To determine whether 6 months of combined androgen blockade (CAB) treatment would result in metabolic changes of hippocampus and whether metabolic changes correlate with changes in cognition in patients with advanced prostate cancer (PCa).

This is an observational study. Proton magnetic resonance spectroscopy (1H-MRS) was used to observe the changes in the ratios of N-acetylaspartate/creatine (NAA/Cr) and choline-containing compounds/creatine (Cho/Cr) on the bilateral hippocampus for the patients before and 6 months after CAB treatment. Cognitive function was also assessed by the Beijing version of the Montreal Cognitive Assessment (MoCA-BJ) at the above two time points. Additionally, a certain number of matched individuals undergoing physical examination were selected as the control group.

CAB group comprised 25 patients with advanced PCa completing follow-up, while control group had 22 healthy controls. Prior to CAB, no significant differences existed in MoCA-BJ scores (including sub-scores) or bilateral hippocampal NAA/Cr and Cho/Cr ratios between groups. Six months after CAB, CAB group exhibited marked declines in MoCA-BJ total score, delayed recall, visuospatial/executive, and attention functions, alongside reduced bilateral hippocampal NAA/Cr and elevated left hippocampal Cho/Cr (P < 0.05).The results of multiple linear regression indicate a positive correlation between NAA/Cr in the left hippocampus and MoCA-BJ total score (β = 4.66, P < 0.001), as well as delayed recall function (β = 2.76, P < 0.001). Mediation analysis confirms that testosterone influences the MoCA-BJ total score and delayed recall function by affecting NAA/Cr in the left hippocampus.

The impact of advanced PCa on cognitive performance could be negligible. However, patients experienced secondary hippocampal injury after CAB, which further led to cognitive dysfunction.

Missense 'hotspot' mutations localized in six p53 codons account for 20% of TP53 mutations in human cancers. Hotspot p53 mutants have lost the tumor suppressive functions of the wildtype protein, but whether and how they may gain additional functions promoting tumorigenesis remain controversial. Here, we generated Trp53Y217C, a mouse model of the human hotspot mutant TP53Y220C. DNA damage responses were lost in Trp53Y217C/Y217C (Trp53YC/YC) cells, and Trp53YC/YC fibroblasts exhibited increased chromosome instability compared to Trp53-/- cells. Furthermore, Trp53YC/YC male mice died earlier than Trp53-/- males, with more aggressive thymic lymphomas. This correlated with an increased expression of inflammation-related genes in Trp53YC/YC thymic cells compared to Trp53-/- cells. Surprisingly, we recovered only one Trp53YC/YC female for 22 Trp53YC/YC males at weaning, a skewed distribution explained by a high frequency of Trp53YC/YC female embryos with exencephaly and the death of most Trp53YC/YC female neonates. Strikingly, however, when we treated pregnant females with the anti-inflammatory drug supformin (LCC-12), we observed a fivefold increase in the proportion of viable Trp53YC/YC weaned females in their progeny. Together, these data suggest that the p53Y217C mutation not only abrogates wildtype p53 functions but also promotes inflammation, with oncogenic effects in males and teratogenic effects in females.

Obesity is a significant health concern associated with various diseases. Accurate measurement of body fat mass (BFM) and local fat thickness (FT) is crucial for health assessment. Ultrasound offers a non-invasive, portable, and cost-effective alternative for measuring FT, but its application for quantitative BFM estimation has not been fully explored. This study aimed to develop and validate a quantitative estimation algorithm for BFM based on local FT measured by ultrasound.

A total of 179 volunteers were randomly divided into modeling and verification groups. BFM was measured using bioelectrical impedance analysis (BIA), and FT was measured at 10 sites throughout the body using ultrasound. In the modeling group, the correlation between FT and BFM at different sites was analyzed, and a BFM estimation algorithm based on FT was developed using multiple linear regression. The accuracy of the estimation equation was validated in the verification group.

Men had lower BFM than women (P < 0.05). At most sites, the FT of males was less than that of females (P < 0.001). Significant positive correlations were observed between FT at various sites (site 1 to 10) and BFM across all groups (P < 0.01). The estimation algorithm revealed that FT at 4 sites (intra-abdominal, posterior right perinephric, abdominal subcutaneous, and anterior upper arm) contributed to BFM estimation for men, while two additional sites (pre-peritoneal and posterior lower leg) were valuable for women. The R2 for the algorithms was 0.882 for men and 0.907 for women, with the standard error of estimate of 2.04 kg for both. The intraclass correlation coefficient between ultrasound-derived estimated BFM and the BFM measured by BIA in the verification group was 0.848 (P < 0.001).

BFM can be quantitatively estimated using a fitting algorithm based on ultrasound-derived local FT.

This study aimed to investigate the association between low basal total testosterone (TT) levels and the risk of recurrent pregnancy loss (RPL) in women with infertility.

The study included women under 40 years with infertility, normal ovarian reserve, and regular ovulation. Participants were categorized into two groups: those with a history of recurrent pregnancy loss (RPL group) and those without a history of miscarriage (control group). All participants underwent in vitro fertilization (IVF) treatment. Serum TT and other sex hormone levels were measured on day 2 of spontaneous menstrual cycles and subsequently evaluated. Endocrine and coagulation conditions were also assessed.

A total of 561 women were enrolled, into either the RPL group (n = 364) or the control group (n = 197) between January 2012 and December 2020. The RPL group demonstrated significantly lower median TT levels and were older compared with the control group (1.21 vs. 1.37 nmol/L, P = 0.001; 34 vs. 33 years, P = 0.010). Additionally, fasting plasma insulin levels were higher in the RPL group (10.67 vs. 8.84 mU/L, P < 0.001). A negative correlation between basal TT levels and pregnancy loss frequency was observed. Low basal TT levels were significantly associated with RPL (OR: 1.58, 95 % CI: 1.04 - 2.41), with TT cut-off value of <1.33 nmol/L indicating an increased likelihood of RPL (P < 0.001).

Low basal serum TT levels are associated with an increased risk of RPL. However, further studies are required to evaluate the predictive value of basal TT levels in RPL risk.

Muscle recovery after damage is mediated by circulating factors and intracellular signaling pathways. Our previous studies have demonstrated that resistance exercise (RE)-induced circulating factors elicited sex-differential responses in damaged muscle. However, the global effects of these circulating factors on damaged muscle are largely understudied. We examined the differential effects of RE-induced circulating factors and sex on the damaged muscle proteome. Damaged vastus lateralis muscle from 3 men and 3 women from a parent study were analyzed. Participants completed 2 identical bouts of unilateral eccentric knee extensions immediately followed by either upper body RE to induce circulating factors (EXE) or 20-min seated rest (CON). Muscle biopsies collected from the damaged leg at 24 h were used. 900 proteins were identified by LC-MS/MS analysis. Ingenuity Pathway Analysis was used to detect activation prediction using z-scores for functional and pathway analyses. In men, 79 proteins were downregulated and 15 were upregulated in EXE versus CON. These differentially expressed proteins were associated with immunological and inflammatory signaling pathways. Biological functions of the differentially expressed proteins in EXE vs. CON in men include inactivating acute inflammatory signaling, neutrophil extracellular trap signaling, ROS production, and activating IL-12 signaling. These results underline that RE-induced circulating factors have a sex-specific effect on the damaged muscle proteome, where immune signaling is altered in men but not women. Given that the immune response is critical for recovery from muscle damage, these results highlight the potential role of RE-induced circulating factors that could be essential in mediating muscle recovery.

