Obstructive Sleep Apnea and Sarcoidosis Interactions.

Obstructive sleep apnea (OSA) is very prevalent in sarcoidosis patients. Sarcoidosis of the upper respiratory tract may affect upper airway patency and increase the risk of OSA. Weight gain due to steroid use, upper airway myopathy due to steroids and sarcoidosis itself, and interstitial lung disease with decreased upper airway patency are other reasons for the higher OSA prevalence seen in sarcoidosis. Several clinical manifestations such as fatigue, hypersomnolence, cognitive deficits, and pulmonary hypertension are common to both OSA and sarcoidosis. Therefore, early screening and treatment for OSA can improve symptoms and overall patient quality of life.

Recommendations for clinical management of excessive daytime sleepiness in obstructive sleep apnoea - A Delphi consensus study.

STUDY OBJECTIVE: Excessive daytime sleepiness is common with obstructive sleep apnoea and can persist despite efforts to optimise primary airway therapy. The literature lacks recommendations regarding differential diagnosis and management of excessive daytime sleepiness in obstructive sleep apnoea. This study sought to develop expert consensus statements to bridge the gap between existing literature/guidelines and clinical practice. METHODS: A panel of 10 international experts was convened to undertake a modified Delphi process. Statements were developed based on available evidence identified through a scoping literature review, and expert opinion. Consensus was achieved through 3 rounds of iterative, blinded survey voting and revision to statements until a predetermined level of agreement was met (≥80 % voting "strongly agree" or "agree with reservation"). RESULTS: Consensus was achieved for 32 final statements. The panel agreed excessive daytime sleepiness is a patient-reported symptom. The importance of subjective/objective evaluation of excessive daytime sleepiness in the initial evaluation and serial management of obstructive sleep apnoea was recognised. The differential diagnosis of residual excessive daytime sleepiness in obstructive sleep apnoea was discussed. Optimizing airway therapy (eg, troubleshooting issues affecting effectiveness) was addressed. The panel recognised occurrence of residual excessive daytime sleepiness in obstructive sleep apnoea despite optimal airway therapy and the need to evaluate patients for underlying causes. CONCLUSIONS: Excessive daytime sleepiness in patients with obstructive sleep apnoea is a public health issue requiring increased awareness, recognition, and attention. Implementation of these statements may improve patient care, long-term management, and clinical outcomes in patients with obstructive sleep apnoea.

The Link between Obstructive Sleep Apnea and Neurocognitive Impairment: An Official American Thoracic Society Workshop Report.

There is emerging evidence that obstructive sleep apnea (OSA) is a risk factor for preclinical Alzheimer's disease (AD). An American Thoracic Society workshop was convened that included clinicians, basic scientists, and epidemiologists with expertise in OSA, cognition, and dementia, with the overall objectives of summarizing the state of knowledge in the field, identifying important research gaps, and identifying potential directions for future research. Although currently available cognitive screening tests may allow for identification of cognitive impairment in patients with OSA, they should be interpreted with caution. Neuroimaging in OSA can provide surrogate measures of disease chronicity, but it has methodological limitations. Most data on the impact of OSA treatment on cognition are for continuous positive airway pressure (CPAP), with limited data for other treatments. The cognitive domains improving with CPAP show considerable heterogeneity across studies. OSA can negatively influence risk, manifestations, and possibly progression of AD and other forms of dementia. Sleep-dependent memory tasks need greater incorporation into OSA testing, with better delineation of sleep fragmentation versus intermittent hypoxia effects. Plasma biomarkers may prove to be sensitive, feasible, and scalable biomarkers for use in clinical trials. There is strong biological plausibility, but insufficient data, to prove bidirectional causality of the associations between OSA and aging pathology. Engaging, recruiting, and retaining diverse populations in health care and research may help to decrease racial and ethnic disparities in OSA and AD. Key recommendations from the workshop include research aimed at underlying mechanisms; longer-term longitudinal studies with objective assessment of OSA, sensitive cognitive markers, and sleep-dependent cognitive tasks; and pragmatic study designs for interventional studies that control for other factors that may impact cognitive outcomes and use novel biomarkers.

Ventricular Arrhythmias in Patients with Implanted Cardiac Devices at High Risk of Obstructive Sleep Apnea.

