Total Testosterone Concentrations Research Articles

Testosterone and the risk of incident atrial fibrillation in older men: further analysis of the ASPREE study

A cardiovascular safety trial of testosterone in men with cardiovascular risk factors or disease found no difference in rates of major adverse cardiovascular events (MACE) or death but noted more atrial fibrillation (AF) events in testosterone-treated men. We investigated the relationship between endogenous testosterone concentrations with risk of developing AF in healthy older men. Post-hoc analysis of 4570 male participants in the ASPirin in Reducing Events in the Elderly (ASPREE) study. Men were aged ≥ 70 years, had no history of cardiovascular disease (including AF), thyroid disease, prostate cancer, dementia, or life-threatening illnesses. Risk of AF was modelled using Cox proportional hazards regression. Median (IQR) age was 73.7 (71.6-77.1) years and median (IQR) follow-up 4.4 (3.3-5.5) years, during which 286 men developed AF (15.3 per 1000 participant-years). Baseline testosterone was higher in men who developed incident AF compared men who did not [17.0 (12.4-21.2) vs 15.7 (12.2-20.0) nmol/L]. There was a non-linear association of baseline testosterone with incident AF. The risk for AF was higher in men with testosterone in quintiles (Q) 4&5 (Q4:Q3, HR=1.91; 95%CI=1.29-2.83 and Q5:Q3HR=1.98; 95%CI=1.33-2.94). Results were similar after excluding men who experienced MACE or heart failure during follow-up. Circulating testosterone concentrations within the high-normal range are independently associated with an increased risk of incident AF amongst healthy older men. This suggests that AF may be an adverse consequence of high-normal total testosterone concentrations. National Institute on Aging and National Cancer Institute at the National Institutes of Health; Australian Government (NHMRC, CSIRO); Monash University; and AlfredHealth.

Association between secondhand smoke exposure and serum sex hormone concentrations among US female adults: a cross-sectional analysis using data from the National Health and Nutrition Examination Survey, 2013–2016

ObjectiveTo estimate the association between secondhand smoke (SHS) exposure and serum sex hormone concentrations in female adults (never smokers and former smokers).DesignCross-sectional analysis.SettingUS National Health and Nutrition Examination Survey, 2013–2016.Outcome...

Association between anti-Müllerian hormone concentrations and sperm retrieval outcomes in patients with idiopathic nonobstructive azoospermia: a systematic review and meta-analysis.

Microdissection testicular sperm extraction (mTESE) is commonly performed to retrieve sperm in the testes for assisted reproductive techniques in patients with idiopathic nonobstructive azoospermia (iNOA). However, the success rate of sperm retrieval varies among individuals. We aim to investigate the association between clinical parameters and sperm retrieval outcomes in patients with iNOA. We searched PubMed, EMBASE, and Web of Science from database inception to August 2, 2023. The main measure was whether sperm retrieval was successful in patients with iNOA who underwent mTESE. Pooled estimates of the sperm retrieval rate and weighted mean differences were calculated using random-effects models. The overall sperm retrieval rate was 36.8% (95% confidence interval [CI]: 27.5%-46.0%, I2 = 95.0%) in nine studies comprising 1892 patients with iNOA. No significant differences were found in age, testicular volume, serum total testosterone concentrations, or inhibin B concentrations between positive and negative sperm retrieval outcomes. Lower anti-Müllerian hormone concentrations in patients with iNOA were associated with a positive outcome of mTESE (weighted mean differences: -2.70; 95% CI: -3.94--1.46, I2 = 79.0%). In conclusion, this study shows a significant relationship between anti-Müllerian hormone and sperm retrieval outcomes in patients with iNOA, while age, testicular volume, total testosterone, and inhibin B show no significant association. These findings have important implications for assessing the potential success of sperm retrieval and selecting appropriate treatment strategies in patients with iNOA.

Population based screening for osteoporosis in men among 40 and 80 years in the brazilian state of Roraima"

The main objective of this study was to conduct population screening for osteoporosis in men between the ages of 40 and 80 in the Boa Vista, the capital of the Brazilian state of Roraima. The population study conducted in this study was basically based on the Fracture Risk Assessment Tool (FRAX®) nomogram model proposed by the World Health Organization (WHO). Specifically, the current work focuses on (i) analyzing the serum concentrations of calcium, vitamin D and total testosterone in relation to the risk of bone event by the FRAX® nomogram and (ii) correlating cardiovascular risk by calculating Framingham score with the FRAX® nomogram. This cohort, and cross-sectional study involves both quantitative and qualitative data obtained in the field from 380 patients. The data obtained were compared to the pre-existing data collected through different bibliography. For the sampling, a cluster method was utilized. Patients with immediate need of health services were referred to the state hospital of Coronel Mota, Boa Vista. This project was approved by the Ethical Committee (number: 50207115.7.0000.5301). While commuting to work or travel around found to be the major reason of the fractures, we observed that older people and people who were involved in physical activities inside a gymnasium had considerably high at risk of fractures. FRAX and TBS femur score (Trabecular Bone Score) was higher for people with fractures. People having lumbar osteopenia and femur osteopenia had higher risk of TBS femur fractures while people having lumbar osteoporosis had higher risk of TBS (femur and hip) as well as FRAX femur factures. All the data obtained in this study were analyzed using SPSS version 21 and a p value of ≤0.05 was considered as statistically significant. Key risk factors for fracture include increased age, physical activities in a gymnasium, lumbar and femur osteopenia and lumbar osteoporosis.

