Low Serum Testosterone Levels Research Articles

Gestational Exposure to Synthetic Steroid Hormones Impaired Sperm Quantity and Quality in Wistar Rats.

This study was designed to investigate the effect of prenatal exposure to synthetic sex steroid on sperm quantity and quality, relative testicular and epididymal weights, and reproductive hormones level in adult Wistar rats. Forty male Wistar rats were divided into two groups: a test group (n = 20) that included mature rats that were born to dams exposed to gestational treatment with hydroxyprogesterone and a control group (n = 20) that included mature rats born to untreated dams. Compared to the control group, the test group showed a significant reduction in the sperm count, viability and motility, relative testicular and epididymal weights together with increased abnormal spermatozoa (p < 0.001). The reproductive hormonal assay revealed significantly lower serum testosterone and higher levels of FSH and LH among the test groups compared to the control (p < 0.05 for all). Prenatal exposure to synthetic progesterone negatively affected sperm production and function, relative testicular and epididymal weights, and reproductive hormone levels.

Inhalation of welding fumes reduced sperm counts and high fat diet reduced testosterone levels; differential effects in Sprague Dawley and Brown Norway rats

BackgroundPrevious studies have shown that inhalation of welding fumes may induce pulmonary and systemic inflammation and organ accumulation of metal, to which spermatogenesis and endocrine function may be sensitive. Also obesity may induce low-grade systemic inflammation. This study aimed to investigate the effects on sperm production of inhaled metal nanoparticles from stainless steel welding, and the potential exacerbation by intake of a high fat diet. Both the inbred Brown Norway and the outbred Sprague Dawley rat strains were included to study the influence of strain on the detection of toxicity. Rats were fed regular or high fat (HF) diet for 24 weeks and were exposed to 20 mg/m3 of gas metal arc-stainless steel (GMA-SS) welding fumes or filtered air for 3 h/day, 4 days/week for 5 weeks, during weeks 7–12. Outcomes were assessed upon termination of exposure (week 12) and after recovery (week 24).ResultsAt week 12, the GMA-SS exposure induced pulmonary inflammation in both strains, without consistent changes in markers of systemic inflammation (CRP, MCP-1, IL-6 and TNFα). GMA-SS exposure lowered daily sperm production compared to air controls in Sprague Dawley rats, but only in GMA-SS Brown Norway rats also fed the HF diet. Overall, HF diet rats had lower serum testosterone levels compared to rats on regular diet. Metal content in the testes was assessed in a limited number of samples in Brown Norway rats, but no increase was obsedrved. At week 24, bronchoalveolar lavage cell counts had returned to background levels for GMA-SS exposed Sprague Dawley rats but remained elevated in Brown Norway rats. GMA-SS did not affect daily sperm production statistically significantly at this time point, but testicular weights were lowered in GMA-SS Sprague Dawley rats. Serum testosterone remained lowered in Sprague Dawley rats fed the HF diet.ConclusionExposure to GMA-SS welding fumes lowered sperm production in two strains of rats, whereas high fat diet lowered serum testosterone. The effect on sperm counts was likely not mediated by inflammation or lowered testosterone levels. The studied reproductive outcomes seemed more prone to disruption in the Sprague Dawley compared to the Brown Norway strain.

Проблемы мужского гипогонадизма при сахарном диабете 2 типа: факты доказательной медицины и реальной клинической практики

Epidemiological studies demonstrate that low levels of serum testosterone are common in men with verified type 2 diabetes (T2D) but also account for higher risks of T2D and mortality. Current data on hypogonadism in T2D are generally similar but controversial in some aspects. Available preclinical studies suggest the mechanisms whereby low testosterone mediates the development of hyperglycemia. Many clinical data demonstrate several effects of testosterone replacement therapy, i.e., reduced fat mass, the increase in muscle mass, improved insulin resistance, the significant improvement in sexual function etc. However, some of the available randomized controlled trials fail to establish the glucose-lowering effect of this therapy. Therefore, this field is important to present systematic reviews and to identify the areas for further studies. This paper reviews currently available evidence-based medicine and routine clinical practice data on the pathogenesis and treatment for androgen deficiency in male patients with T2D.KEYWORDS: testosterone, type 2 diabetes, hypogonadism, androgen deficiency, testosterone replacement therapy.FOR CITATION: Demidova T.Yu., Skuridina D.V. Male hypogonadism and type 2 diabetes: evidence-based medicine versus clinical practice. Russian Medical Inquiry. 2020;4(6):364–371. DOI: 10.32364/2587-6821-2020-4-6-364-371.