Androgen receptors (AR) are promising therapeutic targets for mechanisms of aging, including chronic inflammation, lean mass loss, and worsening bone health. We investigated the impact of RAD140, a selective AR modulator that activates ARs, on frailty and underlying mechanisms in older C57BL/6 mice.

Mice (23.7-25.5 months; N = 21 males; 15 females) received RAD140 (5 mg/kg/day) or placebo (DMSO) daily for 6-weeks. Frailty (clinical and lab-based), body composition, circulating inflammatory markers, grip strength, and genes relating to function/hypertrophy in quadriceps femoris muscles were assessed.

Despite no differences in frailty between treatment and control, there were positive effects in male, but not female mice. RAD140 treated male mice had preserved lean mass (p = 0.024) and bone mineral density (p = 0.004) and lower serum interleukin-6 (p = 0.043) versus controls. In contrast, benefits to body composition and inflammatory markers were not seen in females. In either sex, grip strength, fat mass, and skeletal muscle genes were unaffected.

Six-weeks of RAD140 treatment did not affect frailty in older male or female mice. The beneficial effects in lean mass, bone mineral density, and systemic inflammation warrant longer treatments to explore any positive impact on frailty in males. RAD140 may not be ideal for achieving these in females.

Erectile dysfunction (ED) is a prevalent condition affecting male sexual health, characterized by the inability to achieve or maintain satisfactory erections. ED has a multifactorial pathogenesis in which psychological, hormonal, neurologic, cardiovascular, and lifestyle factors all contribute to a progressive decline of erectile function. A critical underlying mechanism involves oxidative stress (OS), an imbalance between reactive oxygen species (ROS) production and antioxidant defenses, which disrupts endothelial function, reduces nitric oxide (NO) bioavailability, and contributes to vascular dysfunction. This narrative review explores the interplay between OS and ED, focusing on the roles of ROS sources such as NADPH oxidase, xanthine oxidase, uncoupled nitric oxide synthase, and mitochondrial dysfunction. It examines the impact of OS on chronic conditions like hypertension, diabetes mellitus, hyperlipidemia, hypogonadism, and lifestyle factors like smoking and obesity, which exacerbate ED through endothelial and systemic effects. Emerging research underscores the potential of antioxidant therapies and lifestyle interventions to restore redox balance, improve endothelial function, and mitigate ED's progression. This review also highlights gaps in understanding the molecular pathways linking ROS to ED, emphasizing the need for further research to develop targeted therapeutic strategies.

Background: The association between inflammatory markers and depression has garnered increasing attention. The neutrophil percentage-to-albumin ratio (NPAR) is an emerging inflammatory marker, but its association with depression in middle-aged and elderly adults was not previously explored. The purpose of this study was to investigate the association through a national study in the United States. Methods: All study data were weighted to ensure representativeness. Multivariate logistic regression models were applied to explore the independent relationship of NPAR with depression in middle-aged and elderly adults. Restricted cubic splines were employed to examine potential nonlinear association, with turning points calculated using a recursive algorithm upon detecting nonlinearity. Stratified analyses and interaction tests were conducted to explore subgroup differences. Results: In the model adjusted for all confounding factors, no significant relationship was found between NPAR and depression in middle-aged and elderly adults [1.02 (0.92, 1.12)]. Further sensitivity analysis indicated a potential U-shaped relationship between NPAR and depression in middle-aged and elderly adults, with the OR (95% CI) of 0.74 (0.60, 0.92), 0.87 (0.70, 1.08), 0.92 (0.72, 1.19) for Q2, Q3, and Q4, respectively, compared to Q1. The U-shaped association was confirmed by the restricted cubic spline. Subsequent analysis identified an inflection point at 14.05, revealing inverse relationships before and after this point. Subgroup analysis indicated sex differences in this association. Conclusion: This large-scale cross-sectional study identified a U-shaped association between NPAR and depression in American middle-aged and elderly adults.

Whether testosterone replacement therapy (TRT) conveys additional cardiometabolic benefit to an intensive lifestyle therapy (LT) in older men with obesity and hypogonadism remains unclear.

To determine whether TRT augments the effect of LT on metabolic outcomes in older men with obesity and hypogonadism.

Secondary analysis of a randomized, double-blind, placebo-controlled trial.

Veterans Affairs Medical Center.

Eighty-three older (age ≥ 65 years) men with obesity (body mass index ≥ 30 kg/m2) and persistently low Am testosterone (< 10.4 nmol/L) associated with frailty.

LT (weight management and exercise training) plus either testosterone (LT + TRT) or placebo (LT + Pbo) for 6 months.

The primary outcome was change in glycated hemoglobin (HbA1c). Secondary outcomes included changes in other glucometabolic and lipid profile components, liver enzymes, inflammatory markers, and adipokines; subcutaneous, visceral, intramuscular, and hepatic fat; blood pressure; and metabolic syndrome score.

HbA1c decreased similarly in LT + TRT and LT + Pbo groups (-0.5 ± 0.1 vs -0.6 ± 0.1%, respectively; P = 0.35). While TRT showed no synergistic effect with LT on ameliorating secondary outcomes, it eliminated the augmentative effect of LT on high-density lipoprotein cholesterol concentration (5.4 ± 1.0 mg/dL in the LT + Pbo group vs 0.2 ± 1.1 mg/dL in the LT + TRT group, P = .01) and adiponectin levels (-408 ± 489 ng/mL in LT + TRT group vs 1832 ± 468 ng/mL in LT + Pbo group, P = .02).

In older men with obesity and hypogonadism, adding TRT for 6 months to LT does not result in further improved cardiometabolic profiles and could potentially blunt some of the metabolic benefits induced by LT.

