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Purpose: To investigate the influence of menstrual-cycle (MC) phase on objective sleep and perceived recovery following high- (HIT) and low-intensity training (LIT) in endurance-trained women. Methods: Fifteen naturally menstruating, endurance-trained women completed standardized HIT and LIT sessions during the early follicular phase (EFP), ovulatory phase (OP), and midluteal phase (MLP) of 2 MCs. Overnight sleep was monitored using a Somnofy sleep monitor after each training session, and perceived recovery was assessed after 24 hours using self-report scales. MC phases were determined using the 3-step method, and noneumenorrheic MCs were retrospectively excluded from analysis. Results: MC phase had a main effect on wake after sleep onset (P ≤.001), with higher values in MLP (33 [22] min) than EFP (22 [19] min, P =.043) and OP (14 [9] min, P =.001), sleep efficiency (P =.033), with lower values in MLP (87% [6%]) than OP (90% [8%], P =.047), and light sleep (P =.023) with higher values in MLP (59% [6%]) than EFP (54% [7%], P =.037). Session type had a main effect on perceived recovery (P <.018) and perceived muscle soreness (P =.007), indicating lower perceived recovery and higher perceived muscle soreness following HIT compared to LIT (P <.001, P =.018, respectively). No interactions were found between MC phase and session type for any of the measured variables. Conclusions: Objective sleep quality, but not perceived recovery, was influenced by MC phase, as indicated by small impairments to multiple indices of objective sleep during MLP. There were no interactions between MC phase and session type, indicating that the effect of MC on sleep and recovery is consistent regardless of session type. [ABSTRACT FROM AUTHOR]

The cyclical changes in sex hormones across the menstrual cycle (MC) are associated with various biological changes that may alter resting metabolic rate (RMR) and body composition estimates. Hormonal contraceptive (HC) use must also be considered given their impact on endogenous sex hormone concentrations and synchronous exogenous profiles. The purpose of this study was to determine if RMR and dual-energy X-ray absorptiometry body composition estimates change across the MC and differ compared with HC users. This was accomplished during a 5-week training camp involving naturally cycling athletes (n = 11) and HC users (n = 7 subdermal progestin implant, n = 4 combined monophasic oral contraceptive pill, n = 1 injection) from the National Rugby League Indigenous Women's Academy. MC phase was retrospectively confirmed via serum estradiol and progesterone concentrations and a positive ovulation test. HC users had serum estradiol and progesterone concentrations assessed at the time point of testing. Results were analyzed using general linear mixed model. There was no effect of MC phase on absolute RMR (p =.877), relative RMR (p =.957), or dual-energy X-ray absorptiometry body composition estimates (p >.05). There was no effect of HC use on absolute RMR (p =.069), relative RMR (p =.679), or fat mass estimates (p =.766), but HC users had a greater fat-free mass and lean body mass than naturally cycling athletes (p =.028). Our findings suggest that RMR and dual-energy X-ray absorptiometry body composition estimates do not significantly differ due to changes in sex hormones in a group of athletes, and measurements can be compared between MC phases or with HC usage without variations in sex hormones causing additional noise. [ABSTRACT FROM AUTHOR]

PURPOSE: We investigated the effect of metformin and lifestyle intervention on metabolic, inflammatory, and steroid biomarkers of breast cancer (BC) recurrence risk in two intervention trials among BC survivors with overweight or obesity. METHODS: Baseline and follow-up serum samples collected during the two trials were analyzed and data pooled. The USA trial (Reach for Health) included postmenopausal BC survivors (n = 333) randomly assigned to 6-month metformin vs placebo and lifestyle intervention (LSI) vs control (2 × 2 factorial design). The Italian trial (MetBreCS) included BC survivors (n = 40) randomized to 12-month metformin vs placebo. Insulin resistance (HOMA-IR), adipokines, cytokines, and steroids were measured. RESULTS: Metformin compared to placebo showed a favorable decrease in leptin (- 8.8 vs - 3.5 ng/mL; p

