Decreased Testosterone Production Research Articles

Andropause: A Neglected Disease Entity

This review aims to bring attention to the growing issue of andropause, a condition that affects men as they age. The literature was identified by searching the major bibliographic databases, including PubMed, Google Scholar, EBSCOhost, Web of Science, and CINAHL. Studies were included if they focused on strategies for reducing and preventing andropause, published between 1980 and 2023. Andropause, which is often overlooked and misconceived, is the result of a decrease in testosterone production and can result in physical and psychological symptoms such as fatigue, weight gain, decreased libido, and depression. This paper reviews the literature on the prevalence, detection, and management of andropause. It is important for the medical community to recognize andropause, as diagnosing and treating the condition can significantly improve the quality of life. The review canvases several studies to understand andropause comprehensively, highlighting various biomarkers and diagnostic criteria, possible therapies, and potential risks and complications associated with the condition. In addition, this review offers practical suggestions to health professionals, helping them recognize patients at risk of andropause, assess patients for the condition, and provide appropriate treatments. Furthermore, it emphasizes the importance of regular screening and active monitoring for any possible early warning signs of andropause. This review provides a comprehensive overview of andropause, from identification to management. It demonstrates the need for increased awareness and acknowledgment of andropause among medical professionals in order to ensure that all men get the support they need throughout the aging process.

Impact of Exposure to a Mixture of Organophosphate Esters on Adrenal Cell Phenotype, Lipidome, and Function.

Organophosphate esters (OPEs) are used primarily as flame retardants and plasticizers. Previously, we reported that adrenal cells are important targets of individual OPEs. However, real-life exposures are to complex mixtures of these chemicals. To address this, we exposed H295R human adrenal cells to varying dilutions (1/1000K to 1/3K) of a Canadian household dust-based OPE mixture for 48 hours and evaluated effects on phenotypic, lipidomic, and functional parameters. Using a high-content screening approach, we assessed phenotypic markers at mixture concentrations at which there was greater than 70% cell survival; the most striking effect of the OPE mixture was a 2.5-fold increase in the total area of lipid droplets. We then determined the response of specific lipid species to OPE exposures with novel, nontargeted lipidomic analysis of isolated lipid droplets. These data revealed that house dust OPEs induced concentration-dependent alterations in the composition of lipid droplets, particularly affecting the triglyceride, diglyceride, phosphatidylcholine, and cholesterol ester subclasses. The steroid-producing function of adrenal cells in the presence or absence of a steroidogenic stimulus, forskolin, was determined. While the production of 17β-estradiol remained unaffected, a slight decrease in testosterone production was observed after stimulation. Conversely, a 2-fold increase in both basal and stimulated cortisol and aldosterone production was observed. Thus, exposure to a house dust-based mixture of OPEs exerts endocrine-disrupting effects on adrenal cells, highlighting the importance of assessing the effects of environmentally relevant mixtures.

(249) Multiple sclerosis (MS) and Hypogonadism (HG): Is There a Relationship? - A Systematic Review

Abstract Introduction Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system and is widely recognized as a disease primarily affecting women. However, recent studies have shown that patients with MS, both male and female, may also suffer from hypogonadism, a condition characterized by decreased testosterone production and decreased gonadal function. The relationship between MS and hypogonadism is complex and not fully understood, with recent evidence showing that hypogonadism may have a significant impact on the quality of life and disease progression of MS patients. Objective This review aims to provide an overview of the current knowledge regarding the relationship between MS and hypogonadism, including the mechanisms underlying this relationship, the effects of hypogonadism on MS patients, and the potential benefits and drawbacks of testosterone replacement therapy for MS patients with hypogonadism. Methods This scientific review analyzed 19 articles that investigated the potential relationship between MS, testosterone levels, and hypogonadism. The articles were published between November 2008 and March 2022 and were identified through a comprehensive search of the PubMed database. The search terms used included “multiple sclerosis,” “testosterone,” “hypogonadism,” and “MS and testosterone levels.” The inclusion criteria for articles were as follows: (1) articles that investigated the relationship between MS, testosterone levels, and hypogonadism, (2) articles that were published in English, and (3) articles that provided original data. Exclusion criteria included (1) articles that were not related to the topic, (2) reviews and editorials, and (3) articles that did not provide original data. Results Of the 19 articles reviewed, 11 described a positive correlation between low testosterone levels and dysfunction within the hypothalamic-pituitary-gonadal axis in individuals with MS. These findings suggest that low testosterone levels may contribute to dysfunction within the hypothalamus-pituitary-gonadal axis, which plays a crucial role in regulating testosterone production. The results also showed a relationship between sexual dysfunction and low testosterone levels, as well as a positive correlative relationship between these two factors. Conclusions The reviewed articles indicate a complex relationship between MS, testosterone levels, and the hypothalamic-pituitary-gonadal axis, with low testosterone levels potentially contributing to dysfunction in this axis and to sexual dysfunction. Further research is needed to better understand the effects of testosterone therapy on MS and sexual dysfunction in MS patients. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Advisory board and speaker for Coloplast; consultant for Cynosure; advisory board and speaker for Halozyme; intellectual property with Masimo; advisory board for Promescent; consultant for Sprout; advisory board for Xialla.

