Low Testosterone Levels Research Articles

Gut microbiota in women with polycystic ovary syndrome: an individual based analysis of publicly available data

Polycystic ovary syndrome (PCOS) represents a prevalent endocrine disorder affecting numerous females worldwide. Dysbiosis of gut microbiota has been linked to the occurrence of PCOS; however, research into the characteristics of gut microbiota in PCOS patients, especially those from different regions and with different testosterone level, remains limited. Additionally, it is still unclear whether gut microbiota helps to distinguish different PCOS subtypes. We searched four electronic databases (PubMed, Web of Science, Cochrane Library, and ClinicalTrials.gov) from Jan 1, 2010 to May 1, 2024. This combined analysis included studies providing the raw data of gut microbiota in PCOS patients. We reanalyzed the characteristics of gut microbiota in PCOS patients from different regions and with different testosterone level. Fourteen publications satisfying the inclusion criteria were included in the combined analysis. Based on data from 948 individuals, we found alpha-diversity was not significantly different between PCOS and healthy control (HC) groups. However, gut microbiota composition was distinct in PCOS patients compared with healthy individuals. Specifically, Fusobacterium, Ruminococcus_gnavus_group, and Escherichia-Shigella increased, while Dysosmobacter, Schaedlerella, Merdimonas, Clostridiisalibacter, Flintibacter etal. decreased in PCOS women. Regionally, Alistipes was enriched in primarily European patients, while Blautia and Roseburia were more abundant in Chinese patients. Subtype analysis revealed that the gut microbiota of PCOS patients with higher testosterone level (PCOS-HT) differed significantly from those with lower testosterone level (PCOS-LT). Prevotella, Blautia, Dialister, Ruminococcus_torques_group and UCG-002 were enhanced in PCOS-HT patients, while Alistipes, Dysosmobacter, Phocaeicola and Faecalibacterium were diminished. Importantly, a set of eight genera effectively differentiated PCOS-HT patients from PCOS-LT patients with an AUC of 0.95. This systematic anatomization of gut microbiota revealed the microbial characteristics of PCOS patients, particularly those with different testosterone level, thus laying the foundations for further research into pathogenesis of PCOS, and the development of effective diagnostic, treatment, and intervention strategies. This work was supported by the National Natural Science Foundation of China (No. 81973217, 82260304), the Hainan Province Clinical Medical Center (QWYH202175), and the Specific Research Fund of The Innovation Platform for Academicians of Hainan Province (YSPTZX202311).

The CT-derived fat-free muscle fraction is associated with inflammation and predicts outcome in patients with aortic stenosis undergoing TAVR

Abstract Background The ESC guidelines underscore the importance of objective risk stratification in making patient-centered decision for valve interventions. However, they primarily rely on surgical risk scores, not considering essential factors such as frailty. Computed tomography (CT) is a routine part of the pre-interventional workup in patients undergoing TAVR and allows for body composition analysis, including the assessment of fat-free muscle fraction (FFMF) as an indicator of muscle quality. Purpose This study aimed to assess the correlation between FFMF and both inflammation and endocrine disorders, and to investigate the predictive value of FFMF in patients with aortic stenosis undergoing TAVR. Methods The study included 789 patients undergoing TAVR between 2017 and 2019. Evaluations involved CT scans to assess body composition. Using densitometric thresholds, the skeletal muscle area at L3/L4 level was separated into fatty and lean muscle to calculate the FFMF. The cohort was divided into tertiles of high, medium, and low FFMF, Figure 1. Results The study population was 45.5% female with a mean age of 81.2±6.0 years. Overall, 261 (33.1%) patients had a high FFMF, 293 (37.1%) had a medium FFMF, and 235 (29.8%) had a low FFMF. Patients with a low FFMF were older (82.3±5.9 vs 81.6±5.6 vs 79.8±6.2 years, p<0.01) and had higher rates of atrial fibrillation (52 vs 43 vs 37%, p<0.01), compared to those with a medium and high FFMF. Regarding body composition, low FFMF patients had a higher percentage of body fat (28.7±11.2 vs 26.8±9.1 vs 24.2±9.6%, p=0.01) and a lower percentage of body muscle (30.9±5.3 vs 31.3±4.2 vs 32.7±4.4%, p=0.03). Moreover, a low FFMF was associated with inflammation, as indicated by increased levels of C-reactive protein (6.3 vs 4.2 vs 3.1 mg/l, p<0.01) and procalcitonin (0.06 vs 0.05 vs 0.05 µg/l, p=0.01). Endocrinological assessment revealed lower levels of estradiol (6.8 vs 14.7 vs 15.0 pg/ml, p=0.02) and testosterone (0.18 vs 0.48 vs 2.35 ng/ml, p<0.01) as well as higher levels of cortisol (8.9 vs 7.7 vs 7.6μg/dl, p=0.05) in low FFMF patients. Regarding clinical outcomes, low FFMF was associated with increased one-year mortality (23.4%) compared to medium (11.6%) or low FFMF (3.8%, p<0.01), Figure 2A. This difference persisted over five years (p<0.01), Figure 2B. ROC curve analysis showed that FFMF had the strongest association with one-year mortality (AUC 0.75, p<0.01) and was superior to the STS-PROM (AUC 0.65) and EuroSCORE II (AUC 0.64). Multivariate analysis revealed that low FFMF was independently associated with mortality following TAVR (OR: 3.19 [CI: 1.64 – 6.22], p<0.01). Conclusion The CT-derived FFMF is associated with inflammation and endocrinological disorder in patients undergoing TAVR. Importantly, a low FFMF is a strong and independent predictor of dismal outcomes. FFMF assessment can seamlessly integrate into routine pre-interventional CTs, offering a promising objective parameter for outcome prediction.