SHBG gene polymorphisms and their influence on serum SHBG, total and free testosterone concentrations in men.

Genetic variation in sex hormone-binding globulin (SHBG) structure may affect estimates of sex steroid exposure by altering the affinity of the protein for its ligand. Consequently, free hormone calculations assuming constant binding affinity may, for certain genetic variations, lead to incorrect diagnoses if genetic variation is not taken into consideration. To investigate the effects of genetic variation in SHBG on calculated and measured serum free testosterone (T) in men. Population-based sibling-pair study in 999 healthy men aged 25 to 45 (mean: 34.5) years. Genotyping using microarray (Illumina®) for SNPs suggested to affect binding affinity and/or concentration of SHBG or T. SHBG concentrations were measured using immunoassay and in a subset (n = 32) by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Total T was measured using LC-MS/MS. Free T was calculated and in a subset (n = 314) measured directly using LC-MS/MS after equilibrium dialysis. Allelic frequencies of analyzed SNPs ranged from 0.5% to 58.2%. Compared to wild-type, SHBG concentrations were lower in rs6258 heterozygotes (-24.7%; p < 0.05) and higher in rs6259 heterozygotes, rs727428 homozygotes, and carriers of rs1799941 (+10.8 to 23.1%; all p < 0.05). Total T was higher in rs727428 homozygotes and carriers of rs5934505, rs1799941and rs6259 (+3.9 to 21.4%; all p < 0.05). No clear effects on measured free T were found, except for a trend towards higher values in rs6259 homozygotes, significant for calculated free T (+18.7%; p < 0.05) in the larger global study population. In these men, analyzed SNPs were relatively prevalent and affected serum concentrations of total T and SHBG but not calculated or measured free T except for a higher trend in rs6259 homozygotes.

Reflex strategy to ensure accurate total testosterone results from consumer initiated, self-collected capillary samples

BackgroundSelf-collected capillary samples are convenient for direct access testing (DAT), but exogenous testosterone use may cause falsely elevated total testosterone (TT) results.We designed a quality assurance workflow to differentiate between accurate or erroneous supraphysiological TT concentrations. MethodsClinical samples with TT > 1500 ng/dL were reflexed to luteinizing hormone (LH) and follicle stimulating hormone (FSH) and screened for exogenous testosterone use. Samples (n = 120) with normal TT were reflexed to LH/FSH as a control. ResultsA total of 8572 TT samples were evaluated, of which 533 (6.2 %) had TT > 1500 ng/dL and were reflexed. Of these, 441 (82.7 %) had significantly decreased LH/FSH (<0.85/<0.7mIU/mL, respectively), 72 (13.5 %) had normal or borderline normal LH/FSH, and 20 (3.8 %) had insufficient plasma volume. In patients with TT > 1500 ng/dL, injectable exogenous testosterone use was most commonly accompanied by significantly decreased LH/FSH, while topical testosterone use was most commonly accompanied by detectable LH/FSH. Control samples were almost all (99.2 %) within or above the LH/FSH reference intervals. Unique patients ordered 351 TT tests where at least one TT result was > 1500 ng/dL. Based on TT and LH/FSH results, we hypothesized that patients were intermittently or consistently overusing exogenous testosterone, resolved elevated TT with recollection, or repeatedly contaminated their sample. ConclusionSelf-collected capillary specimens are acceptable for TT testing. A quality assurance reflex to LH/FSH can determine the validity of supraphysiological TT results in a consumer initiated/DAT population.

