Dopamine as a potential diagnostic biomarker in women's sexual dysfunction.

Dopamine and prolactin are the key mediators involved in sexual function in both males and females, but the role of dopamine in female sexual dysfunction (FSD) is still unclear. The aim was to investigate the possible role of dopamine and their relationship with sex steroid hormones (estrogen, progesterone and dehydroepiandrosterone; DHEA) and prolactin levels in Egyptian women suffering from sexual dysfunction. This study included 84 women having sexual dysfunction (FSD group) and 84 normal sexual function (control group). All women were subjected to the questionnaire to assess their demographic and gynecological data as well as female sexual function index (FSFI). Blood samples were collected from all women for measuring serum estradiol, progesterone, DHEA, prolactin and dopamine levels. FSD patients had significantly higher serum progesterone and DHEA and prolactin levels; while significantly lower dopamine and estradiol levels versus controls (p < 0.001). In all women, dopamine level appeared as a predictor of FSD at cut-off point ≤8.8 ng/mL with sensitivity (75%), specificity (92%) and accuracy (83%) (p < 0.001). The low levels of dopamine were associated with significantly higher prevalence in patients with low estradiol (p < 0.001) and high progesterone (p < 0.001), DHEA (p < 0.001) and prolactin (p = 0.004). Also, dopamine was significantly positive correlation with arousal score (r = 0.16, p = 0.04), and negative correlation with age (r = -0.31, p < 0.001), pain score (r = -0.19, p = 0.01), DHEA (r = -0.45, p < 0.001) and prolactin (r = -0.28, p < 0.001). Low serum dopamine level is a potential diagnostic biomarker in women's sexual dysfunction and their association with high prolactin and sex steroid hormones dysfunction.

Associations between sex hormones, receptors, binding proteins and inflammatory bowel disease: a Mendelian randomization study.

Background: Gender differences existed in inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). Observational studies have revealed associations between sex hormones and IBD, such as estrogen and testosterone. However, the exact relationship between these sex hormones and IBD is unclear. Method: Based on the genome-wide association studies data of eight sex hormones, two sex hormone receptors, sex hormone-binding globulin (SHBG), total IBD and its two subtypes, we performed a two-sample Mendelian randomization (MR) study to analyze their mutual relationship. For estradiol (E2), progesterone (PROG), bioavailable testosterone (BAT), total testosterone (TT) and SHBG, sex-stratified MR analyses were also performed. Inverse variance weighted method, MR-Egger regression and Weighted median method were used for causal analyses. Sensitivity analyses were conducted to test the stability of causal relationships. Besides, a reverse MR analysis was performed to estimate the reverse causation. Results: E2 (P=0.028) and TT (P=0.034) had protective effects on CD. Sex-stratified analyses revealed protective roles of E2 in males on total IBD (P=0.038) and CD (P=0.020). TT in females had protective effects on total IBD (P=0.025) and CD (P=0.029), and BAT in females decreased the risk of developing CD (P=0.047) and UC (P=0.036). Moreover, SHBG in males was also associated with a decreased risk of CD (P=0.021). The reversed MR analysis showed that CD was negatively correlated with estrogen receptor (P=0.046). UC was negatively correlated with PROG in females (P=0.015) and positively correlated with SHBG levels in males (P=0.046). Conclusion: Findings of this study revealed the mutual causal associations between sex hormones and the risk of developing IBD.

Associations of sex hormone ratios with metabolic syndrome and inflammation in US adult men and women.

Background: 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. Methods: 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). Results: 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. Conclusion: 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.

Causal Relationship between Sex Hormones and Risk of Developing Common Neurodegenerative Diseases: A Mendelian Randomization Study.