Background and Objectives: Patients with pre-existing cardiac disease have a higher prevalence of Obstructive Sleep Apnea (OSA). OSA has been associated with an increased risk of supraventricular and ventricular arrhythmia. We screened subjects with implanted pacemakers and automated implantable cardioverter defibrillators (AICD) for OSA with the Berlin Questionnaire and compared the incidence of ventricular arrhythmias and automated implantable cardioverter defibrillator (AICD) firing between high and low OSA risk groups. Materials and Methods: We contacted 648 consecutive patients from our arrhythmia clinic to participate in the study and performed final analyses on 171 subjects who consented and had follow-up data. Data were abstracted from the electronic health record for the incidence of non-sustained ventricular tachycardia (NSVT), ventricular tachycardia (VT), ventricular fibrillation (VF) and AICD firing and then compared between those at high versus low risk of OSA using the Berlin Questionnaire and multivariate negative binomial regression. Results: The average follow-up period was 24.2 ± 4.4 months. After adjusting for age, gender and history of heart failure, those subjects at high risk of OSA had a higher burden of NSVT vs. those with a low risk of OSA (33.4 ± 96.2 vs. 5.82 ± 17.1 episodes, p = 0.003). A predetermined subgroup analysis of AICD recipients also demonstrated a significantly higher burden of NSVT in the high vs. low OSA risk groups (66.2 ± 128.6 vs. 18.9 ± 36.7 episodes, p = 0.033). There were significant differences in the rates of VT, VF or AICD shock burden between the high and low OSA risk groups and in the AICD subgroup analysis. Conclusions: There was increased ventricular ectopy among pacemaker and AICD recipients at high risk of OSA, but the prevalence of VT, VF or AICD shocks was similar to those with low risk of OSA.

Excessive Daytime Sleepiness in Obstructive Sleep Apnea. Mechanisms and Clinical Management.

Many patients with obstructive sleep apnea (OSA) experience excessive daytime sleepiness (EDS), which can negatively affect daily functioning, cognition, mood, and other aspects of well-being. Although EDS can be reduced with primary OSA treatment, such as continuous positive airway pressure (CPAP) therapy, a significant proportion of patients continue to experience EDS despite receiving optimized therapy for OSA. This article reviews the pathophysiology and clinical evaluation and management of EDS in patients with OSA. The mechanisms underlying EDS in CPAP-treated patients remain unclear. Experimental risk factors include chronic intermittent hypoxia and sleep fragmentation, which lead to oxidative injury and changes in neurons and brain circuit connectedness involving noradrenergic and dopaminergic neurotransmission in wake-promoting regions of the brain. In addition, neuroimaging studies have shown alterations in the brain's white matter and gray matter in patients with OSA and EDS. Clinical management of EDS begins with ruling out other potential causes of EDS and evaluating its severity. Tools to evaluate EDS include objective and self-reported assessments of sleepiness, as well as cognitive assessments. Patients who experience residual EDS despite primary OSA therapy may benefit from wake-promoting pharmacotherapy. Agents that inhibit reuptake of dopamine or of dopamine and norepinephrine (modafinil/armodafinil and solriamfetol, respectively) have demonstrated efficacy in reducing EDS and improving quality of life in patients with OSA. Additional research is needed on the effects of wake-promoting treatments on cognition in these patients and to identify individual or disorder-specific responses.

A population-based estimate of the health care burden of obstructive sleep apnea using a STOP-BAG questionnaire in South Carolina.

STUDY OBJECTIVES: Population based estimates of obstructive sleep apnea (OSA) frequency and health impact are incomplete. The aim of this study was to determine the prevalence of risk factors for physician and sleep study diagnosed OSA among individuals in a state-based surveillance program. METHODS: Using questions inserted into the 2016 (n = 5,564) and 2017 (n = 10,884) South Carolina Behavioral Risk Factor Surveillance System of the Centers for Disease Control and Prevention, we analyzed the prevalence of physician diagnosed OSA and associated comorbidities. The validated STOP-BANG questionnaire without neck circumference (STOP-BAG) defined populations at moderate risk (score 3-4) and high risk (score 5-7). Statistical analysis using weighted prevalence and means and their 95% confidence intervals (CI) thus reflect population estimates of disease burden. RESULTS: The population-based prevalence of physician diagnosed OSA in South Carolina was 9.7% (95% CI: 9.0-10.4). However, the populations with moderate risk (18.5%, 95% CI: 17.3-19.8) and high risk (25.5%, 95% CI: 23.9-27.1) for OSA, as determined by the STOP-BAG questionnaire, were much higher. Compared to those at low risk for OSA, those at high risk were more often diagnosed with coronary heart disease, stroke, asthma, skin cancer, other cancers, chronic obstructive pulmonary disease, arthritis, depression, kidney disease, and diabetes (all P < .001). CONCLUSIONS: OSA is common and strongly associated with major comorbidities. As such, this public health crisis warrants more diagnostic and therapeutic attention. The STOP-BAG questionnaire provides a public health platform to monitor this disease.

