Higher Testosterone Research Articles

Polycystic ovary syndrome in a patient with type B insulin resistance syndrome can improve with glucocorticoid treatment: a case report and literature review.

Polycystic ovary syndrome (PCOS) frequently exhibits hyperinsulinemia due to insulin resistance, but there are many unknown aspects of this disease. This report presents the case of a 31-year-old woman with PCOS and type B insulin resistance syndrome (TBIRS). The patient had repeated hyperglycemia and hypoglycemia, and prominent hyperinsulinemia. The insulin receptor antibody was positive, leading to a diagnosis of TBIRS. She also had amenorrhea during the previous 3 months, high blood testosterone levels, and enlarged polycystic ovaries, leading to a diagnosis of PCOS at the same time. The patient was treated with glucocorticoid for TBIRS. The insulin receptor antibody eliminated at 8 weeks after initiation of glucocorticoid treatment, and the blood glucose levels and hyperinsulinemia improved at 9 weeks. Then, the enlargement of both ovaries diminished at 32 weeks, and the menstruation had normalized since 36 weeks. The blood testosterone level normalized at 41 weeks. To the best of our knowledge, this is the first report to demonstrate that enlarged polycystic ovaries and a menstrual disorder in TBIRS improved after glucocorticoid treatment. It is possible that elimination of insulin receptor antibodies by glucocorticoid treatment attenuated insulin resistance and subsequently improved PCOS in TBIRS.

Predictive Value of Preoperative Prostate Health Index and Serum Testosterone Testing for Biochemical Recurrence after Radical Prostatectomy for Non-Metastatic Prostate Cancer.

To analyse the predictive value of prostate health index (PHI) combined with serum testosterone after radical prostatectomy (RP) for prostate cancer (PCa). A total of 132 PCa patients who received RP treatment from January 2016 to December 2019 were selected, retrospectively. And then these patients were divided into biochemical recurrence (BCR) group (n = 51) and non-biochemical recurrence (non-BCR) group (n = 81) based on whether BCR was present after RP. Basic data of PCa patients were collected, and preoperative prostate health index (PHI) and serum testosterone levels were measured in both groups. Logistic regression analysis was used to analyse the influencing factors of BCR after RP. The predictive value of PHI and serum testosterone on BCR after RP was analysed using the receiver operating characteristic (ROC) curve. The Kaplan-Meier method was used to plot survival curves, and log rank test was used to analyse the differences between survival curves. The BCR rate of patients in this study was 38.64% (51/132). Single-factor analysis showed that BCR after RP in PCa patients was associated with prostate-specific antigen (PSA), Gleason score, pathological stage, postoperative adjuvant therapy, testosterone and PHI (p < 0.05). Logistics regression analysis showed that PSA >20 ng/mL, Gleason score (8 scores), pathological stage pT3, increased PHI and increased testosterone were independent risk factors for BCR after RP. ROC curve analysis showed that the area under curve (AUC) of PHI and serum testosterone predicting BCR after RP alone and in combination were 0.769, 0.725 and 0.906, respectively. Kaplan-Meier survival analysis showed that preoperative high PHI and low testosterone are negatively correlated with recurrence-free survival rate. Preoperative PHI and testosterone can serve as simple prognostic indicators for postoperative BCR in PCa patients undergoing RP. PCa patients with higher PHI levels and lower testosterone levels may be more prone to developing BCR. The combination of PHI and testosterone has a higher value in predicting BCR after RP.

The close proximity between the human rectum and prostate: a functional-anatomic arrangement favoring prostate health

Prostate health is related to the frequency of ejaculation and prostate drainage. Frequent, repetitive ejaculations theoretically may pose a prostate cancer risk due to ensuing high testosterone levels and loss of zinc. In line with this, the proximity of the human rectum and prostate is of diagnostic and therapeutic importance. We provide evidence to support the view that the proximity of the rectum and prostate in men enables lower bowel distention to compress the prostate’s lateral side to facilitate drainage, which might lower cancer risk. This drainage mechanism is likely on-going and gradual, compared to rapid drainage following ejaculation. The physiological context suggests that these mechanisms of prostate drainage are complementary. Dietary content containing polyphenol- and fiber-rich meals, along with voluminous stool formation and increased gastrointestinal transit may all help improve prostate drainage. This may be important in voluntary abstinent men or other categories of sexually limited men. Recognizing that the anatomic relationship between the rectal area and prostate may facilitate prostate drainage, because of diet and gastro-intestinal activity, could be important to prostate health maintenance.