BACKGROUND: Neurodegenerative diseases are a group of unexplained disorders of the central nervous system, and studies have shown that a large number of genetic and environmental factors are associated with these diseases. Since these diseases show significant gender differences in epidemiology, sex hormones are thought to be strongly associated with these diseases. In this study, we used Mendelian randomization to explore the causal relationship between sex hormones and the risk of developing neurodegenerative diseases. METHODS: We obtained genetic instrumental variables for sex hormones (sex hormone-binding globulin [SHBG], estradiol levels [EL], and bioavailable testosterone [BT]) separately through the Integrative Epidemiology Unit (IEU) database (https://gwas.mrcieu.ac.uk/). We analyzed the causal relationship of each with the risk of developing neurodegenerative diseases (Amyotrophic Lateral Sclerosis [ALS], Parkinson's disease [PD], and Alzheimer's disease [AD]) using inverse variance weighted (IVW) in Mendelian randomization. Data were then analyzed for sensitivity. RESULTS: BT was negatively associated with the risk of developing ALS (odds ratio [OR] = 0.794; 95% confidence interval [95% CI] = 0.672-0.938; p = 0.006). EL and SHBG were not associated with a risk for developing neurodegenerative diseases (ALS, PD, AD). CONCLUSIONS: Elevated BT is associated with a reduced risk of developing ALS. Further research is needed to investigate the underlying mechanisms of action for this correlation and how it can be used as a potential target of action to reduce the risk of developing ALS.

Disturbed sex hormone milieu in males and females with major depressive disorder and low-grade inflammation.

Sex hormones have biological effects on inflammation, and these might contribute to the sex-specific features of depression. C-reactive protein (CRP) is the most widely used inflammatory biomarker and consistent evidence shows a significant proportion (20-30 %) of patients with major depressive disorder (MDD) have CRP levels above 3 mg/L, a threshold indicating at least low-grade inflammation. Here, we investigate the interplay between sex hormones and CRP in the cross-sectional, observational Biomarkers in Depression Study. We measured serum high-sensitivity (hs-)CRP, in 64 healthy controls and 178 MDD patients, subdivided into those with hs-CRP below 3 mg/L (low-CRP; 53 males, 72 females) and with hs-CRP above 3 mg/L (high-CRP; 19 males, 34 females). We also measured interleukin-6, testosterone, 17-ß-estradiol (E2), progesterone, sex-hormone binding globulin (SHBG), follicle-stimulating and luteinising hormones, and calculated testosterone-to-E2 ratio (T/E2), free androgen and estradiol indexes (FAI, FEI), and testosterone secretion index. In males, high-CRP patients had lower testosterone than controls (p = 0.001), and lower testosterone (p = 0.013), T/E2 (p < 0.001), and higher FEI (p = 0.015) than low-CRP patients. In females, high-CRP patients showed lower SHGB levels than controls (p = 0.033) and low-CRP patients (p = 0.034). The differences in testosterone, T/E2 ratio, and FEI levels in males survived the Benjamini-Hochberg FDR correction. In linear regression analyses, testosterone (ß = -1.069 p = 0.033) predicted CRP concentrations (R2 = 0.252 p = 0.002) in male patients, and SHBG predicted CRP levels (ß = -0.628 p = 0.009, R2 = 0.172 p = 0.003) in female patients. These findings may guide future research investigating interactions between gonadal and immune systems in depression, and the potential of hormonal therapies in MDD with inflammation.

Sex steroid and cognitive function among community-dwelling older men with or without vascular risk factors: a cross-sectional study.

BACKGROUND: The relationship of testosterone and estradiol concentrations with cognitive function among community-dwelling older men was inconclusive. To examine the association of serum testosterone and estradiol concentrations with cognitive function in older men with or without vascular risk factors (VRFs). METHODS: This cross-sectional study consisted of 224 community-dwelling men aged 65-90 years in the Songjiang District of Shanghai, China. Serum testosterone and estradiol were measured by electrochemiluminescence immunoassay. The following five factors were defined as VRFs in this study: obesity, history of hypertension, diabetes, stroke, and coronary heart disease. Multivariable linear regression was used to examine the association of testosterone and estradiol with the Mini-Mental State Examination (MMSE) in participants with or without VRF. Restricted cubic spline (RCS) regression was performed to account for the nonlinearity of these associations. RESULTS: An inverted "U" shaped non-linear relationship was found between testosterone concentration and MMSE score in men with one VRF (P overall =.003, non-linear P =.002). Estradiol showed an inverted "U" shaped non-linear relationship with MMSE score independent of VRFs (men without VRF, P overall =.049, non-linear P =.015; men with one VRF, overall P =.007, non-linear P =.003; men with two or more VRFs, overall P =.009, non-linear P =.005). CONCLUSION: In older men, an optimal level of sex steroid concentration may be beneficial to cognitive function and the VRFs should be considered when interpreting the relationship between sex steroid and cognitive function.