Although the most common cause of congenital adrenal hyperplasia (CAH) worldwide is 21-hydroxylase deficiency (21-OHD), which accounts for more than 95% of cases, other rare causes of CAH such as 11-beta-hydroxylase deficiency (11β-OHD), 3-beta-hydroxy steroid dehydrogenase (3β-HSD) deficiency, 17-hydroxylase deficiency and lipoid CAH (LCAH) may also be encountered in clinical practice. 11β-OHD is the most common type of CAH after 21-OHD, and CYP11B1 deficiency in adrenal steroidogenesis causes the inability to produce cortisol and aldosterone and the excessive production of adrenal androgens. Although the clinical and laboratory features are similar to 21-OHD, findings of mineralocorticoid deficiency are not observed. 3β-HSD deficiency, with an incidence of less than 1/1,000,000 live births, is characterized by impairment of both adrenal and gonadal steroid biosynthesis very early in life, with inadequate virilization in boys and varying degrees of virilization in girls. It may present with salt wasting crisis or delayed puberty in both genders. While 46,XY disorders of sex development is frequently observed in boys with 17-hydroxylase deficiency, immature pubertal development and primary amenorrhea are observed in girls due to estrogen deficiency throughout adolescence. Patients with LCAH, which develops due to steroidogenic acute regulatory protein deficiency, typically present with salt wasting in the first year of life. It is characterized by complete or near-complete deficiency of adrenal and gonadal steroid hormones and progressive accumulation of cholesterol esters in the adrenal gland. [ABSTRACT FROM AUTHOR]

Purpose: Coronavirus disease 2019 (COVID-19) infection may affect serum hormones levels and male sexual function. This study aims to provide evidence for the causal relationship between COVID-19 infection, serum testosterone levels and the risk of erectile dysfunction (ED) using a two-sample Mendelian randomization (MR) approach. Materials and Methods: Summary-level data for serum testosterone levels (199,569 samples and 12,321,875 single nucleotide polymorphisms [SNPs]) were obtained from Rebecca’s study, while data for ED (6,175 cases and 217,630 controls) were sourced from Bovijn’s study. Genetic variations linked to COVID-19 were used as instrumental variables (IVs) in meta-analyses of genome-wide association studies (GWASs) involving 6,406 cases and 902,088 controls from the COVID-19 Host Genetics Initiative. The inverse-variance weighted (IVW) method was primarily employed to evaluate the potential associations between COVID-19 infection, serum testosterone levels, and the risk of ED. The weighted mode, weighted-median and simple-median method were employed to evaluate the sensitivity. Heterogeneity and pleiotropic outlier were assessed using Cochran’s Q test and MREgger regression. Results: The MR analysis demonstrated that COVID-19 infection was associated with reduced serum testosterone levels (odds ratio [OR] 0.966, 95% confidence interval [CI] 0.938–0.993, p=0.016) and an increased risk of ED (OR 1.205, 95% CI 1.063–1.367, p=0.004) when using IVW methods. Sensitivity analyses utilizing various IV sets and MR approach remained consistent. Conclusions: COVID-19 infection is associated with a decrease in serum testosterone levels and an increased risk of ED. Male patients recovering from COVID-19 need to pay special attention to their sex hormone levels and sexual health. [ABSTRACT FROM AUTHOR]

Photoperiodic changes induce seasonal variations in vitamin D 3 levels, which can affect reproductive function. The muskrat, a seasonal breeder, possesses a pair of scented glands that secrete musky substances to attract mates. The scented glands can also synthesize androgens, which regulate their function through autocrine or paracrine signaling. This study aimed to investigate whether active vitamin D 3 was synthesized locally and to explore how seasonal changes affected the specific mechanisms of androgen synthesis in the scented glands. The scented glands showed significant seasonal changes in morphology and histology. Transcriptomic analysis revealed that differentially expressed genes were enriched in pathways related to sex steroid hormone synthesis and calcium signaling. Quantitative analyses using qPCR and Western blotting demonstrated significant seasonal variations in the expressions of vitamin D 3 receptors (VDR) and key synthetic and metabolic enzymes. Seasonal fluctuations in 1,25(OH)₂D₃ levels were positively correlated with the expressions of steroidogenic enzymes and androgen concentrations in the scented glands. Additionally, 1,25(OH)₂D₃ enhanced the expressions of steroidogenic enzymes in cultured primary cells. ChIP-seq analysis revealed that VD/VDR directly regulated the transcription of Cyp11a1 , Cyp17a1 , and Lhr by binding to their promoter regions. Furthermore, elevated androgen levels were observed when hCG was combined with 1 nM 1,25(OH)₂D₃. This study suggests that the scented glands can produce 1,25(OH)₂D₃ in autocrine or paracrine forms, with levels varying seasonally. VD/VDR enhanced androgen synthesis through a dual mechanism: (1) directly up-regulating the transcription of Cyp11a1 and Cyp17a1 to increase steroidogenic enzyme levels, and (2) indirectly promoting the expressions of steroidogenic enzymes by modulating Lhr transcription. [Display omitted] • The scented glands are targeting organs for vitamin D 3. • The scent glands could synthesize and metabolize vitamin D 3 locally, and the concentration of 1,25(OH) 2 D 3 exhibited significant seasonal variations. • Androgen concentrations were positively correlated with 1,25(OH) 2 D 3 levels in the scented glands. • VD/VDR directly regulated the transcription of Cyp11a1 , Cyp17a1 , and Lhr by binding to their promoter regions to enhance androgen synthesis. • Elevated androgen levels were observed when hCG was combined with 1,25(OH)₂D₃. [ABSTRACT FROM AUTHOR]