Preoperative Predictors for the Presence of Motile Spermatozoa in the Epididymis and Patency of Anastomosis during Microsurgical Vasoepididymal Anastomosis in Patients with Obstructive Azoospermia.

Following microsurgical vaso-epididymal anastomosis (VEA), anastomotic patency with sperm returning to the ejaculate is not always present and may even be delayed. The presence of motile spermatozoa is highly suggestive of future patency following surgery. We prospectively analyse the factors that could predict motile spermatozoa at the epididymis intraoperatively and predictors of patency in patients with obstructive azoospermia (OA) undergoing microsurgical VEA. Department of Urology of a tertiary care centre in Northern India. It is a prospective observational study. Over a 2-year period (July 2019 to June 2021), 26 patients with idiopathic OA were enrolled in the study. Twenty patients underwent microsurgical VEA. Patients were divided into two groups based on the presence/absence of intraoperative motile spermatozoa. Analysis of preoperative and intraoperative factors was done using the Mann-Whitney U-test, Chi-squared test and Fischer exact test. Out of 20 patients, 5 (group 2) had intraoperative motile spermatozoa in the epididymal fluid and 15 (group 1) had nonmotile spermatozoa. Low luteinising hormone (LH) levels (P = 0.01) and high testosterone levels (P = 0.05) were the predictive of presence of motile spermatozoa in epididymal fluid. Mean follow-up was 9 months (6-18 months). Predictors of higher patency were grade 2 epididymis (firm, turgid and tense) (P = 0.003), low LH levels (P = 0.03), low sertoli cell index (P = 0.006), high sperm-Sertoli index (P = 0.002) and better surgeon satisfaction (P = 0.01). Low LH levels and high testosterone levels may be predictive of the presence of motile spermatozoa in epididymal fluid. Firm, turgid and tense epididymis, low Sertoli cell index, high sperm-Sertoli index and surgeon satisfaction suggest a greater chance of success after VEA for idiopathic azoospermia.

Effects of tumor necrosis factor-α on glucose uptake in human granulosa cells under high androgen conditions.

Hyperandrogenism is a key pathological characteristic of polycystic ovary syndrome (PCOS). Tumor necrosis factor α (TNF-α) is both an adipokine and a chronic inflammatory factor, which has been proven to be involved in the pathologic process of PCOS. This study aimed to determine how TNF-α affects glucose uptake in human granulosa cells in the presence of high testosterone concentration. KGN cell line was treated with testosterone and TNF-α alone or co-culture combination for 24 hr, or starved for 24 hr. Quantitative real-time polymerase chain reaction (qPCR) and western blot were performed to measure glucose transporter type 4 (GLUT4) message RNA (mRNA) and protein expression in treated KGN cells. Glucose uptake and GLUT4 expression were detected by immunofluorescence (IF). Furthermore, western blot was performed to measure the contents in the nuclear factor kappa-B (NF-κB) pathway. Meantime, upon addition of TNF-α receptor II (TNFRII) inhibitor or Inhibitor of nuclear factor kappa-B kinase subunit beta (IKKβ) antagonist to block the TNFRII-IKKβ-NF-κB signaling pathway, the glucose uptake in KGN cells and GLUT4 translocation to cytomembrane were detected by IF, and related proteins in TNFRII-IKKβ-NF-κB were detected by western blot. The glucose uptake in Testosterone + TNF-α group was lowered significantly, and Total GLUT4 mRNA and proteins were reduced significantly. GLUT4 translocation to cytomembrane was tarnished visibly; concurrently, the phosphorylated proteins in the TNFRII-IKKβ-NF-κB signaling pathway were enhanced significantly. Furthermore, upon addition of TNFRII inhibitor or IKKβ inhibitor to block the TNFRII-IKKβ-NF-κB signaling pathway, the glucose uptake of treated granulosa cells was improved. TNFRII and IKKβ antagonists may improve glucose uptake in granulosa cells induced by TNF-α by blocking the TNFRII-IKKβ-NF-κB signaling pathway under high androgen conditions.

Analysis of high risk factors for chronic atrophic gastritis.