Use of in vitro methodology to investigate phthalate effects on the differentiation of seminiferous tubule-associated stem cells to form Leydig cells and on the Leydig cells derived from the stem cells.

Introduction: Leydig cells isolated from the testis are able to sustain high levels of testosterone production in vitro, but only for up to 3days. Such cells are valuable for addressing the acute effects of chemicals on steroidogenic function, but not for repeated or chronic effects. Methodology is now available by which adult Leydig cells can be derived in vitro from seminiferous tubule-associated stem cells. In contrast to isolated Leydig cells, the Leydig cells derived in this way can synthesize and secrete high levels of testosterone for months. Herein, we asked whether this system might be used to address the effect of mono-(2-ethylhexyl) phthalate (MEHP) exposure on the formation of Leydig cells from tubule-associated stem cells, and on the Leydig cells after their formation. Methods: Adult Brown Norway rats received an intraperitoneal injection of ethane dimethanesulfonate (EDS) to eliminate the existing Leydig cells. Seminiferous tubules then were isolated and cultured in medium containing Insulin-Transferrin- Selenium (ITS), Smoothened Agonist (SAG), and luteinizing hormone (LH). Results: Culture of the tubules for 8weeks resulted in the formation of cells on the surfaces of the tubules that stained for CYP11A1 and STAR and produced high levels of testosterone. When the tubules were cultured in medium containing increasing concentrations of MEHP, concentration-dependent effects on Leydig cell formation occurred. To determine the effect of MEHP on newly produced Leydig cells, tubules were cultured for 8weeks in the absence of MEHP, resulting in the formation of adult Leydig cells, and then in medium containing increasing concentrations of MEHP. Concentration-dependent decreases in testosterone production by the adult Leydig cells were seen, and these decreases proved to be reversible. Discussion: The use of this new system should make it possible to determine the mechanisms by which acute, repeated, or chronic exposures to increasing concentrations of MEHP and/or exposure to other chemicals affect the formation of Leydig cells from stem cells, as well as the steroidogenic function of adult Leydig cells.

An Overview of the Mechanisms of Cadmium-induced Toxicity in the Male Reproductive System

Cadmium (Cd) is a toxic heavy metal that is known to accumulate in various organs and tissues in the body, including the testes. Exposure to Cd has been shown to cause significant testicular damage, including impaired spermatogenesis and decreased fertility in both humans and animals. This damage is thought to be due to Cd-induced oxidative stress and inflammation, which can lead to cellular damage and apoptosis. Cd has also been shown to disrupt the blood-testis barrier, leading to increased permeability and an altered testicular microenvironment. In addition, Cd exposure has been linked to changes in hormone levels, including decreased testosterone production and altered gonadotropin secretion. Reactive oxygen species (ROS) and an imbalance in the activity of antioxidant enzymes cause oxidative stress. The nuclear factor kappa-B (NF-κB) signaling system, which controls multiple genes involved in inflammatory responses including tumor necrosis factor (TNF-α), is activated by oxidative stress. These effects can contribute to decreased sperm count, motility, and viability. Efforts to reduce exposure to Cd may help to prevent or mitigate the harmful effects on testicular function. This can be achieved through occupational and environmental regulations, as well as public education and awareness programs. In this review, we highlight many of the principal mechanisms included in testicular damage. These pathways could be considered promising targets for the development of potential therapies for a variety of important human diseases.