Effects of Pasturella Multocida B: 2 and its immunogens (LPS and OMP) on reproductive hormones in Nili-Ravi Buffaloes / Efeitos de Pasteurella multocida B: 2 e seus imunógenos (LPS e OMP) em hormônios reprodutivos em búfalos Nili-Ravi

Abstract Livestock is a fundamental part of the agriculture industry in Pakistan and contributes more than 11.53% to GDP. Among livestock species, the buffaloes are regarded as the black gold of Pakistan. Being the highest milk producers globally, Nili-Ravi buffaloes are the most famous ones. Buffaloes are affected by many endemic diseases, and "Hemorrhagic septicemia" (HS) is one of them. This study was designed to ascertain the effects of experimental exposure ofP. multocida B:2 (oral) and its immunogens, i.e., LPS (oral and intravenous) and OMP (oral and subcutaneous) on reproductive hormonal profiles in Nili-Ravi buffaloes. Repeated serum samples were collected from the jugular vein of experimental animals for 21 days (0, 02, 04, 08, 12, 16, 20, 24, 36, 48, 72, 120, 168, 216, 264, 360, 456 and 504 hours). Hormonal assays to determine the serum concentrations of Gonadotropin-releasing hormone (GnRH), Follicle-stimulating hormone (FSH), Luteinizing hormone (LH), Estrogen (E2) and progesterone (P4) were performed using (MyBioSource) commercial Elisa kits. The hormonal profile of all treatment groups of the buffalo heifers exhibited significant (P<0.05) variations as compared to the control group (G-1). These results indicate suppression in Nili-Ravi buffaloes' reproductive hormonal profile on exposure to P. multocida B:2 and its immunogens. This influence warrants that exposure to H.S may be a possible reason for delayed puberty and poor reproduction performance in Nili-Ravi buffaloes.

Resumo A pecuária é uma parte fundamental da indústria agrícola no Paquistão e contribui com 11,53% do PIB nacional. Entre as espécies de gado, os búfalos são considerados o ouro negro do Paquistão. Sendo os maiores produtores de leite em todo o mundo, os búfalos Nili-Ravi são os mais famosos. Os búfalos são afetados por muitas doenças endêmicas, entre as quais a "septicemia hemorrágica" (SH). Este estudo busca verificar os efeitos da exposição experimental de P. multocida B:2 (oral) e seus imunógenos, ou seja, LPS (oral e intravenoso) e OMP (oral e subcutâneo), nos perfis hormonais reprodutivos em búfalos Nili-Ravi. Amostras de soro repetidas foram coletadas da veia jugular de animais experimentais por 21 dias (0, 2, 4, 8, 12, 16, 20, 24, 36, 48, 72, 120, 168, 216, 264, 360, 456 e 504 horas). Os ensaios hormonais para determinar as concentrações séricas do hormônio liberador de gonadotrofina (GnRH), hormônio foliculoestimulante (FSH), hormônio luteinizante (LH), estrogênio (E2) e progesterona (P4) foram realizados usando kits comerciais Elisa (MyBioSource). O perfil hormonal de todos os grupos de tratamento das novilhas bubalinas apresentou variações significativas (P < 0,05) em relação ao grupo controle (G-1). Esses resultados indicam supressão no perfil hormonal reprodutivo de búfalos Nili-Ravi na exposição a P. multocida B:2 e seus imunógenos. Essa influência garante que a exposição à SH possa ser uma possível razão para o atraso da puberdade e o baixo desempenho reprodutivo em búfalos Nili-Ravi.

