Total Testosterone Concentrations Research Articles

Associations between exposure to a mixture of phenols and sex steroid hormones among pre- and postmenopausal women: evidence from NHANES 2015-2016.

Environmental phenols are well known as emerging endocrine-disrupting chemicals; however, their impacts on sex hormone homeostasis among pre- and postmenopausal women remain unknown. Our objective was to evaluate independent and combined relationships between phenol levels in urine and sex steroid hormones among 323 premenopausal women and 263 postmenopausal women from National Health and Nutrition Examination Survey (NHANES) 2015-2016. A total of 10 phenol concentrations in urine were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Serum concentrations of estradiol and total testosterone were measured by LC-MS/MS and serum sex hormone-binding globulin (SHBG) concentrations were measured using an immunofluorometric assay. Multivariable linear regression models were conducted to explore associations of individual phenol concentration in urine with natural logarithm-transformed serum hormone levels. Bayesian kernel machine regression (BKMR) model was conducted to evaluate phenol mixtures exposure in association with sex hormones among pre- and postmenopausal women, respectively. Considering both single-chemical models and multiple-chemical models, each doubling of urinary BPS concentration was significantly inversely related to serum SHBG concentration in premenopausal women (percent change: -6.70%, 95% confidence interval, CI: -11.12%, -2.73%; P = 0.002). Moreover, every doubling of urinary BP-3 concentration was significantly positively associated with SHBG level in serum (percent change: 3.53%, 95%CI: 0.70%, 5.70%; P = 0.008). Regarding postmenopausal women, inverse associations between urinary BPS levels and serum estradiol concentrations were observed (percent change: -8.62%, 95% CI: -15.33%, -2.06%; P = 0.012). The results revealed that BPS and BP-3 exposure may adversely disrupt sex hormone homeostasis at the current exposure levels among women in the USA. The findings and their underlying mechanisms are warranted to be confirmed and comprehensively interpreted in further epidemiological and experimental studies.

Does vitamin D affect strength and speed characteristics and testosterone concentration in elite young track and field athletes in the North European summer?

BackgroundCurrently there are no data examining the relationship between the serum concentration of vitamin D bio-chemical marker 25(OH)D and strength and speed characteristics in elite young track and field athletes. Moreover, there are currently no data examining the correlation of vitamin D status with testosterone concentration in elite young track and field athletes. In studies involving members of the general population and athletes from other sports, conflicting data have been reported.Material and methodsAthletes (n = 68) from both genders took part in this study. Male athletes (n = 23) with mean ± SD age of 18.2 ± 1.9 years and female athletes (n = 45) with mean ± SD age of 17.3 ± 2.6 years participated. All athletes were ranked in the Top-3 in their respective age group and their corresponding results were listed in the Top-20 European records according to https://www.tilastopaja.eu/ in 2021.ResultsThe average 25(OH)D concentration was 36.5 ± 10.8 ng/mL and 37.8 ± 14.5 ng/mL in male and female athletes respectively. The prevalence of 25(OH)D deficiency (below 20 ng/ml) in both genders was only 5.8%. In the whole group, only 27.9% of athletes had 25(OH)D concentrations between 20 and 30 ng/ml, while 66.2% of athletes had concentrations above 30 ng/ml. There was no difference in vitamin D status between male and female athletes. There was no statistically significant Kruskal-Wallace test correlation between 25(OH)D concentration and performance in the 20 m and 30 m sprint, counter-movement jump and broad jump. There was no correlation between serum concentrations of 25(OH)D and total testosterone in either male or female athletes.ConclusionIn elite young track and field athletes who permanently live and train in an area above 50° north latitude, the prevalence of vitamin D deficiency in the summer months was much lower than in previously published studies examining an athletic population, that may be related to the training process. In this specific group of athletes, no correlation was found between serum 25 (OH) D concentration and strength and speed characteristics or total testosterone concentration.

Sexual dysfunction is highly prevalent in male survivors of malignant lymphoma.