The effect of three-month topical testosterone gel application on semen quality in men with oligozoospermia and low serum testosterone levels

Objective: The effects of daily topical application of testosterone gel on semen characteristics in infertile men with oligozoospermia and hypogonadism were assessed. Methods: Sixteen infertile men were included in this prospective study. A daily morning application of 25 mg transdermal testosterone (T) gel was used for 3 months. Semen parameters, serum follicular stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E) and T levels, and seminal plasma E and T levels were measured before treatment and once monthly for three months during the therapy. Results: The baseline median sperm concentration was 5.5 × 106/mL. Median sperm concentrations at the first, second and third months were 9 × 106, 8 × 10 6, and 4 × 106/mL, respectively. The sperm concentrations at the first and second months after starting therapy significantly (p &lt; 0.001) increased compared with the baseline. However, sperm volume, pH, motility, viability and morphology were similar to baseline. Serum T significantly (p &lt; 0.001) increased, while serum FSH significantly (p &lt; 0.001) decreased from baseline. Seminal T and T/E ratios were raised significantly (p = 0.008 and p = 0.004, respectively) after gel application, whereas the seminal E level was not affected. Conclusions: Daily 25 mg T gel applications for oligospermic infertile men with hypogonadism increased the sperm concentration at the first and second months and raised the serum T level to the normal adult male range. Nevertheless, the sperm concentration had a decreasing trend after the third month.

Endocrinological Testicular Dysfunction in Patients with Lepromatous Leprosy and the Impact of Disease on Patient's Quality of Life.

Introduction:Leprosy or Hansen's disease poses a drastic impact on the quality of life in affected patients even after successful completion of treatment. The involvement of the endocrine system in leprosy is usually insidious, silent, and under-reported, especially the testicular dysfunction.Aims and Objectives:The present study was aimed at evaluating the abnormalities of the primary testicular hormone testosterone and the gonadotrophins LH and FSH in male patients affected with lepromatous leprosy and assessing the impact of the disease on quality of life (QOL).Materials and Methods:The study included 43 married male patients diagnosed with lepromatous leprosy. Careful history taking and examination for symptoms of testicular dysfunction were done. Serum concentrations of total testosterone, FSH, and LH were noted. The QOL was evaluated using the WHO Quality of Life-BREF (WHOQoL-BREF).Results:The most common clinical manifestation of testicular dysfunction was reduced or loss of libido reported in 12 (27.9%) patients followed by gynaecomastia in 7 (16.3%). Ultrasonographic (USG) analysis revealed reduced testicular volume in 31 (72.1%) patients, and average testicular volume was 11.9 ± 4.9 mL each. Seventeen (39.5%) patients had low serum testosterone levels, 9 (20.9%) had high serum FSH level, and 11 (25.6%) high LH levels. There was a significant negative correlation between testosterone level and FSH as well as LH. There was also a significantly positive correlation between testicular volume and testosterone level. Symptomatic patients with gynaecomastia/gynaecothelia had higher hormonal derangement than those who had other symptoms. On QOL, most patients scored lowest on the domain of “social relationships” (including sexual wellbeing) followed by “psychological health”.Conclusion:We found a high rate of USG diagnosed testicular atrophy in lepromatous leprosy patients. Therefore, every leprosy patient should be thoroughly examined clinically to rule out features of testicular dysfunction. Testicular function tests should be routinely carried out in all leprosy patients to arrive at an early diagnosis. Leprosy is found to affect all domains of a patient's quality of life.

Low serum testosterone levels and the incidence of chronic kidney disease among male adults: A prospective population-based study.

Despite existing evidence regarding the role of testosterone as a protective factor for the kidney function in male adults, there are conflicting and inconclusive results on the influence of testosterone deficiency on developing chronic kidney disease (CKD). This study aimed to investigate the incidence and hazard ratio of CKD among male adults with low testosterone levels compared to controls with normal testosterone levels. During a 15-year follow-up study, a total of 1277 eligible male adults aged 20-80year consisting of 605 males with low testosterone levels (< 350ng/dL) and 672 controls with normal levels participating in the Tehran Lipid and Glucose Study were recruited. Cox's proportional hazards models were applied to estimate hazard ratios of CKD between the groups after adjusting for confounders. The total cumulative incidence rate of CKD at the median follow-up time of approximately 11.2years was 21/1000 (95% CI: 18/1000, 25/1000) and 18/1000 (95% CI: 16/1000, 22/1000) in the low and normal testosterone groups, respectively (P=.2). The multivariate Cox model adjusted for age, body mass index, dyslipidemia, hypertension, diabetes, and smoking showed that HR of developing CKD in the male adults with low testosterone levels was significantly higher than those with normal levels (HR=1.38; 95% CI: 1.05, 1.80). This study shows a higher hazard ratio of CKD progression in male adults with hypogonadism compared to those with normal levels in their later life. Therefore, timely diagnosis and treatment of kidney diseases in hypogonadal men can prevent the morbidity and mortality from CKD.