The Protective Effects of Aloe Vera Gel Extract on the Sexual Complications Caused by Diabetes in Male Rats

Introduction: Diabetics usually suffer from chronic complications, including microvascular and macrovascular disorders. The capillaries supplying the sexual organs affect normal sexual functions. The erectile process has been shown to be impaired in diabetics. Vascular damage in diabetics may be associated with decreased testosterone production, sperm count, testicular weight, and seminiferous tubule diameter. In this study, we investigated the effects of Aloe vera gel extract (from Sistan and Baluchistan, Iran) on the male genital system in streptozocin-induced diabetic rats. Methods: A total of 24 male Wistar rats were included in the study. Diabetes was induced in 12 rats by intraperitoneal injection of a single dose of streptozotocin (STZ). The rats were divided into four groups. The first and third groups received saline (NaCl) by gavage daily. The second and fourth groups received Aloe vera gel extract daily by gavage. Treatments were continued for 30 days. At the end of the treatment period, blood samples were taken and serum glucose and testosterone levels were measured by photometric methods. Histological examinations were performed on the prostate and testes. Results: Mean weight index, serum levels of glucose and testosterone, mean sperm count, germinal epithelium (GE) thickness, and seminiferous tubule diameter improved significantly in the diabetes+Aloe vera group. Conclusion: We concluded that consumption of Aloe vera gel extract improved sexual complications in diabetic rats.

Sleep duration and testosterone levels in community older men: results from the West China Health and Aging Trend study.

Sleep duration and testosterone levels in community older men: results from the West China Health and Aging Trend study.

Echocardiographic and hemodynamic changes in patients with high-grade varicocele.

Varicocele is abnormal tortuosity and dilatation of the pampiniform plexus veins within the spermatic cord. Varicocele is associated with testicular atrophy, hypogonadism, impaired semen analysis values, or decreased testosterone production. Varicocele is a progressive disease and should be treated because it may be a systemic disease that can be associated with cardiovascular abnormalities. We hypothesize in this study that cardiovascular and hemodynamic pathologies may occur in varicocele patients. In this prospective, multicentric, multidisciplinary study, patients diagnosed with high-grade left varicocele in the urology clinic underwent semen analysis, total testosterone determination, and scrotal Doppler ultrasonography. In addition, blood pressure measurement and echocardiographic evaluation were performed by blinded cardiologists in both the varicocele patients and the healthy control group. The study was carried out with 103 varicocele patients and 133 healthy individuals who formed the control group. Diastolic blood pressure (P = 0.016), left ventricular end diastolic (P < 0.001) and systolic diameter (P < 0.001), ejection fraction (P < 0.001), pulmonary arterial pressure (P < 0.001), and aortic distensibility (P < 0.001) values were significantly higher in varicocele patients compared with controls; interventricular septum wall thickness (P = 0.022), aortic systolic (P < 0.001) and diastolic diameter (P < 0.001), aortic systolic (P < 0.001) and diastolic diameter index (P < 0.001), and aortic stiffness index (P < 0.001) values were significantly lower in varicocele patients. The mean aortic distensibility of non-normozoospermic group was lower than that of normozoospermic group (P = 0.041). There was no statistically significant relationship between thickest vein diameter in spermatic cord and cardiological parameters. This study showed that symptomatic patients with high-grade varicocele had a higher risk of cardiovascular and hemodynamic disease. We recommend that men with high-grade symptomatic varicocele with impaired semen analysis undergo cardiovascular and hemodynamic evaluation regardless of their spermatic vein diameter.