In Alzheimer's disease (AD), Aβ triggers p-tau secretion, which drives tau aggregation. Therefore, it is critical to characterize modulators of Aβ-related p-tau increases which may alter AD trajectories. Here, we assessed whether factors known to alter tau levels in AD modulate the association between fibrillar Aβ and secreted p-tau181 determined in the cerebrospinal fluid (CSF). To assess potentially modulating effects of female sex, younger age, and ApoE4, we included 322 ADNI participants with cross-sectional/longitudinal p-tau181. To determine effects of microglial activation on p-tau181, we included 454 subjects with cross-sectional CSF sTREM2. Running ANCOVAs for nominal and linear regressions for metric variables, we found that women had higher Aβ-related p-tau181 levels. Higher sTREM2 was associated with elevated p-tau181, with stronger associations in women. Similarly, ApoE4 was related to higher p-tau181 levels and faster p-tau181 increases, with stronger effects in female ApoE4 carriers. Our results show that sex alone modulates the Aβ to p-tau axis, where women show higher Aβ-dependent p-tau secretion, potentially driven by elevated sTREM2-related microglial activation and stronger effects of ApoE4 carriership in women.

Castration of adult male rats led to the development of osteoporosis. Oxidative stress and inflammatory factors have been identified as potential causative factors. Notably, oxymatrine (OMT) possesses potent anti-inflammatory and antioxidant activities. This study aims to elucidate the antiosteoporotic effects of OMT compared to testosterone in an orchiectomized (ORX) rat model of osteoporosis.

A total of 60 Wistar male rats were divided into the following groups: control (CTRL), surgery + no orchiectomy (SHAM), ORX, ORX + testosterone, and ORX + OMT. Urinary deoxypyridinoline (DPD), calcium (Ca), and phosphorus (P), as well as serum testosterone, parathormone (PTH), alkaline phosphatase (ALP), osteocalcin, N-telopeptide of type I collagen (NTX I), tartrate resistance acid phosphatase (TRAP), and total Ca and P levels were evaluated. Bone was assessed for malondialdehyde (MDA), reduced glutathione (GSH), interleukin 6 (IL-6), Kelch-like ECH-associated protein 1 (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1) expression, and receptor activator of nuclear factor κB ligand/ osteoprotegerin (RANKL/OPG) ratio. Bone dual-energy X-ray absorptiometry (DEXA) scan and histological and immunohistochemical studies were performed.

Testosterone or OMT treatment ameliorated the reduced bone mineral density (BMD) and bone mineral content (BMC) in the DEXA scan and the changes in PTH and Ca levels. Compared to the ORX group, bone formation, and turnover markers were also significantly reversed in the treatment groups. Treatment with testosterone or OMT significantly reduced bone MDA, IL-6, Keap1, RANKL, and RANKL/OPG ratio, and significantly elevated bone GSH, Nrf2, and HO-1. Moreover, testosterone or OMT treatment has restored cortical bone thickness and osteocyte number and reduced bone levels of TNF-α in ORX rats. Consequently, treatment with either testosterone or OMT exhibited nearly equal therapeutic efficacy; however, neither of them could normalize the measured parameters.

OMT treatment showed equal efficacy compared to testosterone in ameliorating osteoporosis in ORX rats, possibly by improving some inflammatory and oxidative stress parameters.

Osteoarthritis (OA) is a common degenerative joint disease that significantly impacts the quality of life, especially among older adults. Testosterone, a critical hormone for musculoskeletal health, has been suggested to influence OA pathogenesis. However, the relationship between low testosterone levels and OA risk remains underexplored in large, representative populations. This study aimed to investigate the association between low testosterone levels and OA risk using data from the National Health and Nutrition Examination Survey (NHANES, 2011-2016).

This cross-sectional analysis included 4,548 participants from NHANES, a nationally representative U.S.

Testosterone levels were categorized as low or normal, with low testosterone defined as < 300 ng/dL for men and population-based cutoffs for women. The presence of OA was determined through self-reported physician diagnosis. Multivariable logistic regression models were used to examine the association between testosterone levels and OA risk, adjusting for demographic, socioeconomic, lifestyle, and clinical factors. Restricted cubic spline (RCS) analysis was conducted to evaluate non-linear relationships. Subgroup analyses were performed to assess consistency across key demographic and clinical strata.

Among the 4,548 participants, 812 (17.9%) were diagnosed with OA. Participants with OA were older, more likely to be female, and exhibited higher rates of obesity and hyperlipidemia. In fully adjusted models, low testosterone levels were significantly associated with increased OA risk (OR, 1.22; 95% CI, 1.02-1.46; P = 0.028). RCS analysis indicated a non-linear relationship, with a steep increase in OA risk at lower testosterone levels, suggesting a threshold effect. Subgroup analyses demonstrated consistent associations across demographic and clinical groups without significant interactions.

Low testosterone levels are independently associated with an increased risk of OA in the U.S.

These findings underscore the potential role of hormonal health in OA pathogenesis and highlight the need for longitudinal studies to clarify causal pathways. The observed non-linear relationship suggests that maintaining optimal testosterone levels may be important for joint health, and testosterone replacement therapy could be explored as a preventative strategy for individuals with testosterone deficiency.

Therapies involving the use of stem Leydig cells (SLCs), as testicular mesenchymal stromal cells, have shown great promise in the treatment of Leydig cell (LC) dysfunction in aging males. However, the outcomes of these therapies are not satisfactory. In this study, it is demonstrated that the aging microenvironment of the testicular interstitium impairs the function of SLCs, leading to poor regeneration of LCs and, consequently, inefficient functional restoration. The study develops a decellularized testicular extracellular matrix (dTECM) hydrogel from young pigs and evaluates its safety and feasibility as a supportive niche for the expansion and differentiation of SLCs. dTECM hydrogel facilitates the steroidogenic differentiation of SLCs into LCs, the primary producers of testosterone. The combination of SLCs with a dTECM hydrogel leads to a significant and sustained increase in testosterone levels, which promotes the restoration of spermatogenesis and fertility in an LC-deficient and aged mouse model. Mechanistically, collagen 1 within the dTECM is identified as a key factor contributing to these effects. Notably, symptoms associated with testosterone deficiency syndrome are significantly alleviated in aged mice. These findings may aid the design of therapeutic interventions for patients with testosterone deficiency in the clinic.

Chronic pain following traumatic stress exposure (TSE) is common. Increasing evidence suggests inflammatory/immune mechanisms are induced by TSE, play a key role in the recovery process versus development of post-TSE chronic pain, and are sex specific. In this study, we tested the hypothesis that the inflammatory marker C-reactive protein (CRP) is associated with chronic pain after TSE in a sex-specific manner.

We utilized blood-plasma samples and pain questionnaire data from men (n=99) and (n=223) women enrolled in AURORA, a multi-site emergency department (ED)-based longitudinal study of TSE survivors. We measured CRP using Ella/ELISA from plasma samples collected in the ED ('peritraumatic CRP', n=322) and six months following TSE (n=322). Repeated measures mixed-effects models were used to assess the relationship between peritraumatic CRP and post-TSE chronic pain.

Peritraumatic CRP levels significantly predicted post-TSE chronic pain, such that higher levels of CRP were associated with lower levels of pain over time following TSE, but only in men (men:β=-0.24, p=0.037; women:β=0.05, p=0.470). By six months, circulating CRP levels had decreased by more than half in men, but maintained similar levels in women (t(290)=1.926, p=0.055). More men with a decrease in CRP levels had decreasing pain over time versus women (men:83% women:65%; Z=2.21, p=0.027).