Prevalence of low serum testosterone levels among men with type 2 diabetes mellitus attending two outpatient diabetes clinics in KwaZulu-Natal Province, South Africa.

The reported prevalence of low testosterone among men with type 2 diabetes mellitus (T2DM) is high. However, there is a dearth of information on the prevalence of androgen deficiency symptoms and low serum testosterone levels in men with T2DM from sub-Saharan Africa. Scanty data are available from Nigeria, Ghana and South Africa (SA). To determine the prevalence of low serum testosterone and associated risk factors and the prevalence of androgen deficiency symptoms in men with T2DM. In a cross-sectional observational study, androgen deficiency symptoms in men with T2DM attending two outpatient diabetes clinics in Durban, KwaZulu-Natal Province, SA, were assessed using the Ageing Males' Symptoms Scale (AMS) questionnaire and direct enquiry. Serum total testosterone (TT), sex hormone-binding globulin (SHBG), luteinising hormone (LH), fructosamine, serum lipids and glycated haemoglobin (HbA1c) were measured and free testosterone (FT) was calculated. TT, SHBG and FT levels were measured in control subjects with no history of diabetes. There were 148 men with T2DM in the study group and 50 control subjects in the control group. In the study group, the majority were black Africans (58.8%); Indians (39.2%) and whites (2.0%) constituted the remainder. The mean (standard deviation (SD)) age was 57.5 (11.2) years, the mean duration of diabetes 11.4 (8.9) years and the mean HbA1c 8.6% (1.9%). Of the study group, 85.8% had metabolic syndrome. Mean TT, SHBG and FT and median LH (interquartile range) in the study group were within normal ranges. However, mean (SD) serum TT and FT were lower in the study group than in the control subjects (14.5 (5.8) v. 18.8 (7.2) nmol/L; p&lt;0.001 and 265.9 (90.4) v. 351.7 (127.3) pmol/L; p&lt;0.001, respectively). The prevalence of low serum total testosterone (LSTT) and low serum free testosterone (LSFT) in the study group was 35.8% and 16.2%, respectively. The prevalence of androgen deficiency symptoms using the AMS questionnaire was 74.5% and correlated poorly with LSTT or LSFT. In multivariate analysis, LSFT was significantly associated with age (odds ratio (OR) 1.05, 95% confidence interval (CI) 1.02 - 1.218; p=0.043) and waist circumference (WC) (OR 1.033, 95% CI 0.999 - 1.068; p=0.059). LSTT was associated with body mass index (BMI) only (OR 1.138, 95% CI 1.063 - 1.218; p&lt;0.0001). TT correlated inversely with BMI, WC and the number of metabolic syndrome criteria. FT correlated inversely with BMI, WC and WHR. There was a high prevalence of LSTT, LSFT and androgen deficiency symptoms in this study. Serum TT and FT were lower in men with T2DM than in control subjects. Risk factors associated with LSFT or LSTT included higher BMI and WC and older age. The AMS score was a poor predictor of low testosterone. More research is required locally before any screening policy can be recommended.

Anti-androgen hormonal therapy for cancer and other diseases

The development of targeted therapies has been a consistent goal for hormone-related diseases treatment. As a result of increased knowledge of the role of androgens in different diseases, anti-androgen treatment is becoming increasingly important in targeted therapy.Androgens play an important role in different disorders, therefore, androgen receptor signalling is a crucial factor in pathological conditions. The androgen receptor is a transcription factor activated by the testosterone metabolite 5α-dihydrotestosterone and regulates the expression of genes related to sexual differentiation, growth and survival of prostate cells, and to a certain extent, cancer progression.Herein, we review anti-androgen therapies in cancer and other selected diseases and provide examples where anti-androgen drugs can be used as both main and supportive treatments in the multimodal therapeutic scheme. Even in diseases with low serum levels of testosterone or DHT, anti-androgen therapy plays an important role in new treatments. Therefore, the use of anti-androgens is an appealing strategy in which to overcome resistance to primary treatment by assuring better therapy results. In this review, we take into account both older generation hormonal drugs and the new drug classes. Additionally, we review recent studies that suggest new anti-androgen agents have not entirely replaced some of the old standards.