Gender peculiarities of cortisol, testosterone and vitamin D blood levels in athletes

Objective. To assess the gender characteristics of the concentration of cortisol, testosterone and vitamin D in blood serum in athletes, and to analyze the correlations between vitamin D levels and the hormonal status of athletes. Materials and methods. 52 athletes (32 men and 20 women) were examined, their age was 17-23, their sports specialization was cyclic sports (kayaking) and acyclic sports (gymnastics, martial arts), and qualification – candidates for master of sports, masters of sports. Venous blood was taken in the morning on an empty stomach before training loads. Determination of total testosterone and cortisol concentration and assessment of vitamin D level by determination of its metabolite 25(OH)D (25-hydroxyvitamin D) in blood serum was performed by immunochemiluminescent method. Results. In male athletes with vitamin D deficiency, serum testosterone concentration and anabolic index were significantly lower (p = 0.0093 and p = 0.0015, respectively) compared to the same indices in the group of athletes with normal vitamin D content. Correlation analysis in male athletes revealed a positive correlation between serum 25(OH)D (25-hydroxyvitamin D) content and testosterone concentration (r = 0.36; p &lt; 0.05), as well as between 25(OH)D content and anabolic index (r = 0.42; p &lt; 0.05). The group of female athletes with vitamin D deficiency showed significantly lower serum testosterone concentration compared to athletes with normal vitamin D levels (p = 0.0112). No significant relationships were found between vitamin D levels and cortisol concentrations in both male and female athlete groups. Conclusion. The study results can be the evidence of modulation effect of vitamin D on testosterone levels in male athletes, indicating the importance of controlling and correcting vitamin D content in the dynamics of the training process.

Анализ нарушений функции гипофизарно-гонадной регуляции у пациентов с наличием новообразований яичек.

Introduction. The hypothalamic-pituitary-gonadal axis (HPG) is the most important part of the hormonal system that controls testicular function in men. It is known that testicular neoplasms (TN) can disrupt the regulation of HPG due to the occurrence of hormonal imbalance. However, changes in HPG in patients with TN have been little studied, especially before the start of treatment. Aim: to assess the degree of hormonal disorders affecting HPG in men with TN before treatment. Material and methods. The study included 49 patients with newly diagnosed TN. The concentration of total testosterone (T), free testosterone (cT), estradiol (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone binding globulin (SHBG) and prolactin (PRL), as well as tumor markers (β-HCG, AFP) were measured in all men; the body mass index (BMI), tumor size, bad habits and surgical history (treatment of cryp- torchidism, varicocele) were evaluated. Clinically significant T deficiency (DT) was defined as the level of total T &lt;8 nmol/l or the level of T in the range of 8-12.1 nmol/l, taking into account free T &lt;243 pmol/L. Results. There were statistically significant differences in hormone levels between patients with normal 30 (61,2%) and high 19 (38,8%) values of cancer markers (p&lt;0,05). A high concentration of β-hCG was associated with a decrease in the level of FSH and LH below normal values (p&lt;0,001) and an increase in the level of total T (p=0.019), cT (p=0,01) and E2 (p=0,003) compared with patients without hypertension. an increase in this cancer marker. Laboratory signs of DT were found in 15 (30,6%) patients, mostly with normal β-hCG values (p=0,025). However, a causal relationship was not established due to a small sample in this subgroup. The probability of developing DT in men with a history of cryptorchidism (22,4%) was 6,56 times higher (95% CI: 1,532 – 28,120; p=0,021). Correlation analysis revealed the relationship between LH (p=-0,351; p=0,014), FSH (p=-0,3; p=0,041), E2 (p=0,323; p=0,03) and tumor size. When analyzing hormone levels depending on age, smoking and BMI, no statistically significant differences were obtained (p&gt;0,05). Conclusion. Abnormalities in HPG were detected in 30% of patients with TN before treatment. One third of the men had laboratory signs of DT. Further studies involving more patients are required to develop practical recommendations.

Pre-diagnostic free androgen and estradiol levels influence heart failure risk in both women and men: A prospective cohort study in the UK Biobank.

Serum sex hormones have been linked to cardiovascular disease risk. However, their roles in the pathogenesis of heart failure (HF) in both men and women are unclear. We investigated the associations between free androgen, testosterone, and estradiol, and future risk of HF. This prospective cohort study evaluated UK Biobank participants free of prevalent cardiovascular disease and HF at baseline. Unitless free androgen, testosterone, and estradiol indices were generated using serum concentrations of total testosterone (nmol/L), estradiol (pmol/L), sex hormone binding globulin (SHBG, nmol/L), and albumin (g/L) in blood collected at enrolment. Multivariable Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of incident HF in relation to quartiles (Q) of free androgen (FAI), testosterone (FTI), estradiol (FEI) indices, and potential confounders. There were 180 712 men (including 5585 HF cases with FAIand 571 HF cases with FEI), and 177 324 women (including 2858 HF cases with FAIand 314 HF cases with FEI) with complete data. Increased FAIwas associated with decreased HF risk in both men (HRQ4 vs. Q1: 0.86, 95% CI 0.79-0.94, p-trendcontinuous < 0.0001) and post-menopausal women (HRQ4 vs. Q1: 0.83, 95% CI 0.73-0.95). Similar inverse associations were observed for FTIonly in men (HRQ4 vs. Q1: 0.91, 95% CI 0.83-0.98). Higher FEIwas significantly associated with decreased HF risk among men (HRQ4 vs. Q1: 0.76, 95% CI 0.59-0.98), but was positively associated among pre-menopausal women (HRQ4 vs. Q1: 2.16, 95% CI 1.11-4.18). Sex hormones potentially influence HF pathogenesis and may offer pathways for interventions.