In men but not women, we found circulating peritraumatic CRP levels predict chronic pain outcomes following TSE and resolution of CRP levels in men over time might be associated with increased pain recovery. Further studies are needed to validate these results.

Various prenatal factors including the number of littermates (fraternity size) and exposure to male littermate (fraternity sex ratio) during fetal period have been reported to influence postnatal fertility in the mammals. The present research was conducted to study the association of fraternity size and sex ratio with reproductive performance of nulliparous ewes and does. To this end, data associated with number of littermates, exposure to male littermate, birth weight, age at first pregnancy, as well as litter size, sex ratio of offspring, litter weight, and birth weight of female and male offspring after the first parturition retrieved from the database of sheep (n = 536 Romane and 289 Blanche du Massif Central ewes) and goat (n = 174 Alpine and 267 Saanen does) flocks. Fraternity size was negatively associated with birth weight of ewes and does (P < 0.05). Exposure to male littermate during fetal period was associated with younger age at first pregnancy and larger litter size in the does (P < 0.05), but not in the ewes (P > 0.05). Exposure to male littermate during fetal period was positively associated with the odds of male-biased litters in the ewes and does (P < 0.05). Fraternity size was positively associated with litter weight in the does (P < 0.05), but not in the ewes (P > 0.05). In conclusion, the present study showed that the number and sex of littermates during fetal period could impact postnatal reproduction of ewes and does. In this context, some associations, particularly those related to exposure to male littermate during fetal period, were only observed in does, which implicates that the effect of androgens on developmental programming of reproduction may be species-specific.

Chronic spontaneous urticaria (CSU) is defined as the appearance of itchy wheals and/or angioedema for at least 6 weeks. Cigarette smoking is one of the world's most common addictions. It is a cause of serious diseases such as renal cancer or thromboembolic incidents. Nevertheless, some studies show that nicotine might have a protective effect on various autoimmune diseases. The neutrophil-lymphocyte ratio (NLR) is a good marker of inflammation.

To check the prevalence of smokers in our CSU patients and to assess their profile of NLR as a marker of inflammation.

68 adult patients were included (52 females, and 16 males). The average age of respondents was 52. All of the patients were diagnosed with CSU. The group was divided by gender and smoking. The Mann-Whitney U test (Statistica ver.13) was used.

73.5% of the respondents were non-smokers, and the remaining 26.5% were smokers. In the female group, irrespective of smoking, statistically significant different levels of neutrophils (NEU), lymphocytes (LYM), and neutrophil-lymphocyte ratio (NLR) were found compared to males. No statistical difference was found between smokers and non-smokers regarding the level of inflammatory factors. Compared to males, females had significantly different levels of LYM in the group of non-smokers and NEU in the group of smokers.

Our study does not support claims that smoking has a protective effect on CSU. Significant differences in NEU, LYM, and NLR need to be further investigated.

The onset of degenerative joint diseases such as post-traumatic osteoarthritis (PTOA) are associated with joint injury, biomechanical changes, and synovial biochemical anomalies. Sex and reproductive endocrinology have been emerging as potential risk factors, with epidemiological evidence revealing that female's exhibit higher PTOA risk and poorer outcomes post-injury compared to males. Sex hormones, including estradiol, progesterone, and testosterone, have been shown to regulate inflammatory signaling in immune and synovial cells, yet their collective impact on injury-induced joint inflammation and catabolism is poorly understood. Using an in silico kinetic model, we investigated the effects of sex-specific endocrine states on post-injury mechanisms in the human synovial joint. Our model results reveal that heightened estradiol levels in pre-menopausal females during the peri-ovulatory phase increase interleukin (IL)-1β expression and suppress IL-10 expression within the synovium after a simulated injury. Conversely, elevated testosterone levels in males decrease post-injury IL-1β, tumor necrosis factor alpha (TNF)-α, and stromelysin (MMP)-3 expression while increasing IL-10 production compared to females. Gaining insight into the effects of sex hormones on injury-induced inflammation and cartilage degradation provides a basis for designing future experimental and clinical studies to explore their effects on the synovial system, with a particular focus on the female sex.

In recent years, a burgeoning field of research has focused on women's mental health and psychiatric conditions associated with perinatal and postpartum periods. An emerging trend points to the link between hormone fluctuations during pregnancy and postpartum that have immunologic consequences in cases of perinatal depression and postpartum psychosis. The transition to menopause (or "perimenopause") has garnered comparatively less attention, but existing studies point to the influential interaction of hormonal and immune pathways. Moreover, the role of this cross talk in perturbing neural networks has been implicated in risk for cognitive decline, but relatively less work has focused on the depressed brain during perimenopause. This brief review brings a psychoneuroimmunology lens to depression during the perimenopausal period by providing an overview of existing knowledge and suggestions for future research to intertwine these bodies of work.

Major Depressive Disorder (MDD) is a heterogeneous disorder that affects twice as many women than men. Precluding advances in more tailored and efficacious treatments for depression is the lack of reliable biomarkers. While depression is linked to elevations in inflammatory immune system functioning, this relationship is not evident among all individuals with depression and may vary based on symptom subtypes and/or sex. This systematic review and meta-analysis examined whether inflammatory immune peripheral markers of depression are sex-specific. PRISMA guidelines were followed for the systematic review, and a comprehensive search strategy that identified studies from PubMed and PsycInfo was applied. Studies were included if they reported C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor (TNF)-α and/or IL-1β for males and/or females among depressed and healthy adults. We identified 23 studies that satisfied these inclusion criteria. Random-effects meta-analysis models were fit, and measures of association were summarized between levels of circulating markers of inflammation in depressed and healthy males and females. Sex-based analyses revealed elevated levels of CRP among females with depression (Cohen's d = 0.19) relative to their healthy counterparts (p = 0.02), an effect not apparent among males (Cohen's d = -0.01). Similarly, levels of IL-6 were increased among females with depression compared to healthy controls (Cohen's d = 0.51; p = 0.04), but once again this was not found among males (Cohen's d = 0.16). While TNF-α levels were elevated among individuals with depression compared to controls (p = 0.01), no statistically significant sex differences were found. The meta-analysis for IL-1β resulted in only three articles, and thus, results are presented in the supplemental section. This meta-analysis advances our understanding of the unique involvement of inflammatory biomarkers in depression among men and women, which may help inform more tailored sex-specific treatment approaches in the future.