With improved survival in patients with lymphoma, long-term toxicity and quality of life (QoL), including sexual health, have become increasingly important. We aimed to (1) determine the prevalence of erectile dysfunction (ED) in adult male lymphoma survivors; (2) determine whether testosterone deficiency, comorbidities, or lifestyle factors were associated; and (3) evaluate their impact on QoL. A cross-sectional study including 172 male survivors of Hodgkin lymphoma or diffuse large B cell lymphoma diagnosed in adulthood between 2008 and 2018 was performed. Patients were in complete metabolic remission after first-line treatment and remained in remission at follow-up (3-13years after diagnosis). Participants completed 3 questionnaires measuring sexual health and general QoL. Serum concentrations of total testosterone were measured and thorough medical history and sociodemographic factors were obtained. The Danish SEXUS Project, European Male Ageing Study, and European Organization of Research and Treatment of Cancer (EORTC) Reference Manual were used as reference values of the general population. Patient reported outcome measures including the 5-item International Index of Erectile Function, EORTC C30, and EORTC 22-item Sexual Health Questionnaire. ED was reported by 55.2%, which was higher than in an age-matched Danish population cohort (17.5%). Erectile function score (5-item International Index of Erectile Function) was negatively associated with comorbidity, body mass index, smoking, and age and positively with the number of children conceived before treatment and serum concentration of total testosterone. Overt testosterone deficiency in combination with ED was detected in 10 (5.7%) of 176 survivors, including excluded survivors in hormonal treatment, which is higher than for the general population (0.1%-3.2% for men <70years of age). Mean EORTC C30 global health score for survivors with ED was lower (67.7) than for survivors without ED (80.1) but was comparable to the general population (71.2). Furthermore, a positive association was seen between sexual function and both sexual and general QoL. Sexual health is important for QoL and related to comorbidities. The focus on improving QoL requires that both sexual health and comorbidities are addressed in the follow-up of lymphoma patients. Despite the relatively high number of included survivors, the cross-sectional design of this study warrants longitudinal studies to clarify the specific underlying causes of sexual dysfunction. ED was highly prevalent and associated with comorbidity in lymphoma survivors, and more focus on sexual health and treatment related comorbidity is needed to improve sexual and general QoL.

Рівень гормонів у підлітків із фізіологічним і патологічним перебігом пубертатного періоду за різної інтенсивності фізичної активності

Scientific evidence suggests a global pandemic of motor inactivity in adolescents that contributes to a number of chronic diseases. At the same time, regular physical activity has a favorable effect on the growth and sexual development of children and adolescents. Purpose - to evaluate the influence of physical activity (PA) on the hormonal blood spectrum of adolescents with physiological and pathological course of puberty. Materials and methods. We examined 55 boys and 46 girls aged 11-17 years old. Concentration of total testosterone, estradiol, cortisol, prolactin was determined by enzyme immunoassay, serotonin content was determined by fluorometric method. PA was studied using the questionnaire of IPAQ (International Physical Activity Questionnaire). Depending on the course of pubertal period adolescents were divided into 2 groups: the Group 1 - with physiological course of puberty; the Group 2 - with pathological course of puberty (boys with delayed puberty and girls with menstrual disorders). Adolescents were divided into 2 groups according to their PA level: low (&lt;7 points) and high (&gt;9 points) levels of PA. Results. It was found that in boys with a physiological course of puberty high PA compared with low activity leads to an increase in testosterone concentration and has a positive effect on physical development. High PA, on the contrary, decreases the content of testosterone in the pathological course of puberty and possibly aggravates puberty in boys. In girls high PA against the physiological course of puberty leads to an increase in serotonin, an indicator of the stress-limiting system. In the pathological course of puberty high PA has a positive effect, reducing the levels of testosterone and prolactin compared with low activity, which may contribute to the normalization of menstrual function, as well as reducing stress levels. Conclusions. Physical activity in adolescents should continue to be encouraged, given its positive effect on the hormonal blood spectrum. However, gender differences, pubertal development status and different mechanisms of adaptation to PA of girls and boys should be taken into account. It is very important to determine the optimal level of PA to meet the needs of children and adolescents, which would have a beneficial effect on both physical and psycho-emotional development. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Liver phenotypes in PCOS: Analysis of exogenous and inherited risk factors for liver injury in two European cohorts.

Fatty liver disease (FLD) is common in women with polycystic ovary syndrome (PCOS). Here, we use non-invasive tests to quantify liver injury in women with PCOS and analyse whether FLD-associated genetic variants contribute to liver phenotypes in PCOS. Prospectively, we recruited women with PCOS and controls at two university centres in Germany and Poland. Alcohol abuse was regarded as an exclusion criterion. Genotyping of variants associated with FLD was performed using TaqMan assays. Liver stiffness measurements (LSM), controlled attenuation parameters (CAP) and non-invasive HSI, FLI, FIB-4 scores were determined to assess hepatic steatosis and fibrosis. A total of 42 German (age range 18-53 years) and 143 Polish (age range 18-40 years) women with PCOS, as well as 245 German and 289 Polish controlswere recruited. In contrast to Polish patients, Germans were older, presented with more severe metabolic profiles and had significantly higher LSM (median 5.9 kPa vs. 3.8 kPa). In the German cohort, carriers of the PNPLA3 p.I148M risk variant had an increased LSM (p=.01). In the Polish cohort, the minor MTARC1 allele was linked with significantly lower serum aminotransferases activities, whereas the HSD17B13 polymorphism was associated with lower concentrations of 17-OH progesterone, total testosterone, and androstenedione (all p < .05). FLD is common in women with PCOS. Its extent is modulated by both genetic and metabolic risk factors. Genotyping of variants associated with FLD might help to stratify the risk of liver disease progression in women suffering from PCOS.

