Higher Testosterone Research Articles

Hormones do not maketh the mole-rat: No steroid hormone signatures of subordinate behavioral phenotypes

In some cooperatively breeding groups, individuals have distinct behavioral characteristics that are often stable and predictable across time. However, in others, as in the eusocial naked mole-rat, evidence for behavioral phenotypes is ambiguous. Here, we study whether the naked mole-rat can be divided into discrete phenotypes and if circulating hormone concentrations underpin these differences. Naked mole-rat colonies consist of a single breeding female and large numbers of non-reproductive subordinates that in some cases can exceed several hundred in a colony. The subordinates can potentially be divided into soldiers, who defend the colony; workers, who maintain it; and dispersers, who want to leave it. We established six colonies de novo, tracked them over three years, and assessed the behavior and hormone concentrations of the subordinates. We found that soldiers tended to be from earlier litters and were higher ranked compared to workers, whereas dispersers were distributed throughout litters and rankings. There was no difference in estradiol, testosterone, or dehydroepiandrosterone (DHEA) concentrations among phenotypes. Progesterone concentrations were higher in soldiers, but this difference appeared to be driven by a few individuals. Principal component analysis demonstrated that soldiers separated into a discrete category relative to workers/dispersers, with the highest ranked loadings being age, body mass, and testosterone concentrations. However, the higher testosterone in soldiers was correlated with large body size instead of strictly behavioral phenotype. Workers and dispersers have more overlap with each other and no hormonal differences. Thus the behavioral variation in subordinate naked mole-rats is likely not driven by circulating steroid hormone concentrations, but rather it may stem from alternative neural and/or neuroendocrine mechanisms.

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.

Reproductive Cycle and Periodicity of In Situ and Aquarium Female Sand Tiger Sharks Carcharias taurus from the Western North Atlantic

Fundamental characteristics of the reproductive biology of female sand tiger sharks Carcharias taurus are needed to understand the periodicity, seasonality and environmental factors essential for reproduction in this iconic species. Animals in managed care, such as aquariums, provide the unique opportunity for longitudinal study in contrast to in situ sharks that are examined opportunistically, and at a single point in time. Additionally, comparison of reproductive observations from successfully reproducing in situ sharks and aquarium sharks may help elucidate reasons for lack of reproduction among aquarium sharks and aid the development of assisted reproductive techniques for managed populations. Reproductive status of in situ and aquarium female sharks was assessed using ultrasonography and plasma hormone (17β-estradiol, testosterone, and progesterone) monitoring. The reproductive cycle was divided into eight stages based on ovarian activity and uterine contents. In situ sharks were sampled from Delaware Bay (n = 29), North Carolina (n = 39) and South Carolina (n = 11) during April-November from 2015–2020. Nineteen aquarium females from five aquaria were examined longitudinally for two or more consecutive years. Reproductive regionalization was observed among in situ females with the majority (83%) of North Carolina females in an active state of reproduction and all Delaware females in a resting reproductive state. All aquarium females had a pattern of reproductive cycling that was consistent with alternating years of activity and rest with confirmed biennial (n = 7) or triennial (n = 3) reproductive cycles with spring seasonality. In contrast to in situ females, aquarium females often retained uterine eggs for 9-20 months after ovulation in the absence of a developing embryo(s). Pre-ovulatory aquarium females had significantly higher concentrations of 17β-estradiol, testosterone and progesterone than other reproductive stages. For females in the ovulatory stage, in situ females had higher testosterone than aquarium females. Endocrine differences between successfully reproducing in situ females and aquarium females likely contribute to the limited reproductive success observed for this species in managed care and may be a reflection of diminished seasonal cues and environmental differences.

