Serum SHBG Research Articles

Serum calcium improves the relationship between fluoride exposure and hypothalamic-pituitary-testicular axis hormones levels in males—a cross-sectional study on farmers in the lower reaches of the Yellow River

Numerous studies have reported the toxicity of fluoride to the male reproductive system, but epidemiological evidence is limited. We conducted a cross-sectional study in Kaifeng City, Henan Province in 2011 to explore the association between fluoride exposure and hypothalamic-pituitary-testicular (HPT) axis hormones in men. Morning urinary fluoride (UF), serum HPT axis hormones and serum calcium (SC) concentrations were detected. Percent changes and 95% confidence intervals in HPT axis hormones associated with UF were estimated using adjusted linear regression models, and performed subgroup analysis based on SC levels. The restricted cubic spline model was used to fit nonlinear relationships. For every 10% increase in UF, the concentrations of serum GnRH, T, SHBG and TSI decreased by 2.13%, 2.39%, 2.19% and 1.96%, while E2 and FEI increased by 1.11% and 3.33%. Subgroup analysis showed that for every 10% increase in UF, the levels of GnRH, T, TSI and FTI decreased by approximately 3.15%, 5.49%, 4.47% and 5.14%, while the E2 level increased by 2.92% in low-serum-calcium group (LCG). The levels of GnRH and T decreased by approximately 2.97% and 1.82% in medium-serum-calcium group (MCG). In high-serum-calcium group (HCG), serum SHBG levels decreased by 4.70%, while FTI and FEI levels increased by 4.93% and 4.20% as UF concentration increased (P < 0.05, respectively). The non-linear relationship between serum GnRH and UF concentrations presented an approximately inverted U-shaped curve, with a turning point UF concentration of 1.164 mg/L (P < 0.001), and their nonlinear relationship in LCG and MCG were similar to that in the overall subjects. In conclusion, excessive exposure to fluoride can interfere with male serum HPT axis hormones, and a moderate increase in SC alleviates the effect of fluoride. Prospective cohort studies are essential to confirm the causality.

Diabetes surpasses obesity as a risk factor for low serum testosterone level

BackgroundMale obesity is one of the most associated factors with substandard testosterone levels. However, there is growing evidence linking low testosterone levels to insulin resistance and diabetic complications. We aimed to study the impact of diabetes mellitus on testosterone levels and to assess the correlation of various clinical and biochemical factors with hypogonadism.Subjects and methodsThis case-control study was conducted on 160 adult males categorized into four equal groups (40 each); Group A: lean men with T2DM, Group B: obese with T2DM, Group C: lean with normal glycemic profile, Group D: obese with normal glycemic profile. Serum total testosterone (TT), SHBG and HbA1c have been measured. Free testosterone (cFT) and HOMA-IR were calculated.ResultsA significant negative correlation of serum TT and cFTwith BMI (r -0.16, p 0.04/ r -0.26, p < 0.001, respectively) and with waist circumference (WC) (r -0.23, p 0.003 and r -0.3, p < 0.001, respectively). A significant decrease in TT and cFT in the diabetes group versus the non-diabetes one (p < 0.001 for both). TT level was significantly lower in the diabetic lean group than in the non-diabetic lean (p < 0.001), and even significantly lower than in the non-diabetic obese (p < 0.001). TT level in the diabetic obese group was lower than in the non-diabetic obese (p < 0.001). The same for cFT level, lower in the diabetic lean group than in non-diabetic lean (p < 0.001) and lower in the diabetic obese than in the non-diabetic obese (p < 0.001). Concomitant significant reduction in SHBG in the diabetes group (p < 0.001). Linear regression analysis revealed that TT significantly correlated with HOMA-IR. HOMA-IR with WC, age and the duration of diabetes correlated significantly with cFT. In our model, HOMA-IR and HbA1c accounted for approximately 51.3% of TT variability (adjusted R-squared 0.513).ConclusionsThe impact of T2DM on serum testosterone levels was more significant than that of obesity. Our study showed a decrease in SHBG together with cFT among the diabetes group. Hypogonadism is significantly correlated to insulin resistance and poor glycemic control, which implies another perspective on the impact of suboptimal glycemic control on the development of hypogonadism.