The Neural correlates of COVID-19-induced erectile dysfunction in males

Emerging evidence suggests that there are long-term complications after recovery from COVID-19, which involve multiple systems and lead to deterioration of the quality of life. Among these different complications, male sexual dysfunction, in particular erectile dysfunction, is one of the complications being identified recently. It was initially hypothesized that due to the presence of Angiotensin-converting enzyme II (ACE2) and transmembrane protease serine 2 (TMPRSS 2) in testes and Leydig cells, the male reproductive system is vulnerable to the infection of COVID-19, which may lead to a decrease in testosterone production and sexual dysfunction. However, evidence from a recent neurological study suggests that COVID-19 may be directly associated with dysregulation of the nervous systems at the central level in regions including the limbic system (e.g., hippocampus and amygdala), hypothalamus, brainstem, and the peripheral system (e.g., sympathetic nerves, olfactory bulb). As these affected regions are crucial for sexual behaviors, these observations may provide an alternate explanation for sexual dysfunction in COVID-19 survivors. To explore the potential involvement of the nervous system in sexual dysfunction induced by COVID-19, this review discusses the recent findings from the neurological perspective and states the possible research work that may be needed to delineate the underlying pathology.

Grim-19 plays a key role in mitochondrial steroidogenic acute regulatory protein stability and ligand-binding properties in Leydig cells

Grim-19 (gene associated with retinoid-IFN-induced mortality 19), the essential component of complex I of mitochondrial respiratory chain, functions as a noncanonical tumor suppressor by controlling apoptosis and energy metabolism. However, additional biological actions of Grim-19 have been recently suggested in male reproduction. We investigated here the expression and functional role of Grim-19 in murine testis. Testicular Grim-19 expression was detected from mouse puberty and increased progressively thereafter, and GRIM-19 protein was observed to be expressed exclusively in interstitial Leydig cells (LCs), with a prominent mitochondrial localization. Invivo lentiviral vector-mediated knockdown of Grim-19 resulted in a significant decrease in testosterone production and triggered aberrant oxidative stress in testis, thus impairing male fertility by inducing germ cell apoptosis and oligozoospermia. The control of testicular steroidogenesis by GRIM-19 was validated using the invivo knockdown model with isolated primary LCs and invitro experiments with MA-10 mouse Leydig tumor cells. Mechanistically, we suggest that the negative regulation exerted by GRIM-19 deficiency-induced oxidative stress on steroidogenesis may be the result of two phenomena: a direct effect through inhibition of phosphorylation of steroidogenic acute regulatory protein (StAR) and subsequent impediment to StAR localization in mitochondria and an indirect pathway that is to facilitate the inhibiting role exerted by the extracellular matrix on the steroidogenic capacity of LCs via promotion of integrin activation. Altogether, our observations suggest that Grim-19 plays a potent role in testicular steroidogenesis and that its alterations may contribute to testosterone deficiency-related disorders linked to metabolic stress and male infertility.

Disruption of Leydig cell steroidogenic function by sodium arsenite and/or sodium fluoride

Arsenite (As) and fluoride (F), both of which are linked to a variety of human ailments, are regularly found in underground drinking water. Numerous studies have shown that As and/or F have negative impacts on testicular function and fertility. For this purpose, mouse Leydig cells, the main cells responsible for the generation and regulation of steroid hormones such as testosterone, were used to reveal the effects of individual and combined exposure of As and F on the steroidogenic pathway in the male reproductive system. Leydig cells were treated with 0.39 μM (50 ppb) As and 0.0476 mM (2 ppm) F alone and in combination for 24 h. The findings revealed that As and/or F exposure induced oxidative stress and apoptosis in Leydig cells and altered antioxidant equilibrium of the cells by reducing superoxide dismutase, catalase, glutathione peroxidase. Additionally, individual and combined administration of As and/or F significantly supressed the expression of both steroidogenic enzymes and the genes encoding these enzymes. In conclusion, this study showed that exposure to As and F at environmentally relevant concentrations dispersed by water decreased testosterone production in Leydig cells, an important cell of the male reproductive system. The deleterious effects of even the lowest concentrations of As and F elements that can reach humans from the environment on the Leydig cell, and therefore on male infertility, emphasize necessity new safe limits for these elements.

GONADOTROPIN AND SEX STEROID HORMONES IN MALES WITH POST COVID-19 INFECTION.