Prevalence of self-reported sleep problems amongst adults with obstructive airway disease in the NHANES cohort in the United States.

RATIONALE: Sleep and respiratory problems are common in adults in the USA. However, sleep problems often remain undiagnosed in patients with obstructive airway diseases (OADs). This study was designed to examine the association between sleep problems and different categories of OAD amongst US adults. METHODS: We conducted an observational, cross-sectional study using a nationally representative sample of the US civilian non-institutionalized population from 2007 to 2008 National Health and Nutritional Examination Survey (NHANES). A total of 3204 study participants aged ≥35 years were stratified into four groups, using a self-reported history of asthma and data from spirometry: asthma-COPD overlap (ACO) (n = 70, 2.2%), asthma (n = 168, 5.2%), chronic obstructive pulmonary disease (COPD) (n = 412, 12.8%), and those without any OAD (normal) (n = 2554, 79.7%). After characterizing the baseline demographics and health status of the four groups, multivariate logistic regression analysis was performed to estimate the likelihood of sleep problems in adults after adjusting for age, gender, body mass index, smoking, alcohol, obstructive sleep apnea syndrome (OSAS), depression, and diabetes. The index sample was the normal group. Sleep problems were defined as any complaints which affect or involve sleep. RESULTS: The participants with COPD were older (62.0 ± 11.7 years) as compared to ACO (59.1 ± 11.3 years), asthma (53.6 ± 11.3), and normal groups (53.8 ± 12.1) (p < 0.0001). Comparing baseline characteristics between the four groups, there were significant associations between OAD status and sleep problems including inadequate sleep, sleep-onset insomnia, snoring, frequent trouble sleeping, nocturnal arousals, early morning awakenings, fatigue, daytime sleepiness, use of prescription medication for sleep, leg jerks, leg cramps, difficulty in concentration, and difficulty in remembering things when tired. The multivariate logistic regression models evaluating the prevalence of sleep problems in individual OADs showed a stronger association between asthma and sleep problems as compared to COPD and ACO and sleep disorders. CONCLUSION: All OADs are associated with a higher prevalence of sleep problems. There is a stronger association between asthma and sleep problems as compared to COPD and ACO. We speculate that the nocturnal burden of asthma contributes to sleep problems. Our results suggest that adults with OAD should be aggressively screened for sleep problems.

Emerging Treatments for COPD: Evidence to Date on Revefenacin.

Chronic obstructive pulmonary disease (COPD) is the 4th leading cause of death in the United States. Due to the substantial public health burden of COPD, there has been a lot of interest in developing new drug therapies, directed at improving the symptomatology and quality of life in COPD patients. Revefenacin is the first once daily nebulized long acting muscarinic antagonist for COPD treatment. It offers an advantage over other nebulized bronchodilators, as once daily administration may improve patient compliance. Revefenacin has a rapid onset of action, is long acting and significantly improves lung function (FEV1) in patients with COPD. It can play a major role in the management of COPD, especially in patients who have difficulty mastering inhaler techniques and those with low baseline FEV1 who may have difficulty generating flow with an inhaler. This manuscript is a review on revefenacin and outlines the pharmacologic profile and the clinical trials which have evaluated it's the efficacy and safety. The authors also discuss their own perspective on the potential role of revefenacin in COPD management.

Evaluating fluticasone furoate + vilanterol for the treatment of chronic obstructive pulmonary disease (COPD).