The effects of obesity on the menstrual cycle

The prevalence of childhood and adolescent obesity has significantly increased in the United States and worldwide since the 1970s, a trend that has been accelerated by the COVID-19 pandemic. The complications of obesity range from negative effects on the cardiovascular, endocrine, hepatobiliary, and musculoskeletal systems to higher rates of mental health conditions such as depression and eating disorders among affected individuals. Among adolescent girls, childhood obesity has been associated with the earlier onset of puberty and menarche, which can result in negative psychosocial consequences, as well as adverse effects on physical health in adulthood. The hormones leptin, kisspeptin and insulin, and their actions on the hypothalamic-pituitary-ovarian axis, have been implicated in the relationship between childhood obesity and the earlier onset of puberty. Obesity in adolescence is also associated with greater menstrual cycle irregularity and the polycystic ovary syndrome (PCOS), which can result in infrequent or absent menstrual periods, and heavy menstrual bleeding. Hyperandrogenism, higher testosterone and fasting insulin levels, and lower levels of sex hormone-binding globulin, similar to the laboratory findings seen in patients with PCOS, are also seen in individuals with obesity, and help to explain the overlap in phenotype between patients with obesity and those with PCOS. Finally, obesity has been associated with higher rates of premenstrual disorders, including premenstrual syndrome and premenstrual dysphoric disorder, and dysmenorrhea, although the data on dysmenorrhea appears to be mixed. Discussing healthy lifestyle changes and identifying and managing menstrual abnormalities in adolescents with obesity are key to reducing the obstetric and gynecologic complications of obesity in adulthood, including infertility, pregnancy complications, and endometrial cancer.

High Sucrose and Cholic Acid Diet Triggers PCOS-like Phenotype and Reduces Enterobacteriaceae Colonies in Female Wistar Rats.

Polycystic ovary syndrome (PCOS), a common hormonal disorder in women of reproductive age, is associated with a poor and unhealthy diet. This study aimed to investigate the effect of a high sucrose and cholic acid (HSCA) diet in the presence of PCOS-like phenotypes. Female Wistar rats were divided into HSCA and normal diet groups for four weeks, each with twenty rats. Body weight was assessed before and after the study. Blood and fecal samples were obtained to measure HOMA-IR and testosterone level (ELISA) and Enterobacteriaceae isolates grown on MacConkey Agar. Obtained ovarian tissues were H&E-stained. HSCA rats demonstrated a reduction in Enterobacteriaceae colonies (median 4.75 × 105 vs. 2.47 × 104/CFU, p < 0.001) and an elevated HOMA-IR (mean 2.94 ± 1.30 vs. 4.92 ± 0.51, p < 0.001), as well as an increase in testosterone level (median 0.65 vs. 3.00 ng/mL, p < 0.001), despite no statistical differences in the change in body weight (mean −2.31 ± 14.42 vs. −3.45 ± 9.32, p = 0.769). In H&E staining, HSCA rats had a reduction in preovulatory follicle count (median 0.50 vs. 0.00, p = 0.005). The HSCA diet caused insulin resistance and high testosterone levels, which contribute to the development of PCOS, and affected folliculogenesis by altering follicular maturation, but had no effect on ovulation.

Unraveling the Role of Thyroid Hormones in Seasonal Neuroplasticity in European Starlings (Sturnus vulgaris).

Thyroid hormones clearly play a role in the seasonal regulation of reproduction, but any role they might play in song behavior and the associated seasonal neuroplasticity in songbirds remains to be elucidated. To pursue this question, we first established seasonal patterns in the expression of thyroid hormone regulating genes in male European starlings employing in situ hybridization methods. Thyroid hormone transporter LAT1 expression in the song nucleus HVC was elevated during the photosensitive phase, pointing toward an active role of thyroid hormones during this window of possible neuroplasticity. In contrast, DIO3 expression was high in HVC during the photostimulated phase, limiting the possible effect of thyroid hormones to maintain song stability during the breeding season. Next, we studied the effect of hypothyroidism on song behavior and neuroplasticity using in vivo MRI. Both under natural conditions as with methimazole treatment, circulating thyroid hormone levels decreased during the photosensitive period, which coincided with the onset of neuroplasticity. This inverse relationship between thyroid hormones and neuroplasticity was further demonstrated by the negative correlation between plasma T3 and the microstructural changes in several song control nuclei and cerebellum. Furthermore, maintaining hypothyroidism during the photostimulated period inhibited the increase in testosterone, confirming the role of thyroid hormones in activating the hypothalamic–pituitary–gonadal (HPG) axis. The lack of high testosterone levels influenced the song behavior of hypothyroid starlings, while the lack of high plasma T4 during photostimulation affected the myelination of several tracts. Potentially, a global reduction of circulating thyroid hormones during the photosensitive period is necessary to lift the brake on neuroplasticity imposed by the photorefractory period, whereas local fine-tuning of thyroid hormone concentrations through LAT1 could activate underlying neuroplasticity mechanisms. Whereas, an increase in circulating T4 during the photostimulated period potentially influences the myelination of several white matter tracts, which stabilizes the neuroplastic changes. Given the complexity of thyroid hormone effects, this study is a steppingstone to disentangle the influence of thyroid hormones on seasonal neuroplasticity.