Background The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Scoping Review Guidelines were used to conduct a scoping review of weight loss interventions for patients with prostate cancer, with the goal to ascertain the impact of these interventions on body weight, body composition, metabolic biomarkers, and prostate cancer–related outcomes. Methods Six bibliographical databases were searched. Eligible studies included articles reporting weight loss behavioral interventions with at least dietary change as an intervention component, body weight as an outcome, and interventions not solely focused on weight loss maintenance. Patients with prostate cancer of any stage were included. At least 2 independent reviewers used a data-charting form to extract study characteristics and results. Results A total of 12 studies were included. The sample consisted predominately of White patients with prostate cancer (multiple stages) in the United States. Most interventions included both dietary and physical activity components and were delivered 1-on-1 in-person and/or by telephone. Most of the studies reported that participants experienced significant weight loss and beneficial body composition changes, with a higher proportion of studies with a longer intervention period and dose (time) reporting greater magnitude of changes in outcomes. There were mixed results regarding the interventions' impact on metabolic biomarkers and prostate cancer–related outcomes. Discussion Understanding the impact of weight loss interventions on patients with prostate cancer is important. Studies including metabolic biomarkers, prostate cancer outcomes, and more diverse populations are needed. [ABSTRACT FROM AUTHOR]

Context Energy intake may differ across the menstrual cycle, with some studies identifying greater energy intake in the luteal phase (LP) compared with the follicular phase (FP) and others finding no clear differences. To date, no study has systematically synthesized the available data to draw more definite conclusions while considering any methodological inconsistencies between studies. Objective The aim was to conduct a systematic review/meta-analysis in an effort to determine if there are differences in energy intake between the FP and LP. Data Sources A systematic search strategy was developed and the search was conducted in 5 databases for studies that investigated any changes in energy intake across menstrual phases. Data Extraction Using Covidence, studies were identified and included if they contained individuals between the ages of 18 and 45 years, maintained an average body mass index (BMI) of 18.5–25 kg/m2, had no history of disordered eating, and included energy intake and menstrual cycle measurements in the FP and LP. Data Analysis Effect sizes were calculated for each study and a random-effects model was used to pool the results of each study. Results Fifteen datasets were included consisting of 330 female participants with a mean age of 26 ± 4 years and mean BMI of 22.4 ± 2.3 kg/m2. Overall, there was a statistically significant difference (standardized mean difference = 0.69; P = .039) with increased energy intake in the LP compared with the FP (crude 168 kcal⋅d−1 average difference between phases). Conclusion Energy intake was found to be greater in the LP compared with the FP, providing insight into the effect of the menstrual cycle on energy intake. However, there were repeated methodological inconsistencies and future work should strive to utilize best practices for both energy intake measurement and menstrual phase specification. [ABSTRACT FROM AUTHOR]

The article focuses on hormonal side effects associated with the 52-mg levonorgestrel intrauterine device (IUD). Topics include the rate of acne as a side effect, the comparison between participants who used combined hormonal contraceptives versus nonhormonal contraceptives prior to enrollment, and the overall discontinuation rate due to adverse events.