Efficacy and Safety of Microsurgical Subinguinal Varicocelectomy with and without Testicular Delivery for Varicocele Patients: A Systematic Review and Meta-Analysis.

This study reviewed the efficacy and safety of the microsurgical subinguinal varicocelectomy (MSV) with and without testicular delivery (TD) for varicocele patients. A systematic literature search was conducted in EMBASE, PubMed, MEDLINE, Cochrane databases, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), and Google Scholar databases to identify relevant studies that reported MSV with and without TD for varicocele patients published in English or Chinese up to October 2018. The Newcastle-Ottawa Scale (NOS) and the Jadad scores were used to evaluate the methodological quality of all the included studies. We also used the Cochrane Collaboration's tool for assessing risk of bias for each study. The Review Manager Software version 5.3 was used to conduct data analysis. Four RCTs and three retrospective studies consisting of 993 patients were included. Meta-analysis results indicated that both of the two treatments were effective and safe. MSV with TD had a lower recurrence rate (OR = 0.20, 95% CI: 0.06 - 0.65, P = .007, I2 = 0%) and postoperative serum testosterone level (MD = -39.07, 95% CI: -51.95 - -26.18, P = .00001, I2 = 0%) compared with MSV without TD but was associated with higher postopera-tive complications rate (OR=7.35, 95% CI: 2.92-18.53, P < .0001, I2 = 0%). We found no significant differences in operation time (MD = 12.46, 95% CI:0.11-24.81,P= .05, I2 = 87%), sperm concentration (MD = 3.73, 95% CI: -2.88 - 10.35, P = .27, I2 = 81%), sperm motility (MD = 10.96, 95% CI: -11.93 - 33.86, P = .35, I2 = 99%), and pregnancy rate(OR = 0.65, 95% CI: 0.37- 1.16, P = .15, I2 = 0%). This meta-analysis compared efficacy and safety of MSV with and without TD for varicocele pa-tients. MSV with TD was associated with a higher postoperative complication rate but lower recurrence rate and postoperative serum testosterone level than MSV without TD. In terms of preoperative serum testosterone level, operation time, sperm concentration, sperm motility, and pregnancy rate, we found no significant differences.

Paraquat exposure delays late-stage Leydig cell differentiation in rats during puberty

Paraquat is a fast and non-selective herbicide that is widely used in crop cultivation and conservation tillage systems. Animal experiments have shown that paraquat decreases sperm quality and testicular organ coefficient, but its effects on the development of Leydig cells remain unclear. The objective of the current study was to investigate the effects of paraquat exposure on the Leydig cell development in rats during puberty. Twenty-eight male 35-day-old Sprague-Dawley rats were divided into 4 groups: 0, 0.5, 2.0, and 8 mg kg−1 d−1 paraquat. Paraquat was gavaged for 10 d. Adult Leydig cells were isolated and treated with paraquat for 24 h. Paraquat in vivo significantly decreased body and testis weights at 8 mg kg−1 and lowered serum testosterone levels at 2 and 8 mg kg−1 without affecting the levels of serum luteinizing hormone and follicle-stimulating hormone. Paraquat did not alter Leydig cell number and PCNA labeling index. Real-time PCR showed that paraquat down-regulated the expression of Lhcgr, Scarb1, Cyp11a1, Cyp17a1, and Hsd17b3 genes and their proteins at 2 or 8 mg kg−1, while it up-regulated the expression of Srd5a1 at 8 mg kg−1. Paraquat increased ROS and decreased testosterone production by Leydig cells at 1 and 10 μM after in vitro 24-h exposure. Vitamin E (40 μg/ml) reversed paraquat-induced ROS and suppression of testosterone synthesis in vitro. In conclusion, paraquat directly delays Leydig cell differentiation to block testosterone synthesis via down-regulating the expression of critical testosterone synthesis-related genes and up-regulating the expression of testosterone metabolic enzyme (Srd5a1) gene and possibly via increasing ROS production.