Association of sex hormone dynamics with 10-year survival in men with implanted cardiac resynchronization therapy devices

Aim. To assess association of different dynamics of sex hormones with 10-year survival in men with congestive heart failure (CHF) and implanted cardiac resynchronization therapy (CRT) devices.Methods. Based on tercile of testosterone at the end of the study (TESend), 157 men with CRT (mean age 58.7±9.7 years old; 95 men (60.5%) w/ ischemic CHF) were divided into 3 groups: gr. I (n=52) - TESend&lt;13.3 nmol/l; gr. II (n=53) - TESend&gt;13.3&lt;19.2 nmol/l; gr. III (n=52) - TESend&gt;19.2 nmol/l. Parameters of echocardiography (Echo) were investigated in dynamics, N-terminal fragment of probrain natriuretic peptide (NT-proBNP), interleukin-6 (IL-6), total and free testosterone (TES), estradiol (E2), sex hormone-binding globulin (SHBG), progesterone (PGN), dehydroepiandrosterone sulfate (DHEAS), E2/TES ratio were tested in plasma. Survival in groups was assessed using Kaplan-Meier method.Results. Groups were comparable in age, presence of ischemic CHF, arterial hypertension and surgeries on myocardial revascularization. Higher incidence of atrial fibrillation, obesity, complete left bundle branch block, tendency to higher incidence of diabetes mellitus and higher body mass index was revealed in gr. I compared to gr. III. At baseline, groups didn’t differ in Echo parameters; the highest TES levels were found in gr. III. After CRT, there was less reverse cardiac remodeling, decrease of TES level (p&lt;0.001) in gr. I vs increase of TES level in gr. II (p=0.041) and gr. III (&lt;0.001); E2 level increased (p=0.008), levels of NT-proBNP and IL-6 decreased only in gr. III. In absence of dynamics of E2/TES index and DHEAS level in groups, E2/TES index was the highest and DHEAS level was the lowest in gr. I after CRT. 10-year survival of groups was 17.6%, 42.8%, 46.2% (Log Rank test I-II=0.016; Log Rank test I-III=0.004; Log Rank test II-III=0.528).Conclusion. Obtained results indicated different dynamics of sex steroids after CRT. Sex hormones variation pattern, interrelated with increase in levels of testosterone, estradiol, dehydroepiandrosterone sulfate and decrease in testosterone to estradiol ratio, was associated with better 10-year survival in men with implantable CRT devices with greater reverse cardiac remodeling and reduction in activity of systemic immune inflammation.

Body Temperature Patterns and Energy Balance Hormones in Free-Living Thirteen-Lined Ground Squirrels (Ictidomys tridecemlineatus) from Different Latitudes.

AbstractThis article examines hormone concentrations and body temperature (Tb) patterns of free-living thirteen-lined ground squirrels (TLGSs) across the majority of their latitudinal range in the United States (from Texas to Minnesota). Free-living TLGSs () were implanted with Tbdata loggers in 2019 before they entered hibernation. Three adult female TLGSs, one each from Oklahoma (low latitude), Iowa (middle latitude), and Minnesota (high latitude), were recaptured in 2020 after the hibernation season. Although this provides an n of 1 for each location and therefore no statistically supported conclusions can be drawn, the hibernation season was longest in the animal from the highest latitude with coldest winter soil temperatures (Minnesota) and shortest in the animal retrapped at the lowest latitude (Oklahoma). Torpor bouts were generally longer when soil temperatures were lower. The Iowa and Minnesota squirrels had a prolonged period of short torpor bouts with Tb near 20°C at the beginning of the hibernation season. Concentrations of the orexigenic hormone ghrelin and the sex hormones estradiol and testosterone were also compared in populations from different latitudes. In general, Minnesota males had higher testosterone than males from other populations, possibly due to a later breeding season relative to other squirrel populations. Animals trapped in early summer had significantly lower concentrations of ghrelin than those captured in midsummer, potentially driving the fat-storing period before the hibernation season. Together, these results suggest latitudinal variation in physiological regulation of circannual rhythms.

