Higher Testosterone Concentrations Research Articles

Photoperiodism, testosterone and adult neurogenesis in canaries (Serinus canaria).

Domestic strains of canaries (Serinus canaria) variably respond to photoperiod changes and apparently stay in breeding state for extended periods. Fife Fancy canaries are supposed to be similar to the native species living at 27-39° north where photoperiod significantly changes across the year. Our birds showed reproductive cycles when exposed to light regimes mimicking the annual cycle of photoperiod. However after 6 months in short days (SD: 8L:16D), males developed large testes, as observed by X-ray tomography, and intense singing. Switching to long days (LD: 16L:8D) did not further increase song rate nor testes size but increased song duration, number of syllables per song, and trill occurrence frequency. No sign of regression was observed after 12 weeks in LD but return to SD produced a rapid decrease in testes size and singing activity below values in birds maintained throughout in SD. Fife Fancy thus does not seem to develop absolute but only relative refractoriness. The relatively high singing activity expressed by SD-photosensitive males does not seem to depend on high testosterone (T) concentrations. Singing did not correlate with plasma testosterone (T). Treatment with ATD + Flutamide only marginally decreased song rate and did not affect song quality nor song control nuclei volume. These birds are either supersensitive to low T levels or their reproductive physiology is activated by other mechanisms. Neurogenesis is increased by T and by LD but the function of new neurons incorporated in HVC is poorly understood. We developed a procedure based on X-ray focal irradiation to deplete neural progenitors adjacent to HVC and study the functional consequences. The decrease in neurogenesis increased the variability of T-induced songs in females and decreased their bandwidth. Neurogenesis in HVC thus plays a role in song production and X-ray focal irradiation represents an excellent tool to analyze adult neurogenesis.

Decreased AMPK/SIRT1/PDK4 induced by androgen excess inhibits human endometrial stromal cell decidualization in PCOS

Polycystic ovary syndrome (PCOS) is a complex common endocrine disorder affecting women of reproductive age. Ovulatory dysfunction is recognized as a primary infertile factor, however, even when ovulation is medically induced and restored, PCOS patients continue to experience reduced cumulative pregnancy rates and a higher spontaneous miscarriage rate. Hyperandrogenism, a hallmark feature of PCOS, affects ovarian folliculogenesis, endometrial receptivity, and the establishment and maintenance of pregnancy. Decidualization denotes the transformation that the stromal compart of the endometrium must undergo to accommodate pregnancy, driven by the rising progesterone levels and local cAMP production. However, studies on the impact of hyperandrogenism on decidualization are limited. In this study, we observed that primary endometrial stromal cells from women with PCOS exhibit abnormal responses to progesterone during in vitro decidualization. A high concentration of testosterone inhibits human endometrial stromal cells (HESCs) decidualization. RNA-Seq analysis demonstrated that pyruvate dehydrogenase kinase 4 (PDK4) expression was significantly lower in the endometrium of PCOS patients with hyperandrogenism compared to those without hyperandrogenism. We also characterized that the expression of PDK4 is elevated in the endometrium stroma at the mid-secretory phase. Artificial decidualization could enhance PDK4 expression, while downregulation of PDK4 leads to abnormal decidualization both in vivo and in vitro. Mechanistically, testosterone excess inhibits IGFBP1 and PRL expression, followed by phosphorylating of AMPK that stimulates PDK4 expression. Based on co-immunoprecipitation analysis, we observed an interaction between SIRT1 and PDK4, promoting glycolysis to facilitate decidualization. Restrain of AR activation resumes the AMPK/SIRT1/PDK4 pathway suppressed by testosterone excess, indicating that testosterone primarily acts on decidualization through AR stimulation. Androgen excess in the endometrium inhibits decidualization by disrupting the AMPK/SIRT1/PDK4 signaling pathway. These data demonstrate the critical roles of endometrial PDK4 in regulating decidualization and provide valuable information for understanding the underlying mechanism during decidualization.