Low Free Triiodothyronine as a More Sensitive Predictor of Survival Than Total Testosterone among Dialysis Men.

Some endocrine disorders, previously considered benign, may be related to a poorer prognosis for patients with renal failure. Both low serum free triiodothyronine (fT3) and low total testosterone (TT) concentrations have been considered as predictors of death in dialysis patients, but the results of studies are inconsistent. In our study, we evaluated the relationships of the serum thyroid hormone levels and the total testosterone levels with survival in male dialysis patients. Forty-eight male dialysis patients, 31 on hemodialysis (HD) and 17 on peritoneal dialysis (PD), aged 61.4 ± 10.0, 59.2 ± 12.2 years, respectively, were included in the study. Serum thyroid hormones and total testosterone were measured. During the 12-month follow-up, nine all-cause deaths were recorded. The concentrations of fT3 were significantly lower in those who died than in the survivors (p = 0.001). We did not observe any statistically considerable differences between the group of men who died and the rest of the participants in terms of the total serum testosterone concentration (p = 0.350). Total testosterone positively correlated with fT3 (r = 0.463, p = 0.009) in the HD group. In the group of male dialysis patients, the serum concentration of fT3 had a better prognostic value in terms of survival than the total testosterone. A linear relationship between the fT3 levels and testosterone levels in men undergoing hemodialysis may confirm the hypothesis that some of the hormonal changes observed in chronic kidney disease (CKD) may have a common cause.

Urine glyphosate exposure and serum sex hormone disruption within the 2013–2014 National Health and Nutrition Examination survey (NHANES)

Glyphosate-based herbicides (GBHs) are one of the most commonly used herbicides worldwide. Numerous in vitro and in vivo model system studies have demonstrated endocrine-disrupting chemical (EDC) properties associated with glyphosate/GBH exposure. The present hypothesis-testing study evaluated the potential inverse dose-dependent relationship between increasing urinary glyphosate and decreasing concentrations of blood sex hormones. Demographic and newly available lab test data from the 2013–2014 National Health and Nutrition Examination Survey (NHANES) were analyzed with survey regression modeling (adjusted for age, gender, race, and country of birth) in Statistical Analysis System (SAS) software. A total of 225, 615, 858 weighted-persons (sample n = 2130 persons) were examined for concentrations of urinary glyphosate and serum sex hormones (including: total testosterone, total estradiol, and sex hormone binding globulin (SHBG)) among males and females, 6 years-old or older. This study revealed about 82% of the population of the United States examined had detectable urinary concentrations of glyphosate. A significant inverse correlation between concentrations of glyphosate and total estradiol and a trend towards an inverse correlation between concentrations of glyphosate and total testosterone were observed. Concentrations of SHBG and glyphosate did not correlate. Ratios of total testosterone:SHBG and total estradiol:SHBG (estimating the fraction of active sex hormones in the blood) were significantly inversely correlated with urinary concentrations of glyphosate. This epidemiological study associates widespread and ongoing glyphosate/GBH exposures with human endocrine-disruptions. Future studies should examine these phenomena in other databases and other endocrine-related disorders.

Age, weight and circulating concentrations of total testosterone are associated with the relative prostatic size in adult intact male dogs