Abstract 653: Molecular pathology of metastatic prostatic adenocarcinoma treated with bipolar androgen therapy (BAT) reveals a correlation between MYC mRNA and protein

Abstract Molecular analysis of tissue samples from metastatic cancer lesions can improve our understanding of drug response and resistance. Since prostate cancer cells initially require androgen signaling through the androgen receptor (AR) for proliferation, the treatment of metastatic prostate cancer involves surgical or chemical castration. While most patients respond initially, nearly all develop acquired resistance to combined androgen blockade using both first and second line agents. This resistance is often related to overexpression of AR, which is frequently driven by AR gene amplification. In some patients, this increased AR appears to render tumor cells sensitive to high dose androgens in a manner that paradoxically inhibits their growth. Bipolar Androgen Therapy (BAT) was introduced several years ago at our institution in which patients with castration resistant prostate cancer (CRPC) are treated intermittently with high dose testosterone. Prior clinical trials have shown that BAT can produce biochemical and objective responses, and may re-sensitize prostate cancer to subsequent second generation AR inhibitors. To define the mechanism(s) by which BAT results in tumor regression, we performed a clinical trial (NCT03554317) for patients with CRPC that included biopsies of soft tissue metastases before BAT and after 3 cycles of BAT (C4D1). Up to four tissue cores were taken per biopsy with two cores for formalin fixation and paraffin embedding (FFPE) and the others snap frozen. Histologically viable tumor cells were present for both the pretreatment and C4D1 time points for 24 of the 42 enrolled patients. The FFPE samples were stained for H&amp;E and by IHC for AR, MYC and Ki67. MYC and Ki67 IHC stained slides were subjected to quantitative image analysis using HALO software (Indica Labs). Adequate frozen tumor tissue was available for laser capture microdissection and adequate amounts of RNA were obtained from 15 patients with paired pretreatment and C4D1 biopsies. RNAseq libraries were prepared using the NuGEN Ovation RNA-Seq System V2 and barcoded libraries were sequenced to an average depth of &amp;gt; 100 million reads per sample on an Illumina NovaSeq. Gene expression values were obtained with RSEM using Star aligner with GRCh38 (human). When comparing the C4D1 samples to the pretreatment samples, there were marked decreases in tumor MYC protein levels in approximately half of the treated patients, which was associated with decreased Ki67, decreased tumor volume, and prolonged progression-free survival on BAT. Using an image analysis computed H-SCORE for MYC, there was a strong correlation between MYC protein levels and MYC mRNA using RNAseq (r=0.81, p = 2.3 x 10-7). This indicates that MYC protein levels correlate with MYC mRNA and that reductions of MYC protein by BAT are likely related to reductions of MYC mRNA in clinical metastatic tissue samples. Citation Format: Carolina Gomes Alexandre, Tracy Jones, Jessica L. Hicks, John T. Isaacs, Anuj Gupta, Alyza Skaist, Laura Sena, Jennifer Meyers, Emmanuel Antonarakis, Mark Markowski, Samuel Denmeade, Srinivasan Yegnasubramanian, Angelo Michael De Marzo. Molecular pathology of metastatic prostatic adenocarcinoma treated with bipolar androgen therapy (BAT) reveals a correlation between MYC mRNA and protein [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 653.

BCL2-associated athanogene 6 exon24 contributes to testosterone synthesis and male fertility in mammals.