Screening for chronic atrophic gastritis (CAG) is crucial for the prevention and early detection of gastric cancer. Endoscopy is the main method of CAG diagnosis, with high training requirements and limited accuracy, making it difficult to popularize. The study attempts to improve the positive rate and accuracy of CAG screening through non-invasive testing. A total of 2564 patients who underwent gastroscopy were included in this study. The results of gastroscopic evaluation, histological biopsy results (including H. pylori biopsy), urea breath test (UBT) results, serum pepsinogen, and testosterone were statistically analyzed. We found significant differences in the diagnosis of CAG between endoscopy and histological biopsy. Pepsinogen II and pepsinogen I/II ratio were more useful for the diagnosis of CAG compared with pepsinogen I. The risk of CAG was increased when pepsinogen II exceeded 11.05 μg/L, and the pepsinogen I/II ratio was less than 3.75. CAG positivity was higher in patients with positive H. pylori infection on UBT screening. In addition, higher levels of testosterone, SHBG and HSD17B2, and lower level of GNRH1 were found in CAG mucosa. Patients with high serum testosterone had a higher risk of CAG. CAG screening should be combined with endoscopic evaluation, biopsy, and other non-invasive tests. Non-invasive tests include the combination of serum pepsinogen II protein and pepsinogen I/II ratio and high level of serum testosterone. UBT combined with serum pepsinogen testing may improve the positive rate of CAG and reduce gastric mucosal damage from multiple biopsies.

Otizm Spektrum Bozukluğunda El 2D:4D Parmak Oranı ve Yüz Simetrisi

There are many theories about the etiology of autism, and the most striking is the theory of testosterone exposure in the womb. In this study, it was investigated whether the second and fourth finger and face measurements were symmetrical in boys with autism spectrum disorder (ASD) and children with normal development. For the study, 30 boys diagnosed with ASD were compared with 30 normally developing boys. Photographs of each individual's face were taken digitally and measurements were made at eight different reference lengths on the face halves. Half-face measurements in children diagnosed with autism were compared among themselves and with the control group with normal healthy development. In addition, the symmetry level was analyzed by photographing the right and left hands and measuring the lengths of the second (2D) and fourth (4D) fingers for symmetry detection. As a result of the face and finger analysis, it was determined that the faces of the individuals with ASD were more symmetrical than the individuals with normal development, and the 2D-4B finger lengths were closer to each other than the children with normal development. In addition, it was determined that as the severity of autism increased, the tendency for symmetry increased in both the face and fingers. The tendency to symmetry detected in the face and hand is compatible with the high testosterone level exposed in the womb of individuals with autism and, accordingly, the excessive male brain theory.

Rare virilizing tumor: ovarian steroid cell tumor, not otherwise specified: a case report

BackgroundOvarian steroid cell tumors, not otherwise specified is a rare sex cord-stromal tumor. Almost 60% of all steroid cell tumors are categorized as not otherwise specified and represent less than 0.1% of all ovarian neoplasm. Some of them are endocrinologically active, producing virilization signs in young women. The recommended treatment is primarily surgical.Case presentationWe present the case of a 20-year-old Mexican woman with secondary amenorrhea and virilization signs. She was treated with combined oral contraceptives from 13 years old, due to a misdiagnosis of polycystic ovarian syndrome. However, 4 months after stopping medication, amenorrhea and virilization signs worsened. Biochemically, she had high serum total testosterone and free testosterone levels, and a pelvic and transvaginal ultrasound followed by a pelvic tomography scan demonstrated a right adnexal tumor. She underwent right salpingo-oophorectomy and the histopathological and immunochemistry exams confirmed the diagnosis. The patient was followed for a year after surgery and until then, her menses were regular and she had no recurrence of virilization signs. ConclusionThe purpose of this case report is to alert physicians to rule out ovarian steroid cell tumor, not otherwise specified diagnosis in young women with increased testosterone after discarding common causes such as polycystic ovarian syndrome. A multidisciplinary team including a gynecologist, endocrinologist, radiologist, and pathologist should be involved for correct diagnosis at the proper time.

Relationship between thyroid hormone and sex hormone levels and non-suicidal self-injury in male adolescents with depression.