The aim: To understand the effects of COVID-19 infection on gonadotropins and sex steroid hormones in males. Materials and methods: This is a cohort study conducted in fifty males, who had been previously infected with COVID-19 with normal hormonal profile. Fifty Iraqi males were attending the male clinic at Higher Institute of Infertility Diagnosis and Assisted Reproductive Technologies, diagnosed with standard methods. The assessment of serum hormonal levels including (FSH, LH, Prolactin and Testosterone) was done 3 times: 1st time after one-month post recovery after COVID-19, 2nd time after 2 months post recovery and 3rd time - after 3 months post recovery. Results: There was no significant change in the mean level of serum FSH during the first, second and third months (p = 0.630). LH serum level was highly significantly reduced during follow up (p< 0.001). Serum prolactin level, reduced significantly during follow up (p< 0.001). Serum testosterone level was the lowest in the first month and increased during the second month and then during the third month in a highly significant manner (p< 0.001). Conclusions: Sub-clinical hypogonadism may be suspected as a consequence of COVID-19 infection in males as its first presentation characterized by increased LH & decreased testosterone production.

Macroautophagy involved in testosterone synthesis in Leydig cells of male dairy goat (Capra hircus)

Testosterone is an important steroid hormone that is indispensable for male sexual development and the reproductive system. Leydig cells (LCs), where autophagy is extremely active, reside in the testicular interstitium and are the major sites of testosterone production. However, the ultrastructural characteristics and the functional role of autophagy in LCs of livestock remain unknown. In this study, the LCs of the dairy goats were investigated to identify the steroidogenic activity and autophagy levels at different ages of development by light microscopy, immunohistochemistry (IHC), immunofluorescence (IF), and transmission electron microscopy (TEM). Morphological results showed that the steroidogenic activity (3β-HSD staining) and ultrastructural characteristics of the LCs were changed with increasing age. TEM results demonstrated that the organelles involved in testosterone synthesis, e.g., smooth endoplasmic reticulum, mitochondria, and lipid droplets, were abundantly distributed within the cytoplasm of LCs in pubertal and adult testes. Moreover, autophagy activity was enhanced in the testes at pubertal and adult stages compared with that at the juvenile stage. Several different autophagic vacuoles, including pre-autophagosomes, autophagosomes, and autolysosomes, were observed within the cytoplasm of LCs from pubertal and adult testes. However, immunofluorescent staining and TEM results showed that no typical lipophagic or mitophagic vacuoles were observed in the cytoplasm of LCs. Furthermore, primary LCs from dairy goats were used to study the effect of autophagy on testosterone production. After treatment with 3-methyladenine (3-MA, an autophagy inhibitor), the primary LCs decreased testosterone production. In contrast, treatment with rapamycin (an autophagy activator), enhanced steroidogenesis in LCs. Collectively, these in vivo and in vitro results suggested that autophagy activity is related to steroidogenesis in LCs of dairy goats, which may ultimately influence the spermatogenesis and fertility of these animals.

Transcriptomic analysis of MA-10 tumor Leydig cells treated with adipose derived hormones adiponectin and resistin

Obesity contributes to a decrease in testosterone production in men. Indeed, adipose tissue produces several hormones, including adiponectin and resistin, and these may influence the activity of signaling pathways responsible for regulating the expression of genes related to steroidogenesis. In this study, we wanted to identify which genes are directly regulated by these hormones using the MA-10 tumor Leydig cell model. To do this, we treated these cells with adiponectin or resistin, followed by RNA extraction and RNA-Seq transcriptome analysis. Interestingly, genes upregulated by the globular form of adiponectin (gACRP30) were associated to steroid hormones biosynthesis, whereas resistin had no effect on the transcriptome of MA-10 Leydig cells. Moreover, the expression of the Star gene, encoding the steroidogenic acute regulatory protein, was increased in response to treatments with 0.5 mM 8Br-cAMP. Such stimulation was further increased by adiponectin, resulting in increased progesterone production. However, resistin had no effect on steroid production from MA-10 tumor Leydig cells under the treatment conditions investigated. Thus, our data suggest that a direct regulation of steroidogenic genes' expressions in Leydig cells by adipose derived hormones involves cooperation between the cAMP/PKA pathway and adiponectin, but not resistin, to activate Star expression and improve progesterone synthesis.