Oral exposure to phenanthrene during gestation disorders endocrine and spermatogenesis in F1 adult male mice

Phenanthrene (Phe), a typical low-molecular-weight polycyclic aromatic hydrocarbon (PAH) of three benzene rings, is one of the most abundant PAHs detected in daily diets. Pregnant women and infants are at great risk of Phe exposure. In the present study, Phe was administered to pregnant mice at a dose of 0, 60, or 600 μg/kg body weight six times, and the F1 male mice showed significant reproductive disorders: the testicular weight and testis somatic index were significantly reduced; the levels of serum testosterone, GnRH and SHBG were increased, while the FSH levels were reduced; histological analysis showed that the amount of Sertoli cells and primary spermatocytes in seminiferous tubules was increased, while the amount of secondary spermatocytes and spermatids were decreased in Phe groups. The protein levels of PCNA and androgen receptor were reduced. Differently expressed genes in the testis screened by RNA sequence were enriched in antioxidant capacity, reproduction et al.. Further biochemical tests confirmed that the antioxidant capacity in the F1 testis was significantly inhibited by treatment with Phe during pregnancy. Those results suggested that gestational Phe exposure disordered hypothalamic-pituitary-gonadal (HPG) hormones on the one hand, and on the other hand reduced testicular antioxidant capacity and further arrested cell cycle in F1 adult male mice, which co-caused the inhibition of spermatogenesis.

A New Approach to the Assessment of Erectile Dysfunction Based on Vasomotion Monitored by the Flow-Mediated Skin Fluorescence (FMSF) Technique-A Preliminary Study.

Background: Erectile dysfunction (ED) most often has vascular etiology and usually is the earliest symptom of vascular dysfunction. The aim of this study was to evaluate vascular dysfunction with the use of the Flow-Mediated Skin Fluorescence (FMSF) technique in men with and without ED. Methods: Included were 39 men (median age 53) with ED and 40 men (median age 41.5) without ED. Medical interview, physical examination, and anthropometrical measurements were performed for all participants. The serum total testosterone, LH, and SHBG determinations were performed in patients with ED, and the Free Testosterone Index (FTI) was calculated. The FMSF technique was used to measure the microcirculatory oscillations at the baseline and to determine the flowmotion (FM) and vasomotion (VM) parameters. The Normoxia Oscillatory Index (NOI) was calculated, which represents the contribution of the endothelial (ENDO) and neurogenic (NEURO) oscillations relative to all oscillations detected at low-frequency intervals (<0.15 Hz): NOI = (ENDO + NEURO)/(ENDO + NEURO + VM). Results: In men with ED were found significantly lower FM and VM parameters, but the NOI was significantly higher in comparison to men without ED. VM and FM correlated significantly positively with erectile function, orgasmic function, and general sexual satisfaction in the whole group and the FTI in the ED group. The thresholds of 53.5 FM (AUC = 0.7) and 8.4 VM (AUC = 0.7) were predictive values for discriminating men with ED. Conclusions: It was shown that the FMSF diagnostic technique may be helpful in the early diagnosis of microcirculation dysfunction due to impaired vasomotion caused by decreased testosterone activity.

Comparative effects of the antioxidant glutathione with metformin and Diane-35 on hormonal, metabolic, and inflammatory indicators in a DHEA-induced PCOS rat model

Objective Comparison of hormonal, metabolic and inflammatory markers of glutathione with metformin and Diane-35 in a rat model of PCOS induced by dehydroepiandrosterone. Methods Twenty-five female rats were randomized into four groups. Group 1 was administered a subcutaneous dose of 0.2 ml saline/day. Group 2 was given 0.2 ml of 1% carboxymethyl cellulose (CMC)/day orally for 28 days. A PCOS model was established with DHEA in rats. Group 3 was given 4.5 mg/kg/day of Diane-35 orally dissolved in 1% CMC for 28 days. Group 4 was given 300 mg/kg/day of metformin orally dissolved in 1 ml of saline for 28 days, and Group 5 was administered 100 mg/kg of glutathione intraperitoneally on days 35, 42, and 49. On day 56, the rats were sacrificed. Serum markers and follicle count were examined. Results Serum IL-6, hs-CRP, insulin, testosterone, SHBG, and MDA values were significantly lower in the glutathione group than in the PCOS group (p = 0.0006, p = 0.023, p = 0.0082, p = 0.0007, p = 0.0048, and p < 0.0001, respectively). The number of all follicles was similar between the control and glutathione groups (p < 0.05). When we compared the other groups with the PCOS group, the number of primary, secondary, atretic, and cystic follicles was significantly lower in the metformin and glutathione groups. The number of primordial and antral follicles was significantly higher than in the PCOS group. Conclusions Glutathione plays anti-inflammatory and antioxidant roles, similar to metformin, by lowering serum IL-6, insulin, testosterone, CRP, and MDA levels; decreasing atretic/cystic follicle count; and improving antral follicle count and folliculogenesis in PCOS patients.