Non-suicidal self-injury (NSSI) is the intentional and repeated direct injury to one's bodily tissues or organs without the intent to die, which is not socially sanctioned and does not result in death. This study will be the first to explore the relationship between NSSI behavior and thyroid hormone and sex hormone levels in male adolescents with depression. Among the inpatients in the children's ward of Shandong Mental Health Center, eighty male patients with first-episode depressive disorder were randomly selected. Forty male adolescent depressed patients with NSSI behaviors were set as the NSSI group, and forty male adolescent depressed patients without NSSI behaviors were set as the No-NSSI group. Their thyroid hormones (free triiodothyronine, free thyroxine, and thyroid stimulating hormone) and sex hormones (estradiol, progesterone, and testosterone) were measured, and the severity of self-injury in the NSSI group was assessed using the Adolescent Self-Injury Questionnaire. The NSSI group was tested again after 6 weeks of sertraline treatment for biological indicators and assessed by the Self-Injury Questionnaire to compare the hormonal differences between the NSSI group and the No-NSSI group and compare the differences of each index before and after treatment in the NSSI group. T3/T4 (p = 0.001) and FT3 (p = 0.023), TSH levels (p < 0.001) were lower in the NSSI group than in the No-NSSI group before treatment, and FT4 (p = 0.036) and T (p < 0.001) levels were higher than in the No-NSSI group. T3/T4 levels were higher in the NSSI group after treatment (p < 0.001). FT4 (p < 0.001) and T (p = 0.001) levels and self-injury questionnaire scores (p < 0.001) decreased after treatment in the NSSI group. In the NSSI group at baseline, FT4 levels were negatively correlated with self-injury questionnaire scores (r = -0.459, p = 0.003) and testosterone levels were positively correlated with self-injury questionnaire scores (r = 0.383, p = 0.015), and in the NSSI group after treatment, FT4 difference was negatively correlated with self-injury questionnaire score reduction rate (r = -0.037, p = 0.019), and testosterone difference was positively correlated with self-injury questionnaire score reduction rate (r = 0.424, p = 0.006). Logistic regression analysis showed that low TSH and high testosterone levels were independent risk factors for the development of non-suicidal self-harming behaviors in male adolescent depressed patients. Changes in thyroid hormone and sex hormone levels may be associated with non-suicidal self-injurious behavior in male adolescent depressed patients.

Study of Acute Coronary Syndrome in Premenopausal Women in Correlation with Sex Hormones

Objectives: Higher testosterone and lower Estrogen levels are associated with cardiovascular disease in women. However, studies on endogenous sex hormones and acute coronary syndrome (ACS) in pre-menopausal women are sparse. Material and Methods: We studied 50 pre-menopausal women presenting with ACS and age-matched controls who consented to the study with Testosterone, Estradiol, and Sex hormone-binding globulin (SHBG) levels at baseline. They were clinically followed up for 6 months duration. Results: The mean age was 37.42 ± 5.7 years. 48% patients were obese. The mean body mass index was 27.53 ± 5.41 kg/m2. Hypertension followed by Diabetes was the most common risk factor. 14% had family history of coronary artery disease (CAD). 24% had atypical chest pain at presentation. Anterior wall ST elevation myocardial infarction was the most common presentation. Single-vessel disease was seen in 38%; 24% had Non-Obstructive CAD. Ratios of Bioavailable Testosterone: Estradiol, Estradiol: Low-density Lipoprotein (LDL), Estradiol: High-density Lipoprotein, SHBG: LDL, and SHBG: HbA1c were analyzed in cases and controls and were not found to be significantly associated. Conclusion: Endogenous sex hormones were not found to be significantly associated with ACS in premenopausal women.

The effects of melatonin and metformin on histological characteristics of the ovary and uterus in letrozole-induced polycystic ovarian syndrome mice: A stereological study.