Prostatic hyperplasia (PH) is an androgen-dependent condition associated with increased prostatic size that is common in intact dogs, and similar to the condition in men. In dogs, the increase in prostatic size is most prominent the first years, and after approximately four years (in beagles), a plateau is reached, and further growth is slower. Why the prostate continues to grow more in some individuals is not clear. Most testosterone in the circulation is bound to albumin or sex hormone binding globulin (SHBG) and only a minor part is unbound and biologically active. The binding to SHBG has higher affinity than that to albumin. In addition, SHBG has own biological functions, modifying testosterone action. The aim of the present study was to investigate if there is an association between relative prostatic size and the variables total testosterone concentration, SHBG concentration, an estimation of bioavailable testosterone: the ratio between testosterone and SHBG (free androgen index, FAI), estradiol concentration, the estradiol/testosterone ratio, dog age and dog weight. Hormone concentrations were measured in serum from 79 intact male dogs aged ≥ four years, weighing ≥ five kg. The size of the prostate was estimated using ultrasonography, and relative prostate size, Srel, was calculated as the estimated size related to the normal size for a 4-year-old dog of the same weight. There as a negative correlation between testosterone concentration and age (ρ = −0.27, P = 0.018) and a positive correlation between age and Srel (ρ = 0.27, P = 0.016) and between SHBG and weight (ρ = 0.38, P = 0.001). The FAI was negatively correlated with dog weight (ρ = −0.32, P = 0.004). There were no significant correlations between Srel and SHBG or FAI or between estradiol or estradiol/testosterone and Srel, age or weight. A multiple regression analysis showed significant associations between log Srel and log testosterone concentration, log age and log weight of the dog, with an adjusted R2 of 9.5%. Although the variables total testosterone concentration, age and weight of the dog were all significantly associated with Srel, the coefficient of determination was low, indicating that they only explained a minor part of the prostatic size. The results support the analysis of total testosterone in studies of prostatic growth in the dog.

Effects of aging and the body mass index on male sex hormones: a cross-sectional study in 701 Brazilian men

Background: Some studies indicated that body mass index (BMI) is inversely proportional to serum testosterone concentrations in men. Purposes: This study aimed to analyze the effects of aging and obesity on total testosterone (TT), free testosterone (FT), bioavailable testosterone (BT), luteinizing hormone (LH), and sex hormone-binding globulin (SHBG) levels. Methods: A cross-sectional study was performed to assess the clinical and laboratory profiles of 701 patients treated at a private urology clinic in Ponta Grossa, Brazil, from January 2016 to December 2018. Results: Patients’ age ranged from 16 to 88 years (mean, 56.9 ± 13.62 years). Age did not significantly influence serum TT concentrations, except compared to patients aged &gt;70 years. However, changes were observed in FT and BT (p &lt; 0.05). The mean SHBG increased with age (p &lt; 0.05). A tendency toward LH elevation was observed in older patients, but it was not statistically significant. An inverse proportional relationship between TT, FT, and BT and the testosterone deficiency rate (TT &lt; 300 ng/dL) was observed within BMI groups (p &lt; 0.05). The testosterone deficiency rate was 21.5% in individuals with normal BMI, 29% in overweight individuals, and 37% in obese individuals. Conclusions: Aging affected the testosterone concentrations in men and became increasingly evident using FT and BT instead of TT. SHBG increased with age. Obesity was associated with a decrease in TT, FT, and BT but also increased the rate of hypogonadism.

Acute Hormonal Responses to Multi-Joint Resistance Exercises with Blood Flow Restriction.

The purpose of this study was to investigate the acute effects of multi-joint resistance exercises (MJRE) with blood flow restriction on hormonal responses. Ten men participated in the study and underwent two experimental protocols in random order: four sets (30, 15, 15, and 15 reps, respectively) of MJRE (half squat and horizontal chest press) were performed with 20% of 1RM and a rest time between sets of 30 s, combined with intermittent blood flow restriction (LI + BFR protocol); and four sets (8, 8, 8, 20 reps, respectively) of the same MJRE performed with 75% of 1RM load (HI protocol), with a 90 s rest between the first three sets and 30 s between the third to the fourth set. Blood samples were collected before (PRE), immediately after (POST), and 15 min after the performance of MJRE (POST15). A time effect was observed for growth hormone (GH) and insulin-like-growth-factor-1-binding-protein-3 (IGFPB-3), but no protocol effects or interactions between protocol and times were observed (p > 0.05). There was no effect of either protocol or time (p > 0.05) on total testosterone, free testosterone, or cortisol concentrations. However, significant (p < 0.05) increases were observed in the GH serum concentrations of 2072.73% and 2278.5%, HI, and LI + BFR protocols, respectively, from the PRE to POST15 test. In addition, there was an increase of 15.30% and 13.29% in the IGFPB-3 concentrations (p < 0.05) from PRE to POST0 times for HI and LI + BFR protocols, respectively. Furthermore, there was a decrease of −6.17% and −11.54%, p = 0.00, between the times POST0 to POST15 in the IGFPB-3 for the HI and LI + BFR protocols, respectively. It is concluded that multi-joint resistance exercises combined with intermittent blood flow restriction seemed to promote acute hormonal responses in a manner similar to traditional exercise with high loads. Future studies may investigate whether chronic use of LI + BFR with MJRE may promote muscle hypertrophy.