Association between the weight-adjusted-waist index and testosterone deficiency in adult males: a cross-sectional study

Testosterone deficiency has been recognized as a significant health concern and is closely related to obesity. The weight-adjusted-waist index (WWI) is an innovative adiposity parameter that is superior to BMI in certain aspects, but its relationship with testosterone levels has not been elucidated. The aim of this study was to investigate the relationships of the WWI with total testosterone levels and testosterone deficiency. Data from the National Health and Nutrition Examination Survey (NHANES, 2011–2016) were utilized. The WWI was calculated as waist circumference (cm) over the square root of weight (kg), and a total testosterone level of less than 300 ng/dL was defined as testosterone deficiency. Weighted multivariable regression models were used to assess the associations. A total of 6859 participants were included, 26.28% of whom were testosterone deficient. The WWI was inversely related to total testosterone levels (β = -49.93, 95% CI: -60.07, -39.78, P < 0.001) and positively associated with testosterone deficiency (OR = 1.46, 95% CI: 1.23, 1.72, P < 0.001) in the fully adjusted model. A significant nonlinear relationship was also detected between WWI and testosterone deficiency (P for nonlinearity = 0.004) with an inflection point of 9.486 cm/√kg. The associations were consistent in the subgroup analysis (all P > 0.05), except for the participants with eGFR < 60 mL/(min*1.73m2) and hypertension. A higher WWI was linked to lower total testosterone levels and a greater risk of developing testosterone deficiency, especially among those who had an eGFR ≥ 60 mL/(min*1.73m2) and were nonhypertensive.

Aromatase, testosterone, TMPRSS2: determinants of COVID-19 severity

BackgroundMale sex has been identified as a risk factor for worse COVID-19 outcomes. This sex difference has been mostly attributed to the complex role of sex hormones. Cell surface entry of SARS-CoV-2 is mediated by the transmembrane protease serine 2 (TMPRSS2) which is under transcriptional regulation by androgens. P450 aromatase enzyme converts androgens to estrogens. This study measured concentrations of aromatase enzyme, testosterone, estradiol, and TMPRSS-2 in plasma of hospitalized COVID-19 patients to elucidate the dynamics of sex-linked disparity in COVID-19 and correlate them with disease severity and mortality.MethodsIn this prospective cohort study, a total of 265 patients (41% women), age 18 years and older, who had a positive COVID-19 PCR test and were hospitalized for COVID-19 at Memorial Hermann Hospital in Houston, (between May 2020 and May 2021) were enrolled in the study if met inclusion criteria. Plasma concentrations of Testosterone, aromatase, TMPRSS-2, and estradiol were measured by ELISA. COVID-19 patients were dichotomized based on disease severity into moderate-severe (n = 146) or critical (n = 119). Mann Whitney U and logistic regression were used to correlate the analytes with disease severity and mortality.ResultsTMPRSS2 (2.5 ± 0.31 vs. 1.73 ± 0.21 ng/mL, p < 0.01) and testosterone (1.2 ± 0.1 vs. 0.44 ± 0.12 ng/mL, p < 0.01) were significantly higher in men as compared to women with COVID-19 after adjusting for age in a multivariate model. There was no sex difference seen in the level of estradiol and aromatase in COVID-19 patients. TMPRSS2 and aromatase were higher, while testosterone was lower in patients with increased COVID-19 severity. They were independently associated with COVID-19 severity, after adjusting for several baseline risk factors in a multivariate logistic regression model. In terms of mortality, TMPRRS2 and aromatase levels were significantly higher in non-survivors.ConclusionsOur study demonstrates that testosterone, aromatase, and TMPRSS2 are markers of COVID-19 severity. Estradiol levels do not change with disease severity in COVID-19. In terms of mortality prediction, higher aromatase and TMPRSS-2 levels can be used to predict mortality from COVID-19 in hospitalized patients.Plain English SummaryCOVID-19 has caused over a million deaths in the U.S., with men often getting sicker than women. Testosterone, a male hormone, helps control a protein called TMPRSS-2, which allows the COVID-19 virus to spread more easily in the body. A protein called aromatase converts the male hormone testosterone into the female hormone estrogen. It is thought that female hormone estrogen helps protect women from getting seriously ill from COVID-19. To understand the role of these hormones in COVID-19 and sex differences, we measured levels of testosterone, estrogen, aromatase (which turns testosterone into estrogen), and TMPRSS-2 in hospitalized COVID-19 patients. We also checked how this level might reflect the severity of the disease. We found that critically ill COVID-19 patients (the ones in ICU) had higher levels of TMPRSS-2 and aromatase, and lower testosterone levels. When we used these hormone levels to predict death in hospitalized COVID-19 patients, higher levels of TMPRSS-2 and aromatase were linked to a lower chance of survival.