Polycystic ovarian syndrome (PCOS) with anovulation, hyperandrogenism, ovarian and uterine histological changes, menstrual irregularities, etc. signs is an infertility type. It seems that melatonin and metformin can improve these abnormalities. To evaluate the effects of melatonin and metformin on the ovary and uterus in PCOS-induced mice using stereological methods. Seventy-two adult female BALB/c mice (8-wk-old, 20-30 gr) were randomly divided into control (distilled water, gavage), PCOS (90 µg/kg letrozole, gavage), PCOS+metformin (500 mg/kg, gavage), PCOS+melatonin (10 mg/kg, intraperitoneal injection), and PCOS+melatonin control (0.5% ethanol saline) groups (n = 12/each). Another PCOS group was kept for a month to ensure that PCOS features remained. Finally, a stereological evaluation of the uterus and ovary was carried out, and vaginal cytology and serum testosterone levels were assessed. PCOS mice treated with metformin and melatonin had lower testosterone levels, body weight, and more regular estrus cycles than the PCOS group (p 0.001). A significant decrease in conglomerate and daughter gland numbers, and primary, secondary, atretic, and cystic follicles numbers with a significant increase in primordial and Graafian follicles, and corpus luteum numbers (p 0.001) was seen in these treated mice. Also, endometrial vessels' volume and length significantly increased, but ovarian, endometrial, myometrial, stromal, and glands volume, and endometrial and myometrial thickness dramatically declined (p 0.001). It appears that metformin and melatonin could restore the PCOS phenotype including estrus cycle irregularity, high testosterone level, and ovarian and uterine micromorphology to the control levels. However, the 2 treatments had similar effects on the examined parameters.

Lungworm parasite intensity and its association with the endocrine and immune systems and energy reserves in male cane toads

Host-parasite interactions can be harmful or harmless depending on the fitness and stress levels of the organisms. Interactions between the endocrine system, the immune system and energy expenditure are critical in the maintenance of homeostasis during stressful periods in vertebrates. We examined whether lungworm loads (Rhabdias spp.) of male cane toad (Rhinella marina) sampled during the wet season from three different populations, are associated with hormone levels, immune competence, and metabolic status. We found evidence of direct and strong associations between parasite burdens and variables related to hormonal levels, metabolic status and immune competence. We also found that interrelationships among independent variables can change the strength of the association with lungworm loads. These findings suggest that high levels of corticosterone affect immune competence against parasites, both directly and by inducing changes in the metabolic status of the animals. Additionally, high testosterone levels during the reproductive season, influenced variables related to metabolic status, which will also lead to higher parasite loads. Overall, we conclude that the endocrine system and metabolic status in male cane toads are critical to the immune competence against parasites during the reproductive season.

Evening chronotype is associated with hormonal and metabolic disorders in polycystic ovary syndrome.

Despite current treatments for polycystic ovary syndrome (PCOS), a considerable number of women with this syndrome do not reach the treatment goal, suggesting the presence of other probable misdiagnosed features of this syndrome that are not taken into account in the assessment and therefore in the therapeutical approach. The aim of this study was to investigate the prevalence of chronotype categories in women with PCOS and their role in determining hormonal and metabolic aspects of PCOS.This observational case-control study was conducted on 112 women with PCOS and 112 healthy women matched for age and body mass index (BMI). At baseline anthropometric parameters such as weight, height, BMI and waist circumference, clinical parameters such as Ferriman-Gallwey (FG) score, biochemical parameters such as fasting plasma glucose, insulin levels and assessment of the homeostasis model of insulin resistance (HoMA-IR), inflammatory parameters such as C-reactive protein (CRP) and hormonal parameters such as testosterone levels were evaluated.Women with PCOS had a lower chronotype score (p < .001) which indicates a higher prevalence of evening chronotype (EC) category (p = .037) compared to controls. After adjustment for BMI, chronotype score was significantly negatively correlated with CRP levels (r = -0.418, p < .001), testosterone levels (r = -0.543, p < .001) and FG score (r = -0.514, p < .001). Linear regression analysis showed that high testosterone levels were among the factors most associated with a lower chronotype score (p < .001), followed by BMI (p < .001) and HoMA-IR (p < .05).In conclusion, there is a higher prevalence of EC in women with PCOS than in women without the condition, which in turn was associated with a worse hormonal and metabolic profile. These findings provide support for the relevance of including chronotype assessment in the treatment of women with PCOS.

Serum testosterone measured by liquid chromatography-tandem mass spectrometry is an independent predictor of response to castration in metastatic hormone-sensitive prostate cancer