Relationship between Serum Total Testosterone Concentration and Metabolic Syndrome in Premenopausal Obese Women.

Men with low testosterone levels are at an increased risk of developing metabolic syndrome, irrespective of age or obesity. However, the relationship between metabolic syndrome and testosterone levels in women remains unclear. We compared the total testosterone concentrations between premenopausal obese women with and without metabolic syndrome and identified the factors affecting these concentrations. A single-center retrospective analysis was conducted using the medical records of 580 premenopausal women with obesity. The diagnostic criteria for metabolic syndrome were established using the National Cholesterol Education Program Adult Treatment Panel III guidelines. The mean±standard deviation age, weight, and body mass index were 38.8±8.4 years, 78.0±11.8 kg, and 30.0±4.1 kg/m2, respectively. The mean total testosterone concentration was lower in the metabolic syndrome group than in the non-metabolic syndrome group (n=385 vs. n=195; 0.22±0.10 ng/mL vs. 0.24±0.11 ng/mL; P<0.001). In a model adjusted for age, body mass index, skeletal muscle mass, body fat mass, and body fat percentage, the odds ratio for metabolic syndrome with respect to the total testosterone level was 0.128 (P=0.028). Testosterone concentration was negatively correlated with age (r=-0.334), systolic blood pressure (r=-0.084), and triglyceride concentration (r=-0.093) but positively correlated with weight (r=0.144), body mass index (r=0.140), waist circumference (r=0.133), body fat mass (r=0.167), and body fat percentage (r=0.167). Stepwise regression analysis revealed that age (β=-0.004, P<0.001), body mass index (β=0.003, P=0.004), and high-density lipoprotein cholesterol concentration (β=0.001, P=0.019) were independently associated with total testosterone concentration (adjusted R2=12.6%). Metabolic syndrome and obesity may be independently associated with testosterone levels in premenopausal women with obesity.

Polygenic Scores for Adult Testosterone and SHBG Levels Are Associated With Reproductive Hormone Levels in Male Infants.

The Hypothalamic-Pituitary-Gonadal (HPG) axis's transient activity in infancy, i.e, minipuberty, is considered crucial for male reproductive function. Historically, minipuberty has been considered a passive response triggered by the withdrawal of placental steroids at birth. However, given its potential link to adult reproductive function, we hypothesize that minipuberty is a partially genetically regulated process, suggesting a link between the genetic architecture of reproductive hormone concentrations across lifespan. To investigate the association of UK Biobank Study-based Polygenic scores (PGS) of adult total Testosterone (T) and Sex hormone-binding globulin (SHBG) concentrations with trajectories of reproductive hormones concentrations in male infants. Prospective, longitudinal birth cohort (The COPENHAGEN Minipuberty Study, 2016-2018, ClinTrial: NCT02784184). Individual PGSs in male infants derived from published literature were calculated for total testosterone and SHBG. The associations with mean Standard Deviation Scores (SDS) of reproductive hormone concentrations in infancy were tested. Population-based. Healthy, male, term, singleton newborns were followed with repeated clinical examinations including blood sampling during a one-year follow-up (n=109). Circulating reproductive hormone concentrations. T-PGSadult were significant associated with mean T-SDSinfancy, mean SHBG-SDSinfancy and mean LH-SDSinfancy (p=0.02, <0.001 and 0.03, with r2=0.05, 0.21 and 0.04, respectively). SHBG-PGSadult was significantly associated with mean SHBG-SDSinfancy (p<0.001, r2=0.18). T-PGSadult explained 5% and 21% of the phenotypic variation in infancy of mean T-SDSinfancy and SHBG-SDSinfancy, respectively. Our findings suggest that the genetic architecture underlying total testosterone and SHBG in adults also associates with hormone concentrations and their trajectories during infancy.