Adolescence is a sensitive period for acrylamide-induced sex hormone disruption: Evidence from NHANES populations and experimental mice.

Acrylamide (AA) is widely contaminated in environment and diet. However, the association of AA and sex hormones has rarely been investigated, especially in adolescents, a period of particular susceptibility to sex hormone disruption. In this study, survey-weighted multivariate linear regression models were conducted to determine the association between AA Hb biomarkers [HbAA and glycidamide (HbGA)] and sex hormones [total testosterone (TT) and estradiol (E2)] in a total of 3268 subjects from National Health and Nutrition Examination Survey (NHANES) 2013-2016 waves. Additionally, adult and pubertal mice were treated with AA to assess the effect of AA on sex hormones and to explore the potential mechanisms. Among all the subjects, significant negative patterns for HbGA and sex hormones were identified only in youths (6-19 years old), with the lowest ß being - 0.53 (95% CI: -0.80 to -0.26) for TT in males and - 0.58 (95% CI: -0.93 to -0.23) for E2 in females. Stratified analysis further revealed significant negative associations between HbGA and sex hormones in adolescents, with the lowest ß being - 0.58 (95% CI: -1.02 to -0.14) for TT in males and - 0.54 (95% CI: -1.03 to -0.04) for E2 in females, while there were no significant differences between children or late adolescents. In mice, the levels of TT and E2 were dramatically reduced in AA-treated pubertal mice but not in adult mice. AA disturbed the expression of genes in the hypothalamic-pituitary-gonadal (HPG) axis, induced apoptosis of hypothalamus-produced gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus and reduced serum and hypothalamic GnRH levels in pubertal mice. Our study indicates AA could reduce TT and E2 levels by injuring GnRH neurons and disrupting the HPG axis in puberty, which manifested as severe endocrine disruption on adolescents. Our findings reinforce the idea that adolescence is a vulnerable stage in AA-induced sex hormone disruption.

High Follicle-Stimulating Hormone Level Associated With Risk of Rheumatoid Arthritis and Disease Activity.

Background: The prevalence of rheumatoid arthritis (RA) has significant gender and age difference. The peak age of RA is consistent with the age of menopause, which is accompanied by a sharp increase in serum follicle-stimulating hormone (FSH) level. This study aims to identify the FSH levels in female RA patients and the relationship with diseases activity. Methods: In total, 79 female RA patients and 50 age-matched controls were included in our study. Serum sex hormones levels were measured using chemiluminescence. RA patients were grouped by FSH quartile. Disease activity and inflammatory marks were analyzed among groups. Results: Lower sex hormones and higher gonadotropin were found in RA patients. Serum FSH level was significantly higher in RA patients than in the age-match controls (57.58 ± 15.94 vs. 43.11 ± 19.46, p=0.025). Even after adjusting for age (OR: 1.071; 95%CI: 1.006-1.139; p = 0.031), luteinizing hormone (LH), estradiol (E), and testosterone (T) OR: 1.066; 95%CI: 1.003-1.133; p = 0.039), the OR were still more than one. RA patients in the higher quartiles had higher ESR, DAS28-ESR and DAS28-CRP (p<0.05) than the lowest quartile. Besides, menopause age was significantly related with onset age in post-menopause RA patients (r = 0.432, p =0.008). Conclusion: High FSH appears to be a risk factor for RA and is positively associated with their disease activity. Early menopause might be an essential factor of RA.

Associations between endogenous sex hormones and FGF-23 among women and men in the Multi-Ethnic Study of Atherosclerosis.