Aconitine inhibits androgen synthesis enzymes by rat immature Leydig cells via down-regulating androgen synthetic enzyme expression in vitro

Aconitine might have reproductive toxicity and the effects of aconitine on androgen synthesis in Leydig cells remain unclear. Here, we explore how aconitine affects androgen synthesis and metabolism in rat immature Leydig cells in vitro. Immature Leydig cells were isolated from 35-day-old male Sprague Dawley rats and cultured with 0–50 μM aconitine for 3 h in combination with LH, 8Br-cAMP, 22R-hydroxycholesterol, pregnenolone, progesterone, androstenedione, testosterone, and dihydrotestosterone, respectively. Medium androgens were measured. The levels of Leydig cell mRNAs, Lhcgr, Scarb1, Star, Cyp11a1, Hsd3b1, Cyp17a1, Hsd17b3, Srd5a1, and Akr1c14, were measured by qPCR. ROS and apoptosis were determined after 24-h aconitine treatment. Aconitine inhibited basal androgen production in Leydig cells at 0.05 μM and the higher concentrations. Aconitine blocked pregnenolone, progesterone, and androstenedione mediated androgen outputs without affecting 22R-hydroxycholesterol-mediated androgen production at 5 μM. Aconitine also inhibited LH and 8Br-cAMP stimulated androgen outputs at 5 μM. Further investigation showed that aconitine blocked androgen synthesis via down-regulating the expression of Scarb1, Hsd3b1, Cyp17a1, and Hsd17b3. At 50 μM, aconitine also induced ROS generation and increased apoptotic rate of Leydig cells. Aconitine lowered serum testosterone levels at 1.5 mg/kg after 7 days of oral exposure from postnatal day 35. In conclusion, aconitine inhibits androgen synthesis.

The Association between Popular Diets and Serum Testosterone among Men in the United States

We examined the relationship of the serum testosterone level to low fat, Mediterranean and low carbohydrate diets in a large, nationally representative patient sample. We queried the NHANES (National Health and Nutrition Examination Survey) from 1999 to 2000, 2003 to 2004 and 2011 to 2012. Men 18 to 80 years old who completed the 2-day dietary history and underwent serum testosterone testing were included in analysis. Diets were categorized as low fat, Mediterranean, low carbohydrate or nonrestrictive. Multivariable modeling was used to determine the relationship between diet and serum testosterone. Of the 3,128 men who met study inclusion criteria 457 (14.6%) and 764 (24.4%) met the criteria for a low fat and a Mediterranean diet, respectively. Only 2 men (less than 0.1%) met the criteria for a low carbohydrate diet, which was removed from further analysis. Mean ± SD serum testosterone was 435.5 ± 6.7 ng/dl. Mean testosterone was lower among men with a low fat diet (410.8 ± 8.1 vs 443.5 ± 7.3, p=0.005) and a Mediterranean diet (412.9 ± 9.1 vs 443.5 ± 7.3, p=0.002). Multivariable analysis controlling for age, body mass index, activity level, diabetes, comorbidities and prostate cancer showed that men with a nonrestrictive diet had higher serum testosterone than those adhering to a low fat diet (ß -57.2, 95% CI -105.6 to -8.8, p <0.05). Men adhering to low fat diets had lower serum testosterone levels even when controlling for comorbidities, age, body mass index and activity levels. As differences in serum testosterone between the diets were modest, the avoidance of fat restrictive diets should be weighed against the potential benefits on an individual basis.

The Impact of Testosterone on Metformin Action on Hypothalamic-Pituitary-Thyroid Axis Activity in Men: A Pilot Study.

The effect ofmetforminon thyrotrope function seems to be sex dependent. The aim of this study was to determine the role of endogenous testosterone in the impact of metformin on hypothalamic-pituitary-thyroidaxis activity. The study population consisted of 2 groups of men with nonautoimmune hypothyroidism matched for age, weight, insulin sensitivity, and thyrotropin levels. The first group (n = 11) included subjects with low serum testosterone levels, while the second (n = 12) men with testosterone levels within the reference range. Because of concomitant type 2 diabetes, all men were treated withmetformin(2550-3000 mg daily). Circulating levels of glucose, prolactin, testosterone, gonadotropins, thyrotropin, and freethyroidhormones were measured, while thestructure parameters of thyroid homeostasisand the degree of insulin sensitivity were calculated at baseline and 16 weeks later. In both study groups, metformindecreased plasma glucose levels and improved insulin sensitivity. However, only in men with low testosterone levels, the drug decreased thyrotropin levels, reduced Jostel's thyrotropin index, and increased SPINA-GT. Metformin-induced changes in thyrotropin and Jostel's index correlated with their baseline values, baseline levels of testosterone, and with the effect of treatment on insulin sensitivity. In men with neither low or normal testosterone levels, metformin affected free thyroid hormones, prolactin, testosterone, gonadotropins, and SPINA-GD. The obtained results suggest that the impact of metformin on thyrotrope function depends on the androgen status of a patient.