Androgenetic alopecia: evaluation of hormonal profile and its systemic implications

Background: Androgenetic Alopecia is a hereditary androgen-dependent disorder characterized by a gradual conversion of terminal hair into miniaturized hair with typical bitemporal recession and balding vertex and is considered the most common type of baldness characterized by progressive hair loss. This study evaluated the hormonal profile in males with androgenetic alopecia. This study evaluated the hormonal profile of early androgenetic alopecia in males. Methods: This prospective study included 84 patients attending the outpatient Department of Dermatology. Forty-four cases and 40 controls were included in the study. The study had 44 male patients presenting with complaints of grade ≥ 3 androgenetic alopecia in the age group 19-35 years, whereas 40 age and sex-matched patients attending Dermatology OPD for unrelated complaints with no history of hair loss or clinical examination suggestive of androgenetic alopecia were included in the control group. After a detailed history, and examination, testosterone, LH, FSH, Prolactin, and SHBG were estimated. Results: The mean age of onset was found to be 24.29±3.28 years. Positive family history was seen in 65.90% of patients. The mean testosterone, LH, FSH, prolactin, SHBG and free androgen index in cases versus controls was 6.44±2.58 versus 3.32±1.53 ng/ml, 8.01±2.64 IU/l versus 3.01±1.16 IU/l, 3.82±1.33 IU/l versus 5.07±1.27 IU/l, 15.50±5.11 ng/ml versus 9.84±3.91 ng/ml, 12.72±2.63 nmol/l versus 29.18±4.90 nmol/l and 51.03±21.78 versus 11.40±4.66 respectively. LH/FSH ratio was 2.17±0.54 versus 0.63±0.27. These parameters had p values &lt;0.05 and were statistically significant. Conclusions: Our study concluded that serum testosterone, prolactin, LH, LH/FSH, and FAI are increased whereas serum FSH and SHBG are decreased in cases of androgenetic alopecia compared to controls.

Associations of Serum Testosterone and Sex Hormone-binding Globulin With Incident Arrhythmias in Men From UK Biobank.

Sex hormones have been identified as cardiovascular risk factors, whereas the relationship between sex hormones and the risk of arrhythmias in men has not yet been well studied in the prospective cohort study. To analyze associations of serum testosterone and SHBG concentrations and calculate free testosterone (cFT) with arrhythmias in men. Sex hormones were measured at baseline from UK Biobank. Main outcomes were incidence of atrial fibrillation/flutter (AF), ventricular arrhythmia (VA), and bradyarrhythmia (BA). Of 173 498 men (aged 37-73 years, followed for 11 years), 11 368 had incident AF, 1646 had incident VA, and 4788 had incident BA. Compared with the third quartiles, the lowest category of serum testosterone was associated with increased risks of AF (hazard ratio [HR], 1.06; 95% CI, 1.00-1.12) and BA (HR, 1.11; 95% CI, 1.02-1.20) after multivariable adjustment, but no VA. Likewise, similar associations were found between cFT values and AF and BA events. Furthermore, higher levels of cFT were associated with increased risks of AF (HR, 1.07; 95% CI, 1.02-1.13) and VA (HR, 1.18; 95% CI, 1.01-1.37). Higher SHBG concentrations were associated with increased risks of AF (HR, 1.44; 95% CI, 1.34-1.54), VA (HR, 1.27; 95% CI, 1.07-1.52), and BA (HR, 1.17; 95% CI ,1.05-1.29). Lower levels of testosterone and cFT were associated with increased risk of AF and BA. Higher cFT levels were associated with increased risk of AF and VA. Higher SHBG levels were associated with increased risk of AF, VA, and BA.

Association Between Trichoscopic Features and Serum Hormone Levels and Vitamin D Concentration in Patients with Androgenetic Alopecia in Eastern China: A Cross-Sectional Study.

Androgenetic alopecia (AGA) is a common dermatological condition, with reported associations between serum vitamin D and sex hormone levels. However, the relationship between these factors and the severity of hair loss remains unclear. Our cross-sectional study included 310 AGA patients who visited the dermatology clinic and underwent trichoscopy examinations throughout 2021. We collected data on serum sex hormones and 25(OH)D levels during their consultations. TrichoScan analysis was used to characterize and quantify AGA severity based on hair density and vellus hair proportions in the central scalp area, which were then correlated with the collected indicators. The study findings reflect the basic demographic characteristics of AGA patients in the Chinese population. We discovered a significant negative correlation between serum SHBG levels and AGA severity in women, but no association was found in men. Serum testosterone, estradiol, dehydroepiandrosterone sulfate, and 25(OH)D levels showed no significant correlation with the severity of androgenetic alopecia, regardless of gender. To our knowledge, this is the first study to investigate the relationship between serum sex hormones, vitamin D, and AGA severity using trichoscopic scalp hair features.