Limited association between stallion-like behavior and hormonal indicators of testicular remnants in geldings

Persistent stallion-like behavior is a common sign of cryptorchidism in supposed geldings. The presence of testicular tissue can be evaluated by analyzing hormones such as testosterone and anti-Müllerian hormone (AMH). Here, we used hormonal analysis to investigate relationships between the likely presence of testicular tissue and stallion-like behavior in samples submitted from presumptive geldings (n = 1,202), retrospectively. Most geldings with stallion-like behaviors had serum concentrations of testosterone (851/1,056; 80.6 %) and AMH (682/877; 77.8 %) below the laboratory reference range for cryptorchids (< 60 pg/mL and ≤ 0.15 ng/mL for testosterone and AMH, respectively). A total of 13 samples (13/716; 1.8 %) showed AMH concentrations typical for geldings but testosterone above the cryptorchid range. Conversely, 31 samples (31/716; 4.3 %) had high AMH, suggesting cryptorchidism, but testosterone concentrations implied no testicular tissue. Among the cryptorchid stallions, the AMH and testosterone concentrations did not vary based on the season. However, age categories affected the concentration of both hormones among the presumptive true cryptorchid stallions. The results of this study demonstrate that undesirable behavior in geldings is rarely associated with the presence of testicular tissue, as assessed by these two hormonal biomarkers. This information highlights the complexity of behavior and demonstrates that persistent stallion-like behavior in geldings could be related to factors other than the presence of testicular tissue.

Muscle hypertrophy in athlete training from a medical point of view - what do we know

Introduction&#x0D; Hypertrophy is the process of increasing the mass of a tissue. In this article, we focused on the impact of the mechanisms of muscle hypertrophy, its effect on the human body, correlation with the course of diseases and tolerance of treatment. We considered the benefits of having well-developed, and also touched on the problems of underdeveloped muscle mass.&#x0D; Results&#x0D; The main factors causing hypertrophy are resistance exercise training, mechanotransduction, metabolic pathways, ribosomal biogenesis, gene expression and the impact of hormones. The beneficial effect of high concentrations of testosterone and growth hormone, also IGF1, on skeletal muscle hypertrophy has been proven. On the other side, the studies have shown that high concentrations of glucocorticoids, such as cortisol are associated with reduced muscle mass.&#x0D; There are many positive aspects of a well-developed muscle mass such as an impact on the prognosis in patients with cancers and sometimes reduces mortality among them. The problems of low muscle mass and sarcopenia are also mentioned. Low muscle mass can affect the poor prognosis of diseases such as cancer, hepatic cirrhosis and COVID-19. Postoperative complications are more common in patients with low muscle mass. One way to prevent this process may be to introduce resistance exercise training in patients struggling with problems of muscular atrophy.&#x0D; Conclusion&#x0D; Skeletal muscles have multiple functions in the human body. In addition to movement, they play a role in molecular processes like hormonal regulation. In addition, they can, when well developed, positively influence healing processes and the course of disease.

Dietary mannan-oligosaccharides enhance hematological and biochemical parameters, reproductive physiology, and gene expression of hybrid red tilapia (Oreochromis niloticus x O. mossambicus)

This study was carried out to evaluate the effects of dietary supplementation of mannan-oligosaccharides (MOS) on physiological performance, reproduction capacity and gene expression of hybrid red tilapia (Oreochromis. niloticus x O. mossambicus) broodstock reared in concrete tanks (3.5 × 3.2 × 0.9 m). Four isonitrogenous (30% cp), isocaloric (18.72 MJ kg−1) diets containing 0.0, 0.5, 1.0 and 1.5 g kg‐1 MOS were prepared. The diets were fed to triplicate groups of red tilapias broodfish (155 ± 5.65 g) stocked at a male: female ratio of 1:3, to satiation twice a day for two months. At the termination of the feeding trial, fish in each tank were netted and weighed. Blood samples were collected from five fish per tank to determine the hematological and biochemical parameters. The fish were then dissected for assessing the reproductive performance and its related genes. The results indicate that the values of hematological parameters (RBCs, Hb, and Htc) total protein, albumin, globulin, and reproductive hormones (testosterone, follicle-stimulating hormone and luteinizing hormone) were significantly increased by MOS dietary inclusion (1.0–1.5 g kg-1), while liver function enzymes including alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were significantly decreased in fish fed with 1.5 g /kg of MOS (p < 0.05). Reproductive performances, including GSI, total number of fries per female and mean fry weight were significantly improved with increasing dietary MOS to 1.5 g kg−1. Gonads maturation was also enhanced with supplemental MOS to 1.5 g kg−1. In males, the highest testosterone concentration was recorded at 1.5 g MOS kg−1 diet. In females, FSH and LH were significantly increased with increasing MOS levels up to 1.0 g kg−1, and then leveled off. Conversely, the highest E2 and Prog concentration was obtained at 1.5 g kg−1. The expression of CYP19a, FSHR, FOXL2, CYP1A, ESR1, and ESR2A were significantly upregulated in the gonads of fish fed diets treated with MOS, up to a concentration of 1.5 g kg-1. These results suggest that a dietary supplementation of MOS (1.5 g kg−1) could enhance the reproductive performance of red tilapia.