Elevated levels of testosterone and fibroblast growth factor 23 (FGF-23) are both independently associated with a higher risk of cardiovascular disease (CVD). However, the relationship between sex hormones and FGF-23 is not well established. We explored the association between sex hormones and FGF-23 among middle-aged to older men and women in MESA. We studied 3,052 men and 2,868 postmenopausal women free of CVD at the time of enrollment with baseline serum sex hormones [total testosterone (T), free T, estradiol (E2) and sex hormone binding globulin (SHBG)] and intact FGF-23. In sex-stratified analyses, we examined the cross-sectional associations between log-transformed sex hormones (per 1 SD) and log-transformed FGF-23 using multiple linear regression adjusted for socio-demographics, CVD risk factors, estimated glomerular filtration rate and mineral metabolites (25-hydroxyvitamin D, calcium, phosphorus and parathyroid hormone). The mean (SD) age of study participants was 64 (10) years. The median (IQR) of FGF-23 was similar in women and men [38 (30-46) vs 38 (31-47) pg/mL]. In adjusted analyses, among women, 1 SD increment in free T was associated with 3% higher FGF-23 while SHBG was associated with 2% lower FGF-23. In men, 1 SD increment in E2 was associated with 6% higher FGF-23 whereas total T/E2 ratio was associated with 7% lower FGF-23. In conclusion, this exploratory analysis found that a more androgenic sex hormone profile was directly associated with FGF-23 in women and inversely associated with FGF-23 in men. Longitudinal studies are required to determine whether FGF-23 mediates the relationship between sex hormones and CVD risk.

Heart Failure Subtypes and Cardiomyopathies in Women.

Heart failure affects over 2.6 million women and 3.4 million men in the United States with known sex differences in epidemiology, management, response to treatment, and outcomes across a wide spectrum of cardiomyopathies that include peripartum cardiomyopathy, hypertrophic cardiomyopathy, stress cardiomyopathy, cardiac amyloidosis, and sarcoidosis. Some of these sex-specific considerations are driven by the cellular effects of sex hormones on the renin-angiotensin-aldosterone system, endothelial response to injury, vascular aging, and left ventricular remodeling. Other sex differences are perpetuated by implicit bias leading to undertreatment and underrepresentation in clinical trials. The goal of this narrative review is to comprehensively examine the existing literature over the last decade regarding sex differences in various heart failure syndromes from pathophysiological insights to clinical practice.

Effects of Pasturella Multocida B:2 and its immunogens (LPS and OMP) on reproductive hormones in Nili-Ravi Buffaloes.

Livestock is a fundamental part of the agriculture industry in Pakistan and contributes more than 11.53% to GDP. Among livestock species, the buffaloes are regarded as the black gold of Pakistan. Being the highest milk producers globally, Nili-Ravi buffaloes are the most famous ones. Buffaloes are affected by many endemic diseases, and "Hemorrhagic septicemia" (HS) is one of them. This study was designed to ascertain the effects of experimental exposure ofP. multocida B:2 (oral) and its immunogens, i.e., LPS (oral and intravenous) and OMP (oral and subcutaneous) on reproductive hormonal profiles in Nili-Ravi buffaloes. Repeated serum samples were collected from the jugular vein of experimental animals for 21 days (0, 02, 04, 08, 12, 16, 20, 24, 36, 48, 72, 120, 168, 216, 264, 360, 456 and 504 hours). Hormonal assays to determine the serum concentrations of Gonadotropin-releasing hormone (GnRH), Follicle-stimulating hormone (FSH), Luteinizing hormone (LH), Estrogen (E2) and progesterone (P4) were performed using (MyBioSource) commercial Elisa kits. The hormonal profile of all treatment groups of the buffalo heifers exhibited significant (P<0.05) variations as compared to the control group (G-1). These results indicate suppression in Nili-Ravi buffaloes' reproductive hormonal profile on exposure to P. multocida B:2 and its immunogens. This influence warrants that exposure to H.S may be a possible reason for delayed puberty and poor reproduction performance in Nili-Ravi buffaloes.

Alginic acid induces oxidative stress-mediated hormone secretion disorder, apoptosis and autophagy in mouse granulosa cells and ovaries.