The relationship between sex hormone-binding protein and non-alcoholic fatty liver disease using Mendelian randomisation.

The incidence of non-alcohol fatty liver disease (NAFLD) has been increasing annually with the improvement of living standards. Numerous epidemiological observations have linked sex hormone-binding protein (SHBG) levels to NAFLD. However, evidence of the causal role of SHBG in the development and progression of NAFLD is still absent. Therefore, a systematic assessment of the causal relationship is needed. A two-sample Mendelian randomisation (MR) analysis was conducted. Genome-wide association study (GWAS) data for SHBG were obtained online from the IEU database (ebi-a-GCST90012111) as exposure. GWAS data from the NAFLD of the Finngen consortium were used for preliminary analysis, while NAFLD data from another GWAS involving 8434 participants were used for replication and meta-analyses. Causal effects were investigated with inverse variance weighted (IVW), weighted median and MR-Egger regression. Sensitivity analyses including Cochran's Q test, leave-one-out analysis and MR-Egger intercept analysis were simultaneously conducted to assess heterogeneity and pleiotropy. After rigorous selection, 179 single-nucleotide polymorphisms (SNPs) were identified as strongly correlated instrumental variables. Preliminary analysis suggested a significant causal relationship between genetically determined serum SHBG levels and NAFLD [odds ratio (OR) IVW = .54, 95% confidence interval (CI) = .30-.98, p = .043], supported by the results of the replication analysis (ORIVW = .61, 95% CI = .46-.81, p = .0006) and further meta-analysis (OR = .59, 95% CI = .46-.77, p < .0001). The genetic tendency to high levels of SHBG was causally correlated with a reduced risk of NAFLD, indicating that circulating high levels of SHBG was a protective factor for NAFLD.

Extended Use of Levonorgestrel-Releasing Intrauterine System (LNG-IUS) 52 mg: A Population Pharmacokinetic Approach to Estimate In Vivo Levonorgestrel Release Rates and Systemic Exposure Including Comparison With Two Other LNG-IUSs

ABSTRACT With over 30 years of use, levonorgestrel-releasing intrauterine systems (LNG-IUSs) have proven to be highly effective methods of contraceptives. The active ingredient in LNG-IUS, levonorgestrel (LNG), is released directly into the uterine cavity, which causes suppression of endometrial maturation and thickened cervical mucus. A variety of LNG-IUS options exhibit well-established safety profiles and efficacy, providing anywhere between 2 and 18 times lower systemic exposure when compared with LNG-containing pills or implants. Patient-centered decision-making regarding product choice may be encouraged through standardized comparisons of LNG release and exposure during the time of their respective usage periods. Evaluation of the efficacy, safety, and PK of extended Mirena use from beyond 5 years to the conclusion of 8 years was designed in the Mirena Extension Trial (MET), thereby facilitating comparisons with LNG-IUS 19.5 mg and LNG-IUS 13.5 mg. Using validated liquid chromatography-tandem mass spectrometry methods and SHBG concentrations, the authors determined concentrations of plasma LNG levels. Dichloromethane was used for extracting residual LNG from the elastomer material from removed IUS devices, which was then quantified via liquid chromatography and external calibration on a reversed-phase column. Although previous models used measured LNG and SHBG (serum) concentrations, the population pharmacokinetics (popPK) allows for a uniform method of comparison among different pharmacologic studies. The popPK approach allows for a reliable estimates of in vivo LNG exposure and release during the entirety of the 8-year use period. The MET enrolled premenopausal women aged 18–35 years for a multicenter, single-arm study regarding patients who had used LNG-IUS 52 mg for the last 4.5–5 years for up to 8 years. The study took place from December 22, 2016 to May 28, 2021 throughout 54 US centers, with the primary outcome of contraceptive efficacy and failure rate. Participants each provided written, informed consent. Study strengths of the popPK approach included its robust methodology, its ability to provide in vivo release rate estimates, a stepwise demo of model suitability from use years 6 to 8, model-based estimation of unbound LNG, and the ability to provide estimates for both population and individual PK profiles from sparse available sampling. Limitations include the possibility of findings being group effects possibly inapplicable to all LNG-IUS users. In addition, the data fail to provide local endometrial and cervical LNG concentrations due to the systemic nature of the LNG exposure. Finally, the popPK Mondale should not be used for theoretical question addressing (such as creating rate release estimates outside of available data sets). In conclusion, a broad data set indicates that reliable LNG exposure is delivered by 8-year popPK and release models for up to 7 years of LNG-IUs 52 mg use. Efficacy is data-supported for 6–8 years of use, with constant LNG release throughout this time frame. Systemic LNG exposure from LNG-IUD 52 mg proved both comparable to other LNG-IUS devices and significantly lower than oral and implanted LNG-containing contraceptives.