Androgen blockage impairs proliferation and function of Sertoli cells via Wee1 and Lfng

BackgroundAndrogens are essential hormones for testicular development and the maintenance of male fertility. Environmental factors, stress, aging, and psychological conditions can disrupt androgen production, impacting the androgen signaling pathway and consequently spermatogenesis. Within the testes, testosterone is produced by Leydig cells and acts on Sertoli cells by activating the androgen receptor (AR), which then translocates to the nucleus to function as a transcription factor. Despite clinical correlations between low testosterone levels and diminished sperm quality, the precise mechanism remains unclear.MethodsThis study explores the hypothesis that reduced androgen levels impair Sertoli cell function by disrupting AR transcriptional regulation. Using an androgen blockade model with enzalutamide, we investigated the impact of low androgen levels on AR target genes in Sertoli cells through ChIP-seq and RNA-seq assays.ResultsOur results reveal that androgen blockage increases AR enrichment on the promoter region of Wee1, promoting Wee1 expression, while decreasing binding to the promoter region of Lfng, inhibiting its expression. Increased WEE1 protein inhibits Sertoli cell proliferation, whereas reduced LFNG affects Notch modification, leading to decreased production of glial cell line-derived neurotrophic factor (GDNF), a key growth factor for spermatogonial stem cell self-renewal.ConclusionsThese findings provide new insights into the molecular mechanisms by which low androgen levels interfere with Sertoli cell functions, offering novel perspectives for the clinical treatment of male reproductive disorders.

The Effect of the Severity of Chronic Obstructive Pulmonary Disease on the Pituitary Gonadal Axis

This study aims to investigate the levels of anabolic hormone implicated in specific clinical symptoms of chronic obstructive pulmonary disease (COPD) in relation to disease severity. Sixty-four male patients with COPD for at least two years were included. COPD diagnosed was based on pulmonary function tests, with severity classified using the CAT score and mMRC breathlessness scale. Levels of various hormones including TSH T3 T4, FSH, LH, testesterone, prolactin, progesterone and CRP were measured. Arterial blood gases were also analyzed. Patients were categorized according to GOLD stages. LH, FSH levels decreased during exacerbation, with a significant positive correlation between LH and low arterial oxygen levels. lower testosterone levels were statistically significant in severe COPD patients with FEV1 &lt; 50%. A decrease in LH, testosterone FSH, TSH, progesterone and prolactin was observed with low blood oxygen levels, indicating dysfunction in the hypothalamic-pituitary-gonadal axis. However,stastistical significance varied.In conclusion, hormonal changes occur in male COPD patients, particulary related to disease severity. Testesterone levels correlate significantly with COPD severity. LH decrease during pronounced hypoxemia period was notable. Further research is necessary to evaluate the safety and efficacy of testosterone supplementation in COPD patients.

Experimentally Elevated Levels of Testosterone Advance Daily Onset of Activity in Short-Day Housed Male House Sparrows (Passer domesticus).

Seasonal changes in sleep/wake cycles and behaviors related to reproduction often co-occur with seasonal fluctuations in sex hormones. Experimental studies have established that fluctuations in circulating testosterone mediate circadian rhythms. However, most studies are performed under constant lighting conditions and fail to investigate the effects of testosterone on the phenotypic output of circadian rhythms, that is, chronotype (daily activity patterns under light:dark cycles). Here, we experimentally elevated testosterone with implants during short nonbreeding daylengths in male house sparrows (Passer domesticus) to test if observed seasonal changes in chronotype are directly in response to photoperiod or to testosterone. We fitted individuals with accelerometers to track activity across treatment periods. Birds experienced three treatments periods: short day photoperiods before manipulation (SD), followed by testosterone implants while still on short days (SD + T). Implants were then removed. After a decrease in cloacal protuberance size, an indicator of low testosterone levels, birds were then photostimulated on long days (LD). Blood samples were collected at night, when testosterone peaks, to compare testosterone levels to daily onset/offset activity for experimental periods. Our results indicate that experimentally elevated testosterone under short nonbreeding photoperiods significantly advanced daily onset of activity and total daily activity relative to daylength. This suggests that testosterone, independent of photoperiod, is responsible for seasonal shifts in chronotypes and daily activity rhythms. These findings suggest that sex steroid hormone actions regulate timing of daily behaviors, likely coordinating expression of reproductive behaviors to appropriate times of the day.