Sex-differences in pain perception have been documented; however, the role of sex hormones in chronic musculoskeletal pain (CMP) remains unclear. Therefore, this study investigated whether sex hormones and sex hormone-binding globulin (SHBG) are associated with CMP. We utilised data from the UK Biobank (n =357 424; females: 51.6%; white: 95.2%). Serum concentrations of oestradiol (E2), testosterone (T), and SHBG were measured at baseline. Chronic pain (≥3 months) in the neck/shoulder, back, hip, knee, or 'all over the body' was assessed at baseline and three follow-ups. Mixed-effects multinomial/logistic regression models were used. In multivariable analyses, greater concentrations of T and T/SHBG were associated with a lower number of CMP sites in both males (T: relative risk ratio=0.81 per standard deviation, 95% confidence interval [0.77–0.86] and T/SHBG: 0.85 [0.80–0.92]) and females (T: 0.85 [0.81–0.89] and T/SHBG: 0.93 [0.89–0.97] [all P -values for trend ≤0.001]). Greater T concentrations and T/SHBG were also associated with lower odds of CMP across all sites, while higher concentrations of SHBG were associated with lower odds of neck/shoulder CMP in both sexes. There was no association between concentrations of E2, SHBG, or E2/SHBG and number of CMP or site-specific CMP in either sex. In both sexes, greater T concentrations and T/SHBG were associated with lower number of CMP sites and site-specific CMP, while greater concentrations of SHBG were linked to lower odds of neck/shoulder CMP. These findings suggest a potential involvement of sex steroids in the pathogenesis of CMP and underscore the need for further investigation into their potential in chronic pain management strategies. [ABSTRACT FROM AUTHOR]

Sexual health is multidimensional across the lifespan. At midlife, women may face challenges to sexuality, often requiring intervention. Menopause-related and age-related hormonal changes intermingle with common medical conditions and contribute to biological substrates less favorable to a healthy sexual response. Psychological, sociocultural, and relational factors modulate the impact of such changes positively or negatively, contributing to adaptation or manifestation of sexually related distress. A comprehensive diagnostic approach and multidimensional management are needed to address sexual symptoms due to both menopause and aging, individualizing non-pharmacological and pharmacological evidence-based treatment options according to personal goals and expectations in the woman/couple. [ABSTRACT FROM AUTHOR]

Introduction: The reduction in sex hormone production across the menopause transition is thought to accelerate age-related decline in muscle mass, strength, and stability, increasing the risk of falls and fractures. We aimed to investigate whether a novel low-impact resistance exercise program could improve strength, balance, and body composition and whether any improvement was affected by menopause status. Methods: Seventy healthy, moderately active pre- (PRE; 46.7 ± (SD) 3.2 yr), peri- (PERI; 52.3 ± 2.2 yr), or post- (POST; 57.0 ± 2.5 yr) menopausal females, not taking hormone replacement therapy (HRT), were randomized to continue habitual physical activity (CON; n = 25) or complete a supervised resistance exercise program 4 d·wk−1 for 12 wk (EXC; n = 45). Strength at the hip and shoulder (isokinetic dynamometer), dynamic balance (Y-balance), flexibility (sit-and-reach and back-scratch), muscle thickness (rectus femoris, vastus intermedius (VI), and medial deltoid), and lean and % body fat (dual-energy x-ray absorptiometry) were measured before and after training. Results: Hip abduction and flexion peak torque (19% ± 48% and 20% ± 17%, respectively; P < 0.05), posterolateral and posteromedial balance (12% ± 15% and 13% ± 15%, respectively; P < 0.001), flexibility (21% ± 36%, P < 0.001), VI thickness (12% ± 19%, P = 0.032), and lean mass (2% ± 2%, P = 0.007) all increased over 12 wk in EXC, but not CON, with no difference in response between PRE, PERI, and POST. The changes in shoulder strength and body mass over 12 wk were not different between CON and EXC. Conclusions: This is the first study to demonstrate that the decline in sex hormones and an increase in age across the menopause transition do not affect the ability of lower limb (hip) strength and balance to adapt to a low-impact resistance exercise training program in females not taking HRT. [ABSTRACT FROM AUTHOR]