Clinical significance of endocrine disorders in the development of early vascular aging in males with abdominal obesity and concomitant arterial hypertension: An observational cohort study

Background. Visceral obesity is a risk factor in the development of metabolic and endocrine disorders leading to arterial hypertension and cardiovascular complications. Their early predictors include increased vascular stiffness and early vascular aging. The current literature lacks studies into the effects of changes in testosterone, cortisol, and aldosterone levels in serum on vascular stiffness and the development of early vascular aging in patients with visceral obesity. Objective. To determine the relationship between hypercortisolemia, hyperaldosteronemia, and hypotestosteronemia and vascular stiffness and the presence of early vascular aging in male patients with visceral obesity. Methods. An observational cohort study of 78 males aged 35–45 years (mean age 38.1 ± 6.5 years) diagnosed with abdominal obesity and grade 1 arterial hypertension was conducted. The mean waist circumference ranged 105.5 ± 6.9 cm; systolic and diastolic blood pressure ranged 152.5 ± 5.0 and 92.5 ± 5.0 mm Hg, respectively. The vascular age of the studied patients (n = 78) comprised 44.1 ± 6.2 years, which was statistically higher than their passport age (р &lt; 0.001). The studied patients were divided into subgroups according to both total testosterone (&lt; 12.1 nmol/l in subgroup 1A (n = 49) and ≥ 12.1 nmol/L in subgroup 1B (n = 29)) and cortisol in the evening saliva portion (&gt; 4.5 nmol/L in subgroup 2A (n = 24) and ≤ 4.5 nmol/L in subgroup 2B (n = 24)). All the patients completed the study. To assess the hormonal status, the total testosterone sex steroid-binding globulin (SSBP) and insulin in morning serum samples were investigated. Insulin resistance was assessed based on the NOMA-IR index. The concentration of total testosterone was determined by enhanced chemiluminescence (Ortho-Clinical Diagnostics, J&amp;J); the SSBP and insulin levels were determined by delayed fluorescence. Aldosterone content was determined by radioimmunoassay; free cortisol and testosterone were measured by luminescent LIA. Free and bioavailable testosterone concentrations in serum were calculated using an online calculator (issam.ch/freetesto.htm). The cardio-ankle vascular index (CAVI) was determined using a VaSera VS-15000N device, which automatically calculated the vascular age. Statistical analysis was performed using the Statistica 10.0 Windows package (StatSoft, Inc., USA). Results. The vascular age of patients with hypogonadism was statistically significantly ( р &lt; 0.001) higher than their passport age and the vascular age in males without hypogonadism. The CAVI and vascular age were also statistically significantly higher in males with functional hypercorticism (р &lt; 0.001) compared with a subgroup of patients without hypercorticism. The vascular age and CAVI increased with an increase in the salivary cortisol concentration 2200 (r = 0.5; р &lt; 0.05) and decreased with an increase in the salivary cortisol level 900 (r = –0.5; р &lt; 0.05). These parameters decreased with an increase in serum aldosterone obtained in the morning (r = –0.4; p &lt; 0.05) and increased with an increase in serum aldosterone in the evening (r = 0.4; p &lt; 0.05). In 23% (n = 18), an inversion of the daily rhythm of cortisol production was observed; in these patients, salivary cortisol levels of 2200 exceeded salivary cortisol levels of 900. The vascular age of patients with the inversion of cortisol production (49.4 ± 4.4 years) was statistically significantly ( р &lt; 0.001) different from that of patients with normal changes in salivary cortisol concentrations (41.9 ± 4.9 years). CAVI was also higher (р &lt; 0.001) in males with inverted fluctuations in salivary cortisol levels (7.51 ± 0.62) compared to those with normal diurnal rhythm (6.45 ± 0.69). The results of aldosterone evaluation revealed that 17% of the patients (n = 13) had higher aldosterone levels in the evening serum portion compared to the morning serum portion. In these patients, the vascular age (45.8 ± 5.1 years) was higher ( р &lt; 0.001) than that in males with normal physiologic changes in aldosterone levels (41.6 ± 5.7 years). A similar pattern was observed when comparing vascular stiffness indices. Thus, the CAVI in men with inverted changes in aldosterone concentration (6.9 ± 0.8) was significantly higher ( р &lt; 0.001), compared to that in men with physiological changes in blood aldosterone levels (6.4 ± 0.8). Conclusion. Endocrinologic disorders in male patients with visceral obesity and concomitant arterial hypertension (functional hypogonadism, functional hypercorticism, inverted daily rhythms of cortisol and aldosterone production) contribute to the development of early vascular aging by increasing vascular stiffness.

Analysis of the association between testosterone and cardiovascular disease potential risk factor apolipoprotein B in adult males without cancer: national health and nutrition examination survey 2011-2016.