ObjectivesBCL2‐associated athanogene 6 (BAG6) plays critical roles in spermatogenesis by maintaining testicular cell survival. Our previous data showed porcine BAG6 exon24‐skipped transcript is highly expressed in immature testes compared with mature testes. The objective of this study is to reveal the functional significance of BAG6 exon24 in mammalian spermatogenesis.Materials and MethodsCRISPR/Cas9 system was used to generate Bag6 exon24 knockout mice. Testes and cauda epididymal sperm were collected from mice. TMT proteomics analysis was used to discover the protein differences induced by Bag6 exon24 deletion. Testosterone enanthate was injected into mice to generate a high‐testosterone mice model. H&E staining, qRT‐PCR, western blotting, vector/siRNA transfection, immunofluorescence, immunoprecipitation, transmission electron microscopy, TUNEL and ELISA were performed to investigate the phenotypes and molecular basis.Results Bag6 exon24 knockout mice show sub‐fertility along with partially impaired blood‐testis barrier, increased apoptotic testicular cell rate and abnormal sperm morphology. Endoplasmic reticulum stress occurs in Bag6 exon24‐deficient testes and sterol regulatory element‐binding transcription factor 2 is activated; as a result, cytochrome P450 family 51 subfamily A member 1 expression is up‐regulated, which causes a high serum testosterone level. Additionally, serine/arginine‐rich splicing factor 1 down‐regulates BAG6 exon24‐skipped transcripts in porcine Sertoli cells by binding to 35–51 nt on BAG6 exon24 via its N‐terminal RNA‐recognition domain.ConclusionsOur findings reveal the critical roles of BAG6 exon24 in testosterone biosynthesis and male fertility, which provides new insights into the regulation of spermatogenesis and pathogenesis of subfertility in mammals.

Decreased sperm counts in Swedish users of oral tobacco.

BackgroundSmoke‐free tobacco via moist oral snuff (snus) is used daily in more than 20% of Swedish men. Negative effects of cigarette smoking on sperm parameters are well documented, unlike for snuff, despite relevance also for other smoke‐free nicotine products.ObjectivesWe wanted to investigate whether reproductive parameters differed between users and non‐users of snuff, and whether the amount of snuff and nicotine exposure mattered.Materials and methodsMen (n = 613) from the general population, recruited 2000–2010, were physically examined, answered questions on smoking and snuff use, and delivered urine, blood and semen samples. Sperm concentration, total sperm count, semen volume, percent morphologically normal and progressively motile sperm, and DNA fragmentation index (by the Sperm Chromatin Structure Assay) and reproductive hormones were analysed. Nicotine exposure was measured through urinary levels of cotinine. We used general linear models, with adjustments including cigarette smoking, and for semen parameters also abstinence time.ResultsAfter adjustments, total sperm count was 24% lower (P = 0.03) and testosterone 14% higher (P < 0.001) in 109 users of snuff than in non‐users, whereas cotinine was positively associated with testosterone and oestradiol (P < 0.001). Numbers of boxes of snuff used per week were associated with testosterone and FSH (P < 0.001).DiscussionApplied to the general population, the consumption of smoke‐free tobacco by the use of snuff was associated with a lower sperm count and a higher testosterone, for which the extent seemed to play a role.ConclusionsIndependent of smoking, consumption of snuff was associated with lower total sperm count and different hormone levels. Applying these results to a reported association between sperm count and the chance of pregnancy, men who used snuff would have about a 10% lower chance of fathering a child.

Gender Differences and Relationship of 2D:4D-Ratio, Mental Toughness and Dark Triad Traits among Active Young Adults.

There is consistent evidence that prenatal exposures to higher testosterone and lower estrogen concentrations during the first trimester of embryonal and fetal development are associated with a lower 2D:4D-ratio, which is to say: The index finger (2D) is shorter, compared to the ring finger (4D). Compared to non-active, athletes show lower 2D:4D ratios. However, athletes also report specific personality traits such as mental toughness, assertiveness, and competitive behavior. Here, we tested if 2D:4D-ratios were related to specific personality traits. We further investigated possible gender differences. A total of 460 active young adults (mean age: 24.81 years; 67% females) completed a series of self-rating questionnaires covering sociodemographic information and traits of the dark triad and mental toughness. Participants also provided a scan of their right palm hand to measure and calculate 2D:4D-ratios. t-tests, Pearson's correlations, and multiple regression analysis were performed to analyze data. Compared to male participants, female participants had a higher 2D:4D-ratio. Female and male participants did not differ as regards dark triad traits and mental toughness traits. Irrespective of gender, and based on correlational computations, 2D:4D-ratios were unrelated to the dark triad (DT) and mental toughness (MT) scores. Higher DT scores were modestly associated with higher MT scores among females, but not among males. Lower 2D:4D-ratios were associated with higher constancy scores and the male gender. The constancy and male gender appeared to be associated with lower 2D:4D-ratios.

