). It is expected that participants who play higher frequency of action games will perform better under distraction than lower frequency players. Driver performance, conversation recall, frequency and durations of eye fixations will be analyzed based on previous research which has validated those variables as a measure of distraction and higher workload.

Objectives: 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., Methods: 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., Results: 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)., Conclusions: 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., (Copyright © 2011 Wiley-Liss, Inc.)

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.

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., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: 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., Methodology: 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., Significance: 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.

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., (2010 Elsevier Inc. All rights reserved.)

Modern tools often separate the visual and physical aspects of operation, requiring users to manipulate an instrument while viewing the results indirectly on a display. This can pose usability challenges particularly in applications, such as laparoscopic surgery, that require a high degree of movement precision. Magnification used to augment the view and, theoretically, enable finer movements, may introduce other visual-motor disruptions due to the apparent speed of the visual motion on screen (i.e., motion scaling). In this research, we sought to better understand the effects of visual magnification on human movement performance and control in operating a tool via indirect vision. Ten adult participants manipulated a computer mouse to direct a pointer to targets on a display. Results (Experiment 1) showed that, despite increased motion scaling, magnification of the view on screen enabled higher precision control of the mouse pointer. However, the relative effectiveness of visual magnification ultimately depended on the scale of the physical movement, and more specifically the precision limits of the whole-hand grip afforded by the mouse. When the physical scale of the hand/mouse movement was reduced (Experiment 2), fine-precision control began to reach its limits, even at full magnification. The role of magnification can thus be understood as "amplifying" the particular skill level afforded by the effecting limb. These findings suggest a fruitful area for future research is the optimization of hand-control interfaces of tools to maximize movement precision.

Background and Aim: 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., Methods: 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., Results: 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)., Conclusion: Future investigations should consider that a high prevalence of asymptomatic liver disease may alter associations between hormone concentrations and chronic disease etiology.

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.

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.

The current experiment suggests that the speed/accuracy tradeoff is composed of two classes of constraints, effector and task. We examined the effects of movement distance, target size, orientation of the movement in the workspace, and C-D gain on the kinematics of discrete pointing movements made with computer mouse. It was found that target size influenced the shape of velocity profiles by elongating the duration of the corrective sub-movement phase, while movement distance scaled the entire velocity curve without affecting its shape. C-D gain and orientation of the movement exhibited two kinds of effects: an overall scaling of the velocity curve and a change in its shape. We conclude that target size is a task constraint and movement distance is an effector constraint, while movement orientation exhibited characteristics of both. C-D gain by itself was not a constraint, but interacted with both task and effector constrains. These results highlight the roles of biomechanical and information processing factors in the speed/accuracy tradeoff.

Context: 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., Objective: The objective of the study was to develop and characterize a cell-based bioassay that measures the androgen receptor-mediated signal transduction in serum., Design: This was a clinically relevant experimental study nested in a sample population of a longitudinal cohort study., Setting: The study was conducted at a university laboratory., Methods: 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., Results: 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., Conclusions: 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.

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 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.

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.

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.