Over the years, there has been extensive exploration of the association between testosterone and lipid profiles, yet the precise mechanisms underlying their interaction remain incompletely elucidated. Similarly, there is a dearth of research on the correlation between serum apolipoprotein B (apoB) and serum total testosterone (TT), particularly within specific populations. We conducted a cross-sectional study to assess the relationship between serum TT concentration and serum apoB concentration. Using the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2016, we employed weighted generalized linear models, weighted univariate, weighted multivariate analysis, and smooth curve fitting to assist in exploring the relationship between serum TT and apoB. Serum apoB concentration served as the independent variable, and serum TT concentration as the dependent variable. ApoB was divided into four quartiles-Q1 (<0.7g/L, N=691), Q2 (≥0.7g/L to <0.9g/L, N=710), Q3 (≥0.9g/L to <1.1g/L, N=696), and Q4 (≥1.1g/L, N=708)-thereby further solidifying the stable association between the two. Additionally, the application of smooth curve fitting will contribute to a more detailed elucidation of the specific relationship between serum TT concentration and serum apoB concentration under different factors (Drinking, Smoke, Diabetes, Hypertension, and High cholesterol level.). The results indicate a negative correlation between serum TT concentration and apoB concentration (β=-113.4; 95% CI: -146.6, -80.2; P<0.001). After adjusting for confounding variables, the negative correlation between apoB concentration and TT concentration remains significant (β=-61.0; 95% CI: -116.7, -5.2; P=0.040). When apoB concentration was converted from a continuous variable to a categorical variable (quartiles: Q1<0.7g/L; Q2:≥0.7g/L to<0.9g/L; Q3:≥0.9g/L to <1.1g/L; Q4: ≥1.1g/L), TT level of participants in the highest quartile (≥1.1g/L) was -47.2 pg/mL (95% CI: -91.2, -3.3; P=0.045) lower than that in the lowest quartile (<0.7g/L). The smooth curve fitting diagram revealed differences in the relationship between TT concentration and apoB among individuals with different cardiovascular disease (CVD) risk factors. This study elucidates a robust inverse correlation between serum TT concentration and apoB concentration, maintaining statistical significance even upon adjustment for confounding factors. These findings present a promising avenue for addressing the prevention and treatment of low testosterone and CVD.

Sex-steroid hormones and risk of postmenopausal estrogen receptor-positive breast cancer: a case-cohort analysis.

Sex-steroid hormones are associated with postmenopausal breast cancer but potential confounding from other biological pathways is rarely considered. We estimated risk ratios for sex-steroid hormone biomarkers in relation to postmenopausal estrogen receptor (ER)-positive breast cancer, while accounting for biomarkers from insulin/insulin-like growth factor-signaling and inflammatory pathways. This analysis included 1208 women from a case-cohort study of postmenopausal breast cancer within the Melbourne Collaborative Cohort Study. Weighted Poisson regression with a robust variance estimator was used to estimate risk ratios (RRs) and 95% confidence intervals (CIs) of postmenopausal ER-positive breast cancer, per doubling plasma concentration of progesterone, estrogens, androgens, and sex-hormone binding globulin (SHBG). Analyses included sociodemographic and lifestyle confounders, and other biomarkers identified as potential confounders. Increased risks of postmenopausal ER-positive breast cancer were observed per doubling plasma concentration of progesterone (RR: 1.22, 95% CI 1.03 to 1.44), androstenedione (RR 1.20, 95% CI 0.99 to 1.45), dehydroepiandrosterone (RR: 1.15, 95% CI 1.00 to 1.34), total testosterone (RR: 1.11, 95% CI 0.96 to 1.29), free testosterone (RR: 1.12, 95% CI 0.98 to 1.28), estrone (RR 1.21, 95% CI 0.99 to 1.48), total estradiol (RR 1.19, 95% CI 1.02 to 1.39) and free estradiol (RR 1.22, 95% CI 1.05 to 1.41). A possible decreased risk was observed for SHBG (RR 0.83, 95% CI 0.66 to 1.05). Progesterone, estrogens and androgens likely increase postmenopausal ER-positive breast cancer risk, whereas SHBG may decrease risk. These findings strengthen the causal evidence surrounding the sex-hormone-driven nature of postmenopausal breast cancer.