7778 Factors Predicting Recovery of Hypogonadism in Men with Prolactinoma Treated with Dopamine Agonists

Abstract Disclosure: S. Constantinescu: None. O. Alexopoulou: None. D.M. Maiter: None. Introduction: Recovery of hypogonadism is an important objective of dopamine agonist (DA) treatment in men with prolactinoma. However, the extent, timeline, and predictive factors of gonadotrope axis recovery are still unclear. Methods: We report data from a large cohort of 89 men with prolactinoma, looking at the evolution of testosterone levels after 6 and 12 months of treatment with DA. We excluded patients with peripheral hypogonadism, surgical treatment performed less than 12 months after onset of DA treatment, and patients with small tumors (≤ 5 mm and prolactin ≤ 50 µg/l) who did not achieve tumor shrinkage during treatment. We defined low testosterone as a morning value &amp;lt; 10 nmol/l. Patients who had started testosterone supplementation were considered as having persistent hypogonadism. Results: Among the 89 men (mean age ± SD: 44 ± 14 years; 65/89 with a macroprolactinoma), 14 (16%) had normal initial testosterone levels (NT) and 75 (84%) had low testosterone at diagnosis (LT). Compared to LT, NT patients had significantly lower PRL (median 53 µg/l versus 490 µg/l, p=0.009) and smaller tumors (median 6.5 mm versus 21.2 mm, p=0.013). In the NT group, after 6 (n=11) and 12 months (n=10), testosterone rose from a median of 13.4 to 16.6 (p=0.266) and 17.9 nmol/l (p=0.012), respectively. In LT patients, after 6 (n=56) and 12 months (n=42), testosterone rose significantly from a median of 5.8 to 10.7 (p&amp;lt;0.001) and 12.5 nmol/l (p&amp;lt;0.001).In the LT group, 45% (32/71) had recovered eugonadism at 6 months and 57% (40/70) at 12 months. These proportions rose to 61% (22/36) and 67% (n=26/39) at 6 and 12 months when prolactin concentrations were normalized. Factors associated with persistent hypogonadism after one year were chiasmal compression at diagnosis (p=0.05), cavernous sinus invasion (p=0.042), cystic tumoral component (p=0.038), a greater tumoral diameter (mean 25 mm vs 15 mm, p&amp;lt;0.01), lower testosterone concentrations at diagnosis (mean 3.6 nmol/l vs 6.8 nmol/l, p&amp;lt;0.001) and at 6 months (mean 6.0 nmol/l vs 13.0 nmol/l, p&amp;lt;0.03), and higher prolactin levels at one year (median 17.15 µg/l vs 8.4 µg/l, p=0.064). Testosterone &amp;lt; 6.7 nmol/l at 6 months predicted the long-term persistence of hypogonadism with 72% sensitivity and 92% specificity. Conclusion: The sensitivity of the gonadotrope axis to high prolactin levels is highly variable in men with prolactinoma and 16% of them retain normal testosterone concentrations. However, this finding does not exclude partial inhibition of the gonadotrope axis that will improve with DA treatment. In patients with low testosterone levels, the recovery rate of hypogonadism is 45% at 6 months and 57% at 12 months, increasing to 67% if prolactin is normalized. Testosterone supplementation could be started early in patients with large, invasive, cystic and/or compressive tumors, with a testosterone concentration lower than 6.7 nmol/L after 6 months of treatment. Presentation: 6/3/2024

8059 An Interesting Case Of Hypogonadism Likely Caused By Cushing's Syndrome

Abstract Disclosure: R. Ripa: None. J. Su: None. R. Patel: None. Introduction: Cushing’s Syndrome is a rare endocrine disorder that comprises a multitude of symptoms caused by hypercortisolism. Given non-specific symptoms, the disease can often be overlooked for more common diseases, such as diabetes, obesity, and even hypogonadism. Hypogonadism is a clinical disorder defined by decreased functional activity of the gonads. The diagnosis can often be challenging in developed males, who present with hypogonadotropic hypogonadism without an obvious cause. Here we present a case of a male who presented with hypogonadism symptoms for at least 5 years before being diagnosed with Cushing’s syndrome. Case Presentation: 58-year-old Caucasian male with a medical history of hypertension, cardiomyopathy and a BMI of 23, presented with decreased libido and erectile dysfunction. He was started on testosterone therapy three years prior, however it was discontinued due to heart failure. Without testosterone replacement, lab work was notable for: low free and total testosterone, 21.4 and 50.6 ng/dL, respectively, inappropriately normal findings of LH, FSH (1.0 and 4.9 IU/L, respectively), as well as unremarkable findings of GH, Prolactin, TSH, pituitary MRI and testes ultrasound, leading to a suspicion of hypogonadism. Due to persistent symptoms of hypogonadism and low testosterone, clomiphene was started but later changed to testosterone therapy after cardiology consultation. Shortly after, he began reporting facial flushing, associated with facial roundedness and elevated blood pressure. Upon further work up, hyperaldosteronism and pheochromocytoma testing was negative and his baseline cortisol was 21.9 mcg/dL with a low adrenocorticotropic hormone (ACTH), &amp;lt;5 pg/mL. Further, dexamethasone suppression testing showed suboptimally suppressed cortisol (14.4 mcg/dL). An abdomen MRI with and without contrast revealed a 2.3 cm adrenal adenoma, confirming an adrenal source of Cushing’s syndrome, and he underwent an adrenalectomy. Post-procedure, his cortisol and ACTH levels normalized to 10.5 mcg/dL and 39 pg/mL, respectively, showing a revival of his hypothalamic - pituitary - adrenal axis. Unfortunately, however, his free and total testosterone levels continued to remain low (38.9 and 152 ng/dL, respectively) and he was continued on testosterone therapy. Discussion: Our patient initially presented with decreased libido, and low testosterone levels and was treated for hypogonadism, as he did not have typical Cushing’s symptoms. Due to eventual weight gain and facial edema, it was only then that work up was pursued showing hypercortisolism release, leading to a proper diagnosis of Cushing’s syndrome. Hypercortisolism can affect all parts of the body, including hormones, muscles, joints and bones. When presenting in the initial stages and with mild symptoms, the diagnosis of hypercortisolism is often challenging and can go undetected for many years. Presentation: 6/2/2024