Relationship between High Sensitivity C-Reactive Protein and Total Testosterone Levels in Male Patients with Stage V Chronic Kidney Disease

The incidence of decreased total testosterone level increases in stage V CKD patients. Decreased total testosterone levels is influenced by uremia and hemodialysis bioincompatibility through an increase in the inflammatory mediator hs-CRP. Obesity and age are risk factors of CKD incidence which can directly affect testosterone level. This study aimed to analyze the relationship between hs-CRP, serum urea, age, obesity, and hemodialysis duration with decreased total testosterone levels in stage V CKD patients. This observational study with cross-sectional approach was performed are 60 stage V CKD patients treated in Dr. Moewardi General Hospital, Surakarta on November 2020. The data were analyzed with 2x2 table test, followed by multivariate analysis using logistic regression. The examinations of total testosterone and hsRP used ECLIA and immunoturbidimetric assay, respectively. This study obtained 21 (37%) study who experienced a decreased total testosterone level (&lt;3ng/mL). hs-CRP level [PR 3.656 (95% CI: 1.202-11,124; p=0.020)]; obesity [PR 4.156 (95% CI: 1.272-13.581; p=0.015)] and urea [PR 4.474 (95% CI: 1.273-15.728; p=0.015)] significantly associated with decreased total testosterone level of &lt;3 ng/ml. Meanwhile age was not statistically significant (p=0.694) and hemodialysis duration obtained PR &lt;1 and CI 95% &lt; 1 (p=0.018). Therefore in patients with stage V, hs-CRP levels ≥ 0.65 mg/dl, serum urea ≥ 120 mg/dL, and obesity correlate with decreased total testosterone level while age is not associated with decreased total testosterone level. The hemodialysis duration is not a risk factor of decreased total testosterone.

Assessing the immunomodulatory effect of testosterone on outcomes of patients with advanced solid tumors treated with immunotherapy using the National Cancer Database.

e18805 Background: Androgens have been described to suppress immune responses to various benign and pathogenic antigens, accounting in part for sex-based differences in incidence and severity of autoimmunity, infection, and malignancy. We hypothesized that testosterone exposure alters immune tolerance to solid tumors and outcomes to cancer immunotherapy. In an attempt to isolate the effect of testosterone exposure on outcomes to treatment with immunotherapy, we utilized age as a surrogate for testosterone level and sought to test whether younger men with higher testosterone would have different outcomes following immunotherapy than older men with lower testosterone, relative to women. Methods: National Cancer Database (NCDB) was queried for patients with advanced non-small-cell lung cancer (NSCLC), renal cell carcinoma (RCC), or melanoma, who received immunotherapy as first-line systemic treatment. These patients were divided by quartiles for age (Q1 (youngest) through Q4 (oldest)) and a Multivariate Cox proportional hazard model was used to test the interaction between sex and age on survival outcomes for each cancer type while adjusting for the Charlson-Deyo comorbidity index. Results: The study included 23,741 NSCLC (median age 66 years, interquartile range (IQR) 59 – 74), 1741 RCC (62 y, IQR 55 – 69), and 5825 melanoma (64 y, IQR 54 - 73) patients. The majority of patients were male – 52.3%, 71.3%, and 68.2% for each cancer type respectively. The median overall survival (OS) following first-line immunotherapy declined with increasing age in each cancer type (Q1 &gt; Q4). No significant interaction between age group and sex for any of the cancer types was identified (table). Notably, male patients in any group and cancer type did not have statistically longer OS following immunotherapy than female patients. Conclusions: This study did not show that age altered sex-based differences in outcomes to immunotherapy in patients with advanced solid tumors. It is possible that age is a poor surrogate for testosterone level in this patient population, that additional confounding factors were present, or that testosterone exposure does not modify outcomes to immunotherapy. Future studies will directly correlate serum testosterone levels with outcomes to immunotherapy in patients with advanced cancer.[Table: see text]

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.