Erectile function in men with COVID-19 six months after recovery

Background. Based on the results of epidemiological studies, it was found that coronavirus disease 2019 (COVID-19) affects men more often than women. Among COVID-19 complications, erectile dysfunction is considered a marker of endothelial dysfunction and one of the main factors for the development of cardiovascular diseases. Lower total and free testosterone levels are predictors of adverse prognosis in males with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Testosterone deficiency syndrome is considered an independent risk factor of cardiometabolic disorders. The purpose of the study is to investigate the state of erectile function in men who suffered from COVID-19 six months after recovery. Materials and methods. Seventy-two men suffering from COVID-19 and being treated in an infectious disease hospital were examined 6.90 ± 0.29 months after recovery. Their average age was 45.23 ± 3.01 years. The control group included 18 conditionally healthy men aged 43.18 ± 2.90 years. The state of erectile function was assessed using the International Index of Erectile Function (IIEF). The concentration of testosterone was determined by the enzyme-linked immunosorbent assay with DRG (Germany) and DiaMetra (Italy) kits. All measurements were performed on the Stat Fax 3200 analyzer. Statistical comparison of the obtained results between groups was performed according to the Student’s test. A value of p &lt; 0.05 was considered to be signifi­cant. Results. In addition to erectile dysfunction, as evidenced by a reduced corresponding integrative indicator “erectile function” of IIEF-15 in men with COVID-19, a decrease in sexual desire was found, as well as a deterioration of sensations in the form of a decrease in ejaculation frequency and orgasmic sensations during sex contacts. The average serum level of total testosterone was 10.9 nmol/l and was significantly reduced compared to that in the control group. Analysis of individual indicators showed that testosterone level was decreased in 10 patients and was within the normal range in 13 men with COVID-19. The average serum concentration of total testosterone in the examined men after the disease was 10.73 ± 1.07 nmol/l and was significantly reduced compared to that of the control group. Conclusions. There was an erectile dysfunction in men who suffered COVID-19, it was confirmed by a probable decrease in IIEF-15 score and integrative indicators of erectile function. A significant decrease in the blood concentration of total testosterone was detected in the examined men, which may be one of the causes of erectile dysfunction. Large-scale prospective, randomized, controlled trials in patients infected with SARS-CoV-2 are needed to provide an understanding of the molecular mechanisms that cause erectile dysfunction.

The impact of serum testosterone level to reflect age-related multi-organ functions.

The aim of this study is to examine the correlation between aging, serum total testosterone and biomarkers of multiple organ functions in men. The participants consisted of 12,547 outpatients, whose serum testosterone level was measured. A multiple regression analysis was conducted to determine whether biomarkers including hemoglobin (Hb), hematocrit (Hct), luteinizing hormone (LH), follicle stimulating hormone (FSH), alkaline phosphatase (ALP), albumin (ALB), creatinine (Cre), aspartate aminotransferase (AST), alanine aminotransferase (ALT), glucose (Glu), C-reactive protein (CRP), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) values were associated with serum total testosterone concentration. Significant correlations (p < 0.05) were found between total testosterone and Hb, Hct, LH, FSH, ALP, ALB, TG, HDL-C, AST, ALT, Glu, and CRP. In addition, significant correlations (p < 0.05) were found between Hb, Hct, LH, FSH, ALP, ALB, TG and HDL-C associated with [age × testosterone]. This large-scale study provided new insights into correlations between serum testosterone and biomarkers associated with age-related diseases, suggesting that testosterone is especially important for maintaining homeostasis in aging males. Thus, hypogonadism in elderly patients may be associated with multiple organ dysfunctions.

The association between testosterone deficiency and nocturia: Insights from The National Health and Nutrition Examination Survey data set.

To examine the association between testosterone deficiency (TD) and nocturia in males, with specific attention to age and cardiovascular disease (CVD) comorbidity. This cross-sectional study utilized the National Health and Nutrition Examination Survey (NHANES) data from 2011 to 2016, assessing 6137 adult male participants. TD was defined by a serum total testosterone (TT) concentration less than 300 ng/dL. Nocturia was determined based on participants'responses to a standard NHANES question regarding the frequency of urination during the night. The study observed a significant association between TD and nocturia (adjusted odds ratio [95% confidence interval] = 1.211 [1.060-1.384], p = 0.005). Moreover, a U-shape pattern was noted in the relationship between serum TT concentration and the relative odds of nocturia. Subgroup analysis revealed a robust correlation between TD and nocturia in those over 60 years old, and those with hypertension, dyslipidemia, and CVDs. Our findings suggest a positive correlation between TD and nocturia, particularly among elderly individuals with CVD. This association underscores the potential therapeutic significance of addressing TD in the management of nocturia. Furthermore, longitudinal studies are needed to establish a causal relationship between TD and nocturia.

Influence of oral hormonal contraception on the concentration of anti-Müllerian and reproductive hormones in patients with polycystic ovary syndrome

Aim: To investigate the effects of three-month use of oral hormonal contraception (OHC) on hormonal status and ovarian reserve indicator (anti-Müllerian hormone, AMH) in patients with polycystic ovary syndrome (PCOS).Methods: 19 patients with diagnosed PCOS and clinical and laboratory signs of hyperandrogenism without additional comorbidities and co-medication were included in the study. All participants received therapy with the same oral hormonal contraceptive (fixed combination of 0.035 mg ethinyl estradiol and 2 mg cyproterone acetate). The main outcomes were the concentrations of reproductive hormones measured before starting therapy and in the first cycle following therapy. Hormone concentrations were analysed using the immunochemical electrochemiluminescence (ECLIA) method.Results: Initial concentrations of total and free testosterone and AMH were elevated, while initial concentrations of other reproductive hormones were within reference values. By applying the therapy, the concentrations of AMH, luteinizing hormone (LH) and estradiol decreased by more than 20% and those of free testosterone by 85%. The concentration of sex hormone binding globulin (SHBG) increased by 44%.Conclusions: Three months of oral hormonal contraception with 35 μg ethinyl estradiol and 2 mg cyproterone acetate reduced elevated concentrations of AMH and free testosterone in PCOS patients. The decrease in serum AMH concentration indicates a temporary interruption of folliculogenesis as well as the selection of follicles from preantral to antral, and the decrease in androgens has a positive effect on the clinical condition and symptoms of patients with PCOS.