Associations between cognitive function and endogenous levels of estradiol and testosterone in adults with Type 2 diabetes?

AbstractBackgroundType 2 diabetes mellitus (T2D) accelerates cognitive decline in women and men. Among older women, prior reports suggest that higher endogenous estradiol levels may further accelerate the cognitive decline associated with T2D and increase risks for cognitive impairment. Testosterone may interact directly with cognitive decline in T2D, or through its conversion to estradiol via the aromatase enzyme.MethodsEstradiol (E2) and total testosterone (TT) concentrations were determined using stored serum from 996 individuals, mean (±SD) age 69±6 and not receiving hormone therapies, collected at two times (averaging 4 years apart). Serum was collected during follow‐up years 8‐18 of the Look AHEAD cohort, a randomized controlled clinical trial of a 10‐year behavioral weight loss intervention in individuals with T2D and overweight or obesity at trial enrollment. One to four standardized assessments of attention, executive function, memory, and verbal fluency were collected during follow‐up years 8‐18. Mixed effects models were used to assess associations that E2 and TT concentrations had with current body mass index (BMI) and cognitive function.ResultsGreater current BMI was associated with higher E2 concentrations in women and men, and greater TT concentrations in women, but lower TT concentrations in men (all p&lt;0.001). The weight loss intervention did not leave a legacy of differences in E2 and TT concentrations. E2 concentrations were not associated with cognitive function in women or men. TT concentrations were not associated with cognitive function in women, but greater TT concentrations were associated with better verbal fluency in men (p&lt;0.001), most strongly among those carrying the APOE‐e4 allele (interaction p = 0.02). While the weight loss intervention left a legacy of relatively lower cognitive functioning among women, this was not mediated by current concentrations of E2 and TT.ConclusionsContrary to prior reports, we found no evidence that higher endogenous E2 concentrations were related to worse cognitive functioning in women with T2D. Higher TT concentrations were associated with better verbal fluency in men, but not women. The legacy of modestly lower cognitive function in women left by a 10‐year weight loss intervention was unrelated to any long‐term alterations in E2 or TT concentrations.

Relationship between Serum Testosterone Level and Carotid Intima-Media Thickness among Korean Men and Postmenopausal Women.

Given that the role of serum testosterone on incident cardiovascular disease has been uncertain, it is necessary to find out the relationship between serum testosterone and carotid atherosclerosis. The study participants included 1,302 Korean adults (873 men and 429 postmenopausal women) who participated in the Healthy Twin Study and were not receiving androgen deprivation therapy. The participants were classified into three groups: men aged <40 and ≥40 years and postmenopausal women. Total testosterone (TT) and sex hormone-binding globulin (SHBG) concentrations were measured using electrochemiluminescence immunoassays, and free testosterone (cFT) levels were calculated using Vermeulen's method. Carotid intima-media thickness (IMT) was measured at three levels using a high-resolution B-mode ultrasound equipped with a 7-MHz linear transducer. The associations between sex hormone concentrations and carotid IMT were evaluated using a mixed linear regression analysis. After adjusting for cardiovascular risk factors, TT was found to be inversely associated with common carotid IMT in men aged ≥40 years, with a 4.5% decrease in common carotid IMT for every one-standard deviation increase in TT concentration (P=0.0063). In contrast, TT was not significantly associated with carotid IMT in all segments in men aged <40 years and postmenopausal women. Additionally, SHBG and cFT were not associated with carotid IMT in any segment. The significant association between TT level and common carotid IMT in men aged ≥40 years suggests that decreased testosterone levels are involved in the development of atherosclerosis in men.

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.

ODP419 Measurement of Free Testosterone in Serum using Equilibrium Dialysis Coupled with ID-UHPLC-MS/MS: in Comparison to Calculated FT