7883 Atypical Presentation of Macroprolactinoma: Discordantly Low Serum Prolactin and Therapeutic Challenges

Abstract Disclosure: S. Hossain: None. M.S. Hossain: None. B. Gautam: None. S.C. Kumar: None. H. Liao: None. D.S. Rosenthal: None. Introduction: Pituitary tumors are categorized as microadenomas (&amp;lt;1 cm) and macroadenomas (&amp;gt;1 cm) with prolactinomas being one of the most common causes. The mean prevalence of prolactinomas is 10 per 100,000 in men and 30 per 100,000 in women. Serum prolactin levels corresponds to the size of the prolactinoma and any discrepancy should be treated with caution as that may indicate co-existence of pluripotent cells. We present a patient who presented with visual field defect and headaches, found to have a pituitary macroadenoma with discordantly low serum prolactin level compared to the size of adenoma, prompting a change in the treatment course. Case Presentation: A 42 year old male with no past medical history was seen as an endocrinology consult requested by neurosurgery for frequent headaches and visual problems for 1 year. Vital signs were normal, with negative orthostatic drop of blood pressure. He had prominent bitemporal hemianopsia confirmed by formal visual field testing by Ophthalmology. No galactorrhea or features suggestive of acromegaly or hyperthyroidism. He complained of erectile dysfunction but appeared to have normal male secondary sexual characteristics. MRI of brain showed a suprasellar mass measuring 3.8 x 2.6 x 2.2 cm with mass effect on the optic chiasm, hypothalamus with extension and infiltration into the right cavernous sinus. Lab results showed elevated prolactin of 1343.5 ng/ml confirmed by serial dilution, low serum testosterone level of 134 ng/dl and inappropriately normal FSH and LH. Complete blood counts, comprehensive metabolic panel, TFT, ACTH, cortisol and IGF-1 were normal. Patient was started on bromocriptine and he noticed improvement in his field of vision and acuity within one week of starting therapy. He continued to show sustained improvement in vision and resolution of his headaches at the one-month mark. MRI 2 months from starting bromocriptine showed modest reduction in size of the tumor to 2.1 x 2.3 x 2.4 cm with continued mass effect on the optic chiasm. Prolactin level decreased to 69.3 ng/ml. Therefore, although there was some improvement in visual fields, surgical resection was recommended to alleviate the mass effect on the optic chiasm. Conclusion: Our case highlights the significance of identifying discrepancies between the size of a prolactinoma and serum prolactin levels. Expected prolactin level from a prolactinoma similar in size to our case would be &amp;gt;3000 ng/ml when ours was 1343.5ng/ml. Despite undergoing treatment and lowering of prolactin levels our patient's pituitary adenoma did not significantly reduce in size after two months of treatment with bromocriptine and the mass continued to exert pressure on the optic chiasm. This suggests possible presence of pluripotent cells in addition to prolactin-producing cells within the tumor. The recommended course of action was surgical resection of the mass. Presentation: 6/1/2024

Analyzing the impact of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) on the reproductive system using network toxicology and molecular docking

Growing evidence suggests that perfluorinated compounds (PFCs) contribute to reproductive toxicity, with perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) being the most extensively studied. These chemicals are known to lower testosterone levels and compromise the integrity of the blood-testis barrier. However, the specific mechanisms of their reproductive toxicity remain largely unknown due to research limitations. In this study, we utilized network pharmacology to pinpoint the core genes and signaling pathways implicated in the reproductive toxicity caused by PFOA and PFOS. Molecular docking was employed to validate the interactions between these compounds and their targets. Key targets identified include CCL2, CXCR4, RPS27A, RPL5, PSMA7, and PSMC1, which are crucial in mediating reproductive toxicity. These genes are primarily involved in the chemokine signaling pathway, viral protein interactions with cytokines and cytokine receptors, and ribosomal functions. This study underscores the effectiveness of combining network toxicology and molecular docking to analyze the toxicity and molecular mechanisms of mixed environmental pollutants.

The relationship between remnant cholesterol and the risk of testosterone deficiency in US adults: a cross-sectional study based on the NHANES database.