Association of blood metals with serum sex hormones in adults: A cross-sectional study

Heavy metals such as lead, mercury, and cadmium have been identified to have negative impacts on human health. Although the individual effects of these metals have been extensively researched, the present study aims to explore their combined effects and their association with serum sex hormones among adults. Data for this study were obtained from the general adult population of the 2013-2016 National Health and Nutrition Survey (NHANES) and included five metal (mercury, cadmium, manganese, lead, and selenium) exposures and three sex hormones (total testosterone [TT], estradiol [E2], and sex hormone-binding globulin [SHBG]) levels. The free androgen index (FAI) and TT/E2 ratio were also calculated. The relationships between blood metals and serum sex hormones were analysed using linear regression and restricted cubic spline regression. The effect of blood metal mixtures on sex hormone levels was examined using the quantile g-computation (qgcomp) model. There were 3,499 participants in this study, including 1,940 males and 1,559 females. In males, positive relationships between blood cadmium and serum SHBG (β=0.049 [0.006, 0.093]), lead and SHBG (β=0.040 [0.002, 0.079]), manganese and FAI (β=0.080 [0.016, 0.144]), and selenium and FAI (β=0.278 [0.054, 0.502]) were observed. In contrast, manganese and SHBG (β=-0.137 [-0.237, -0.037]), selenium and SHBG (β=-0.281 [-0.533, -0.028]), and manganese and TT/E2 ratio (β=-0.094 [-0.158, -0.029]) were negative associations. In females, blood cadmium and serum TT (β=0.082 [0.023, 0.141]), manganese and E2 (β=0.282 [0.072, 0.493]), cadmium and SHBG (β=0.146 [0.089, 0.203]), lead and SHBG (β=0.163 [0.095, 0.231]), and lead and TT/E2 ratio (β=0.174 [0.056, 0.292]) were positive relationships, while lead and E2 (β=-0.168 [-0.315, -0.021]) and FAI (β=-0.157 [-0.228, -0.086]) were negative associations. This correlation was stronger among elderly women (>50 years old). The qgcomp analysis revealed that the positive effect of mixed metals on SHBG was mainly driven by cadmium, while the negative effect of mixed metals on FAI was mainly driven by lead. Our findings indicate that exposure to heavy metals may disrupt hormonal homeostasis in adults, particularly in older women.

An antibody-free LC-MS/MS method for the quantification of sex hormone binding globulin in human serum and plasma.

Sex hormone binding globulin (SHBG) is a hormone binding protein which plays an important role in regulating the transport and availability of biologically active androgens and estradiol to target cells and used to calculate free testosterone concentrations. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed, featuring an albumin removal step followed by a tryptic digestion. After a reduction step with dithiothreitol and alkylation with iodoacetamide three signature peptides were used for the quantification of SHBG. The method enables the quantification of serum and plasma SHBG over the clinically relevant range of 200-20,000ng/mL and was validated according to the mostrecent guidelines. The LC-MS/MS method correlates wellwith the Abbott Alinity immunoassay (R2>0.95), but theLC-MS/MS results are on average 16-17% lower than the immunoassay results, which is consistent for all three signature peptides. The LC-MS/MS method which includes an albumin depletion step allows quantification of SHBG in serum and plasma without an immunocapture step at clinically relevant SHBG levels, thus contributing to better lab-to-lab consistency of results.

Association of Hormonal imbalance in menopausal women with cardiovascular disease in Erbil city

Menopausal women have a higher risk of cardiovascular disease (CVD), which is thought to be due to an imbalance in serum estradiol and total testosterone level. To find out the effect of menopause on sex hormone levels such as estrogen, testosterone, and progesterone in serum menopausal women and to elevate the relationship between these hormones and CVD. This case-control study included (224) participants (menopausal women with CVD and non-CVD) in the age range (of 40-69 years) who visited (The surgical specialty hospital cardiac center and Hawler teaching hospital). A self-administered questionnaire was used for data collection. Fasting serum metabolic parameters and hormones were measured which included (E2, TT, P, SHBG) and (Total Cholesterol, Triglycerides, HDL, LDL, and VLDL). Women with CVD represented 60.7%., who had previously been diagnosed by specializes in the cardiac center, and healthy menopausal women represented 39.3%. The mean value of E2 was significantly lower in menopausal women with CVD (20.066±1.773 Pg/ml vs 29.455±3.807 Pg/ml) along with serum progesterone level (0.234±0.0102 ng/ml vs 0.452±0.137 ng/ml) and SHBG level (31.705±1.085 nmol/L vs 37.191±1.804 nmol/L) compared to healthy menopausal women (for all, p&lt;0.05). On the other hand, a significantly elevated level of total testosterone (17.970±1.28 nmol/L vs 10.552±.99nmol/L) was observed in menopausal women with CVD compared with healthy women (p&lt;0.001). Multiple linear regression analysis showed the E2 negative correlation with LDL-C (p&lt;0.01), and TT negative correlation with HDL-C (P&lt;0.01). Low serum levels in terms of sex hormones, (E2, P, and SHBG) with high-level serum TT might be contributed to cardiovascular disease.