Alginic acid (AA) is a kind of polysaccharide extracted from brown seaweeds and has been widely used in food industry. Certain positive effects of AA, such as anti-inflammation and anti-allergy, have been reported. Nevertheless, as a potential chemical contaminant of the environment, its impact on female reproductive system remains to be investigated. The purpose of this study is to explore the impact of AA on ovary and to investigate the further cellular mechanism. Primarily, in vitro cultured mouse ovary granulosa cells (GCs) were treated with AA at a concentration of 10µM for 24 h. The cells and supernatant were collected and subjected to further measures. The results demonstrated that after being treated with 10µM AA for 24 h the levels of estradiol and progesterone in supernatant were down-regulated. And excessive reactive oxygen species (ROS) and declined antioxidant capacity were also determined. Additionally, a large number of apoptotic bodies and autophagic vesicles were found in the experimental cells, and the mitochondria-mediated apoptotic pathway was demonstrated to play a main role in GCs apoptosis. To further investigate the effect of AA on ovary, the female ICR mice were administered with AA (10 mg/ kg bodyweight) intraperitoneally for successive 35 days, and the estrus phase was recorded simultaneously. After exposure, the ovaries and blood samples were collected for further analysis. The results revealed that the estrus period of the mice was shortened and the interestrus period was extended after being treated with AA for 35 days. At the organismal level, the numbers of antral follicles and atresia follicles increased and the levels of pro-apoptosis and autophagy-related proteins were detected upregulated after AA treatment. Taken together, both in vivo and in vitro data suggested that AA has toxicity on female reproduction by disrupting estrogen production and inducing oxidative stress, mitochondria-mediated apoptosis and autophagy. Our results provide new scientific basis and the concern for controlling the increasing use of AA.

Comprehensive Sex Steroid Profiling in Multiple Tissues Reveals Novel Insights in Sex Steroid Distribution in Male Mice.

A comprehensive atlas of sex steroid distribution in multiple tissues is currently lacking, and how circulating and tissue sex steroid levels correlate remains unknown. Here, we adapted and validated a gas chromatography tandem mass spectrometry method for simultaneous measurement of testosterone (T), dihydrotestosterone (DHT), androstenedione, progesterone (Prog), estradiol, and estrone in mouse tissues. We then mapped the sex steroid pattern in 10 different endocrine, reproductive, and major body compartment tissues and serum of gonadal intact and orchiectomized (ORX) male mice. In gonadal intact males, high levels of DHT were observed in reproductive tissues, but also in white adipose tissue (WAT). A major part of the total body reservoir of androgens (T and DHT) and Prog was found in WAT. Serum levels of androgens and Prog were strongly correlated with corresponding levels in the brain while only modestly correlated with corresponding levels in WAT. After orchiectomy, the levels of the active androgens T and DHT decreased markedly while Prog levels in male reproductive tissues increased slightly. In ORX mice, Prog was by far the most abundant sex steroid, and, again, WAT constituted the major reservoir of Prog in the body. In conclusion, we present a comprehensive atlas of tissue and serum concentrations of sex hormones in male mice, revealing novel insights in sex steroid distribution. Brain sex steroid levels are well reflected by serum levels and WAT constitutes a large reservoir of sex steroids in male mice. In addition, Prog is the most abundant sex hormone in ORX mice.

Modulatory effects of R10 fraction of garlic (Allium sativum L.) on hormonal levels, T cell polarization, and fertility-related genes in mice model of polycystic ovarian syndrome.