Testosterone deficiency (TD) is an urgent health issue that requires attention, associated with various adverse health outcomes including cardiovascular diseases (CVD) and metabolic syndrome. Remnant cholesterol (RC) has emerged as a potential biomarker for cardiovascular risk, but its relationship with testosterone levels and TD has not been thoroughly investigated. This study aims to explore the association between RC and TD in adult American males using data from the National Health and Nutrition Examination Survey (NHANES). This cross-sectional study utilized data from three NHANES cycles (2011-2016), including 2,848 adult male participants. RC was calculated as total cholesterol minus high-density lipoprotein cholesterol (HDL) and low-density lipoprotein cholesterol (LDL). TD was defined as total testosterone levels below 300 ng/dL. Multivariable linear and logistic regression analyses, as well as smooth curve fitting and generalized additive models, were performed to assess the associations between RC and total testosterone levels and TD, adjusting for potential confounders. Subgroup analyses were conducted based on age, BMI, smoking status, diabetes, hypertension, CVD, and chronic kidney disease (CKD). Higher RC levels were significantly associated with lower total testosterone levels (β = -53.87, 95% CI: -77.69 to -30.06, p<0.001) and an increased risk of TD (OR = 1.85, 95% CI: 1.29 to 2.66, p=0.002) in fully adjusted models. When RC was analyzed as quartiles, participants in the highest quartile (Q4) had significantly lower total testosterone levels (β = -62.19, 95% CI: -93.62 to -30.76, p<0.001) and higher odds of TD (OR = 2.15, 95% CI: 1.21 to 3.84, p=0.01) compared to those in the lowest quartile (Q1). Subgroup analyses revealed consistent associations across different age groups, particularly strong in participants over 60 years, and in never smokers. The associations remained significant in both hypertensive and non-hypertensive groups, as well as in those with and without CKD. No significant interactions were found across subgroups. This study demonstrates a significant inverse association between RC levels and total testosterone levels, along with a positive association with the risk of TD. These findings suggest that RC could serve as a valuable biomarker for early identification of individuals at risk for TD. Future longitudinal studies are needed to confirm these findings and explore the underlying mechanisms.

Perceived Chronic Traumatic Encephalopathy and Suicidality in Former Professional Football Players

ImportanceParticipation in American-style football (ASF) has been linked to chronic traumatic encephalopathy neuropathological change (CTE-NC), a specific neuropathologic finding that can only be established at autopsy. Despite being a postmortem diagnosis, living former ASF players may perceive themselves to have CTE-NC. At present, the proportion and clinical correlates of living former professional ASF athletes with perceived CTE who report suicidality are unknown.ObjectiveTo determine the proportion, clinical correlates, and suicidality of living former professional ASF players with perceived CTE.Design, Setting, and ParticipantsA cross-sectional study within the Football Players Health Study at Harvard University was conducted from 2017 to 2020. Using electronic and paper surveys, this population-based study included former ASF players who contracted with a professional league from 1960 to 2020 and volunteered to fill out a baseline survey. Data for this study were analyzed from June 2023 through March 2024.ExposuresData included demographics, football-related exposures (eg, position, career duration), and current health problems (anxiety, attention-deficit/hyperactivity disorder, depression, diabetes, emotional and behavioral dyscontrol symptoms, headache, hyperlipidemia, hypertension, low testosterone level, pain, sleep apnea, and subjective cognitive function).Main Outcomes and MeasuresThe proportion of participants reporting perceived CTE. Univariable and multivariable models were used to determine clinical and suicidality correlates of perceived CTE.ResultsAmong 4180 former professional ASF players who volunteered to fill out a baseline survey, 1980 (47.4%) provided follow-up data (mean [SD] age, 57.7 [13.9] years). A total of 681 participants (34.4%) reported perceived CTE. Subjective cognitive difficulties, low testosterone level, headache, concussion signs and symptoms accrued during playing years, depressive/emotional and behavioral dyscontrol symptoms, pain, and younger age were significantly associated with perceived CTE. Suicidality was reported by 171 of 681 participants with perceived CTE (25.4%) and 64 of 1299 without perceived CTE (5.0%). After adjusting for established suicidality predictors (eg, depression), men with perceived CTE remained twice as likely to report suicidality (odds ratio, 2.06; 95% CI, 1.36-3.12; P &amp;amp;lt; .001).Conclusions and RelevanceThis study found that approximately one-third of living former professional ASF players reported perceived CTE. Men with perceived CTE had an increased prevalence of suicidality and were more likely to have health problems associated with cognitive impairment compared with men without perceived CTE. Perceived CTE represents a novel risk factor for suicidality and, if present, should motivate the diagnostic assessment and treatment of medical and behavioral conditions that may be misattributed to CTE-NC.