High testosterone/estradiol ratio in men with erectile dysfunction may have a predictive value for chronic viral hepatitis

The increased level of SHBG may suggest hepatic distress regardless of aetiology. A low T/E2 ratio was associated with increased systemic inflammation, inflammatory proteins in the plaque, and a higher risk of major CV events in future, compared to a high T/E2 ratio. This study was carried out with the purpose of evaluating the relationship between the high T/E2 ratio and the prevalence of chronic hepatitis of viral aetiology in males with ED. Twenty-six males (aged 38 ± 6.44) with ED, normal hormonal values and increased T/E2 ratio were selected. The T/E2 ratio was calculated by the formula: testosterone (ng/dL) / estradiol (pg/ml). A high T/E ratio was considered > 14.1. All men were screened for HBsAg, HBcAb and anti-HCV. Liver function tests were done for those with positive markers. Serum testosterone, SHBG and estradiol levels were assessed in all participants. Results demonstrated the mean total testosterone level to be 460 ± 40.41 ng/dL, mean total estradiol level 22 ± 6.23 pg/ml and mean SHBG level 50.32 ± 6.42 nmol/L. The T/E ratio was ranged between 23.12 the highest level and 16.45 the lowest level. The ED evaluation (IIEF-5) - 12% severe, 41% moderate, 33% mild to moderate and 14% mild. Of twenty-six screened males, 12 (46.15%) were with HBsAg positive, 2 (7.69%) with positive anti-HCV and 3 with only HBcAb. In 15 marker positive patients, liver function tests were within normal range and only 2 had slightly changed bilirubin and AST level. All 14 patients (HBsAg and anti-HCV positive) were diagnosed with liver chronic disease for the first time. The increased T/E2 ratio with normal SHBG, testosterone and estradiol values, may serve as a reason for screening for viral hepatitis in patients with erectile dysfunction as the primary symptom. Normal hormonal values in patients with erectile dysfunction should be individually interpreted and T/E ratio considered. No conflict of interest.

Bisphenol A analogues in associations with serum hormone levels among reproductive-aged Chinese men.

Bisphenol A (BPA) as an endocrine disrupting chemical has been shown to alter reproductive endocrine function, but little is known on its analogues such as bisphenol F (BPF) and bisphenol S (BPS) with increasing usage and exposure. To explore the associations between exposures to BPA, BPF and BPS and serum reproductive hormones among reproductive-aged Chinese men. We measured BPA, BPF and BPS concentrations in repeated urine samples and multiple reproductive hormones in the serum samples collected from 462 men attending an infertility clinic in Wuhan, China. Linear regression models were applied to assess the associations between averaged urinary BPA, BPF and BPS levels and serum hormone concentrations, and restricted cubic spline (RCS) models were further utilized to explore potential non-linear associations. We also examined potential modifying effects by age and body mass index (BMI). There was little evidence of associations between BPA exposure and altered reproductive hormones. However, we found that elevated BPF and BPS exposures were in negative associations with estrogen (E2) levels and E2/T (total testosterone) ratio (all P for trends<0.05), and that elevated BPS exposure was negatively associated with SHBG levels (P for trend=0.09). Based on the RCS models, these linear negative associations except that between BPS exposure and E2/T ratio were further confirmed. In stratified analyses, BPF and BPS exposures in relation to reduced E2 and E2/T ratio were more pronounced among men aged>30years, whereas their associations with reduced SHBG levels were more pronounced among men aged≤30. Also, BPS exposure in negative association with FSH only emerged among men with BMI≥24kg/m2 (P for interaction=0.03). BPF and BPS exposures were negatively associated with male serum E2, E2/T ratio and SHBG levels, and these associations varied by age and BMI.

FGF21 Is Released During Increased Lipogenesis State Following Rapid-Onset Radioiodine-Induced Hypothyroidism.