Sex-specific differences in lifespan and ageing are observed in various species. In humans, women generally live longer but are frailer and suffer from different age-related diseases compared to men. The hallmarks of ageing, such as genomic instability, telomere attrition or loss of proteostasis, exhibit sex-specific patterns. Sex chromosomes and sex hormones, as well as the epigenetic regulation of the inactive X chromosome, have been shown to affect lifespan and age-related diseases. Here we review the current knowledge on the biological basis of sex-biased ageing. While our review is focused on humans, we also discuss examples of model organisms such as the mouse, fruit fly or the killifish. Understanding these molecular differences is crucial as the elderly population is expected to double worldwide by 2050, making sex-specific approaches in the diagnosis, treatment, therapeutic development and prevention of age-related diseases a pressing need.

Inflammation likely mediates associations between nicotine use and negative health outcomes. Sex differences have been observed in nicotine use-inflammation links, and physiological processes during puberty might allow for these differences to arise. In this cross-sectional study of 498 youth (ages 8-13, 52% girls, 77% with history of child maltreatment (CM) investigation), sex-differentiated associations between self-reported nicotine use and high-sensitivity C-reactive protein (hs-CRP) were explored. Additionally, self-reported pubertal stage was investigated as a moderator of such nicotine use-hs-CRP links. Hierarchical generalized estimating equation models were adjusted for a wide range of adversity effects: CM investigation history derived from state records, self- and caregiver-report of traumatic life events, adversity-related demographic risk factors (i.e., identification with historically marginalized racial and ethnic groups, household income), and other characteristics that may influence the variables of interest (e.g., medication use, age, body mass index). Nicotine use had a negative main effect on hs-CRP among boys (β = -0.50, p = 0.02), and pubertal stage did not moderate this association (β = 0.06, p = 0.71). In contrast, pubertal stage moderated the association between nicotine use and hs-CRP among girls (β = 0.48, p = 0.02) such that a positive association between nicotine use and hs-CRP levels was stronger at more advanced pubertal stages (β = 0.45, SE = 0.21, 95% CI [0.03, 0.87]). Findings suggest that puberty may influence the effect of nicotine on inflammation in sex-differentiated ways and have implications for timing of prevention and treatment efforts geared toward reducing nicotine use and subsequent inflammation-related health risk among youth.

Rheumatoid arthritis (RA) is characterized by erosive pathology associated with joint inflammation and a sexual dimorphism with increased prevalence in females. Here, we aim to determine whether androgen is protective against inflammatory-erosive disease in TNF-transgenic (TNF-Tg) mice. Wild-type (WT) and TNF-Tg male mice underwent sham (WT, n = 3; TNF-Tg, n = 7) or orchiectomy (WT, n = 3; TNF-Tg, n = 7) surgery at 1 month old to remove androgen production confirmed by serum testosterone concentration. Cohorts of orchiectomized TNF-Tg males were treated with either 5ɑ-dihydrotestosterone (.025 mg/day) (n = 3) or placebo (n = 3) via subcutaneous pellet insertion. Weekly clinical measures, along with mid-hindpaw bone volumes and ankle histology at 3 months old were evaluated for all groups. Orchiectomies in TNF-Tg males significantly decreased serum testosterone (P < .05), weight gain (P < .001), and mid-hindpaw bone volumes (P < .05) in comparison to sham TNF-Tg mice. The cuboid bone also had increased synovitis by histology with the loss of androgen (P < .05). Treatment of orchiectomized TNF-Tg males with 5ɑ-dihydrotestosterone protected against the changes in weight gain (P < .01) and bone erosion (P < .05) associated with decreased osteoclast number in the cuboid (P < .01). In the TNF-Tg model of chronic inflammatory arthritis, androgen is protective in erosive disease. The loss of endogenous androgen significantly accelerated the progression of inflammatory-erosive arthritis in male TNF-Tg mice to a similar severity as age-matched female mice. In addition, treatment with exogenous androgen prevented this observed bone loss in orchiectomized TNF-Tg males. Overall, androgen delays and limits bone erosion even in the presence of active inflammation and future studies are warranted to elucidate the associated mechanisms.

The relationship between sex steroid hormones and high-sensitivity C-reactive protein(hs-CRP) levels in American children and adolescents is understudied. This research will examine this association.

The study conducted a data analysis from the National Health and Nutrition Examination Survey (NHANES) 2015-2016, adjusting multiple linear regression models with R 4.2.2 and EmpowerStats. A total of 1,768 children and adolescents were surveyed. Data collection involved measurements of serum levels of testosterone, estradiol, sex hormone-binding globulin (SHBG) and hs-CRP.

With the increase in testosterone, a brief rise (β=0.082, P=0.047) followed by an overall decline (β=-0.028, P=0.023) in hs-CRP was observed in the Male Prepubertal population, while a continuous decline (β=-0.002, P<0.05) was seen in the Male Pubertal group. A positive correlation (β=0.047, P<0.05) was found between testosterone and hs-CRP in the Female Prepubertal population, whereas no significant association (β=0.002, P>0.05) was detected in the Female Pubertal group. A significant inverse correlation was observed between estradiol and hs-CRP solely in the Female Pubertal group (β=-0.002, P<0.05), while no association was found in other populations. An inverse relationship between SHBG and hs-CRP was consistently noted across all groups: Male Prepubertal, Male Pubertal, Female Prepubertal, and Female Pubertal.

The association between sex steroid hormones and high-sensitivity C-reactive protein (hs-CRP) levels among American children and adolescents is conditional and influenced by multiple factors.

Failure rates after first-line treatment of localized prostate cancer (PCa) treatment remain high; therefore, it is essential to improve the selection and identification of at-risk patients to reduce mortality. The aim of the ANDROCAN study was to evaluate the biochemical recurrence (BCR) in patients with localized PCa treated by total prostatectomy at 5 yr after surgery, according to their presurgery gonadal status.

A prospective cohort study was conducted including 1318 patients undergoing total prostatectomy for localized PCa with a 5-yr postoperative follow-up. Clinical and hormonal data (assays of total testosterone [TT], bioavailable testosterone [BT], dihydrotestosterone, estrone, and estradiol were performed by gas chromatography/mass spectrometry) as well as metabolic syndrome parameters were collected at baseline before surgery. Pathological data (predominant Gleason grade 4 and stage) were collected and cross-referenced centrally. Factors associated with BCR were assessed by a multivariate analysis, and BCR-free survival was assessed by a Kaplan-Meier analysis.

Among the 1318 patients, 237 had BCR of PCa. Considering demographic characteristics, populations with and without BCR were similar. However, patients with BCR had cancers with a higher Gleason score (p = 0.0001) and higher prostate-specific antigen (PSA) values (p = 0.0005) at baseline. Gleason score, pT >3a, and PSA level at baseline were positively correlated with BCR (p < 0.0001, p < 0.0001, and p = 0.0048, respectively), while BT and TT levels were not associated with BCR. This study includes patients with varying clinical characteristics, such as cancer history and metabolic syndrome, introducing variability that makes it challenging to isolate the specific effects of gonadal status on BCR. Another limitation is the lack of evaluation of long-term BCR beyond 5 yr, potentially overlooking recurrences that occur between 5 and 15 yr after surgery. This could lead to an underestimation of the actual long-term recurrence rates.