Evaluation of serum irisin level and severity of erectile dysfunction in diabetic males: a cross sectional prospective study

BackgroundIrisin is an exercise-induced myokine that alleviates endothelial dysfunction and reduces insulin resistance in type 2 diabetes mellitus (T2DM). The current study aimed to assess the serum level of irisin in T2DM men with erectile dysfunction (ED) compared to T2DM patients with normal erectile function and healthy controls, as well as investigate the association between serum irisin level and the severity of ED in T2DM patients.Patients and methodsA cross-sectional study was conducted on 90 males, divided into three groups: 32 T2DM patients with ED, 24 T2DM patients without ED, and 34 healthy controls. Socio-demographic characteristics and scores of the validated Arabic version of the international Index of Erectile Function-5 (ArIIEF-5), Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) were obtained. Furthermore, routine laboratory tests employed for diabetes monitoring and serum levels of total testosterone and irisin were assessed within these groups.ResultsT2DM men with ED had significantly lower serum levels of irisin and testosterone, as well as a lower ArIIEF-5 score, but their GAD-7 and PHQ-9 scores were significantly higher than those without ED or controls (p < 0.001). Among T2DM men, serum irisin levels positively associated with ArIIEF-5 scores and serum testosterone (r = 0.413, p = 0.002; r = 0.936, p < 0.001, respectively) but negatively associated with glycosylated hemoglobin levels (r = -0.377, p = 0.004). Multivariate regression analysis to predict ED in T2DM patients found that GAD-7 score was the only most significant predictor for ED (ꞵ = − 1.176, standard error = 0.062, p < 0.001).ConclusionThe current study had demonstrated that irisin positively correlated with the ArIIEF-5 and serum testosterone but negatively correlated with HbA1c in T2DM men. Nevertheless, further validation of these findings is necessary through cohort studies.

Clomiphene Citrate Treatment as an Alternative Therapeutic Approach for Male Hypogonadism: Mechanisms and Clinical Implications.

Male hypogonadism, which is characterized by low testosterone levels, has a significant impact on male sexual function, overall health, and fertility. Testosterone replacement therapy (TRT) is the conventional treatment for this condition, but it has potential adverse effects and is not suitable for men seeking to conceive. Testosterone plays an essential role in male sexual function, metabolism, mood, and overall well-being. Clomiphene citrate, a drug originally developed for female infertility, has recently gained attention as an off-label treatment for male hypogonadism. By blocking the negative feedback of estrogen on the hypothalamus and pituitary glands, clomiphene stimulates gonadotropin secretion, leading to increased endogenous testosterone production, which, in turn, improves sperm parameters and fertility and alleviates the symptoms of hypogonadism. Regarding the safety profile of clomiphene compared with TRT, clomiphene appears to confer a lower risk than TRT, which is associated with adverse effects such as polycythemia. Furthermore, combination therapy with clomiphene and anastrozole or human chorionic gonadotropin has been investigated as a potential approach to enhancing the effectiveness of treatments for improving hypogonadism symptoms. In conclusion, clomiphene citrate may offer a promising alternative to TRT for men with hypogonadism, particularly those desiring fertility preservations. However, its long-term efficacy and safety remain inadequately understood. Future research should focus on exploring the benefits of combination therapies and personalized treatment strategies based on individual patient characteristics.

Testosterone and resistance training improved physical performance and reduced fatigue in frail older men: 1 year follow-up of a randomized clinicaltrial.

To improve health conditions among hypogonadal men ≥70 years of age using testosterone undecanoate (TU) injections, progressive strength training, and oral supplements of vitamin D, calcium, and protein. This study is a 1-year follow-up of a double-blind RCT lasting 20 weeks, including 148 older men ≥70 years old with low testosterone levels and mobility problems. During 52 weeks, 4 groups received either testosterone therapy (TU) or progressive resistance training (Training), both (Combo), or no intervention (Controls). Physiotherapists supported the training groups until week 20, while these participants continued trained on their own during weeks 21 to 52. The main outcome measure was the 30-s chair stand test. The following numbers of participants completed the trial: 20 (Combo), 20 (Controls), 24 (TU), and 14 (Training). When examining 30-s chair stand test performance within each group at baseline, and at weeks 4, 20 and 52, only the Combo group improved (p = 0.001, Friedman Test). Compared to controls, only the Combo group experienced reduced fatigue and tiredness (p < 0.05). Fifty-two weeks of testosterone supplementation combined with progressive resistance training may enhance physical performance, alleviate fatigue, and had no notable detrimental impacts among males aged ≥70 suffering from mobility issues and testosterone insufficiency.Trial registration - Clinical Trials NCT02873559.

Marital Status and Serum Level of Testosterone: In Relation to Serum Level of Cortisol

Purpose: To explore the association between marital status and testosterone, and cortisol serum levels in 119 healthy men aged 45 to 60 years representing the general population. Material and Methods: Data on men’s age, waist circumference, body mass index, smoking, alcohol consumption, and marital status were collected. Serum levels of LH, testosterone, and cortisol were also measured. Two groups were identified according to marital status: paired (married, living together, and living apart) and unpaired men (divorced or separated). Results: The participants had a mean age of 55 (± 4.0 years). Testosterone level was significantly lower in paired as compared to unpaired men (14 nmol/L vs. 19 nmol/L, p = 0.01). The opposite trend was found regarding cortisol levels (350 nmol/L vs. 293 nmol/L, p = 0.01). No significant differences between the two groups were found regarding men’s age, body mass index, waist circumference, and LH level (p &gt; 0.05). Using a multivariate regression analysis test adjusted for men’s age, body mass index, waist circumference, smoking, and alcohol consumption; a significant negative association between marital status and testosterone level (β = -04.00; 95% CI = -7.00, -1.00; p = 0.01), and a significant positive association between marital status and cortisol level (β = 47.00; 95% CI = 6.00, 89.00; p = 0.03) were found. Conclusions: Paired men were associated with lower testosterone levels. These findings might be partially explained by the concomitant higher cortisol level found in this group of men.