Low serum testosterone levels in male psoriasis patients correlate with disease severity.

Psoriasis is a chronic inflammatory skin disease with a genetic and autoimmune background. The involvement of sex hormones as a trigger factor for psoriasis has been suspected. Recently, low serum testosterone has been associated with autoimmune diseases in males, and the role of testosterone in psoriasis is unknown. To investigate serum testosterone levels in male psoriasis patients compared to control individuals with regards to the severity of psoriasis. A total of 121 male psoriasis patients and 217 control individuals were enrolled. The severity of psoriasis was documented using the Psoriasis Area Severity Index (PASI). Serum testosterone, sex hormone binding globulin (SHBG), and albumin were analysed. Moreover, psoriasis medication and the incidence of metabolic syndrome were recorded. In 52.1% psoriasis patients, low total testosterone values were detected. Compared to the control cohort, total testosterone (tT) and free testosterone (fT) in psoriasis patients were significantly lower. Despite psoriasis-specific medication, there was a significant inverse correlation between tT or fT and PASI, irrespective of age above or below 40 years. Low tT levels also correlated with the prevalence of metabolic syndrome. Nevertheless, in psoriasis patients without metabolic syndrome, higher PASI (≥10) was associated with significantly lower tT values. In addition, low tT was associated with clinical symptoms of testosterone deficiency. Severe psoriasis is associated with low serum testosterone. However, further studies are required to investigate whether this observation is an epiphenomenon and whether testosterone substitution might decrease the severity of psoriasis.

Aflatoxin B1 impairs leydig cells through inhibiting AMPK/mTOR-mediated autophagy flux pathway

Aflatoxin B1 (AFB1), a potential endocrine disrupter, has been shown to induce hepatotoxicity in animal models, but the effects of AFB1 on Leydig cell function are unclear. In this study, in vivo exposure to AFB1 at 15 and 150 μg/kg/day lowered serum testosterone (T), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels, reduced Leydig cell number, and down-regulated the expression of testosterone biosynthesis-related genes. In vitro study showed that AFB1 (10 μM) significantly increased ROS levels, and decreased T production in Leydig cells by suppressing certain T-biosynthesis gene expressions. Moreover, AFB1 induced Leydig cell apoptosis through lowering pAMPK/AMPK ratio and increasing pmTOR/mTOR ratio, and then further up-regulating autophagy and apoptosis proteins, LC3, BECLIN 1, and BAX, as well as down-regulating autophagy flux protein P62 and anti-apoptosis protein BCL-2. AFB1-induced toxicity in Leydig cells was characterized by inhibiting T-biosynthesis gene expression, reducing Leydig cell number, promoting ROS production, and inducing cell apoptosis via suppressing AMPK/mTOR-mediated autophagy flux pathway.

Cross-Sectional Association of Metabolic Syndrome and Its Components with Serum Testosterone Levels in a Korean-Screened Population.

PurposeWe evaluated the associations of metabolic syndrome (MetS) and its components with testosterone levels in the Korean population.Materials and MethodsThis cross-sectional study was performed among 6,967 adult (age≥20 years) men who attended health screening during 2006 to 2015. MetS was defined using the National Cholesterol Education Program Adult Treatment Panel III criteria. Associations were evaluated using unconditional logistic regression.ResultsThe estimated age-adjusted prevalence of MetS in adult and middle-aged (≥40 years) Korean men was 27.5% and 30.6%, respectively. Quartile analysis showed that high serum testosterone levels were significantly associated with a low risk of MetS (highest vs. lowest quartile, odds ratio=0.528; ptrend<0.001), with an approximately 13% reduction in MetS risk per 1 ng/mL increment of serum testosterone levels. After considering covariates such as age and body mass index (BMI), the reduction in MetS risk was attenuated but remained significant (7% reduced risk per 1 ng/mL). Testosterone levels were inversely correlated with all MetS components, including hyperglycemia (r=−0.041), increased body size (r=−0.093), increased triglyceride levels (r=−0.090), decreased high-density lipoprotein cholesterol levels (r=−0.030), and elevated blood pressure (r=−0.071, all p<0.05). Among them, elevated triglyceride levels and blood pressure were independently associated with low serum testosterone levels, even after adjustment for age and BMI.ConclusionsSerum testosterone levels were inversely associated with MetS in Korean men. This association was attenuated after adjustment for age and BMI but remained significant. Among MetS components, increased triglyceride levels and elevated blood pressure were independently associated with testosterone levels, regardless of obesity.