Overall, PSA levels, high Gleason score, and pT >3a are associated with a greater likelihood of disease recurrence following initial treatment and could serve as important prognostic indicators for predicting the risk of BCR. In this prospective study, biochemical hypogonadism was not associated with a higher occurrence of BCR within 5 yr of prostatectomy. The biological gonadal status of preoperative patients could potentially be useful for therapeutic decisions but does not provide an indication for the oncological follow-up.

Five-year follow up of patients after surgery showed that there is no association between hypogonadism (low levels of total testosterone and bioavailable testosterone) and cancer recurrence. However, cancer recurrence seems to be more associated with aggressiveness of cancer at the time of detection.

Repetitive transcranial magnetic stimulation (rTMS) has recently gained relevance in treating different psychiatric disorders. Limited evidence suggests that the beneficial effects of rTMS on psychopathology could be at least partly mediated through changes in inflammatory response. This systematic review summarizes the literature on whether rTMS can modulate inflammatory markers and thus positively influence the course of psychiatric illnesses.

A systematic review of rTMS and inflammatory markers in psychiatric diseases was conducted according to PRISMA guidelines. Information on the association between rTMS treatment response and changes of inflammatory markers was extracted. The quality of the studies was assessed using the National Heart, Lung, and Blood Institute for human studies and the Systematic Review Center for Laboratory Animal Experimentation for animal studies.

This review includes 17 studies (2 animal and 15 human studies) on the relationship between rTMS treatment response and changes of inflammatory markers. Positive changes in microglial activity and anti-inflammatory effects were associated with behavioral improvement in animal models of depression. However, these findings have not been consistently replicated in human studies focusing on treatment-resistant depression. While several studies reported rTMS-induced alterations in peripheral inflammatory markers, only two could demonstrate their association to clinical treatment response. Notably, most studies showed poor or moderate quality in the bias assessment.

While certain human studies suggest an association between rTMS-induced anti-inflammatory effects and improvement in psychopathology, heterogeneity, and underpowered analyses constrain the generalizability of these results. The discrepancy between animal and human findings highlights the need for larger, standardized human studies.

(PROSPERO Registration: CRD42023492732).

The primary mechanism of traumatic spinal cord injury (SCI) comprises the initial mechanical trauma due to the transmission of energy to the spinal cord, subsequent deformity, and persistent compression. The secondary mechanism of injury, which involves structures that remained undamaged after the initial trauma, triggers alterations in microvascular perfusion, the liberation of free radicals and neurotransmitters, lipid peroxidation, alteration in ionic concentrations, and the consequent cell death by necrosis and apoptosis. Research in the treatment of SCI has sought to develop early therapeutic interventions that mitigate the effects of these pathophysiological mechanisms. Clinical and experimental evidence has demonstrated the therapeutic benefits of sex-steroid hormone administration after traumatic brain injury and SCI. The administration of estradiol, progesterone, and testosterone has been associated with neuroprotective effects, better neurological recovery, and decreased mortality after SCI. This review evaluated evidence supporting hormone-related neuroprotection over SCI and the possible underlying mechanisms in animal models. As neuroprotection has been associated with signaling pathways, the effects of these hormones are observed on astrocytes and microglia, modulating the inflammatory response, cerebral blood flow, and metabolism, mediating glutamate excitotoxicity, and their antioxidant effects. Based on the current evidence, it is essential to analyze the benefit of sex steroid hormone therapy in the clinical management of patients with SCI.

The sex steroid hormones fluctuate during the menstrual cycle, which affects the strength and postural stability of females and leads to injuries and risk of falls. These hormones may be modulated by exercise to impact the overall health of females.

To determine the effects of exercise on sex steroid hormones in eumenorrheic females.

This review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA) guidelines in Lahore, Pakistan. The full-length articles were searched using these databases/search engines (PubMed, Web of Science and Google Scholar, Sci-Hub). Randomized controlled trials along with single group experimental studies were also included. All types of exercises were compared with no exercise in the control group. The Cochrane Risk of Bias assessment tool assessed and screened the articles. The data were then analyzed. The primary outcomes were the levels of estrogen, progesterone and testosterone.

Eleven studies were included (5 randomized controlled trials and 6 quasi-experimental studies). The effects of exercise on free estradiol concentration and serum progesterone level were not significant [p = 0.37 (SMD = 0.33, 95% CI = 0.14 to 0.74, I2 = 0%) and p = 0.84 (S.D= -0.65, C.I= -6.92 to 5.62, I2 = 94%)] respectively, whereas, the effects on testosterone levels were significant [p value < 0.00001 (M.D = 0.89, 95% C.I= -2.16 to 3.95, I2 = 94%)].

A blinded randomized controlled trial should be conducted in which a structured approach should be followed by women along with warm-ups, cool down and rest intervals.

The systematic review was registered prospectively on PROSPERO with registration number CRD42023473767.

Many transgender and gender non-conforming (TGNC) people seek gender-affirming hormone therapy (GAHT). While GAHT is generally safe and increases well-being, it is essential to accurately understand potential unintended effects and risk factors to better inform and manage treatment. This narrative review covers recent literature documenting changes in sexual function following the initiation of GAHT and explores inflammation as a potential mediator of these changes.

Generally, the initiation of GAHT is correlated with increased sexual desire in transgender men and decreased sexual desire in transgender women, with time-limited effects that return to levels approaching baseline after about a year; there are also changes in inflammation markers that parallel this timeline. Findings on other aspects of sexual function (e.g., orgasm, pain, and sexual quality of life) are more limited. As there is evidence from cisgender populations that inflammation acts as a mechanism by which hormones influence sexual function, we propose applying this model to TGNC people taking GAHT.

Sexual function may change in TGNC patients receiving GAHT, and those changes may be influenced by inflammation. However, these changes often return to baseline as TGNC patients' bodies adjust to a new hormonal equilibrium.

The proportion of heart failure patients with preserved ejection fraction has been rising over the past decades and has coincided with increases in the prevalence of obesity and metabolic syndrome. The relationship between these interconnected comorbidities and heart failure with preserved ejection fraction (HFpEF) is still poorly understood. This study characterized obesity and metabolic syndrome among real-world patients with HFpEF.

We identified adults with heart failure in the Veradigm Cardiology Registry, previously the PINNACLE Registry, with a left ventricular ejection fraction measurement ≥ 50% between 01/01/2016 and 12/31/2019. Patients were stratified by obesity diagnosis and presence of metabolic syndrome (≥ 3 of the following: diabetes, hypertension, hyperlipidemia, and obesity). We captured baseline demographic and clinical characteristics and used multivariable logistic regression to examine the odds of having cardiac (atrial fibrillation, coronary artery disease, coronary artery bypass surgery, myocardial infarction, and stroke/transient ischemic attack) and non-cardiac (chronic kidney disease, chronic liver disease, and peripheral artery disease) comorbidities of interest. The models adjusted for age and sex, and the main covariates of interest were obesity and metabolic burden score (0-3 based on the presence of diabetes, hypertension, and hyperlipidemia). The models were run with and without an obesity*metabolic burden score interaction term.

