OBJECTIVE: To perform a systematic review of clinical trials examining non-small cell lung cancer (NSCLC) to better understand the equity afforded to women in the study of lung cancer.
METHODS: An electronic search was conducted for all NSCLC clinical trials published between 2010 and 2020 with included words \"carcinoma, non-small cell, lung\" and \"non-small cell lung cancer.\" Studies from PubMed, Cochrane, and SCOPUS were included and were uploaded into Covidence to assist with systematic review. All articles were screened by two separate individuals and reviewed for location, study type, cancer stage, field of study of the research team, and percentage of females included. Student\'s t-test was used to compare the means of males and females.
RESULTS: Across the 269 studies that met inclusion criteria, fewer females than males were enrolled (38.7% vs. 61.1%; p < 0.0001). Compared with studies from 2010 to 2015, those from 2016 to 2020 had greater representation of females (36.7% vs. 41.4%, p = 0.0091, respectively). Both nonsurgical and surgical studies enrolled fewer female than male patients (38.1% vs. 61.7%, p < 0.0001; 43.1% vs. 57.2%, p = 0.0002, respectively). Clinical trials from the USA had the least difference between sexes with an average of 46.7% females enrolled. Less females compared with males were enrolled in early-stage NSCLC (37.6% female vs. 62.6% male, p < 0.0001) and late-stage NSCLC trials (37.6% female vs. 62.0% male, p < 0.0001).
CONCLUSIONS: Despite recent improvement, there continues to be significant underrepresentation of females compared with males in NSCLC clinical trials.

OBJECTIVE: This study compared the effects of polarized running training adapted to the menstrual cycle (MC) phases versus polarized training adapted contrary to the MC on endurance performance and cardiovascular parameters.
METHODS: Thirty-three naturally menstruating, moderately trained females (age: 26 ± 4 years; BMI: 22.3 ± 3.2 kg/m2; V ˙ O2max/rel: 40.35 ± 4.61 ml/min/kg) were randomly assigned to a control (CON) and intervention (INT) group. Both groups participated in a load-matched eight-week running training intervention. In the INT, high-intensity sessions were aligned with the mid and late follicular phase, low-intensity sessions with the early and mid-luteal phase, and recovery with the late luteal and early follicular phase. In the CON, high-intensity sessions were matched to the late luteal and early follicular phase, and recovery to the mid and late follicular phase. Endurance performance and cardiovascular parameters were assessed at baseline and after the intervention.
RESULTS: Twenty-six females completed the intervention. A repeated measures ANOVA determined no time × group interaction effect for any parameter. A significant time effect was found for maximal oxygen uptake (F(1,12) = 18.753, p = 0.005, ηp2 = 0.630), the velocity at the ventilatory threshold one (F(1,12) = 10.704, p = 0.007, ηp2 = 0.493) and two (F(1,12) = 7.746, p = .018, ηp2 = .413).
CONCLUSIONS: The training intervention improved endurance performance in both groups, with no further benefit observed from the MC-adapted polarized training in a group-based analysis. Replications with an extended intervention period, a larger sample size, and a more reliable MC determination are warranted.

OBJECTIVE: Familial hypercholesterolaemia (FH) is a highly prevalent monogenic disorder characterized by elevated LDL cholesterol (LDL-C) levels and premature atherosclerotic cardiovascular disease. Sex disparities in diagnosis, lipid-lowering therapy, and achieved lipid levels have emerged worldwide, resulting in barriers to care in FH. A systematic review was performed to investigate sex-related disparities in treatment, response, and lipid target achievement in FH (PROSPERO, CRD42022353297).
METHODS: MEDLINE, Embase, The Cochrane library, PubMed, Scopus, PsycInfo, and grey literature databases were searched from inception to 26 April 2023. Records were eligible if they described sex differences in the treatment of adults with FH.
RESULTS: Of 4432 publications reviewed, 133 met our eligibility criteria. In 16 interventional clinical trials (eight randomized and eight non-randomized; 1840 participants, 49.4% females), there were no differences between males and females in response to fixed doses of lipid-lowering therapy, suggesting that sex was not a determinant of response. Meta-analysis of 25 real-world observational studies (129 441 participants, 53.4% females) found that females were less likely to be on lipid-lowering therapy compared with males (odds ratio .74, 95% confidence interval .66-.85). Importantly, females were less likely to reach an LDL-C < 2.5 mmol/L (odds ratio .85, 95% confidence interval .74-.97). Similarly, treated LDL-C levels were higher in females. Despite this, male sex was associated with a two-fold greater relative risk of major adverse cardiovascular events including myocardial infarction, atherosclerotic cardiovascular disease, and cardiovascular mortality.
CONCLUSIONS: Females with FH were less likely to be treated intensively and to reach guideline-recommended LDL-C targets. This sex bias represents a surmountable barrier to clinical care.