Serum testosterone level is a useful biomarker for determining the optimal treatment for castration-resistant prostate cancer

ObjectiveOur aim was to evaluate the usefulness of serum testosterone to guide treatment decision for castration-resistant prostate cancer (CRPC). MethodsWe conducted a retrospective analysis of 115 patients with CRPC treated with either abiraterone (n = 43) or enzalutamide (n = 72). A serum testosterone level was measured at time of starting of abiraterone or enzalutamide. We determined whether serum testosterone influenced the outcomes of androgen receptor (AR)-targeted therapy. ResultsIn the very-low testosterone group (<5 ng/dl), the rate of prostate-specific antigen (PSA) response was significantly higher among patients treated with abiraterone compared to enzalutamide (62 vs. 32%, respectively; P = 0.033), with no difference in the low testosterone group (5–<50 ng/dl) (93 vs. 81%, respectively; P = 0.429). During the median follow-up of 26 months, PSA progression-free survival was significantly longer in the low testosterone group than in the very-low testosterone group (12.2 vs. 4.5 months, P<0.001). In the very-low testosterone group, enzalutamide use (HR 3.07, 95% CI 1.36–6.94; P = 0.007), primary androgen deprivation therapy <12 months (HR 2.50, 95% CI 1.23–5.08; P = 0.011) and bone metastases (HR 2.60, 95% CI 1.20–5.64; P = 0.015) were significantly associated with PSA progression. ConclusionPatients with a serum testosterone level ≥5 ng/dl were more likely to receive therapeutic benefits from AR-targeted therapy compared to those with serum testosterone levels <5 ng/dl. However, even for those with a very low serum testosterone level, the efficacy of abiraterone was slightly higher than that of enzalutamide. Therefore, serum testosterone level is a useful biomarker for informing treatment selection for CRPC.

SAT-482 Pituitary Tumor Apoplexy Due to a Nonfunctioning Hemorrhagic Pituitary Macroadenoma

BACKGROUND Pituitary apoplexy is characterized by acute neuroophthalmologic features due to bleeding in pituitary adenoma. Clinical manifestations occur due to local mass effect, spread of blood in subarachnoid space and deficiency of pituitary hormones. Clinical features include headache, visual impairment, external ophthalmoparesis, altered sensorium and hormone deficiencies. Causes of pituitary apoplexy are infarction, bleeding within the pituitary adenoma or metastasis. Surgery is indicated for decompression and relief of neuroophthalmic features. THE CASE A 65-year old male was admitted due to right eye ptosis, diplopia and blurring of vision. Two days prior, he was rushed to hospital due to headache and BP elevations. Plain cranial CT scan revealed age-related brain atrophy and gliosis. He was then discharged, with Losartan 100mg once daily, taken with good compliance. Examination showed stable vital signs. He was awake, coherent and oriented. Cranial nerves examination revealed right eye ptosis with medial, upward and downward gaze palsy. Pupillary sizes were 3 mm O.D. with nonreactive light reflex, 2 mm O.S. with brisk light reflex; no bitemporal hemianopsia. He was unable to read from 1.5 feet with both eyes. CT angiogram revealed suprasellar mass (1.4 x 2.3 x 1.2 cm), no evidence of vascular malformation. Cranial MRI with contrast defined the mass to be 2.6 cm lobulated sellar-suprasellar mass, compressing the optic chiasm, consistent of hemorrhagic pituitary macroadenoma. Hormonal studies showed low levels of serum cortisol (11.3 nmol/L; N 171- 536 nmol/L), FT4 (5.07 pmol/L N; 12-22 pmol/L), FT3 (2.5 pmol/L; N 3.1-6.8 pmol/L), LH (0.19 mIU/ml; N 0.57- 12.07 mIU/ml), testosterone (0.03 ng/mL; N 2.8-8ng/ml) and prolactin (2.26 ng/ml; N 3.46-19 ng/ml). TSH (0.30 uIU/ml; N 0.27-4.2 uIU/ml) and FSH (1.35 mIU/ml; N 0.95-11.95 mIU/ml) were normal. Hydrocortisone IV and levothyroxine were administered prior surgery. Patient underwent transphenoidal excision of pituitary tumor with no intraoperative complications. Biopsy of tumor revealed pituitary adenoma. Patient manifested postoperatively with improvement of ptosis and extraocular muscle movement on right eye. There was full lateral and downward gaze. Gradual recovery of upward and medial gaze on right eye was also seen. Patient was discharged with steroid and hormone replacement. CONCLUSION Pituitary apoplexy is a rare but life-threatening condition. Commonly implicated cause is pituitary macroadenoma. Immediate recognition allows prompt steroid administration and surgical decompression. Long-term hormone replacement is required. Recovery of visual symptoms is commonly realized. REFERENCE Rajesh Verma et al. Pituitary apoplexy syndrome as the manifestation of intracranial tuberculoma. BMJ Case Rep. 2014