EMAS position statement: Testosterone replacement therapy in older men.

Late-onset hypogonadism is the clinical entity characterised by low testosterone concentrations associated with clinical symptoms in the absence of organic disease in ageing men. It has been associated with metabolic syndrome, reduced bone mineral density, and increased cardiovascular morbidity and mortality risk. Although testosterone replacement therapy (TRT) reverses most of these conditions in young hypogonadal men, the risk/benefit ratio of TRT in older men is debatable. To update the 2015 EMAS statement on TRT in older men with new research on late-onset hypogonadism and TRT. Literature review and consensus of expert opinion. TRT should be offered only to symptomatic older men with confirmed low testosterone concentrations after explaining the uncertainties regarding the long-term safety of this treatment. TRT may be offered to men with severe hypogonadism and erectile dysfunction to improve sexual desire, erectile, and orgasmic function. It should also be considered in hypogonadal men with severe insulin resistance or pre-diabetes mellitus. TRT may also be considered, in combination with proven treatment strategies, for osteoporosis, or for selected patients with persistent mild depressive symptoms and/or low self-perceived quality of life, combined with standard medical care for each condition. TRT is contraindicated in hypogonadal men actively seeking fertility treatment. Due to a lack of data, TRT should not be routinely used in older men to improve exercise capacity/physical function, improve cognitive function, or prevent cognitive decline. TRT must be avoided in older, frail men with known breast cancer or untreated prostate cancer and all men who have had myocardial infarction or stroke within the last four months, and those with severe or decompensated heart failure. The quality of evidence regarding patients with previous prostate cancer or cardiovascular disease is too low to draw definitive conclusions. Any limits on duration of use are arbitrary, and treatment should continue for as long as the man feels the benefits outweigh the risks for him, and decisions must be made on an individual basis. Withdrawal should be considered when hypogonadism is reversed after the resolution of underlying disorder. Short-acting transdermal preparations should be preferred for TRT initiation in older men, but injectable forms may be considered subsequently. Older men on TRT should be monitored at 3, 6, and 12months after initiation and at least yearly thereafter, or earlier and more frequently if indicated. Evaluation should include assessment of the clinical response, and measurement of total testosterone, haematocrit, and prostate-specific antigen (PSA) concentrations. Bone density and/or quality should also be assessed. Obese and overweight patients should be encouraged to undergo lifestyle modifications, including exercise and weight loss, to increase endogenous testosterone.

Myo-inositol versus metformin effects on clinical features, endocrine and metabolic profiles in infertile women with polycystic ovary syndrome: A randomized controlled trial

Objective: To compare the effectiveness of inositol and metformin on the clinical characteristics, and endocrine and metabolic profiles of infertile polycystic ovarian syndrome (PCOS) women from Vietnam. Methods: From June 2018 to August 2022, a randomized trial was undertaken at the Hue Center for Endocrinology and Reproduction on infertile women aged 18 to 40 years with polycystic ovarian syndrome. The clinical, endocrine, and metabolic features of these individuals were assessed before and after 3 months of treatment with 2 g of inositol or 1700 mg of metformin per day. Natural pregnancy rates, adverse effects, and tolerance of inositol were recorded. Results: The study included 171 infertile PCOS women who were eligible to participate and took part in the baseline assessment, of whom 132 women participated in data analysis after 3 months. After metformin treatment, 42.1% of women with oligomenorrhea experienced regular menstruation. Metformin significantly lowered body mass index (BMI), waist circumference and testosterone levels, but had no effect on other clinical characteristics, endocrine profiles, or metabolic profiles. 29.2% Of women reported experiencing side effects. 21% Of them attained pregnancy, which resulted in 17.1% of live births. In the inositol group, the rate of regular cycle increased by 18.2% and the total testosterone concentration significantly decreased. In overweight/obese women with PCOS, inositol significantly decreased weight, BMI, waist and hip circumferences (P&lt;0.05). 100% Of women tolerated inositol and continued treatment. 18.9% Of them became pregnant, leading to 17% of live births. Conclusions: Metformin and inositol can improve weight and waist circumference in overweight/obese infertile women with PCOS. Metformin is associated with a higher rate of regular menstruation, whereas inositol is associated with a lower rate of adverse effects. The spontaneous conception, clinical pregnancy, and live birth rates between two groups are comparable.