BackgroundAlthough testosterone levels have been associated with progression-free survival (PFS) in metastatic hormone-sensitive prostate cancer (mHSPC) patients, this has primarily been investigated using inaccurate immunoassays (IA). Here, we investigated whether castrate testosterone levels determined by a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay is an independent risk factor for treatment response in mHSPC. MethodsIn total, 106 mHSPC patients treated with luteinizing-hormone releasing-hormone (LHRH) agonists were retrospectively analyzed between March 2018 and August 2021. Testosterone levels in serum samples were quantitated using an LC-MS/MS assay. In a subset of patients, IA (Roche Cobas Pro) values were compared with LC-MS/MS results. Survival analysis was performed using Kaplan-Meier curves and Cox proportional hazard models. ResultsMedian PFS was shorter for high testosterone levels (>0.231 nmol/L, 18.4 v. 42.6 months, HR 1.7, p = 0.018). Low testosterone levels and a PSA response below 4 ng/mL was associated with longer median PFS (46.2 months) than the remaining combinations (13.8–19.3 months, 3.4–5.8, overall p < 0.01). In 67 patients, testosterone levels below the median remained associated with longer PFS, whereas IA measurements did not show a similar difference. ConclusionOur results suggest that high castration testosterone levels measured by LC-MS/MS is an independent response predictor for mHSPC patients.

Nimbin analog N2 alleviates high testosterone induced oxidative stress in CHO cells and alters the expression of Tox3 and Dennd1a signal transduction pathway involved in the PCOS zebrafish.

Polycystic ovarian syndrome (PCOS) is a hormonal disorder that causes enlargement of ovaries and follicular maturation arrest, which lacks efficient treatment. N2, a semi-natural triterpenoid from the neem family, was already reported to have antioxidant and antiinflammatory properties in our previous report. This study investigated the anti-androgenic property of N2 on testosterone-induced oxidative stress in Chinese Hamster Ovarian cells (CHO) and PCOS zebrafish model. The testosterone exposure disrupted the antioxidant enzymes and ROS level and enhanced the apoptosis in both CHO cells and PCOS zebrafish. However, N2 significantly protected the CHO cells from ROS and apoptosis. N2 improved the Gonado somatic index (GSI) and upregulated the expression of the SOD enzyme in zebrafish ovaries. Moreover, the testosterone-induced follicular maturation arrest was normalized by N2 treatment in histopathology studies. In addition, the gene expression studies of Tox3 and Denndla in zebrafish demonstrated that N2 could impair PCOS condition. Furthermore, to confirm the N2 activity, the in-silico studies were performed against PCOS susceptible genes Tox3 and Dennd1a using molecular docking and molecular dynamic simulations. The results suggested that N2 alleviated the oxidative stress and apoptosis in-vitro and in-vivo and altered the expression of PCOS key genes.

Sex-specific differences in atherosclerosis, thrombospondin-1, and smooth muscle cell differentiation in metabolic syndrome versus non-metabolic syndrome mice.

Metabolic syndrome (MetS) amplifies the risks of atherosclerosis. Despite well-known sexual dimorphism in atherosclerosis, underlying mechanisms are poorly understood. Our previous findings highlight a proatherogenic protein, thrombospondin-1 (TSP-1), in hyperglycemia- or hyperleptinemia (mimicking obesity)-induced atherosclerosis. However, the role of TSP-1 in the development of atherosclerosis prompted by co-existing hyperglycemia and obesity, characteristic of MetS, is unknown. The goal of this study was to examine sex-specific differences in lesion progression in a model of combined MetS and atherosclerosis (KKAyApoE) and interrogate how these differences relate to TSP-1 expression. Male and female KKAy+/-ApoE-/- (with ectopic agouti gene expression) and age-matched non-agouti KKAy-/-ApoE-/- littermates were placed on a standard laboratory diet from 4 to 24 weeks age followed by blood and tissue harvests for biochemical, molecular, and aortic root morphometric studies. Metabolic profiling confirmed MetS phenotype of KKAy+/-ApoE-/-; however, only male genotypes were glucose intolerant with elevated VLDL-cholesterol and VLDL-triglyceride levels. Aortic root morphometry demonstrated profound lipid-filled lesions, increased plaque area, and augmented inflammatory and SMC abundance in MetS vs non-MetS males. This increase in lesion burden was accompanied with elevated TSP-1 and attenuated LMOD-1 (SM contractile marker) and SRF (transcriptional activator of SM differentiation) expression in male MetS aortic vessels. In contrast, while lipid burden, plaque area, and TSP-1 expression increased in MetS and non-MetS female mice, there was no significant difference between these genotypes. Increased collagen content was noted in MetS and non-MetS genotypes, specific to female mice. Measurement of plasma testosterone revealed a link between the atherogenic phenotype and abnormally high or low testosterone levels. To interrogate whether TSP-1 plays a direct role in SMC de-differentiation in MetS, we generated KKAy+/- mice with and without global TSP-1 deletion. Immunoblotting showed increased SM contractile markers in male KKAy+/-TSP-1-/- aortic vessels vs male KKAy+/-TSP-1+/ +. In contrast, TSP-1 deletion had no effect on SM contractile marker expression in female genotypes. Together, the current study implicates a role of plasma testosterone in sex-specific differences in atherosclerosis and TSP-1 expression in MetS vs non-MetS mice. Our data suggest a sex-dependent differential role of TSP-1 on SMC de-differentiation in MetS. Collectively, these findings underscore a fundamental link between TSP-1 and VSMC phenotypic transformation in MetS.