Effect of baseline oestradiol serum concentration on the efficacy of anastrozole for preventing breast cancer in postmenopausal women at high risk: a case-control study of the IBIS-II prevention trial

An increased risk of breast cancer is associated with high serum concentrations of oestradiol and testosterone in postmenopausal women, but little is known about how these hormones affect response to endocrine therapy for breast cancer prevention or treatment. We aimed to assess the effects of serum oestradiol and testosterone concentrations on the efficacy of the aromatase inhibitor anastrozole for the prevention of breast cancer in postmenopausal women at high risk. In this case-control study we used data from the IBIS-II prevention trial, a randomised, controlled, double-blind trial in postmenopausal women aged 40-70 years at high risk of breast cancer, conducted in 153 breast cancer treatment centres across 18 countries. In the trial, women were randomly assigned (1:1) to receive anastrozole (1 mg/day, orally) or placebo daily for 5 years. In this pre-planned case-control study, the primary analysis was the effect of the baseline oestradiol to sex hormone binding globulin (SHBG) ratio (oestradiol-SHBG ratio) on the development of all breast cancers, including ductal carcinoma in situ (the primary endpoint in the trial). Cases were participants in whom breast cancer was reported after trial entry and until the cutoff on Oct 22, 2019, and who had valid blood samples and no use of hormone replacement therapy within 3 months of trial entry or during the trial. For each case, two controls without breast cancer were selected at random, matched on treatment group, age (within 2 years), and follow-up time (at least that of the matching case). For each treatment group, we applied a multinominal logistic regression likelihood-ratio trend test to assess what change in the proportion of cases was associated with a one-quartile change in hormone ratio. Controls were used only to determine quartile cutoffs. Profile likelihood 95% CIs were used to indicate the precision of estimates. A secondary analysis also investigated the effect of the baseline testosterone-SHBG ratio on breast cancer development. We also assessed relative benefit of anastrozole versus placebo (calculated as 1 - the ratio of breast cancer cases in the anastrozole group to cases in the placebo group). The trial was registered with ISRCTN (number ISRCTN31488319) and completed recruitment on Jan 31, 2012, but long-term follow-up is ongoing. 3864 women were recruited into the trial between Feb 2, 2003, and Jan 31, 2012, and randomly assigned to receive anastrozole (n=1920) or placebo (n=1944). Median follow-up time was 131 months (IQR 106-156), during which 85 (4·4%) cases of breast cancer in the anastrozole group and 165 (8·5%) in the placebo group were identified. No data on gender, race, or ethnicity were collected. After exclusions, the case-control study included 212 participants from the anastrozole group (72 cases, 140 controls) and 416 from the placebo group (142 cases, 274 controls). A trend of increasing breast cancer risk with increasing oestradiol-SHBG ratio was found in the placebo group (trend per quartile 1·25 [95% CI 1·08 to 1·45], p=0·0033), but not in the anastrozole group (1·06 [0·86 to 1·30], p=0·60). A weaker effect was seen for the testosterone-SHBG ratio in the placebo group (trend 1·21 [1·05 to 1·41], p=0·011), but again not in the anastrozole group (trend 1·18 [0·96 to 1·46], p=0·11). A relative benefit of anastrozole was seen in quartile 2 (0·55 [95% CI 0·13 to 0·78]), quartile 3 (0·54 [0·22 to 0·74], and quartile 4 (0·56 [0·23 to 0·76]) of oestradiol-SHBG ratio, but not in quartile 1 (0·18 [-0·60 to 0·59]). These results suggest that serum hormones should be measured more routinely and integrated into risk management decisions. Measuring serum hormone concentrations is inexpensive and might help clinicians differentiate which women will benefit most from an aromatase inhibitor. Cancer Research UK, National Health and Medical Research Council (Australia), Breast Cancer Research Foundation, and DaCosta Fund.