Testosterone levels and risk of newly diagnosed type 2 diabetes mellitus in adult men: systematic review and meta-analysis.

Testosterone is a metabolically active hormone in males for metabolic homeostasis. Although the coexistence of low testosterone levels and type 2 diabetes mellitus (T2DM) have been associated, there are no reports that evaluate alterations in total testosterone (TT) levels and the risk of newly diagnosed T2DM. This review evaluates this question in adult men with high or low levels of total testosterone (TT), as well as the role played by other hormones such as free testosterone (FT), sex hormone binding globulin (SHBG), dihydrotestosterone (DHT), estrogens and testosterone bioavailable (bT). We searched for studies published up to July 30, 2023, in five databases, following a PECO strategy. We found twenty-two studies for quantitative analysis and meta-analyzed the same quantity of studies. This first meta-analysis incorporates the assessment of the risk of low TT and T2DM in longitudinal studies. 43,038 adult men are included. Our meta-analysis shows that there is an association between low TT levels and the risk of newly diagnosed T2DM (OR 1.52; 95% CI 1.10-2.10; p < 0.05; I²: 79%). It is also evident that SHBG in low TT studies behaves as a risk factor for T2DM in the same way as FT, although without statistical significance. bT behaves as a protective factor. There is no association between estrogen, DHT and T2DM. In adult men with low TT values, there is a greater risk of developing a newly diagnosed of T2DM. SHBG values in low TT patients also present a higher risk of T2DM as the same FT but without statistical significance. bT behaves as a protective factor We have not found an association between risk of T2DM and the levels of estrogen, DHT although there are very few studies that report these hormones.

Effects of Heat Stress-Induced Sex Hormone Dysregulation on Reproduction and Growth in Male Adolescents and Beneficial Foods.

Heat stress due to climate warming can significantly affect the synthesis of sex hormones in male adolescents, which can impair the ability of the hypothalamus to secrete gonadotropin-releasing hormone on the hypothalamic-pituitary-gonadal axis, which leads to a decrease in luteinizing hormone and follicle-stimulating hormone, which ultimately negatively affects spermatogenesis and testosterone synthesis. For optimal spermatogenesis, the testicular temperature should be 2-6 °C lower than body temperature. Heat stress directly affects the testes, damaging them and reducing testosterone synthesis. Additionally, chronic heat stress abnormally increases the level of aromatase in Leydig cells, which increases estradiol synthesis while decreasing testosterone, leading to an imbalance of sex hormones and spermatogenesis failure. Low levels of testosterone in male adolescents lead to delayed puberty and incomplete sexual maturation, negatively affect height growth and bone mineral density, and can lead to a decrease in lean body mass and an increase in fat mass. In order for male adolescents to acquire healthy reproductive capacity, it is recommended to provide sufficient nutrition and energy, avoid exposure to heat stress, and provide foods and supplements to prevent or repair testosterone reduction, germ cell damage, and sperm count reduction caused by heat stress so that they can enter a healthy adulthood.

Frailty and the Correlation Between Total Testosterone Levels and Urinary Incontinence Among Elderly Women.

The objective was to explore the correlation between total testosterone levels and stress urinary incontinence (SUI) and urgency urinary incontinence (UUI) in older patients, emphasizing frailty. This prospective cross-sectional study included 1,328 women over 60 years of age at an incontinence specialty clinic. Participants were assessed for UI, frailty, using the Japanese Frailty Scale, and total testosterone levels. Analysis of a logistic regression model was employed for age, body mass index (BMI), and vaginal deliveries adjustment, with association and multivariate analyses to evaluate the associations with SUI and UUI. The frailty and nonfrailty groups each consisted of 664 individuals. After age, BMI, and the number of vaginal deliveries adjustment, the analysis showed a negative association between total testosterone levels and both SUI (p < 0.001) and UUI (p < 0.001) in the frailty group. Multivariate analysis revealed that, in the nonfrailty group, factors such as low total testosterone levels (p = 0.0145), diabetes (p = 0.0052), and cerebral infarction (p = 0.0254) were related to SUI, whereas no significant factors were associated with UUI. In the frailty group, factors associated with SUI included low total testosterone levels (p < 0.0001), the number of vaginal deliveries (p < 0.0001), smoking (p = 0.0240), chronic lung disease (p < 0.0248), and hypertension (p < 0.0265). Factors associated with UUI were age (p < 0.0001), low total testosterone levels (p = 0.0025), diabetes (p < 0.0001), and the number of vaginal deliveries (p = 0.0152). The study highlights the significance of incorporating the assessment of frailty and testosterone levels in addressing UI among older women, particularly in the aged population, underscoring the need for tailored approaches in this demographic.