Mutational Screening of Androgen Receptor Gene in 8224 Men of Infertile Couples.

Mutations in the androgen receptor (AR) gene might be associated with infertility mainly because they cause various degrees of androgen insensitivity. The aim of the study was to evaluate the frequency and type of AR variants in a large cohort of infertile males. A total of 8224 males of Italian idiopathic infertile couples were referred to the University Hospital of Padova. The main outcome measures were mutational screening of AR, computational, and functional analyses. We found 131 patients (1.6%) harboring 45 variants in AR gene, of which 18 were novel missense AR variants. Patients with AR gene variants had lower sperm count (P = .048), higher testosterone (T) concentration (P < .0001), and higher androgen sensitivity index (ASI) (luteinizing hormone × T, P < .001) than patients without variants. Statistical analyses found T ≥ 15.38 nmol/L and ASI ≥ 180 IU × nmol/L2 as the threshold values to discriminate with good accuracy patients with AR variants. Patients with oligozoospermia and T ≥ 15.38 nmol/L had a 9-fold increased risk of harboring mutations compared with patients with normal sperm count and T < 15.38 nmol/L (odds ratio 9.29, 95% CI 5.07-17.02). Using computational and functional approaches, we identified 2 novel variants, L595P and L791I, as potentially pathogenic. This is the largest study screening AR gene variants in men of idiopathic infertile couples. We found that the prevalence of variants increased to 3.4% in oligozoospermic subjects with T ≥ 15.38 nmol/L. Conversely, more than 80% of men with AR gene variants had low sperm count and high T levels. Based on our findings, we suggest AR sequencing as a routine genetic test in cases of idiopathic oligozoospermia with T ≥ 15.38 nmol/L.

Correlations of selenium and selenoprotein P with asymmetric dimethylarginine and lipid profile in patients with polycystic ovary syndrome

BackgroundPolycystic ovary syndrome (PCOS) is associated with an increased risk of cardiovascular diseases (CVD). Accumulating evidence has suggested that selenium (Se) is of importance for optimal function of the cardiovascular system. This study aimed to investigate the associations of selenium and selenoprotein P (SePP) with asymmetric dimethylarginine (ADMA) and lipid profile in women with PCOS. MethodsIn this cross-sectional study, 125 females aged 18–45 years diagnosed with PCOS were recruited. An interviewer-administered questionnaire was applied to gather the relevant demographic characteristics, detailed clinical information, and lifestyle habits of participants. Fasting blood samples were obtained to measure biochemical parameters. Serum concentrations of total testosterone, sex hormone-binding globulin (SHBG), ADMA, and lipid profiles as well as anthropometric measurements were assessed across tertiles of serum Se and SePP concentrations. ResultsThere was a positive correlation between serum Se and SePP concentrations (r = 0.434, p < 0.001). Serum Se level was inversely correlated with ADMA (r = −0.21, p = 0.025) and TG (r = −0.17, p = 0.041) concentrations. There were also inverse correlations between SePP and ADMA (r = −0.34, p < 0.001), TG (r = −0.21, p = 0.019), and oxidized low density lipoprotein (ox-LDL) (r = −0.25, p = 0.007) levels. No significant relationship was found between serum Se and SePP concentrations with total cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), apolipoprotein-A1 (Apo-A1), apolipoprotein-B (Apo-B100), total testosterone, SHBG, and free androgen index as well as anthropometric parameters (All p > 0.05). ConclusionThe present study found that Se and SePP levels were inversely correlated with ADMA and TG concentrations as well as ox-LDL levels.

Associations between salivary testosterone levels and cognitive function among 70-year-old Japanese elderly: A cross-sectional analysis of the SONIC study.