This study included 264,571 patients with HFpEF, of whom 55.7% had obesity, 52.5% had metabolic syndrome, 42.5% had both, and 34.3% had neither. After adjusting for age, sex, and burden of other metabolic syndrome-associated diagnoses, patients with HFpEF with obesity had lower odds of a diagnosis of other evaluated comorbidities relative to patients without obesity. The presence of metabolic syndrome in HFpEF appears to increase comorbidity burden as each additional metabolic syndrome-associated diagnosis was associated with higher odds of assessed comorbidities except atrial fibrillation.

Obesity was common among patients with HFpEF and not always co-occurring with metabolic syndrome. Multivariable analysis suggested that patients with obesity may develop HFpEF in the absence of other driving factors such as cardiovascular disease or metabolic syndrome.

Endometriosis is a complex gynecological pathology with a broad spectrum of symptoms, affecting around 10% of reproductive-aged women. Ovarian cancer (OC) is a heterogeneous disease for which we lack effective diagnostic and therapeutic strategies. The etiology and pathogenesis of both diseases remain ambiguous. Androgens in endometriosis could have a distinct role beyond serving as estrogen sources, whereas in the case of serous OC could be important in the formation of precursor lesions which ultimately lead to tumor formation. Here we performed two-sample Mendelian randomization (MR) analysis to examine the causal relationship between the androgen precursor - dehydroepiandrosterone sulphate (DHEAS), bioactive androgen - testosterone (T), androgen metabolite - androsterone sulphate, steroid hormone binding globulin (SHBG) and albumin and the risk of endometrioses of various sub-phenotypes and ovarian neoplasms across the benign-borderline-malignant spectrum. Stringent quality control procedures were followed to select eligible instrumental variables that were strongly associated with the selected exposures, sensitivity analyses were performed to assess the heterogeneities, horizontal pleiotropy, and stabilities of SNPs in endometriosis and ovarian neoplasms. We discovered an inverse association between genetically predicted levels of all androgens and risk of endometriosis, the same trend was most evident in the ovarian sub-phenotype. Total T levels were also inversely associated with peritoneal sub-phenotype of endometriosis. Likewise, T was causally associated with decreased risk of clear-cell OC, an endometriosis-associated OC subtype, and with malignant serous OC of both low- and high-grade, but with higher risk of their counterpart of low malignant potential. These findings support further investigation of androgen's action at a molecular level in ovary-associated endometriotic lesions, clear cell ovarian tumors and serous precursor lesions.

Pregnane neuroactive steroids, notably allopregnanolone and pregnenolone, exhibit efficacy in mitigating inflammatory signals triggered by toll-like receptor (TLR) activation, thus attenuating the production of inflammatory factors. Clinical studies highlight their therapeutic potential, particularly in conditions like postpartum depression (PPD), where the FDA-approved compound brexanolone, an intravenous formulation of allopregnanolone, effectively suppresses TLR-mediated inflammatory pathways, predicting symptom improvement. Additionally, pregnane neurosteroids exhibit trophic and anti-inflammatory properties, stimulating the production of vital trophic proteins and anti-inflammatory factors. Androstane neuroactive steroids, including estrogens and androgens, along with dehydroepiandrosterone (DHEA), display diverse effects on TLR expression and activation. Notably, androstenediol (ADIOL), an androstane neurosteroid, emerges as a potent anti-inflammatory agent, promising for therapeutic interventions. The dysregulation of immune responses via TLR signaling alongside reduced levels of endogenous neurosteroids significantly contributes to symptom severity across various neuropsychiatric disorders. Neuroactive steroids, such as allopregnanolone, demonstrate efficacy in alleviating symptoms of various neuropsychiatric disorders and modulating neuroimmune responses, offering potential intervention avenues. This review emphasizes the significant therapeutic potential of neuroactive steroids in modulating TLR signaling pathways, particularly in addressing inflammatory processes associated with neuropsychiatric disorders. It advances our understanding of the complex interplay between neuroactive steroids and immune responses, paving the way for personalized treatment strategies tailored to individual needs and providing insights for future research aimed at unraveling the intricacies of neuropsychiatric disorders.

Sex hormones play a critical role in sex differences and cardiovascular disease risk associated with metabolic syndrome (MS) and inflammation. However, the associations of sex hormone ratios with metabolic and inflammatory markers are unclear according to sex and age differences. We evaluated the associations of sex hormone ratios with MS and inflammation among males and females.

A retrospective cross-sectional study was conducted by including all adults from the National Health and Nutrition Examination Survey cycles 2013-2016 and excluding any pregnant women, heart disease, diabetes, and those currently taking insulin. MS was defined using the National Cholesterol Education Program criteria and a high-sensitivity C-reactive protein (CRP) level>3 mg/L was defined as a high CRP. Measures of MS components and CRP concentrations were also analyzed. The primary exposures were testosterone to estradiol (excess androgen index), testosterone to sex hormone-binding globulin (free androgen index), and estradiol to sex hormone-binding globulin (free estradiol index). The adjusted associations were summarized with a relative risk (RR) and 95% confidence interval (CI).

This study included 9167 subjects with 4360 males and 4807 females. Increases in free estradiol index were positively associated with MS (RR=1.48; 95%CI: 1.39, 1.58; RR=1.31; 95%CI: 1.22, 1.40) and high CRP (RR=1.49; 95%CI: 1.25, 1.77; RR=1.26; 95%CI: 1.06, 1.50) in men with age<50 years and age≥50 years, respectively. Similarly, higher free estradiol index was also robustly associated with increased prevalence of MS (RR=1.22; 95%CI: 1.15, 1.28) and high CRP (RR=1.68; 95%CI: 1.48, 1.90) in women with age ≥50 years. Among women with age<50 years, a higher free androgen index was associated with MS (RR=1.34; 95%CI: 1.25, 1.42) and high CRP (RR=1.13; 95%CI: 1.02, 1.25). These associations were unchanged even after adjusting for all sex hormones.

Free estradiol index was consistently and positively associated with MS and high CRP in males of all ages and older females. Free androgen index was positively associated with MS and high CRP in females with age<50 years.