The effect of oral contraceptive use on sympatic nerve activity in patients with polycystic ovary syndrome

Objective High sympathetic nerve activity, is thought to be a cardiovascular risk factor, has been shown to correlate with circulating high testosterone levels. However its role on the pathophysiology of the polycystic ovarian syndrome has not been clearly established. The aim of our study is to compare the sympathetic nerve activity between polycystic ovarian syndrome and control group and to determine whether the use of oral contraceptives for contraception has any effect on this activity. Materials and methods Our study has designed as a prospective, case–control study including patients diagnosed with polycystic ovarian syndrome. Antropometric measurements were calculated, hormone levels were measured and sympathetic skin response and heart rate variability measurements were performed in the laboratory to assess sympathetic activity before starting oral contraceptive pill therapy and at the end of 1 month follow up. Results In the baseline condition LH/FSH ratio, LH, DHEAS, and total testosterone levels were significantly higher in women with PCOS. After 1 month of treatment, reductions in Ferriman–Gallwey score, ovarian volumes, number of follicles, LH/FSH ratio, LH, and androgen hormone levels were statistically significant. The mean values of sympathetic skin response amplitude and R–R analysis-Valsalva test were higher in PCOS group as compared to the control group. However, these differences were not statistically significant. Similarly, no statistically significant difference in SSR latency and R–R analysis-standup test were demonstrated between PCOS and control groups. Conclusion In conclusion, our study supports the increased sympatovagal activity in patients with polycystic ovarian syndrome.

Adrenal carcinoma: a case report

BackgroundAdrenocortical carcinoma is a rare malignancy (0.5–2 cases/million/year) with a poor prognosis. Hypercortisolism, virilization, and compressive features are among the common presentations of adrenocortical carcinoma. Hematuria is one of the rare initial presentations of adrenocortical carcinoma reported in the literature. We report a case of adrenal carcinoma presenting with microscopic hematuria.Case presentationA 67-year-old Sri Lankan patient with diabetes, hypertension, and ischemic heart disease presented with an acute coronary event. During the routine evaluation, microscopic hematuria was detected without proteinuria or active sediments. She denied any painful micturition, previous similar episodes, or abdominal pain. Further evaluation revealed a hypokalemia with biochemical evidence of hypercortisolism and high testosterone levels with suppressed adrenocorticotropic hormone levels. On imaging, there was evidence of a right suprarenal mass 7 cm × 3 cm × 6 cm in size that was hypoechoic and lobulated and suggestive of a lipid-poor tumor. She underwent adrenalectomy. By the time of surgery 3 weeks later, significant weight gain with features of Cushing syndrome, including hirsutism, skin atrophy, easy bruising without virilization, and proximal myopathy, were noted. Histology identified a right-sided adrenal tumor with capsular and vascular invasion. Hypercortisolism and hematuria disappeared after surgery. The patient was referred for further oncological management.ConclusionThis case illustrates a rare presentation of adrenal carcinoma. Awareness of this presentation may facilitate early evaluation and management.

Association of Sex Hormones and Sex Hormone-Binding Globulin Levels With Bone Mineral Density in Adolescents Aged 12-19 Years.

BackgroundSex hormones are recognized to play a significant role in increasing bone mineral density (BMD) and promoting bone maturation during adolescence. The purpose of our study was to use a database with large population data to evaluate the association of BMD with sex hormones (including testosterone and estradiol) and sex hormone-binding globulin (SHBG) in adolescent boys and girls aged 12–19 years.MethodsThe data for our study were taken from the National Health and Nutrition Examination Survey 2013-2016, and we used weighted multiple linear regression models to assess the relationship between testosterone, estradiol, and SHBG and total BMD. We use weighted generalized additive models and smooth curve fitting to discover underlying nonlinear relationships.ResultsA total of 1648 teenagers (853 boys, 795 girls) were selected for the final analysis. In boys, testosterone and estradiol levels were positively associated with total BMD, whereas SHBG levels were negatively associated with total BMD after adjusting for covariates [P < 0.05; 95% confidence interval (CI)]. In addition, there was a point between estradiol and total BMD, after which the positive correlation between estradiol and total BMD was relatively insignificant in boys. In girls, there was a positive association between estradiol and total BMD (P < 0.05; 95% CI), but there was no significant association between the testosterone (β 0.0004; 95% CI -0.0001 to 0.0008) or SHBG (β -0.0001; 95% CI -0.0002 to 0.0001) levels and total BMD. We also found an inverted U-shaped association between testosterone and total BMD with the inflection point at 25.4 ng/dL of testosterone.ConclusionsWe found differences in the association of sex hormones with total BMD in boys and girls. Based on our findings, an appropriate increase in serum testosterone levels may be beneficial for skeletal development in girls because of the inverted U-shaped relationship (with the inflection point at 25.4 ng/dL of testosterone), and a high testosterone level might be detrimental to BMD. Furthermore, keeping estradiol levels below a certain level in boys (24.3 pg/mL) may be considered.