Falsely elevated serum testosterone measurements resulting from testosterone topical gel contamination of the venipuncture site: Case Series and retrospective review

Testosterone as replacement therapy for male hypogonadism or as gender-affirming hormone therapy for transgender and non-binary patients has increased worldwide. Commonly used formulations of testosterone include intramuscular, transdermal patch, and topical gel, each of which has differing pharmacokinetics and practical challenges. In monitoring testosterone serum concentrations, contamination of the phlebotomy site by testosterone topical gel can lead to supraphysiologic (>1000 ng/dL or 34.7 nmol/L) serum concentrations of testosterone, as demonstrated in a few published case reports. The frequency of this issue is currently not known. The present study involves a retrospective search over a 13-year period across all clinical sites at an academic medical center. Out of 578 unique patients using testosterone topical gel, a total of 48 patients had at least 1 testosterone serum concentration exceed 1000 ng/dL. Documentation in the electronic health record revealed 7 patients where contamination of the phlebotomy site by topical gel was strongly supported as the cause of supraphysiologic testosterone serum concentrations. These included 5 males with primary hypogonadism, 1 male with panhypopituitarism, and a non-binary patient with gender dysphoria. The high testosterone concentrations prompted further work-up, including retesting and endocrinology consultation. There were additional cases of high testosterone serum concentration that may have been falsely elevated due to gel contamination but without sufficient supporting evidence available in the health record. Overall, we present 7 cases of spuriously high testosterone concentrations strongly suspected to be due to venipuncture performed near or at the location of prior testosterone gel application. Gel contamination should be considered as a possible cause of otherwise unexplained high testosterone serum concentration in patients receiving topical testosterone gel formulations. Patient counseling and provider awareness of this potential cause of spuriously high testosterone serum concentrations is important.

THU574 Hsd17b1 Partially Compensates For The Lack Of Hsd17b3 In Testicular Testosterone Production In Fetal Mice, But Not In Adults

Abstract Disclosure: M. Poutanen: None. A. Junnila: None. P. Sipilä: None. I.T. Huhtaniemi: None. Hydroxysteroid (17β) dehydrogenase type 3 (Hsd17b3) is the primary enzyme converting androstenedione to testosterone in human testes. HSD17B3 deficiency is a known cause of a disorder of sex development (DSD), where XY individuals are born with a female appearance, but are virilized during puberty as testosterone starts to suddenly rise due to unknown compensatory mechanisms. We have previously established and characterized an Hsd17b3 knockout mouse line (HSD17B3KO). HSD17B3KO males were born phenotypically normal, but presented various signs of under-masculinization at later ages. However, although they have very high circulating androstenedione at adulthood, they also maintain normal-to-high concentrations of testosterone. Indeed, testosterone was only seen to be low during certain fetal and pubertal time points. We suspected that Hsd17b1, capable of catalyzing the same reaction and expressed in testes towards the end of the fetal development, could be responsible for the compensation in the testosterone production, especially in the presence of higher than normal concentrations of androstenedione. To test this, we created an Hsd17b1-Hsd17b3 double KO (DKO) mouse line. The loss of both Hsd17b1 and Hsd17b3 had a more drastic effect on the phenotype of the male animals than was observed in HSD17B3KO. The outward appearance of the DKO males was completely feminized both as newborns and at adulthood, with an anogenital distance comparable to females. The male internal genitalia were present, but compared to HSD17B3KO they were further reduced in size, as were several other androgen-sensitive tissues. However, the testes and epididymides of the DKO contained high number of mature spermatozoa. The loss of both enzymes had a clear effect on the testis steroidogenesis of the newborn animals, with a 2-fold increase in intra testis androstenedione and 6-fold decrease in testosterone concentration compared to WT and HSD17B3KO males. In contrast, at the age of 3 months, no difference in the circulating steroid concentrations was observed between the DKO and HSD17B3KO, and high concentrations of androstenedione and testosterone was present in both mice. This, along with the active spermatogenesis, imply that in a presence of high LH, a further compensatory mechanism of testosterone production is present in the adult testes. In conclusion, our results demonstrate that in the absence of Hsd17b3, Hsd17b1 is crucial for the remaining testosterone production capacity in fetal mouse testis. However, in adult animals, the compensatory role is taken over by other, so far unknown, enzymes. Compared to HSD17B3KO, the overall phenotype of the DKO male mice is more similar to that of the humans with HSD17B3 deficiency, while the phenotype of HSD17B3KO is less feminized. Presentation Date: Thursday, June 15, 2023