Abstract Assessment of free testosterone (FT) has been recommended in recent clinical practice guidelines as a biomarker for diagnosis and management of testosterone related disorders such as male testosterone deficiency due to hypogonadism and female androgen excess due to polycystic ovary syndrome (PCOS). FT is currently measured using direct commercial immunoassays, assays using equilibrium dialysis (ED) or other separation techniques, or estimated by calculating free testosterone (cFT) using different formulas. The most widely used formula was developed by Vermeulen et al and uses total testosterone and sex hormone binding globulin (SHBG) concentrations. The ED approach is recognized as the gold standard; however, it is technically challenging for routine clinical use. CDC's Clinical Standardization Program (CDC CSP) has developed a high throughput method using ED coupled with isotope dilution ultra-high-performance liquid chromatography tandem mass spectrometry. The study to evaluate the agreement of this ED-based method to the cFT using different algorithms is being conducted. Serum samples are dialyzed in a custom-designed multi-well plate against a protein-free HEPES buffer (pH 7.4) at 37 °C until equilibrium. After isolating endogenous FT from protein-bound testosterone by ED, isotope-labeled internal standard (13C3-testosterone) was added to the resulting dialysate for quantification. Certified pure primary reference material (National Measurement Institute-M914) was used to prepare calibrators, enabling traceable quantitation and ensuring measurement trueness. FT was further isolated from the dialysate matrix using supported liquid extraction and a chromatographic separation from interfering compounds and quantitation by tandem MS. The assay allowed detection of 2.9 pg/mL FT, with the bias within ± 5% and precision less than 10% CV. A total of 45 samples with a wide range of TT (21-912 ng/dL) and SHBG (11-129 nmol/L) were analyzed. The obtained FT values were compared to the cFT values obtained with the Vermeulen algorithm. The mean difference of 34.1% (95% CI 29.1% to 39.9%) between the measured and calculated FT were observed, with majority of the calculated values overestimating FT concentrations. The described high throughput method for FT allows for sufficiently accurate and precise measurement and can provide more reliable FT measurements compared to cFT (that can lead to overestimation of FT) for routine applications including large epidemiologic studies. Presentation: No date and time listed

Androgen receptors immunoreactivity in the rat brain of males with same-sex preference

Androgen receptors (AR) are crucial in the control of male sexual behavior and sex preference. AR are particularly concentrated in areas related with the neuroendocrine control of sex preference including the medial amygdala (MeA), the ventromedial nucleus of the hypothalamus (VMH), the bed nucleus of the stria terminalis (BNST), the medial preoptic area (MPOA), the nucleus accumbens (Acb), the suprachiasmatic (SCh) and supraoptic (SO) nuclei, but also seem to be important for the control of reproductive processes in the hippocampus (CA1-CA4 and dentate gyrus, DG). In the present study we analyzed the density of AR in these brain areas of adult male rats with sexual preference (established in a three-compartment box). Same-sex preference was produced in male rats by the prenatal administration of the aromatase inhibitor, letrozole (0.56 μg/kg/ml s.c. G10-22) that usually produces 1–2 animals per litter with same sex preference, while the others retain a female sex preference. We also included a group of proestrus females that had a clear preference for a sexually active male. AR were analyzed by immunocytochemistry using PG21 as primary antibody. We also measured total plasma testosterone concentrations by radioimmunoassay. In males with same sex preference there was a specific AR overexpression in CA3 and CA4 that suggests a feminized pattern because females in proestrus trend to show a higher density of AR in these hippocampal areas. Sex differences in AR density were found in the anterior cingulate cortex (ACg) and frontoparietal cortex (FrPa). Serum levels of testosterone did not differ between groups. Data are discussed based on the role of AR in the hippocampus.

PMON267 Comparison Between Single Time Point Testing and 24-Hour Average Concentration of Total Testosterone in Hypogonadal Men Treated with an Oral Testosterone Undecanoate Softgel (JATENZO®)

Abstract In 2019, a novel, first-in-class testosterone (T) replacement therapy (TRT), oral testosterone undecanoate (TU) was approved by the U.S. FDA for the treatment of male hypogonadism. During clinical trials, dose adjustments were based on 24-hr average T concentration (Cavg) because single T measurements were considered less accurate. Subsequent, concordance analyses for this oral TU product have shown that a single total T value 6-hrs after the morning oral TU dose best corresponds to Cavg. Nonetheless, a conversion factor for T values obtained at other post-dose time points would be useful for healthcare providers (HCPs) and ease potential scheduling challenges for patients. Consequently, the relationship between other T sampling time points and Cavg was examined to determine if a reliable conversion factor could be derived to help HCPs monitor a patient's serum T concentration at times other than 6-hrs after oral TU administration. Hypogonadal men, age 18–65 y/o, were recruited into a randomized, open-label, multicenter, dose-titration trial. Overall, 166 men were randomized into the oral TU arm. Dose titration was based on Cavg calculated from serial pharmacokinetic (PK) samples. There were three pre-designated PK visits, to individualize the appropriate TU dose and to achieve a eugonadal T Cavg by the final study visit. Ratios between different timepoints and Cavg were determined for PK samples following morning drug administration. Overall, 87.3% (95% CI: 81.3%, 92.0%) of hypogonadal men had a final Cavg in the eugonadal range, with a mean serum total T = 488.7 ± 154.5 ng/dL (16.95 ± 5.37 nmol/L). Pooled values from all PK days demonstrated a linear relationship between T concentrations at 4, 6, and 9-hrs and Cavg (p &amp;lt; 0.0001). Visit and time of sampling interaction were not statistically significant (p &amp;gt;&amp;gt; 0.50), indicating consistency in results among PK visits and among sampling timepoints. A factor was derived to enable conversion of T values assessed at a time other than 6-hrs (post oral TU dose) into a close approximation of Cavg: 1/[1.870–0.14×(hours after AM dose)]. Therefore, a sample drawn at 4-hrs after the morning oral TU dose would be multiplied by 0.75; while one drawn at 8-hrs would be multiplied by 1.33. Hence, T Cavg can be approximated after morning JATENZO administration if a blood sample cannot be collected precisely 6-hrs thereafter. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Testosterone Deficiency and Nutritional Parameters as Predictors of All-Cause Mortality among Male Dialysis Patients.