Post-traumatic stress disorder (PTSD) is associated with increased cardiovascular disease (CVD) risk. Compared with males, females are twice as likely to develop PTSD after trauma exposure, and cardiovascular reactivity to stress is a known risk factor for CVD. We aimed to examine hemodynamic responses to acute mental stress in trauma-exposed females with and without a clinical diagnosis of PTSD. We hypothesized that females with PTSD would have higher heart rate (HR), blood pressure (BP), and lower blood flow velocity (BFV) responsiveness compared with controls. We enrolled 21 females with PTSD and 21 trauma-exposed controls. We continuously measured HR using a three-lead electrocardiogram, BP using finger plethysmography, and brachial BFV using Doppler ultrasound. All variables were recorded during 10 min of supine rest, 5 min of mental arithmetic, and 5 min of recovery. Females with PTSD were older, and had higher BMI and higher resting diastolic BP. Accordingly, age, BMI, and diastolic BP were covariates for all repeated measures analyses. Females with PTSD had a blunted brachial BFV response to mental stress (time × group, p = 0.005) compared with controls, suggesting greater vasoconstriction. HR and BP responses were comparable. In conclusion, our results suggest early impairment of vascular function in premenopausal females with PTSD.

Women have a higher incidence of Alzheimer\'s disease (AD), even after adjusting for increased longevity. Thus, there is an urgent need to identify genes that underpin sex-associated risk of AD. PIN1 is a key regulator of the tau phosphorylation signaling pathway; however, potential differences in PIN1 expression, in males and females, are still unknown. We analyzed brain transcriptomic datasets focusing on sex differences in PIN1 mRNA levels in an aging and AD cohort, which revealed reduced PIN1 levels primarily within females. We validated this observation in an independent dataset (ROS/MAP), which also revealed that PIN1 is negatively correlated with multiregional neurofibrillary tangle density and global cognitive function in females only. Additional analysis revealed a decrease in PIN1 in subjects with mild cognitive impairment (MCI) compared with aged individuals, again driven predominantly by female subjects. Histochemical analysis of PIN1 in AD and control male and female neocortex revealed an overall decrease in axonal PIN1 protein levels in females. These findings emphasize the importance of considering sex differences in AD research.

OBJECTIVE: This study tested the feasibility and efficacy of two iterations of a low-intensity online writing intervention, Expand Your Horizon (EYH), in improving body image and distress in a cancer population.
METHODS: In study 1 (3-session version of EYH), adult female cancer survivors (N = 201) were randomised to EYH, where they described their body functionality, or a creative writing control. Outcomes assessed at baseline and one-week follow-up included body appreciation, body dissatisfaction, and distress. In study 2 (1 session version of EYH), adult female cancer survivors (N = 65) were randomised to EYH or a neutral writing control. Outcomes (assessed at baseline, immediately post-intervention and one-week follow-up) included body appreciation, body functionality appreciation, body dissatisfaction and distress.
RESULTS: Study 1 experienced severe attrition; only 14 participants (7 %) completed the intervention and follow-up. Study 2 had higher retention, with 74 % completing the study. In study 2, while no significant differences emerged between EYH or control, both groups significantly improved immediately post-intervention across all outcomes. No differences were found at follow-up.
CONCLUSIONS: A single-session online writing intervention for cancer survivors appears to be more feasible than multi-session, however the efficacy of EYH for this population remains to be established.

In addition to metabolic and cardiovascular disorders, obesity is associated with cognitive deficits in humans and animal models. We have previously shown that obesogenic high-fat and sugar diet intake during adolescence (adoHFSD) impairs hippocampus (HPC)-dependent memory in rodents. These results were obtained in males only and it remains to evaluate whether adoHFSD has similar effect in females. Therefore, here, we investigated the effects of adoHFSD consumption on HPC-dependent contextual fear memory and associated brain activation in male and female mice. Exposure to adoHFSD increased fat mass accumulation and glucose levels in both males and females but impaired contextual fear memory only in males. Compared with females, contextual fear conditioning induced higher neuronal activation in the dorsal and ventral HPC (CA1 and CA3 subfields) as well as in the medial prefrontal cortex in males. Also, adoHFSD-fed males showed enhanced c-Fos expression in the dorsal HPC, particularly in the dentate gyrus, and in the basolateral amygdala compared with the other groups. Finally, chemogenetic inactivation of the dorsal HPC rescued adoHFSD-induced memory deficits in males. Our results suggest that males are more vulnerable to the effects of adoHFSD on HPC-dependent aversive memory than females, due to overactivation of the dorsal HPC.