Polycystic ovary syndrome (PCOS) is an inflammatory endocrine-metabolic disorder related to reproductive system characterized by polycystic ovarian morphology, androgen excess, and chronic anovulation. Current treatments haven't been very successful in PCOS treatment and the problem still remains as a challenge. Therefore, new approaches should be applied to overcome the disease. Previous studies demonstrated immunomodulatory effects of R10 fraction of garlic in the treatment of inflammatory conditions such as cancer. Considering previous studies suggesting immunomodulatory therapy for PCOS, therapeutic effects of R10 fraction was evaluated in a mouse model of PCOS. To do so, PCOS was developed by intramuscular injection of estradiol valerate. Treatment with R10 fraction, isolated from garlic, was performed and the alterations in hormonal levels (estradiol, progesterone, and testosterone), T cell polarization markers (IFN-γ, IL-4, and IL-17), and expression of fertility-related genes (Gpx3 and Ptx3) were evaluated. The results showed that hormonal levels were elevated in PCOS model comparing to normal animals but were markedly modulated after treatment with R10 fraction. Moreover, a severe disturbance in T cell polarization with a significant reduction of fertility-related genes expression were detected in PCOS-induced ovaries. Treatment with R10 fraction also represented modulatory effects on T cell polarization by increasing IL-4 and decreasing IL-17 and IFN-γ levels. Accordingly, fertility-related genes were also modulated following treatment with R10 fraction in PCOS. Our study elucidated that R10 fraction of garlic possess immunomodulatory effects alleviating PCOS symptoms. This approach could be adjusted to give rise the optimum therapeutic results and considered as a candidate therapeutic approach for PCOS.

Association of sex hormones with hepatic steatosis in men with chronic hepatitis B.

BACKGROUND: No study on the relationship between hepatic steatosis and sex hormone levels in male patients with chronic hepatitis B (CHB) infection has been conducted. AIMS: We aimed to investigate the association between serum sex hormones and hepatic steatosis among a cohort of males with CHB. METHODS: In this cross-sectional study, 268 male patients with CHB were enrolled. All participants underwent anthropometric measurement, blood testing, and FibroScan test. Multiple logistic regression analysis was used to investigate the association of serum sex hormones with hepatic steatosis. RESULTS: We included 137 males with and 131 without hepatic steatosis in this study. Subjects with serum testosterone (T) levels in the highest tertile had an odds ratio (OR) (95% confidence interval [CI]) of 0.35 (0.18-0.70) (P for trend=0.003); those with serum prolactin (PRL) levels in the highest tertile had an OR (95%CI) of 0.21 (0.10-0.45) (P for trend<0.001); and those with serum estradiol/testosterone (E2/T) in the highest tertile had an OR (95%CI) of 4.02 (1.97-8.20) (P for trend<0.001) for hepatic steatosis. CONCLUSION: Lower serum total T and PRL levels and higher total E2/T are independently associated with presence of hepatic steatosis in male patients with CHB.

Linking Physical Activity to Breast Cancer via Sex Hormones, Part 1: The Effect of Physical Activity on Sex Steroid Hormones.

The effect of physical activity on breast cancer risk may be partly mediated by sex steroid hormones. This review synthesized and appraised the evidence for an effect of physical activity on sex steroid hormones. Systematic searches were performed using MEDLINE (Ovid), EMBASE (Ovid), and SPORTDiscus to identify experimental studies and prospective cohort studies that examined physical activity and estrogens, progestins, and/or androgens, as well as sex hormone binding globulin (SHBG) and glucocorticoids in pre- and postmenopausal women. Meta-analyses were performed to generate effect estimates. Risk of bias was assessed, and the GRADE system was used to appraise quality of the evidence. Twenty-eight randomized controlled trials (RCT), 81 nonrandomized interventions, and six observational studies were included. Estrogens, progesterone, and androgens mostly decreased, and SHBG increased, in response to physical activity. Effect sizes were small, and evidence quality was graded moderate or high for each outcome. Reductions in select sex steroid hormones following exercise supports the biological plausibility of the first part of the physical activity-sex hormone-breast cancer pathway. The confirmed effect of physical activity on decreasing circulating sex steroid hormones supports its causal role in preventing breast cancer.See related reviews by Lynch et al., p. 11 and Drummond et al., p. 28.

Linking Physical Activity to Breast Cancer: Text Mining Results and a Protocol for Systematically Reviewing Three Potential Mechanistic Pathways.