Fluoride Exposure and Age of Menarche: Potential Differences Among Adolescent Girls and Women in the United States

Fluoride exposure is associated with later pubertal development and decreased testosterone production in adolescent and adult males. However, its effects on female reproductive health and pubertal development are unclear. Therefore, we examined associations of fluoride exposure with reproductive health outcomes among adolescent girls and women in the United States. Participants were from The National Health and Nutrition Examination Surveys (2013 to 2016), aged 16–19 and identified as female. There were 524 and 460 participants with measures of plasma fluoride and household tap water fluoride respectively, who had at least one reproductive health outcome examined, and complete covariate data. We applied covariate adjusted survey-weighted linear or logistic regression to examine associations of fluoride exposure with age of menarche, menstrual cycle regularity, or serum sex steroid hormone levels. Median interquartile range (IQR) water and plasma fluoride concentrations were 0.48 (0.53) mg/L and 0.34 (0.30) µmol/L respectively. An IQR increase in water fluoride was associated with a 3.3 month earlier first menstrual period (B = − 0.28, 95%CI − 0.54, − 0.02, p = 0.05). Additionally, we observed a significant interaction between plasma fluoride and race/ethnicity in association with age of menarche (p = 0.01). Among Non-Hispanic Black adolescents, each IQR increase in plasma fluoride was associated with a 5-month earlier age of menarche (B = − 0.42, 95%CI − 0.61, − 0.23, p < 0.001). Potential impacts of chronic low-level fluoride exposure on reproductive health outcomes are an important area of study. Current study findings, as well as potential health disparities due to disproportionate fluoride exposure should be examined in prospective studies.

EVALUATION OF DOSE-DEPENDENT ACTIVITY OF BISPHENOL F ON VIABILITY PARAMETERS AND STEROIDOGENESIS IN H295R CELLS

Increasing concern over bisphenol A (BPA) as an endocrine-disrupting chemical and recent imposition of restriction on the use of BPA paved the way for entry of its analogues in the market. Bisphenol F (BPF) is one of the major analogues of commercial value. Thus, its increasing production and application make it vulnerable to human exposure. The aim of our in vitro study was to assess the potential effect of BPF on H295R cells mitochondrial activity, metabolic activity, membrane integrity, lysosomal function, and testosterone synthesis. Adrenocortical carcinoma cells were cultivated during 24 h in the presence of BPF (0.1, 0.5, 1, 10, 25, 50, 75, 100, 300, 500 μM). Exposure doses of BPF caused a significant decrease of mitochondrial activity starting from 1 μM, we observed a slight increase in mitochondrial activity at the lowest concentration (0.1 μM). Metabolic activity decreased with increasing dose of BPF - from 10 to 500 μM. A significant increase in metabolic activity was observed after cultivation with 0.1 μM BPF and a slight increase was observed after cultivation with 0.5 μM BPF. We observed a slight increase in lysosomal function and membrane integrity after cultivation with 0.1 and 1 μM, although higher exposure doses (25 - 500 μM) caused significant decrease in membrane integrity and lysosomal function. Lowest exposure dose of BPF (0.1 μM) caused a significant increase in testosterone synthesis, on the other hand, higher exposure doses (50 - 500 μM) caused significant decrease of testosterone production. The obtained results confirmed that BPF at higher concentrations caused cytotoxicity and possibly have endocrine-disrupting potential.

Рівень прозапальних лімфокінів і гормонів у чоловіків, хворих на цукровий діабет 2-го типу

Актуальність. Відомо, що розвиток інсулінорезистентності (ІР), основного чинника метаболічного синдрому (МС), супроводжується дисбалансом у системі цитокінів: підвищенням рівня інтерлейкіну-6 (ІЛ-6), фактора некрозу пухлини α (ФНП-α) та зниженням ІЛ-10, ІЛ-4. Однією з причин інсулінорезистентності у чоловіків може бути зменшення продукції тестостерону, оскільки його достатня кількість посилює чутливість до інсуліну. Мета дослідження: визначити рівні прозапальних лімфокінів і гормонів у хворих на цукровий діабет (ЦД) 2-го типу з МС та андрогенним дефіцитом. Матеріали та методи. Обстежені 76 чоловіків віком від 35 до 68 років (29 — з МС та 47 — хворих на ЦД 2-го типу). Рівні прозапальних лімфокінів, естрадіо­лу, тестостерону вільного та загального визначали у сироватці крові радіоімунним методом, рівні ФНП-α, ІЛ-6, лептину — імуноферментними методами. ІР визначали за індексом НОМА. Діагноз МС встановлювали на підставі критеріїв АТР III — NCEP. У контрольну групу (n = 21) ввійшли умовно здорові люди. Результати. У хворих на ЦД 2-го типу з МС та у групі з МС без ЦД були підвищені рівні ФНП-α й ІЛ-6, кортизолу, альдостерону, адренокортикотропного гормону (АКТГ) та інсуліну. Проведені дослідження показали наявність андрогенного дефіциту в усіх групах пацієнтів. Більш виражені ознаки андрогенного дефіциту спостерігали в обстежених чоловіків із МС та ЦД 2-го типу. Рівень інсуліну й АКТГ прямо пропорційно залежить від індексу маси тіла. У пацієнтів із МС без ЦД спостерігалася лише тенденція до підвищення рівня лептину. Встановлена тенденція підвищення рівня естрадіолу у чоловіків з ЦД 2-го типу та МС. Висновки. Отримані результати відповідають гіпотезі щодо визначальної ролі прозапальних цитокінів імунної системи у генезі ЦД 2-го типу. У даному випадку причиною розвитку ЦД є дисфункція не жирової тканини, а неспецифічної ланки імунітету.