BackgroundFGF21 pharmacological treatment reverses fatty liver and lowers serum triglyceride concentration but FGF21 serum level is increased in hepatic steatosis. FGF21 secretion is induced by thyroid hormones in vitro.PurposeTo determine the influence of thyroid hormones and metabolic changes secondary to thyroid dysfunction on FGF21 secretion in humans.Materials and MethodsThis was a case-control study. 82 hyperthyroid and 15 hypothyroid patients were recruited together with 25 healthy controls. Of those with hyperthyroidism, 56 received radioiodine treatment and 42 of them achieved hypothyroidism and then euthyroidism within one year following therapy. Radioiodine-induced hypothyroidism developed abruptly within a six week interval between clinic visits. FGF21 serum levels were determined with an ELISA method.ResultsSerum FGF21 levels did not differ in hyper- and hypothyroid patients in comparison to controls [median 103.25 (interquartile range, 60.90-189.48) and 86.10 (54.05-251.02) vs 85.20 (58.00-116.80) pg/mL P=0.200 and 0.503, respectively]. In hyperthyroid patients treated with radioiodine, serum FGF21 levels increased significantly in rapid-onset hypothyroidism in comparison to the hyperthyroid and euthyroid phase [median 160.55 (interquartile range, 92.48 - 259.35) vs 119.55 (67.78-192.32) and 104.43 (55.93-231.93) pg/mL, P=0.034 and 0.033, respectively]. The rising serum FGF21 level correlated positively with serum triglycerides (Spearman coefficient rs=0.36, P=0.017) and inversely with serum SHBG (rs=-0.41, P=0.007), but did not correlate with thyroid hormone levels.ConclusionsThere was a transient increase in FGF21 serum level during rapid-onset hypothyroidism following radioiodine treatment. There was no association between FGF21 serum level and thyroid hormones. In radioiodine-induced hypothyroidism, the rising serum FGF21 concentration correlated positively with rising serum triglycerides and negatively with falling SHBG, reflecting increased hepatic lipogenesis.

Effects of berberine on LPS /NF-κB and MAPK signaling pathways in PCOS model rats

Objective: To investigate the effects of berberine on glucose and lipid metabolism, sex hormone binding protein, adiponectin (LPS), NF-κB and MAPK signaling pathways in polycystic ovary syndrome (PCOS) model rats. Methods: Female SD rats were randomly divided into control group, PCOS model group, berberine (0.216 g/kg) group, metformin (0.135 g/kg) group and Dyne-35 (0.18 mg/kg) group, 10 rats in each group. The rats in PCOS model group were treated with letrozole 1 mg.kg-1 by ig for 3 weeks. After 28 days of drug intervention, the body constitution, ovarian and uterine indexes of the rats were detected, and the changes in the number of ovarian follicles were observed by HE staining. The levels of serum sex hormone, glucose and insulin, triglyceride and cholesterol, sex hormone-binding protein and adiponectin were determined by ELISA, and the protein expressions of p38-MAPK, C-Jun and NF-κB in ovarian tissues were determined by Western blot. Results: Compared with control group, body weight of model group was increased (P＜0.05), and uterine index was decreased (P＜0.05); The number of follicles was increased (P＜0.05). Serum levels of luteinizing hormone (LH), testosterone (T) and LH/FSH ratio were increased (P＜0.05), follicular estrogen (FSH) level was decreased (P＜0.05), total cholesterol (TC), triglyceride (TG), fasting insulin and insulin index (HOMA) were increased (P＜ 0.05). The content of sex hormone binding protein (SHBG) was decreased and the content of adiponectin (LPS) was increased (P＜0.05). The protein expressions of p38-MAPK, c-Jun and NF-κB in ovarian tissue were up-regulated (P＜0.05). Compared with model group, in berberine group, the uterine index and the number of secondary follicles were increased(P＜0.05), the serum levels of luteinizing hormone (LH) , testosterone (T) and the ratio of LH/FSH were decreased (P＜0.05), and the protein expression levels of p38-MAPK and NF-κB in ovarian tissue were down-regulated (P＜0.05), which were similar to those of Dyne-35 group. Berberine significantly decreased serum triglyceride (TG), insulin level and insulin index (P＜0.05), increased serum SHBG level and decreased serum LPS level (P＜0.05), which were similar to those of metformin. Conclusion: Berberine can regulate sex hormone disorder and insulin resistance (IR) in PCOS rats by down-regulating the expressions of p38-MAPK and NF-κB protein in ovarian tissues and decreasing the serum content of LPS.