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Background: The effects of the menstrual cycle on neuropsychiatric and physical symptoms have been examined in multiple psychiatric illnesses, but research on Tourette syndrome (TS) and menstruation is limited and inconclusive. One study published in 1992 reported that 34% of female respondents experienced tic fluctuations with their menstrual cycles; however, a subsequent 2001 study found no significant relationship between menstrual cycle-related hormonal changes and tic symptoms across participants. There has been no further published exploration of this topic in the intervening 20+ years, and thus these discrepant results have not been reconciled. The current study aimed to assess tic changes across the menstrual cycle and to explore clinical predictors of tic fluctuations in adult females with TS. Methods: An online survey was completed by 112 of 315 eligible female adults with TS. Respondents were asked to share their age of TS symptom onset, history of OCD and ADHD diagnoses, and current tic symptoms and severity. Participants also retrospectively reported their experiences with fluctuations in tics and other physical and psychiatric symptoms over the course of the menstrual cycle. Results: 26% of the 112 respondents endorsed tic changes in relation to their menstrual cycles. Univariable and multivariable logistic regression demonstrated that higher current tic severity and impairment as well as co-occurring cycle-related mood and anxiety changes significantly predicted the presence of self-reported tic fluctuations during the menstrual cycle. Discussion: Results suggest that some females with TS experience changes in tic symptoms during their menstrual cycles, although future research is required to clarify the complex relationships between the menstrual cycle, tics, and other psychiatric symptoms. The low response rate, retrospective recall of symptoms, and lack of information about hormonal influences such as contraceptives and menopause are notable study limitations. [ABSTRACT FROM AUTHOR]

Transient Receptor Potential Melastatin 3 (TRPM3) channels are Ca2+ permeable ion channels that act as polymodal sensors of mechanical, thermal, and various chemical stimuli. TRPM3 channels are highly expressed in the trigeminovascular system, including trigeminal neurons and the vasculature. Their presence in dural afferents suggests that they are potential triggers of migraine pain, which is originating from the meningeal area. This area is densely innervated by autonomous and trigeminal nerves that contain the major migraine mediator calcitonin gene-related peptide (CGRP) in peptidergic nerve fibers. Co-expression of TRPM3 channels and CGRP receptors in meningeal nerves suggests a potential interplay between both signalling systems. Compared to other members of the TRP family, TRPM3 channels have a high sensitivity to sex hormones and to the endogenous neurosteroid pregnenolone sulfate (PregS). The predominantly female sex hormones estrogen and progesterone, of which the levels drop during menses, act as natural inhibitors of TRPM3 channels, while PregS is a known endogenous agonist of these channels. A decrease in sex hormone levels has also been suggested as trigger for attacks of menstrually-related migraine. Notably, there is a remarkable sex difference in TRPM3-mediated effects in trigeminal nociceptive signalling and the vasculature. In line with this, the relaxation of human isolated meningeal arteries induced by the activation of TRPM3 channels is greater in females. Additionally, the sex-dependent vasodilatory responses to CGRP in meningeal arteries seem to be influenced by age-related hormonal changes, which could contribute to sex differences in migraine pathology. Consistent with these observations, activation of TRPM3 channels triggers nociceptive sensory firing much more prominently in female than male mouse meninges, suggesting that pain processing in female patients with migraine may differ. Overall, the combined TRPM3-related neuronal and vascular mechanisms could provide a possible explanation for the higher prevalence and even the more severe quality of migraine attacks in females. This narrative review summarizes recent data on the sex-dependent roles of TRPM3 channels in migraine pathophysiology, the potential interplay between TRPM3 and CGRP signalling, and highlights the prospects for translational therapies targeting TRPM3 channels, which may be of particular relevance for women with migraine. [ABSTRACT FROM AUTHOR]