Respiratory-related diseases are a leading cause of death in rheumatoid arthritis (RA) and are disproportionately higher in men, which may be attributable to environmental risk factors. Animal studies have demonstrated potentiated autoimmunity, arthritis, and profibrotic/inflammatory lung disease with a combination of airborne exposures and collagen-induced arthritis (CIA). This study aimed to determine whether hormone-dependent differences explained these observations. Arthritis-prone male intact and castrated DBA/1J mice received intranasal inhalation of lipopolysaccharide (LPS) daily for 5 wk and CIA induction. Arthritis scores and serum pentraxin-2 levels were increased in castrated versus intact mice. In contrast, airway cell influx, lung tissue infiltrates, and lung levels of proinflammatory and profibrotic markers (C5a, IL-33, and matrix metalloproteinases) were reduced in castrated versus intact mice. CIA + LPS-induced lung histopathology changes and the expression of lung autoantigens including malondialdehyde acetaldehyde (MAA)- and citrulline (CIT)-modified proteins and vimentin were reduced in castrated animals. There were no differences in serum anti-MAA or anti-CIT protein antibody (ACPA) levels or serum pentraxin levels between groups. Testosterone replacement led to a reversal of several lung inflammatory/profibrotic endpoints noted earlier in castrated male CIA + LPS-treated mice with testosterone supplementation promoting neutrophil influx, MAA expression, and TNF-α, IL-6, and MMP-9. These findings imply that testosterone contributes to lung and arthritis inflammatory responses following CIA + LPS coexposure, but not to systemic autoantibody responses. The CIA + LPS model provides a paradigm for investigations focused on the mechanistic underpinnings for epidemiologic and phenotypic sex differences in RA-related lung disease.NEW & NOTEWORTHY Our study shows that testosterone acts as a key immunomodulatory hormone contributing to critical features of rheumatoid arthritis (RA)-associated lung disease in the setting of airborne endotoxin (lipopolysaccharide; LPS) exposures and concomitant arthritis induction in mice. The exaggerated airway inflammation observed following combined exposures in male mice was accompanied by increases in profibrotic mediators, netosis, and increased expression of lung autoantigens, all relevant to the pathogenesis of lung disease in arthritis.

Individuals with inflammatory bowel disease (IBD) have been reported to be at an increased risk of infertility and sexual dysfunction. Although the relationship between them remains unclear, IBD severity is suspected to affect hormone levels and fertility. To analyze the impact of IBD severity on semen parameters and sex hormone levels in ulcerative colitis-type IBD (UC-IBD), we conducted a cross-sectional study involving 120 patients with UC-IBD in Adam Malik General Hospital, Medan, Indonesia. The patients were classified into three groups based on the Mayo score for UC, followed by a comparison of various semen and hormone parameters among these groups. In addition to the cross-sectional analysis, a simple correlation test was conducted irrespective of the patient grouping. Sperm concentration, motility, and morphology were found to decline significantly with an increase in IBD severity. Without classifying patients with IBD into subgroups, the Mayo score showed negative correlations with sperm concentration ( r = -0.375, P < 0.0001), rapid progressive motility ( r = -0.660, P < 0.0001), free testosterone ( r = -0.732, P < 0.0001), and total testosterone ( r = -0.721, P < 0.0001), and positive correlations with immotile sperm ( r = 0.660, P < 0.0001), abnormal morphology ( r = 0.657, P < 0.0001), and sex hormone-binding globulin (SHBG; r = 0.278, P = 0.002). Sperm concentration, motility, and morphology declined significantly with the severity of IBD. This study suggests a significant negative impact of IBD severity on semen quality and sex hormones.

The prevalence of metabolic-associated fatty liver disease (MAFLD) has increased substantially in recent years because of the global obesity pandemic. MAFLD, now recognized as the number one cause of chronic liver disease in the world, not only increases liver-related morbidity and mortality among sufferers but also worsens the complications associated with other comorbid conditions such as cardiovascular disease, type 2 diabetes mellitus, obstructive sleep apnoea, lipid disorders and sarcopenia. Understanding the interplay between MAFLD and these comorbidities is important to design optimal therapeutic strategies. Sarcopenia can be either part of the disease process that results in MAFLD (e.g., obesity or adiposity) or a consequence of MAFLD, especially in the advanced stages such as fibrosis and cirrhosis. Sarcopenia can also worsen MAFLD by reducing exercise capacity and by the production of various muscle-related chemical factors. Therefore, it is crucial to thoroughly understand how we deal with these diseases, especially when they coexist. We explore the pathobiological interlinks between MAFLD and sarcopenia in this comprehensive clinical update review article and propose evidence-based therapeutic strategies to enhance patient care.

Athletes often take sport supplements to reduce fatigue and immune disturbances during or after training. This study evaluated the acute effects of concurrent ingestion of alkaline water and L-glutamine on the salivary immunity and hormone responses of boxers after training. Twelve male boxing athletes were recruited in this study. During regular training, the participants were randomly divided into three groups and asked to consume 400 mL of alkaline water (Group A), 0.15 g/kg body weight of L-glutamine with 400 mL of water (Group G), and 0.15 g/kg of L-glutamine with 400 mL of alkaline water (Group A+G) at the same time each day for three consecutive weeks. Before and immediately after the training, saliva, heart rates, and the rate of perceived exertion were investigated. The activity of α-amylase and concentrations of lactoferrin, immunoglobulin A (IgA), testosterone, and cortisol in saliva were measured. The results showed that the ratio of α-amylase activity/total protein (TP) significantly increased after training in Group A+G but not in Group A or G, whereas the ratios of lactoferrin/TP and IgA/TP were unaffected in all three groups. The concentrations of salivary testosterone after training increased significantly in Group A+G but not in Group A or G, whereas the salivary cortisol concentrations were unaltered in all groups. In conclusion, concurrent ingestion of 400 mL of alkaline water and 0.15 g/kg of L-glutamine before training enhanced the salivary α-amylase activity and testosterone concentration of boxers, which would be beneficial for post-exercise recovery.

In the past two decades, oxidative stress (OS) has drawn a lot of interest due to the revelation that individuals with many persistent disorders including diabetes, polycystic ovarian syndrome (PCOS), cardiovascular, and other disorders often have aberrant oxidation statuses. OS has a close interplay with PCOS features such as insulin resistance, hyperandrogenism, and chronic inflammation; there is a belief that OS might contribute to the development of PCOS. PCOS is currently recognized as not only one of the most prevalent endocrine disorders but also a significant contributor to female infertility, affecting a considerable proportion of women globally. Therefore, the understanding of the relationship between OS and PCOS is crucial to the development of therapeutic and preventive strategies for PCOS. Moreover, the mechanistic study of intracellular reactive oxygen species/ reactive nitrogen species formation and its possible interaction with women's reproductive health is required, which includes complex enzymatic and non-enzymatic antioxidant systems. Apart from that, our current review includes possible regulation of the pathogenesis of OS. A change in lifestyle, including physical activity, various supplements that boost antioxidant levels, particularly vitamins, and the usage of medicinal herbs, is thought to be the best way to combat this occurrence of OS and improve the pathophysiologic conditions associated with PCOS.