INTRODUCTION: Inhaled corticosteroid/long-acting ß-2 agonists (ICS/LABA) combination inhalers have been a lifeline for a generation of chronic obstructive pulmonary disease (COPD) and asthma patients. Fluticasone furoate and Vilanterol (FF/VI) as a once-daily ICS/LABA combination have an extensive clinical trial and real-world data to support its use in COPD patients. Areas covered: The authors provide pharmacological profiles of fluticasone furoate, vilanterol and the FF/VI fixed dose combination. Salient clinical trials evaluating efficacy and safety of the FF/VI combination, and studies demonstrating the impact on COPD exacerbation risk and mortality are also discussed. Expert opinion: ICS/LABA combinations provide bronchodilation and decrease the frequency of COPD exacerbations. Individualizing treatment of each COPD patient based on unique phenotypes will maximize chances of therapeutic responsiveness. Asthma-COPD overlap (ACO), patients with sputum and/or blood eosinophilia, patients with a brisk bronchodilator response, and patients with frequent exacerbations are more likely to show a therapeutic response to ICS than populations who have none of these features. FF/VI will likely remain a popular ICS/LBA combination to treat COPD, as a once-daily inhaled therapy delivered via the Ellipta device popular with COPD patients, with extensive clinical trial and real-world data to support its use.

Proteomic biomarkers of cognitive impairment in obstructive sleep apnea syndrome.

PURPOSE: There are currently no biomarkers that are associated with cognitive impairment (CI) in patients with obstructive sleep apnea syndrome (OSAS). This pilot study performed an exploratory plasma proteomic analysis to discover potential biomarkers and explore proteomic pathways that differentiate OSAS subjects with and without CI. METHODS: Participants were selected from a cohort of women within 5 years of menopause not on hormone replacement therapy between the ages of 45-60 years. The Berlin questionnaire was used to select OSAS participants who then completed the MCFSI (Mail-In Cognitive Function Screening Instrument) to measure cognition. Six subjects with the highest MCFSI scores (≥ 5 denoting CI) were compared to six with normal scores. Proteomic analysis was done by Myriad RBM using a targeted ELISA for 254 serum proteins. Pathway analysis of differentially expressed proteins was performed using STRING (Search Tool for the Retrieval of Interacting Genes/Proteins) software. RESULTS: Distinct proteomic signatures were seen in OSAS subjects with CI as compared to those without CI. Proteins including insulin, prostasin, angiopoietin-1, plasminogen activator inhibitor 1, and interleukin-1 beta were overexpressed in OSAS subjects with CI. Proteins underexpressed in CI participants included cathepsin B, ceruloplasmin, and adiponectin. Pathway analysis revealed prominence of insulin-regulated vascular disease biomarkers. CONCLUSIONS: Proteomic biomarkers in participants with cognitive impairment suggest roles for insulin, and vascular signaling pathways, some of which are similar to findings in Alzheimer's disease. A better understanding of the pathogenic mechanisms of CI in OSAS will help focus clinical trials needed in this patient population.

Down syndrome and pediatric obstructive sleep apnea surgery: A national cohort.

OBJECTIVES/HYPOTHESIS: To analyze the trend of sleep surgeries in pediatric patients with Down syndrome (DS) and obstructive sleep apnea (OSA), and to compare this to nonsyndromic (NS) children with OSA. STUDY DESIGN: Retrospective cohort database analysis. METHODS: Analysis of the 1997 to 2012 editions of the Kid's Inpatient Database was conducted. Using International Classification of Diseases, Ninth Revision codes, all patients with OSA were identified, and subsequently, subgroups of NS children and children with DS were identified. Trends of the number and types of sleep surgeries were analyzed. RESULTS: A total of 48,301 and 2,991 sleep surgeries were identified in the NS and DS groups, respectively, during the study period. Tonsillectomy with adenoidectomy was the most common procedure in both groups, but the proportion of tonsillectomy with adenoidectomy decreased over time (P < .01). The proportion of palatal surgery and tracheostomy also decreased significantly, whereas there was an increase in the proportion of lingual tonsillectomies, tongue-base reduction procedures, and supraglottoplasties performed in both groups over time. The relative rates of change in these procedures were higher in the DS population. CONCLUSIONS: Tonsillectomy with adenoidectomy remains the most commonly performed procedure, although there was a significant increase in other sleep surgeries performed (lingual tonsillectomy, tongue-base reduction, and supraglottoplasty) between the two study periods, especially in children with DS. LEVEL OF EVIDENCE: 2c. Laryngoscope, 1963-1969, 2018.

A review of current and developing fixed-dose LABA/LAMA combinations for treating COPD.