Background: Sex differences in brain development are thought to lead to sex variation in social behavior. Sex differences are fundamentally driven by both gonadal hormones and sex chromosomes, yet little is known about the independent effects of each on social behavior. Further, mouse models of the genetic liability for the neurodevelopmental disorder MYT1L Syndrome have shown sex-specific deficits in social motivation. In this study, we aimed to determine if gonadal hormones or sex chromosomes primarily mediate the sex differences seen in mouse social behavior, both at baseline and in the context of Myt1l haploinsufficiency. Methods: Four-core genotypes (FCG) mice, which uncouple gonadal and chromosomal sex, were crossed with MYT1L heterozygous mice to create eight different groups with unique combinations of sex factors and MYT1L genotype. A total of 131 mice from all eight groups were assayed for activity and social behavior via the open field and social operant paradigms. Measures of social seeking and orienting were analyzed for main effects of chromosome, gonads, and their interactions with Myt1l mutation. Results: The FCGxMYT1L cross revealed independent effects of both gonadal and chromosomal sex on activity and social behavior. Specifically, the presence of ovarian hormones led to greater overall activity, social seeking, and social orienting regardless of MYT1L genotype. In contrast, sex chromosomes affected social behavior mainly in the MYT1L heterozygous group, with XX MYT1L mutant mice demonstrating elevated levels of social orienting and seeking compared to XY MYT1L mutant mice. Conclusions: Gonadal and chromosomal sex have independent mechanisms of driving greater social motivation in females. Additionally, genes on the sex chromosomes may interact with neurodevelopmental risk genes to influence sex variation in atypical social behavior. Plain Language Summary: As our brain develops, many factors influence how we behave later in life. The brain forms differently in males and females, potentially leading to sex variation seen in many behaviors including sociability. In addition, conditions defined by differences in social behaviors, such as autism, are diagnosed more in males than females. However, researchers don't know exactly how distinct sex factors, such as gonadal hormones and sex chromosome genes, lead to different behaviors in males and females. In this study, we used mouse models and tests of mouse behavior to explore these differences. Results show that gonadal hormones primarily contributed to differences in social motivation between sexes. Yet, when we repeated these same assays in a mouse model of genetic liability for a human neurodevelopmental syndrome, we found that sex chromosome genes rather than gonadal hormones played a larger role in the behavioral consequences of impaired neurodevelopment. These insights can inform future research on the biological mechanisms of social behavior in the context of genetic liability for neurodevelopmental disorders. Highlights: Four-core genotypes mouse model crossed with MYT1L heterozygous mouse reveals independent effects of sex chromosomes and gonadal hormones on social motivation. Myt1l haploinsufficiency causes higher activity in both males and females. While females are more active, contributions of sex chromosomes and gonadal hormones to this higher activity are environment dependent. Gonadal hormones influence social seeking and orienting regardless of MYT1L genotype. Chromosomal sex interacts with MYT1L genotype to elevate social orienting and seeking only in XX MYT1L heterozygous mice. [ABSTRACT FROM AUTHOR]

Objective: This study aims to investigate the relationship between metabolic dysfunction-associated fatty liver disease (MAFLD) and sex hormones and sex hormone-binding globulin (SHBG) in boys with obesity. Methods: Retrospective analysis of metabolic indicators and sex hormone levels in boys with obesity who sought medical attention at the First People's Hospital of Lianyungang City from January 2020 to December 2023. Based on abdominal ultrasound results, they were categorized into a simple obesity group and MAFLD group, and differences between the two groups were compared. Utilizing logistic regression analysis to explore the risk factors for developing MAFLD, and through the construction of Receiver Operating Characteristic (ROC) curves, conducting a preliminary assessment of the diagnostic value for MAFLD. Results: A total of 155 male children with obesity were included in the study, mean age of 11.07 ± 1.53 years. Children in the MAFLD group had higher levels of height[(159.49 ± 12.73)cm vs.(155.55 ± 10.50)cm], weight[(82.32 ± 18.75)kg vs.(68.28 ± 15.00)kg], BMI[(32.08 ± 4.49)kg/m2 vs.(27.85 ± 4.21)kg/m2],fasting insulin[33.42(24.07,43.93)uIU/ml vs.23.91(15.72,31.52)uIU/ml],HOMA-IR[7.27(5.26,10.71) vs.4.87(3.27,6.86)],fastingC-peptide[1409.00(1175.00,1668.00)pmol/L vs.1020.00(849.05,1303.00)pmol/L], WBC[(7.85 ± 1.80)×109/L vs.(7.15 ± 1.42)×109/L], HbA1c[5.40(5.30,5.70)% vs.(5.30(5.20,5.60)%],ALT[48.00(27.00,80.00)U/L vs.19.00(15.00,26.50)U/L], and AST[31.00(24.00,60.00)U/L vs.21.00(18.50, 26.00)U/L] compared to the simple obesity group (P<0.05). Children in the MAFLD group had lower levels of HDL[(1.05 ± 0.21)mmol/L vs.(1.16 ± 0.26)mmol/L], testosterone [42.41(30.33,143.28)ng/dl vs.125.41(23.41,221.57)ng/dl], and SHBG[13.20(9.10,17.30)nmol/l vs.19.60(13.50,29.85)nmol/l] compared to the simple obesity group (P<0.05). Logistic regression showed that BMI, testosterone, and SHBG were independent risk factors for MAFLD in boys, and ROC curve analysis indicated their potential value in the early diagnosis of MAFLD. Conclusion: BMI, testosterone, and SHBG are independent risk factors for the occurrence of MAFLD in boys with obesity. To control the occurrence of MAFLD, it is essential to address the root cause of the high growth rate of obesity. The roles of testosterone and SHBG in MAFLD merit further research. [ABSTRACT FROM AUTHOR]