Corticosterone rather than ethanol epigenetic programmed testicular dysplasia caused by prenatal ethanol exposure in male offspring rats

ABSTRACTPrenatal ethanol exposure (PEE) could affect offspring’s testicular development. This study aimed to illuminate its intrauterine origin and the programming mechanism caused by PEE. Pregnant Wistar rats were given ethanol (4 g/kg.d) by gavage administration during gestational days (GD) 9–20. Serum samples and testes of male offspring rats were collected on GD20, postnatal week (PW) 6, and PW12. We found that PEE induced testicular morphological abnormality, low serum testosterone levels, expressive suppression of 3β-hydroxysteroid dehydrogenase (3β-HSD), and low acetylation levels of histone 3 lysine 14 (H3K14ac) of 3β-HSD before and after birth. In utero, when fetal rats were overexposed to corticosterone by PEE, the expression levels of testicular glucocorticoid receptor (GR) and histone deacetylase 2 (HDAC2) were increased, while that of steroidogenic factor 1 (SF1) was decreased. In vitro, corticosterone (rather than ethanol) at 500 to 2,000 nM concentration decreased testosterone production and 3β-HSD expression in a concentration-dependent manner. Moreover, corticosterone downregulated SF1 and upregulated HDAC2 via activating GR, accompanied by a low H3K14ac level of 3β-HSD; SF1 overexpression could reverse the increased HDAC2 expression, and knockdown of HDAC2 could partially reverse the inhibitory effects of corticosterone on H3K14ac level and 3β-HSD expression but not on SF1 expression. Taken together, PEE caused testicular dysplasia in male offspring rats, which was associated with corticosterone-induced low-functional programming of 3β-HSD through the GR/SF1/HDAC2/H3K14ac pathway. This study provides new academic perspectives to illuminate the theory of ‘Developmental Origins of Health and Disease.’

Oxidative Stress Parameters, Selenium Levels, DNA Damage, and Phthalate Levels in Plastic Workers.

Di(2-ethylhexyl)phthalate (DEHP) is the most widely used phthalate. DEHP is highly used in PVC floorings and PVC windows and carpeting. The objective of this study was to determine sex hormone levels, oxidative stress parameters, selenium levels, DNA damage, and phthalate levels in plastics workers (n = 24, age = 20-58 years) working in the production of rubber mechanical goods and exposed to DEHP in workplace. The control group (n = 29, age = 25-54, all male) was selected from age-matched healthy adults. Antioxidant parameters and DNA damage were determined by spectrophotometry. Selenium levels were determined by atomic absorption spectroscopy. Plasma hormone levels were measured by chemiluminescence microparticle immunoassay. Plasma phthalate levels were determined by high-pressure liquid chromatography. Plastic workers had lower serum testosterone and free T4 levels and higher follicle-stimulating hormone levels vs. controls. Liver enzyme activities were markedly higher in workers vs. controls. There were also increases in plasma glutathione peroxidase levels and marked decreases in plasma selenium and erythrocyte total glutathione levels in plastics workers (P < 0.05 vs. control). Plasma 8-hydroxy-2'-deoxyguanosine levels were 14-fold higher in plastics workers than in controls. Plasma DEHP and mono(2-ethylhexyl)phthalate were also markedly higher in workers vs. controls. The results of this study show that occupational exposure to DEHP may lead to disturbances in sex hormones, increased liver problems, higher oxidative stress and DNA damage levels, and lower trace element concentrations in workers. More comprehensive and mechanistic studies with higher numbers of subjects are needed to show the unwanted effects of occupational exposure to DEHP.