INTRODUCTION: The current GOLD (Global Initiative for Chronic Obstructive Lung Disease) recommendations suggest using long acting ß2 agonists (LABA) and long acting muscarinic antagonists (LAMA) in combination for group B COPD patients with persistent symptoms, group C COPD patients with further exacerbations on LAMA therapy alone and for group D COPD patients with or without combination with inhaled corticosteroids (ICS). Thus, there is a lot of interest in developing LABA/LAMA combinations for maintenance therapy of chronic stable COPD. Areas covered: Many LABA/LAMA combinations have successfully been approved through carefully designed pivotal clinical trials. The current clinical use of LABA/LAMA combinations in COPD will continue to evolve as new trials with and without inhaled corticosteroids are completed. Expert opinion: Combining different classes of bronchodilators in a single inhaler is an attractive concept that can potentially improve patient adherence to therapy. Because LABA/LAMA combinations are the preferred treatment option for preventing COPD exacerbations in the updated GOLD guidelines for COPD, they will be clinically used. Future treatment of COPD should revolve around a personalized approach based on characterization of the COPD phenotype.

Assessment of weight gain following adenotonsillectomy in children with Down syndrome.

INTRODUCTION: Adenotonsillectomy (T&A) has been associated with postoperative weight gain in children. The purpose of this study is to determine whether a similar association exists in children with Down syndrome (DS). METHODS: The medical records of 311 DS patients were reviewed. Subjects were classified into either a control group or surgical group based on whether they had undergone adenotonsillectomy (T&A). Subjects were excluded if they only had one recorded BMI. Cases were analyzed in a pairwise fashion to maximize available data. 113 total patients with DS were identified: 84 (74.3%) in the control group and 29 (25.7%) in the T&A group. Height, weight, BMI, and Z-score data were compared between the control and T&A groups at 6-month intervals over a 24-month period. RESULTS: Children with DS who underwent T&A were comparable by demographics to children with DS who did not undergo T&A. Mean weight gain at 24 months for the T&A group was 8.07 ± 5.66 kg compared with 5.76 ± 13.20 kg in controls. The median Z-score at 24 months for the T&A group was 1.11 (0.10-1.88) compared with 1.17 (0.80-1.75) in controls. Children undergoing T&A had a stable median Z-score change of 0.09 at 24 months (p = 0.861, compared to baseline) while children who did not undergo T&A had a significantly increased median Z-score of 0.52 (p = 0.035, compared to baseline). Despite this, there were no significant intergroup differences between weight change, BMI, nor Z-score at any interval (p > 0.05). CONCLUSIONS AND RELEVANCE: Children with DS did not have an increased rate of weight gain or increased BMI after T&A. BMI Z-scores were shown to stabilize over 24 months in the T&A group and increase in the control group. While this suggests that T&A provides an added benefit of weight control in patients with DS, the results should be interpreted with caution due to the small sample size and the fact that not all patients had complete follow up across a 24-month period.

Meta-Analysis of Cardiovascular Outcomes With Continuous Positive Airway Pressure Therapy in Patients With Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is associated with increased cardiovascular morbidity and mortality. Continuous positive airway pressure (CPAP) is the main treatment of OSA. The present study explores the impact of CPAP on cardiovascular outcomes. A systematic search of electronic databases for randomized controlled trials comparing CPAP with medical therapy alone in patients with OSA who reported cardiovascular outcomes of interest was performed. The main outcome was major adverse cardiac events. Other outcomes included cardiac mortality, myocardial infarction, angina pectoris, stroke, and transient ischemic attack. Fixed effect model was used in all analyses except for subgroup analysis in which the random effect DerSimonian and Laird's model was used. Four randomized controlled trials with a total of 3,780 patients were included. Compared with medical therapy alone, CPAP use was not associated with reduced risk of major adverse cardiac events (relative risk [RR] 0.94, 95% confidence interval [CI] 0.78 to 1.15, p = 0.93, I2 = 0%) except in the subgroup that wore CPAP >4 hours (RR 0.70, 95% CI 0.52 to 0.94, p = 0.02, I2 = 0%). Furthermore, no reduction in the risk of cardiac mortality (RR 1.14, 95% CI 0.66 to 1.97, p <0.36, I2 = 2%), myocardial infarction (RR 0.96, 95% CI 0.64 to 1.44, p <0.15, I2 = 47%), angina pectoris (RR 1.16, 95% CI 0.9 to 1.50, p <0.51, I2 = 0%), stroke (RR 1.01, 95% CI 0.73 to 1.38, p <0.0.86, I2 = 0%), and transient ischemic attack (RR 1.36, 95% CI 00.69 to 2.68, p <0.24, I2 = 30%) was observed. Subgroup analysis of CPAP adherence in regards to cardiac outcomes showed that CPAP use is not associated with decreased risk of heart failure (RR 0.91, 95% CI 0.50 to 1.66, p <0.55, I2 = 0%). In conclusion, compared with medical therapy alone, utilization of CPAP in patients with OSA is not associated with improved cardiac outcomes except in patients who wore it for >4 hours.