The Effects of Sex Hormones and some Respiratory Diseases on the Severity of Corona Virus Infection

Sex hormones and chronic respiratory diseases play a role in the pathogenesis and the management of Covid-19 infection. Present research tries to shed light on the role of sex hormones, bronchial asthma and lung cancer on the severity of Covid-19 infection and the resulting mortality rate. This study included a follow-up of the health status of 85 patients infected with Covid-19, and all the patients previously diagnosed had hereditary respiratory diseases (bronchial asthma (64) and lung cancer (21)). The serum level of progesterone and testosterone and the stages of lung cancer development were measured in the laboratories of Diwaniyah Teaching Hospital. After conducting medical examinations, computed tomography and x-rays, the severity of Covid-19 infection was classified according to the WHO to moderate, severe and critical infection. The current results showed that most of the hospitalized cases were males (65%) with a death rate (18%), so bronchial asthma was associated with the death rate in males (70% of dead males), followed by postmenopausal (POM) women (66.7% of the dead woman), while pre-menopausal (PRM) women had the highest cure rate (100%). The results of the study showed that the rise in the mean of progesterone in PRM (13.55 ng/ml) was associated with moderate symptoms of Covid-19, while the increased testosterone in males and POM (1018 ng/dL and 67.3 ng/dL, respectively) was associated with an increase in the severity of the infection. In conclusion, asthma and high testosterone directly affected the increase in the severity of Covid-19 and the high mortality rate among the Corona sufferers. While advanced lung cancer had a clear role in that, at the same time, progesterone appeared as a protective factor in young women. Keywords: Covid-19, bronchial asthma, lung cancer, testosterone, progesterone

Review of Mendelian Randomization Studies on Endometrial Cancer.

Endometrial cancer (EC) is a common gynecological cancer. In some parts of the world, the incidence and mortality of EC are on the rise. Understanding the risk factors of EC is necessary to prevent the occurrence of this disease. Observational studies have revealed the association between certain modifiable environmental risk factors and EC risk. However, due to unmeasured confounding, measurement errors, and reverse causality, observational studies sometimes have limited ability to judge robust causal inferences. In recent years, Mendelian randomization (MR) analysis has received extensive attention, providing valuable insights for cancer-related research, and is expected to identify potential therapeutic interventions. In MR analysis, genetic variation (alleles are randomly assigned during meiosis and are usually independent of environmental or lifestyle factors) is used instead of modifiable exposure to study the relationship between risk factors and disease. Therefore, MR analysis can make causal inference about exposure and disease risk. This review briefly describes the key principles and assumptions of MR analysis; summarizes published MR studies on EC; focuses on the correlation between different risk factors and EC risks; and discusses the application of MR methods in EC research. The results of MR studies on EC showed that type 2 diabetes, uterine fibroids, higher body mass index, higher plasminogen activator inhibitor-1 (PAI-1), higher fasting insulin, early insulin secretion, longer telomere length, higher testosterone and higher plasma cortisol levels are associated with increased risk of EC. In contrast, later age of menarche, higher circulatory tumor necrosis factor, higher low-density lipoprotein cholesterol, and higher sex hormone-binding globulin levels are associated with reduced risk of EC. In general, despite some limitations, MR analysis still provides an effective way to explore the causal relationship between different risk factors and EC.