This cross-sectional study aimed to investigate the associations between salivary testosterone concentrations and cognitive function in 70-year-old Japanese elderly people without dementia and stroke. Participants were 197 Japanese community-dwelling people aged 69-71 years. Their salivary samples were collected, and their cognitive function was assessed using the Japanese version of the Montreal Cognitive Assessment (MoCA-J). Participants were also administered a 10-item recall and a 24-item recognition test. The data for 179 (106 men and 73 women) individuals were analyzed, excluding individuals with a past history of stroke and dementia. Multivariate logistic regression analyses were performed after adjusting for lifestyle factors and analyzing data separately for men and women. MoCA-J scores showed that men with low testosterone concentrations had a significantly greater risk of low cognitive performance than those with high testosterone concentrations (adjusted odds ratio: 4.72, 95% confidence interval: 1.06-21.00), while no significant association was found in women. The 10-item recall test scores showed that higher testosterone concentrations were significantly associated with greater recall in the second trial in women (standardized beta=0.24, P=0.040), whereas no significant association was found in men. Salivary testosterone concentrations were positively associated with better cognitive performance in older men and women. The associations between salivary testosterone concentrations and cognitive function were shown by different tasks for men and women. Geriatr Gerontol Int 2022; 22: 1040-1046.

RF01 | PMON77 Low Libido Despite High Testosterone Levels in a Man With FSH-Secreting Pituitary Macroadenoma

Abstract Background Up to 60% of non-functioning pituitary adenomas stain for gonadotrophins on immunocytochemistry but do not secrete excess gonadotrophins. Functioning gonadotroph adenomas with clinical manifestations are extremely rare and majority of these are FSH secreting macroadenomas. Diagnosis may be difficult in pre-menopausal women with high oestrogen and variable FSH levels but in men, the unusually high gonadotrophins give the clues for diagnosis. Clinical Case We present the case of a 37-year-old Caucasian male with clinical manifestations of an FSH-secreting pituitary macroadenoma. He had sexual dysfunction with loss of libido for a year followed by bilateral testicular pain and enlargement (right &amp;gt;left). He was initially investigated under urology and had repeated treatment for suspected epididymitis. The diagnosis came to light many months later when he presented to emergency department with headaches and visual disturbance. Brain imaging confirmed a pituitary macroadenoma (3×2.5×3cm) with optic chiasm compression. He had bilateral superior temporal visual field defects. Pituitary profile showed unusually high FSH 200 IU/L (0.7-11.1), normal LH 7.6 IU/L (0.8-7.6) and a high normal testosterone 27 nmol/L (8.5-29). Prolactin was slightly elevated at 474mIU/L (0-350), cortisol and TSH were in normal range. He had polycythaemia (Haemoglobin 181g/l and HCT 0.51 L/L) and old blood results indicate his haemoglobin was above the upper limit of normal for previous 10 years. This gentleman had a successful transsphenoidal hypophysectomy with near complete resection of pituitary adenoma. His vison improved immediately after surgery. Histology of the resected adenoma showed gonadotroph differentiation and immunoreactivity predominantly with FSH and also with LH and prolactin stains. A day after surgery, his FSH levels dropped to 18 IU/L and LH was undetectable. Symptoms of hypogonadism had gradually worsened post-surgery and 2 months later, his pituitary profile showed severe hypogonadotrophic hypogonadism (FSH 3.6 IU/L, undetectable LH and testosterone 0.9 nmol/L). He was started on testosterone replacement which he continues till date. He remains asymptomatic with no testicular pain and the last MR imaging, a year after his surgery showed no recurrence in the pituitary adenoma. Conclusion Testicular enlargement and hypogonadal symptoms with low testosterone levels are recognised features in FSH secreting pituitary adenomas. Our patient had testicular enlargement but consistently high testosterone levels prior to surgery and polycythaemia for many years prior to presentation. This may be due concomitant hypersecretion of both FSH and LH from his pituitary adenoma. The reason for low libido despite high androgen levels was not entirely clear. Symptoms of hypogonadism overlap with many non-gonadal illnesses. A normal testosterone level in most cases would not lead to further endocrine investigations. Our case highlights the need to suspect such rare underlying pituitary pathology when dealing with unusual combination of hypogonadal symptoms, testicular enlargement and normal or high normal testosterone levels. Presentation: Saturday, June 11, 2022 1:30 p.m. - 1:35 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.