Chronic kidney disease (CKD) is associated with an accelerated risk of cardiovascular mortality. Hormonal and metabolic disorders in CKD may constitute novel risk factors. Our objective was to characterize and evaluate prognostic implications of circulating sex steroids and selected nutritional parameters in patients at different stages of CKD. Studied groups were composed of 78 men: 31 on hemodialysis (HD), 17 on peritoneal dialysis (PD), 30 with CKD stage G3-G4. Total testosterone (TT), dehydroepiandrosterone sulphate (DHEA-S), androstenedione, luteinizing hormone (LH), prolactin (PRL), and biochemical parameters were measured; Free testosterone (FT) was calculated. The lowest TT and FT were observed in HD, the highest- in CKD (p = 0.006 for TT, p = 0.005 for FT). TT positively correlated with total cholesterol in HD (p = 0.012), FT negatively correlated with BMI in CKD (p = 0.023). During the 12 months, 9 patients died (5 in the HD, 4 in the PD group). The deceased group had significantly lower concentrations of albumin (p = 0.006) and prealbumin (p = 0.001), and a significantly higher concentration of androstenedione (p = 0.019) than the surviving group. In the group of men on dialysis, a serum TT concentration &lt;2.55 ng/mL (Q1-first quartile) was associated with a 3.7-fold higher risk of death, although statistical significance was not achieved (p = 0.198). After analysis of the ROC curves, the FT level was the best prognostic marker in HD (AUC = 0.788; 95% CI: 0.581-0.996; p = 0.006) Conclusions: Total and free testosterone levels were lower in the HD group than in the CKD group. The nutritional status undoubtedly affects the survival of dialysis patients but also the concentrations of testosterone significantly contributes to further worsening the prognosis.

Predicting pregnancy chances leading to term live birth in oligo/anovulatory women diagnosed with PCOS

Research questionWhich patient features predict the time to pregnancy (TTP) leading to term live birth in infertile women diagnosed with polycystic ovary syndrome (PCOS)? DesignProspective cohort follow-up study was completed, in which initial standardized phenotyping was conducted at two Dutch university medical centres from January 2004 to January 2014. Data were linked to the Netherlands Perinatal Registry to obtain pregnancy outcomes for each participant. All women underwent treatment according to a standardized protocol, starting with ovulation induction as first-line treatment. Predictors of pregnancies (leading to term live births) during the first year after PCOS diagnosis were evaluated. ResultsA total of 1779 consecutive women diagnosed with PCOS between January 2004 and January 2014 were included. In the first year following screening, 659 (37%) women with PCOS attained a pregnancy leading to term birth (≥37 weeks of gestational age). A higher chance of pregnancy was associated with race, smoking, body mass index (BMI), insulin, total testosterone and sex hormone-binding globulin (SHBG) concentrations (c-statistic = 0.59). ConclusionsPredictors of an increased chance of a live birth include White race, no current smoking, lower BMI, insulin and total testosterone concentrations, and higher SHBG concentrations. This study presents a nomogram to predict the chances of achieving a pregnancy (leading to a term live birth) within 1 year of treatment.