The heart is a highly sex-biased organ, as sex shapes innumerable aspects of heart health and disease. Sex chromosomes and sex hormones —testosterone, progesterone, and estrogen— establish and perpetuate the division between male and female myocardium. Of these differentiating factors, the insulating effects of estrogen have been rigorously interrogated and reviewed, whereas the influence of sex chromosomes, testosterone, and progesterone remains in dispute or ill-defined. Here, we synthesize growing evidence that sex chromosomes and sex hormones substantially bias heart form, function, and dysfunction in a context-dependent fashion. The discrete protective functions ascribed to each of the 3 estrogen receptors are also enumerated. Subsequently, we overview obstacles that have historically discouraged the inclusion of female subjects in basic science such as the impact of the female estrus cycle and reproductive senescence on data reliability and reproducibility. Furthermore, we weigh the utility of several common strategies to intercept and rescue sex-specific protection. Last, we warn of common compounds in animal chow and cell culture that interfere with estrogen signaling. In sum, we survey the controversies and challenges that stem from sex-inclusive cardiovascular research, comparing the possible causes of cardiac sex bias, elucidating sex chromosome or hormone-dependent processes in the heart, describing common lapses that imperil female and male cell and animal work, and illuminating facets of the female heart yet unexplored or still uncertain. [ABSTRACT FROM AUTHOR]

Autophagy, a cellular process essential for maintaining homeostasis, plays a fundamental role in recycling damaged components and in adapting to stress. The dysregulation of autophagy is implicated in numerous human diseases, including cancer, where it exhibits a dual role as both a suppressor and a promoter, depending on the context and the stage of tumor development. The significant sex differences observed in autophagic processes are determined by biological factors, such as genetic makeup and sex hormones. Estrogens, through their interaction with specific receptors, modulate autophagy and influence tumor progression, therapy resistance, and the immune response to tumors. In females, the escape from X inactivation and estrogen signaling may be responsible for the advantages, in terms of lower incidence and longer survival, observed in oncology. Women often show better responses to traditional chemotherapy, while men respond better to immunotherapy. The action of sex hormones on the immune system could contribute to these differences. However, women experience more severe adverse reactions to anticancer drugs. The estrogen/autophagy crosstalk—involved in multiple aspects of the tumor, i.e., development, progression and the response to therapy—deserves an in-depth study, as it could highlight sex-specific mechanisms useful for designing innovative and gender-tailored treatments from the perspective of precision medicine. [ABSTRACT FROM AUTHOR]

Progesterone (P4) is an endogenous sex steroid hormone involved in the ovulatory cycle and pregnancy of animal species. In sheep and goats, P4 analogues are used to induce synchronized ovulations and oestrus behavior of the females. In humans, P4 from chemical synthesis is used to treat peri-menopausal disorders. However, such molecules are released into aquatic environment and can be a source of pollution, are prohibited in organic farms and go against the trend of "naturality" in animal production as well as in human health. A natural alternative may consist in the extraction and use of P4 in plants. Mammalian hormones were discovered in an increasing number of plant species, including walnut leaves that contain high levels of P4. We compared the content of P4 in leaves of 170 accessions of Juglans regia from the walnut germplasm collection of INRAE Prunus-Juglans Biological Resources Center previously genotyped using the Axiom™ J. regia 700 K SNP array. We conducted a genome-wide association study (GWAS) using multi-locus models. When collected in October, P4 content goes from 34,1 to 287,5 mg/kg dry weight of leaves. The two laciniate accessions have the largest P4 content. We identified seven significant marker-trait associations on chromosomes 1, 2, 3, 6, 7, 15 and 16, and a candidate gene involved in the metabolism of sterols, precursors of plant steroid hormones. Our results raise the huge variability of P4 content within J. regia and propose a candidate gene which may have a role in the control of this variability, opening the way to a potential use of walnut P4 by the pharmaceutical industry towards more natural source of chemical compounds. [ABSTRACT FROM AUTHOR]