THU645 Comparison Of LC-MS/MS Testosterone Assays Towards Standardization Of Lower Testosterone Ranges

Abstract Disclosure: M.G. Cree: Consulting Fee; Self; Pollie, Inc. Research Investigator; Self; Eli-Lilly, Amino Co. S. Ottey: None. K.D. Sherif: None. O. Sugahara: None. F. Pokuah: None. A.N. Lyle: None. V. Hubert: None. Objective: Polycystic ovary syndrome (PCOS) is a common disorder in women. The diagnosis of PCOS often includes elevated concentrations of serum testosterone. Previous work has harmonized the higher range of the testosterone assay and normative cut-offs for low and high testosterone concentrations for the male gender. However, similar work is needed to better align existing Liquid Chromatography Tandem Mass Spectroscopy (LC-MS/MS) methods in the lower range of testosterone and determine upper limits of normal for females. Methods: This is a secondary analysis of a pooled cohort of 60 obese adolescents with and without PCOS, enrolled in 1 of three studies (NCT02157974; NCT03041129; NCT03717935) at the University of Colorado, Anschutz. None of the participants were taking hormonal medication to treat PCOS. Frozen plasma samples collected between 6-7 AM were analyzed by Esoterix hormone branch of LabCorp (Agoura Hills, CA) and by the Centers for Disease Control (CDC) Clinical Standardization Programs with LC-MS/MS. Samples were selected from the available participants to encompass the full range of testosterone concentrations available within the cohort. Results: Within the entire cohort (N=60, Age = 15.8, SD: ± 1.7 years, BMI 35.4, SD: ± 5.5 kg/m2), the means between the assays were statistically, but not clinically different (CDC 48.4 SD: ±24.4 ng/dL vs OL 45.4 SD: ±22.1, p=0.013).Deming regression indicated that the assays were not different with an intercept of 2.05 (-3.69 to 7.79, 95% confidence interval) and slope of 0.895 (0.753 to 1.04, 95% confidence interval). The two assays were highly correlated via linear regression (R2=0.859, p&amp;lt;0.001) and with a Bland-Altman comparison, the CDC assay only had a slight positive bias of 3.04, SD: ± 9.18 ng/dL relative to Esoterix. When divided by PCOS status (PCOS N=52, Hirsutism score 6.5±5.9, Control N=8, Hirsutism score 2.1±4.5), the CDC assay ROC demonstrated discrimination of PCOS status with an AUC of 0.903 (0.800-1.00), p&amp;lt;0.001 and the Youden index was &amp;lt;27.1 ng/dL with a sensitivity of 87.5% and a specificity of 86.5%. However, when the sensitivity was at 100%, the specificity was 57.7% and the cut-off &amp;lt;43.0 ng/dL. Conclusions: The Esoterix, a major commercial lab, assay is very similar to that of CDC LC-MS/MS, and able to discriminate PCOS status at 43.0 ng/dL. Future work is needed to 1) align more clinical assays to the CDC standard and 2) define a common cut-off to describe hyperandrogenism in females across the weight and age spectrum. Presentation: Thursday, June 15, 2023

Testosterone concentration and aromatisation efficiency at different stages of gonad development: a case study with Mytilus edulis trossulus

ABSTRACT Sex steroid hormones occur in the bivalve tissues. Testosterone (T), various oestrogens, and progesterone have been reported in this group of organisms and the amounts of these hormones have been correlated with seasonal variation and reproduction. Yet, neither the role nor the origins of sex steroids are fully clarified. Thus, we tested the hypothesis that, apart from the esterification process, the aromatisation of androgens to oestrogens can help balance T levels during gonadal development in both sexes using Mytilus edulis trossulus as a model species. The highest testosterone concentrations were found in developed male and female gonads (IV reproductive stage of gametogenesis). The highest aromatisation efficiency was also found in the developed male and female gonads, but also in the gills. During the other stages of gametogenesis (II, III, V-I), a decrease in both testosterone concentration and aromatisation efficiency was observed in the gonads of males and females, as well as in the gills of males. However, the decrease in testosterone concentration did not affect the 17β-oestradiol concentration in mussel tissues. Thus, together with the esterification process, the ongoing aromatisation in bivalve tissues may help keeping balanced T levels.