Smoking promotes vascular damage in apparently healthy men with low testosterone and increased subclinical inflammation

Abstract Background Testosterone deficiency and increased inflammation are both associated with an unfavourable vascular profile. Aim of the study was to examine whether smoking significantly deteriorates the effect of these pathophysiological mechanisms on arterial wall properties. Methods Carotid intima media thickness (cIMT) and aortic pulse wave velocity (aPWV) were measured in 87 smokers and 112 aged-matched never smokers (mean age: 49±5 yrs) with no other cardiovascular (CV) risk factors/or manifest CV/atherosclerotic disease. Plasma total testosterone (TT) and high sensitivity reactive protein (hsCRP) levels were measured in the whole study population. Results Both smokers and never smokers were divided into four subgroups according to measured low or normal TT levels (low TT&amp;lt;3.5 ng/ml) and high or low hsCRP levels. BMI and LDL-C levels were not different between the subgroups. In smokers the four TT/CRP subgroups had comparable cumulative tobacco smoke exposure. In smokers the low TT/high CRP subgroup had significantly higher aPWV and cIMT compared to the three other subgroups (P&amp;lt;0.01 and P&amp;lt;0.05, respectively by ANOVA, figures A-B) while in never smokers the four TT/CRP subgroups had comparable aPWV and cIMT (all P&amp;gt;0.05, figures C-D). The differences in aPWV and cIMT measurements between TT/CRP subgroups in smokers remained statistically significant after adjustment for age. Conclusions The study shows that low TT combined with high CRP are associated with increased carotid IMT and aortic PWV in smokers with no other CV risk factors, while in never smokers the effect of combined low TT and high CRP concentration was not significant. Considering the predictive value of aortic stiffness and carotid thickness, the finding of this study imply interrelationships between tobacco cigarette smoke, subclinical inflammation and low testosterone level regarding changes in arterial wall properties. Funding Acknowledgement Type of funding sources: None.

Association of Exposure to Phthalate Metabolites With Sex Hormones, Obesity, and Metabolic Syndrome in US Women

Obesity and metabolic syndrome are highly prevalent among the US population and are associated with the dysregulation of sex hormones. An increase in obesity and metabolic syndrome may also be associated with exposure to phthalates. The association of exposure to phthalate metabolites with sex hormones and metabolic health has been understudied in the female population. To evaluate the association between exposure to common phthalate metabolites with total testosterone (TT) levels, sex hormone-binding globulin (SHBG) levels, obesity, and metabolic syndrome among women. This cross-sectional study used data collected from the National Health and Nutrition Examination Survey during 2013 to 2016. Female participants aged 15 years or older with urinary profiles containing common phthalate metabolites were included in this study. Statistical analyses were performed from March 15, 2021, to April 30, 2022. Urinary concentrations of phthalate metabolites were classified into tertiles, and the lowest tertile was used as a reference category. The concentrations of phthalate metabolites and their composite scores based on clustering were also used in the analysis. Serum concentrations of TT and SHBG were dichotomized into high TT levels (>46 ng/dL [to convert to nanomoles per liter, multiply by 0.0347] for age <50 years and >32 ng/dL for age ≥50 years) and low SHBG levels (<2.85 μg/mL [to convert to nanomoles per liter, multiply by 10.53]) as established for the female population. Obesity was defined as a body mass index of 30 or more (calculated as weight in kilograms divided by height in meters squared), and metabolic syndrome was defined using the National Cholesterol Education Program criteria. The serum concentrations of TT and SHBG were also included in the validation analyses. Modified Poisson models were used to estimate the adjusted relative risk (RR) with 95% CIs for the associations. Among the 2004 women included in this study, the mean (SD) age was 46.6 (18.5) years (14.7% Hispanic participants, 62.7% non-Hispanic White participants, and 13.2% non-Hispanic Black participants; 17.4% of participants were born outside the US [weighted percentages]; 230 (11.8%) had high TT levels, 210 (10.4%) had low SHBG levels, 825 (39.8%) had obesity, and 965 (45.5%) had metabolic syndrome (weighted percentages). Of the 13 phthalate metabolites, 8 had the highest tertile level greater than 6.2 ng/mL (range, 0.5-75.2 ng/mL). High levels of exposure to mono(2-ethyl-5-carboxypentyl) phthalate (RR, 1.84 [95% CI, 1.33-2.54]), mono(2-ethyl-5-oxohexyl) phthalate (RR, 1.77 [95% CI, 1.21-2.59]), mono(2-ethyl-5-hydroxyhexyl) phthalate (RR, 1.94 [95% CI, 1.34-2.81]), and monobenzyl phthalate (RR, 1.75 [95% CI, 1.21-2.54]) were associated with low SHBG levels but not with high TT levels. High levels of exposure to some of these metabolites were also associated with obesity and metabolic syndrome. Most associations were specific to premenopausal or postmenopausal women. In this cross-sectional study, exposure to certain phthalate metabolites could be associated with low SHBG levels, obesity, and metabolic syndrome depending on menopausal status.