Epidemiologic research suggests that physical activity is associated with a reduced risk of breast cancer, but the causal nature of this link is not clear. Investigating mechanistic pathways can provide evidence of biological plausibility and improve causal inference. This project will examine three putative pathways (sex steroid hormones, insulin signaling, and inflammation) in a series of two-stage systematic reviews. Stage 1 used Text Mining for Mechanism Prioritisation (TeMMPo) to identify and prioritize relevant biological intermediates. Stage 2 will systematically review the findings from studies of (i) physical activity and intermediates and (ii) intermediates and breast cancer. Ovid MEDLINE, EMBASE, and SPORTDiscus will be searched using a combination of subject headings and free-text terms. Human intervention and prospective, observational studies will be eligible for inclusion. Meta-analysis will be performed where possible. Risk of bias will be assessed using the Cochrane Collaboration tool, or the ROBINS-I or ROBINS-E tool, depending on study type. Strength of evidence will be assessed using the GRADE system. In addition to synthesizing the mechanistic evidence that links physical activity with breast cancer risk, this project may also identify priority areas for future research and help inform the design and implementation of physical activity interventions.See related reviews by Swain et al., p. 16 and Drummond et al., p. 28.

The effect of metformin and myoinositol on metabolic outcomes in women with polycystic ovary syndrome: role of body mass and adiponectin in a randomized controlled trial.

PURPOSE: To compare the effects of insulin sensitizers metformin (MET) and myo-inositol (MI) on adiponectin levels and metabolic characteristics in women with polycystic ovary syndrome (PCOS) with respect to their body mass index (BMI). METHODS: In this open label, parallel randomized clinical trial, 66 women with PCOS (33 normal-weight and 33 overweight/obese) were randomized to either MI (4 g/day) or MET (1500 mg/day) for a period of 6 months. Serum concentration of adiponectin, hormonal and metabolic laboratory outcomes and clinical assessment of BMI, body composition and Ferriman-Gallwey score (FG score) were evaluated before and after treatment. RESULTS: After the 6-month intervention, comparison between MET and MI in time to treatment analysis showed no significant differences between the two treatments for all analyzed parameters. Only borderline significantly lower AUC glucose was found in the MET group in comparison to the MI group (p = 0.071). The main effect of treatment was shown for glucose concentration at 120 min OGTT (p = 0.032) and testosterone (p = 0.002). The main effect of time was shown for body mass (p = 0.004), waist circumference (p < 0.001), BMI (p = 0.003), body fat mass (p = 0.001), adiponectin (p = 0.020), fasting glucose (p = 0.001), testosterone (p = 0.015), SHBG (p = 0.013), 17OH progesterone (p = 0.008), LH (p = 0.004) and estradiol (p = 0.014). CONCLUSION: Our study showed similar effects of MET and MI on BMI, body composition, hormonal profile, metabolism of glucose and insulin, and adiponectin level. The two insulin sensitizers, MET and MI, were useful in reducing BMI and improving body composition without significant differences between the two treatments in PCOS women. TRIAL REGISTRATION: ISRCTN13199265. Trial registration date: 14.04.2021. (ISRCTN Registry), retrospectively registered.

Circulating Sex Hormones and Risk of Colorectal Adenomas and Serrated Lesions in Men.

BACKGROUND: Sex hormones have been implicated in the etiology of colorectal neoplasia in women for over 40 years, but there has been very little investigation of the role of these hormones in men. METHODS: Using data from an adenoma chemoprevention trial, we conducted a secondary analysis to examine serum hormone levels [testosterone, androstenedione, DHEA sulfate (DHEAS), and sex hormone binding globulin (SHBG)] and risk of colorectal precursors in 925 men. Multivariable logistic regression models were fit to evaluate adjusted associations between hormone levels and risk of "low-risk" (single tubular adenoma < 1 cm) and "high-risk" lesions (advanced adenoma or sessile serrated adenoma or right-sided serrated polyp or >2 adenomas of any size). RESULTS: Overall, levels of free testosterone, total testosterone, androstenedione, DHEAS, or SHBG were not associated with either "low-risk" or "high-risk" early precursor lesions in the colorectum. CONCLUSIONS: These findings do not support the role of sex hormones in early colorectal neoplasia among men. IMPACT: This large prospective study address a missing gap in knowledge by providing information on the role of sex hormones in colorectal neoplasia in males.