Testosterone and psychophysiological aspects of personality in sports

Recent studies have shown that testosterone, in addition to its well-known anabolic effect, has a relationship with a number of psychological and psychophysiological characteristics. The purpose of the study is to generalize information about the relationship between psychophysiological aspects of personality and the level of testosterone in athletes. Methodology: analysis and generalization of data of modern scientific and methodological literature from scientometric bases and resources of Google Scholar, PubMed, Web of Science, Scopus. Research results and their discussion. Research by scientists has shown that high concentrations of basal testosterone are associated with a number of character traits and behavior. Competition, rivalry, competitions affect changes in testosterone levels and cause behavior modification. Scientists express the opinion that the basal level of testosterone before competitions can be an individual biopsychophysiological marker that interacts in the regulation of the hypothalamic-pituitary hormonal axis (HPA) under stress conditions and reflects the degree of dominance, the level of power motivation and obtaining a winning status. In separate studies, the positive effect of testosterone on cognitive functions and visual-spatial abilities was established, the relationship of this hormone with the propensity to take risks, reducing the feeling of fear, increasing attention in the face of threat, which can contribute to the combat readiness of the athlete and the desire to win, was established. Scientists have observed a connection between testosterone and such personality traits as fearless dominance, impulsiveness. Conclusions. According to literary sources, the level of testosterone is associated with a number of psychophysiological and psychological characteristics of an athlete, namely, it increases aggression, the motivation to dominate, which contributes to the motivation to achieve success in sports. High endogenous concentrations of testosterone can provide both a physiological and a psychological advantage in sports. The study of hormonal and psychophysiological parameters can provide an opportunity for a more complete assessment of human stress reactions in the conditions of sports competition.

Cord blood myostatin concentrations by gestational diabetes mellitus and fetal sex.

Myostatin is a member of the transforming growth factor β superfamily, and is mainly secreted from skeletal muscle. Animal studies have demonstrated that deficiency in myostatin promotes muscle growth and protects against insulin resistance. In humans, gestational diabetes mellitus (GDM) affects fetal insulin sensitivity. Females are more insulin resistant and weigh less than males at birth. We sought to assess whether cord blood myostatin concentrations vary by GDM and fetal sex, and the associations with fetal growth factors. In a study of 44 GDM and 66 euglycemic mother-newborn dyads, myostatin, insulin, proinsulin, insulin-like growth factor (IGF)-1, IGF-2 and testosterone were measured in cord blood samples. Cord blood myostatin concentrations were similar in GDM vs. euglycemic pregnancies (mean ± SD: 5.5 ± 1.4 vs. 5.8 ± 1.4 ng/mL, P=0.28), and were higher in males vs. females (6.1 ± 1.6 vs. 5.3 ± 1.0 ng/mL, P=0.006). Adjusting for gestational age, myostatin was negatively correlated with IGF-2 (r=-0.23, P=0.02), but not correlated with IGF-1 (P=0.60) or birth weight (P=0.23). Myostatin was strongly correlated with testosterone in males (r=0.56, P<0.001), but not in females (r=-0.08, P=0.58) (test for difference in r, P<0.001). Testosterone concentrations were higher in males vs. females (9.5 ± 6.4 vs. 7.1 ± 4.0 nmol/L, P=0.017), and could explain 30.0% (P=0.039) of sex differences in myostatin concentrations. The study is the first to demonstrate that GDM does not impact cord blood myostatin concentration, but fetal sex does. The higher myostatin concentrations in males appear to be partly mediated by higher testosterone concentrations. These findings shed novel insight on developmental sex differences in insulin sensitivity regulation relevant molecules.

The risk of hypogonadism after testicular sperm extraction in men with various types of azoospermia: a prospective cohort study

Research questionWhat is the risk of hypogonadism in men with obstructive azoospermia, non-obstructive azoospermia (NOA) or Klinefelter syndrome after testicular sperm extraction (TESE)? DesignThis prospective longitudinal cohort study was carried out between 2007 and 2015. ResultsAround 36% of men with Klinefelter syndrome, 4% of men with obstructive azoospermia and 3% of men with NOA needed testosterone replacement therapy (TRT). Klinefelter syndrome was strongly associated with TRT while no association was found between obstructive azoospermia or NOA and TRT. Irrespective of the pre-operative diagnosis, a higher testosterone concentration before TESE was associated with a lower chance of needing TRT. ConclusionsMen with obstructive azoospermia or NOA have a similar moderate risk of clinical hypogonadism after TESE, while this risk is much larger for men with Klinefelter syndrome. The risk of clinical hypogonadism is lower when testosterone concentrations are high before TESE.