The hypothesis of this randomized controlled trial was that a clinical decision support system (CDSS) would increase adherence to the Mediterranean diet (MD) among adolescent females with polycystic ovary syndrome (PCOS). The objective was to assess the impact of personalized MD plans delivered via a CDSS on nutritional status and psychological well-being. Forty adolescent females (15-17 years) with PCOS were randomly assigned to the MD group (n = 20) or the Control group (n = 20). The MD group received personalized MD plans every 15 days via a CDSS, while the Control group received general nutritional advice. Assessments were conducted at baseline and after 3 months. Results showed significantly increased MD adherence in the MD group compared to the Control group (p < 0.001). The MD group exhibited lower intakes of energy, total fat, saturated fat, and cholesterol, and higher intakes of monounsaturated fat and fiber (p < 0.05). Serum calcium and vitamin D status (p < 0.05), as well as anxiety (p < 0.05) were improved. In conclusion, tailored dietary interventions based on MD principles, delivered via a CDSS, effectively manage PCOS in adolescent females. These findings highlight the potential benefits of using technology to promote dietary adherence and improve health outcomes in this population. ClinicalTrials.gov registry: NCT06380010.

UNASSIGNED: Stress is associated with alcohol drinking, and epidemiological studies document the comorbidity of alcohol use disorder (AUD) and post-traumatic stress disorder (PTSD), with higher comorbid prevalence in females than in males. The aim of this paper is to highlight information related to sex differences in stress-enhanced alcohol drinking from clinical studies and from preclinical studies utilizing an animal model of traumatic stress.
UNASSIGNED: Stress is associated with alcohol drinking and relapse in males and females, but there are sex differences in the alcohol-related adaptation of stress pathways and in the association of different prefrontal regions with stress-induced anxiety. The predator stress model of traumatic stress produced enhanced alcohol drinking in a subgroup of stress-sensitive male and female animals, which could be associated with sex and subgroup differences in stress axis responsivity, behavioral responses to predator odors, and epigenetic mechanisms engaged by traumatic experiences.
UNASSIGNED: While additional studies in females are necessary, existing clinical and preclinical evidence suggests that biological mechanisms underlying stress-enhanced drinking likely differ between males and females. Thus, effective treatment strategies may differ between the sexes.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are endocrine-disrupting chemicals used in commercial and consumer products.
OBJECTIVE: We evaluated PFAS exposure in relation to incidence and growth of uterine leiomyomata (UL), hormone-dependent neoplasms that are associated with severe gynecologic morbidity.
METHODS: We studied 1158 participants in the Study of Environment, Lifestyle, and Fibroids, a Detroit-based prospective cohort study of Black females aged 23-35 years at enrollment (2010-2012). At enrollment and four subsequent visits during 10 years of follow-up, participants attended in-person clinic visits, completed questionnaires, provided non-fasting blood samples, and underwent ultrasound for UL detection. We quantified 7 PFAS in baseline plasma samples using mass spectrometry. We used Cox regression and probit Bayesian kernel machine regression to estimate individual and joint effects of PFAS on UL incidence. We fit linear mixed models to estimate effects of individual PFAS on UL growth. We stratified by parity, an important route of PFAS elimination and determinant of UL.
RESULTS: In individual PFAS analyses, we observed inverse associations for perfluorodecanoate (PFDA; ≥0.3 vs. <0.2 ng/ml: hazard ratio [HR] = 0.74; 95% confidence interval [CI]: 0.54-1.00) and perfluoroundecanoate (detected vs. non-detected: HR = 0.78; 95% CI: 0.61-1.01) and a weak positive association for perfluorohexane sulfonate (≥1 vs. <0.6 ng/ml: HR = 1.17; 95% CI: 0.85-1.61), while perfluorooctane sulfonate, perfluorooctanoate, perfluorononanoate (PFNA), and 2-N-methyl-perfluorooctane sulfonamido acetate (MeFOSAA) showed little association with UL incidence. The PFAS mixture was inversely associated with UL incidence, a finding driven by MeFOSAA and PFDA; however, PFNA was positively associated with UL incidence. The inverse association for PFDA and positive association for PFNA were stronger among nulliparous participants. Most PFAS showed slight inverse associations with UL growth.
UNASSIGNED: In this prospective ultrasound study of 1158 Black females aged 23-35 years at enrollment, we conducted a mixtures analysis to account for co-pollutant confounding and interaction. MeFOSAA and PFDA concentrations were inversely associated with UL incidence, while PFNA concentrations were positively associated with UL incidence. Concentrations of most PFAS were associated with decreased UL growth. This study contributes data to the sparse literature on PFAS exposure and UL development.