Spotlight on fluticasone furoate/umeclidinium/vilanterol in COPD: design, development, and potential place in therapy.

COPD is characterized by persistent airflow obstruction caused by exposure to irritants including cigarette smoke, dust, and fumes. According to the latest GOLD (Global Initiative for Chronic Obstructive Lung Disease) guidelines, a combination of inhaled corticosteroids, long-acting ß2 agonists, and long-acting muscarinic receptor antagonists can be used for group D COPD patients who are at high risk for exacerbations. Umeclidinium/fluticasone furoate/vilanterol is one such triple-combination therapy currently under development with some completed and several ongoing clinical trials. This review paper summarizes the pharmacologic profiles of these medications and highlights findings from clinical trials, including safety and efficacy data, while speculating on the role of this therapy in current treatment for COPD.

Impact of obstructive sleep apnea syndrome on cognition in early postmenopausal women.

PURPOSE: Obstructive sleep apnea syndrome (OSAS) has a higher prevalence in postmenopausal women who are not on hormone replacement therapy (HRT), as compared to premenopausal women. Cognitive impairment (CI) is associated with OSAS and the early postmenopausal state. We hypothesized that compared to postmenopausal women at low risk for OSAS, postmenopausal women at high risk for OSAS would report worse cognitive function. METHODS: Early postmenopausal women not on HRT between the ages of 45 and 60 years, within 5 years of natural menopause, were enrolled. Participants completed a REDCap survey which collected information on demographics and risk factors, Berlin questionnaire to screen subjects for OSAS risk, and the Mail-In Cognitive Function Screening Instrument (MCFSI) score which was used to assess CI. RESULTS: Of 381 respondents, 127 were omitted due to missing/duplicate data or not meeting inclusion criteria. One hundred fifty-four women were classified as high risk for OSAS (OSAS+), and 100 were classified as low risk for OSAS (OSAS-). OSAS- women reported lifetime smoking, lifetime drinking, and recreational drug use more often than OSAS+ women, while OSAS+ women reported a depression diagnosis more often. The mean MCFSI score in the OSAS+ group was significantly higher (worse cognition) than in the OSAS- group after controlling for covariates (5.59, 95 % CI 5.08-6.11 vs. 4.29, 95 % CI 3.64-4.93, p < 0.05). CONCLUSION: Early postmenopausal women at high risk for OSAS report more CI than those at low risk for OSAS. Future studies should identify biomarkers of this CI and define the degree of reversibility of CI with OSAS treatment.

Altered functional brain asymmetry for mental rotation: effect of estradiol changes across the menstrual cycle.

Mental rotation is a visuospatial task associated with pronounced sex differences. Performance is also affected by gonadal hormones such as testosterone and estradiol. To better understand hormonal modulation of the neural substrates of mental rotation, the present study examined the influence of estradiol using functional MRI. Ten premenopausal women were tested on a 3D mental rotation task during the early follicular and late follicular phases of the menstrual cycle. Change in estradiol between the two phases was confirmed by hormone assays. Brain activation patterns were similar across the two phases, but the change in estradiol had different associations with the two hemispheres. Better performance in the late follicular than the early follicular phase was associated with a pattern of reduced recruitment of the right hemisphere and increased recruitment of the left hemisphere. The increased recruitment of the left hemisphere was directly associated with greater changes in estradiol. Given that the right hemisphere is the dominant hemisphere in visuospatial processing, our results suggest that estradiol is associated with reduced functional asymmetry, consistent with recent accounts of hormonal modulation of neurocognitive function.