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.

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.

Pregnancy rate and reproductive hormones in humpback whale blubber: Dominant form of progesterone differs during pregnancy

To better understand reproductive physiology of humpback whales Megaptera novaeangliae that reside in Hawai’i and Alaska, enzyme immunoassays were validated for both progesterone and testosterone in free-ranging and stranded animals (n = 185 biopsies). Concentrations were analyzed between different depths of large segments of blubber taken from skin to muscle layers of stranded female (n = 2, 1 pregnant, 1 non-pregnant) and male (n = 1) whales. Additionally, progesterone metabolites were identified between pregnant (n = 1) and non-pregnant (n = 3) females using high pressure liquid chromatography (HPLC). Progesterone concentrations were compared between juvenile (i.e., sexually immature), lactating, and pregnant females, and male whales, and pregnancy rates of sexually mature females were calculated. Based on replicate samples from ship struck animals collected at 7 depth locations, blubber containing the highest concentration of progesterone was located 1 cm below the skin for females, and the highest concentration of testosterone was in the skin layer of one male whale. HPLC of blubber samples of pregnant and non-pregnant females contain different immunoreactive progesterone metabolites, with the non-pregnant female eluate comprised of a more polar, and possibly conjugated, form of progesterone than the pregnant female. In females, concentrations of progesterone were highest in the blubber of pregnant (n = 28, 28.6 ± 6.9 ng/g), followed by lactating (n = 16, 0.9 ± 0.1 ng/g), and female juvenile (n = 5, 1.0 ± 0.2 ng/g) whales. Progesterone concentrations in male (n = 24, 0.6 ng/g ± 0.1 ng/g) tissues were the lowest all groups, and not different from lactating or juvenile females. Estimated summer season pregnancy rate among sexually mature females from the Hawai’i stock of humpback whales was 0.562 (95 % confidence interval 0.528–0.605). For lactating females, the year-round pregnancy rate was 0.243 (0.09–0.59), and varies depending on the threshold of progesterone assumed for pregnancy in the range between 3.1 and 28.5 ng/g. Our results demonstrate the synergistic value added when combining immunoreactive assays, HPLC, and long-term sighting histories to further knowledge of humpback whale reproductive physiology.

Biochemical aspect of crime: a case study of testosterone levels among rapists in Enugu State

Testosterone concentration is a contributing factor to rape tendency. Our research aimed to determine the plasma testosterone concentrations in male rapists. Subjects (100) recruited from Enugu state prison grouped viz: Violent-rapist (VR), nonviolent-rapist (NVR), violent child-molester (VCM), nonviolent child-molester (NCM), and none rapist (NR). The blood sample was collected in the morning (8-9) for four months by veno-puncture and used in the determination. The testosterone levels determination was by the enzyme-linked immunosorbent assay method. The results indicated the mean age of 33 (VR), 34 (NVR), 46 (VCM), 47 (NCM), and 32 (NR). The age at first intercourse was highest in NCM (18) and lowest in VR (13). Heterosexuals were highest in VR (14) and lowest in NCM (6). Homosexuals were highest in NCM (4) and non in VM, NVR, and NR (0). In bisexuals, NVR and NCM were the highest (4), the NR (1) was the lowest. The concentrations of testosterone (in ng/100ml) were 8.65 (VR), 9.23 (NVR), 9.63 (VCM), 7.73 (NCM) and 7.95 (NR). The testosterone concentration of the VR, NVR, and VCM is higher than NR. The NCM was lower than the NR. This result suggests that VR, NVR, and VCM are associated with higher testosterone concentrations in males. The modest associations indicate that there might be other influencing factors. The relationship between testosterone levels in rapists and child molestation is, at best, tentative. In some people, hormonal factors might influence the likelihood of rape and child molestation.

Correlations between behavior and hormone concentrations or gut microbiome imply that domestic cats (Felis silvestris catus) living in a group are not like 'groupmates'.