Transient Hypogonadism Induced by SARS-CoV-2 during COVID-19 in Men Aged under 65 Years

Background: The presence of the angiotensin-converting enzyme 2 (ACE2) receptor, the main entry receptor for SARS-CoV-2 in lung alveolar tissue, in Sertoli and Leydig cells of the adult testis, may suggest possible testicular involvement during SARS-CoV-2 infection. Our aim was to investigate the impact of COVID-19 on gonadal function in men. Methods: This was a cross-sectional descriptive and analytical study in a population of men aged below 65 years of age with SARS-CoV-2. Not included in the study were any subjects on testosterone replacement therapy or with a known condition that could create hypogonadism. We recruited patients through a questionnaire and then performed total testosterone and SHBG analysis at 8 hours and 2 months post infection by ELISA. We used the Spearman Rho test for statistical analysis of correlations. The significance level was set at 0.05. Results: The sample consisted of 40 male COVID positive patients with a mean age of 46.4 ± 11.8 years. Eight patients were reviewed after infection. The mean total testosterone was 11 ng/ml ± 2.4 and the SHBG was 113 nmol/l ± 66.9 during infection. In the 8 patients reviewed after infection, median total testosterone decreased during infection (11 ng/ml) and increased after infection (12.7 ng/ml), this result was statistically significant (P = 0.028). Median SHBG during infection was increased (115.7 nmol/l) and after infection was decreased (82 nmol/l). There was a statistically significant (P = 0.04) and positive correlation between serum testosterone and SHBG levels in patients with severe infection. Conclusion: There could be a transient relative hypogonadism during SARS-CoV-2 infection, more marked in the severe forms of the disease with a tendency to improve after infection.

Estetrol: A New Choice for Contraception.

Estetrol (E4) is a natural estrogenic steroid that is normally produced by human fetal liver. Recent research has demonstrated that it is a potent, orally bioavailable, natural selective estrogen receptor modulator; it has a moderate affinity for both human estrogen receptor alpha (ERα) and ERβ, with a preference for ERα. Clinical studies have demonstrated possible use as an estrogen in combined oral contraceptives (COC). COCs containing E4 and drospirenone (DRSP) showed a high acceptability, tolerability, and user satisfaction also when compared to COCs containing ethinylestradiol (EE). E4/DRSP effectively inhibits ovulation, with a similar effect on endometrium thickness than that of EE-containing COCs. Low doses (15 mg) of E4 with DRSP (3 mg) showed promising results in term of bleeding pattern and cycle control, also when compared to other COCs containing synthetic estrogens. Moreover, the association has limited effects on serum lipids, liver, SHBG levels, and carbohydrate metabolism. This combination also could drive a lower risk of venous thromboembolism than EE-containing COCs. In this review, we will summarize the actual knowledge about the new E4-containing contraceptive. Further large-scale studies in the full target population are needed to provide more insights into the cardiovascular safety profile and user satisfaction of E4/DRSP.

The Comparison of Predictive Value Among Chemerin, IL-18 and Hormonal Parameters in Assessing the Risk of Metabolic Syndrome in Men.

Chemerin (CHEM) is a new proinflammatory adipokine involved in the immune, metabolic and reproductive processes. Low–grade state inflammation (LGSI) is a key element in the pathogenesis of metabolic syndrome (MS). Low SHBG is a good marker of male hypogonadism in MS. This study evaluated the prognostic value of selected adipokine, LGSI, and androgenic parameters in predicting the risk of MS among men. One hundred thirty-two random men aged 40 to 70 years old were enrolled. Measurements of anthropometric indices, blood pressure, and laboratory tests were carried out. A total of 62 men (47%) were diagnosed with MS. Chemerin concentrations were higher in men diagnosed with MS compared to healthy: 89.48 (78.12–112.10) vs. 77.9 (65.12–98.64) ng/mL; p = .002. Men diagnosed with MS presented with lower levels of total testosterone: 5.75 (4.00–6.57) vs. 6.40 (5.50–8.40) ng/mL; p = .0014 and SHBG: 46.58 (35.13–66.28) vs. 71.97 (56.1–92.7) nM/L; p < 0.000001. Elevated LGSI indices were demonstrated in men with MS as opposed to healthy [IL–18: 530.64 (409.12–640.56) vs. 418.85 (348.14–496.44) pg/mL; p = .000033 and hs–CRP: 2.15 (0.97–4.26) vs. 1.01 (0.41–2.68) ng/mL; p = .0057)]. In multivariate regression analysis, the highest negative predictive value in assessing the risk of MS was SHBG serum concentration, while the highest positive predictive values were: IL-18, hypertriglyceridemia, and waist circumference. Decreased SHBG levels, combined with elevated IL-18 concentrations in men showing hypertriglyceridemic waist phenotype, significantly increase the risk of MS.