Domestic cats (Felis silvestris catus) can live in high densities, although most feline species are solitary and exclusively territorial animals; it is possible that certain behavioral strategies enable this phenomenon. These behaviors are regulated by hormones and the gut microbiome, which, in turn, is influenced by domestication. Therefore, we investigated the relationships between the sociality, hormone concentrations, and gut microbiome of domestic cats by conducting three sets of experiments for each group of five cats and analyzing their behavior, hormone concentrations (cortisol, oxytocin, and testosterone), and their gut microbiomes. We observed that individuals with high cortisol and testosterone concentrations established less contact with others, and individuals with high oxytocin concentrations did not exhibit affiliative behaviors as much as expected. Additionally, the higher the frequency of contact among the individuals, the greater the similarity in gut microbiome; gut microbial composition was also related to behavioral patterns and cortisol secretion. Notably, individuals with low cortisol and testosterone concentrations were highly tolerant, making high-density living easy. Oxytocin usually functions in an affiliative manner within groups, but our results suggest that even if typically solitary and territorial animals live in high densities, their oxytocin functions are opposite to those of typically group-living animals.

Factors Predicting Training Delays and Attrition of Recruits during Basic Military Training.

Ensuring a balance between training demands and recovery during basic military training (BMT) is necessary for avoiding maladaptive training responses (e.g., illness or injury). These can lead to delays in training completion and to training attrition. Previously identified predictors of injury and attrition during BMT include demographic and performance data, which are typically collected at a single time point. The aim of this study was to determine individual risk factors for injury and training delays from a suite of measures collected across BMT. A total of 46 male and female recruits undertaking the 12-week Australian Army BMT course consented to this study. Injury, illness, attrition, and demographic data were collected across BMT. Objective measures included salivary cortisol and testosterone, step counts, cardiorespiratory fitness, and muscular endurance. Perceptions of well-being, recovery, workload, fatigue, and sleep were assessed with questionnaires. Baseline and mean scores across BMT were evaluated as predictors of injury and attrition using generalized linear regressions, while repeated-measures ANOVA was used for the group comparisons. From the 46 recruits, 36 recruits completed BMT on time; 10 were delayed in completion or discharged. Multiple risk factors for injury during BMT included higher subjective ratings of training load, fatigue, and stress, lower sleep quality, and higher cortisol concentrations. Higher ratings of depression, anxiety, and stress, and more injuries were associated with a higher risk of delayed completion. Higher concentrations of testosterone and higher levels of fitness upon entry to BMT were associated with reduced risk of injury and delayed completion of BMT. Ongoing monitoring with a suite of easily administered measures may have utility in forewarning risk of training maladaptation in recruits and may complement strategies to address previously identified demographic and performance-based risk factors to mitigate injury, training delays, and attrition.

Higher premorbid serum testosterone predicts COVID-19-related mortality risk in men.

ObjectiveMen are at greater risk from COVID-19 than women. Older, overweight men, and those with type 2 diabetes, have lower testosterone concentrations and poorer COVID-19-related outcomes. We analysed the associations of premorbid serum testosterone concentrations, not confounded by the effects of acute SARS-CoV-2 infection, with COVID-19-related mortality risk in men.DesignThis study is a United Kingdom Biobank prospective cohort study of community-dwelling men aged 40–69 years.MethodsSerum total testosterone and sex hormone-binding globulin (SHBG) were measured at baseline (2006–2010). Free testosterone values were calculated (cFT). the incidence of SARS-CoV-2 infections and deaths related to COVID-19 were ascertained from 16 March 2020 to 31 January 2021 and modelled using time-stratified Cox regression.ResultsIn 159 964 men, there were 5558 SARS-CoV-2 infections and 438 COVID-19 deaths. Younger age, higher BMI, non-White ethnicity, lower educational attainment, and socioeconomic deprivation were associated with incidence of SARS-CoV-2 infections but total testosterone, SHBG, and cFT were not. Adjusting for potential confounders, higher total testosterone was associated with COVID-19-related mortality risk (overall trend P = 0.008; hazard ratios (95% CIs) quintile 1, Q1 vs Q5 (reference), 0.84 (0.65–1.12) Q2:Q5, 0.82 (0.63–1.10); Q3:Q5, 0.80 (0.66–1.00); Q4:Q5, 0.82 (0.75–0.93)). Higher SHBG was also associated with COVID-19 mortality risk (P = 0.008), but cFT was not (P = 0.248).ConclusionsMiddle-aged to older men with the highest premorbid serum total testosterone and SHBG concentrations are at greater risk of COVID-19-related mortality. Men could be advised that having relatively high serum testosterone concentrations does not protect against future COVID-19-related mortality. Further investigation of causality and potential underlying mechanisms is warranted.