Comparative characteristics of endocrine profile in males with infertility as well as in adolescents with varicocele

Introduction. Male infertility poses a pressing issue due to escalating prevalence of males with reproductive system diseases, the most common among which is varicocele being diagnosed in childhood and adolescence. Measuring level of hormones such as follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and estradiol is the key element while assessing the reproductive male potential.Aim: to compare the parameters of hormonal status in adolescents with varicocele as well as males with diagnosed infertility and identify predictors of hypogonadism in pubertal period.Materials and Methods. Males with diagnosed infertility as well fertile males underwent a single measurement of serum FSH, LH, testosterone and estradiol levels. Adolescents with/without varicocele were measured the serum hormones noted above in dynamics annually between studies for the period within the 14 to 17 years of age. The data obtained were compared in infertile and fertile males, adolescents with/without varicocele, as well as assessed hormone status between different age groups in both cohorts and adolescents aged 17 years.Results. Our study allowed to identify significant differences in hormone level in male patients with infertility and varicocele lacking reproductive pathology. Infertile males had significantly higher levels of LH and estradiol (for both: p &lt; 0.001). The LH level in infertile vs. fertile males was 5.01 ± 2.69 IU/L vs. 3.40 ± 1.17 IU/L, respectively, whereas estradiol level was 136.51 ± 92.79 pmol/l and 82.49 ± 48.33 pmol/l, respectively that might indicate at lowered testosterone level. Fifteenand sixteen-year-old-adolescents with varicocele had significantly lower LH level: 15 years old – 3.72 ± 1.92 IU/L vs. 2.71 ± 1.65 IU/L (p &lt; 0.0123) in subjects without vs. with varicocele; 16 years old – 3.42 ± 1.16 IU/L vs. 2.81 ± 1.66 IU/L (p &lt; 0.0381) in subjects without vs. with varicocele. It may account for decreased testosterone level. Active puberty in adolescents is accompanied by dynamically increased testosterone levels. Starting from the age of 15 years, adolescents with varicocele had significantly increased testosterone level in each subsequent age group. Thus, at 14 and 15 years of age, testosterone level in adolescents with varicocele was 10.61 ± 4.70 nmol/l and 13.60 ± 5.64 nmol/l (p &lt; 0.0001), respectively, whereas at 16 and 17 years of age it continued to rise reaching 16.65 ± 6.44 nmol/l (p &lt; 0.001) and 19.22 ± 7.36 nmol/l (p &lt; 0.0160), respectively. In contrast, age-matched adolescents without varicocele had significantly elevated testosterone level solely at age of 15 vs. 14 years. Whereas at 14 years of age testosterone level in comparison group was 15.73 ± 7.2 nmol/l, at 15 years of age it was significantly increased up to 21.45 ± 9.51 nmol/l (p &lt; 0.0113). In the subsequent age categories of this group, no significant difference in testosterone level was found. While comparing such parameter between the main and control adolescent groups, testosterone level was significantly higher in adolescents lacking varicocele at the age of 14, 15 and 16 years compared with age-matched subjects with varicocele. At 14 years of age, testosterone level in adolescents without/with varicocele was 15.73 ± 7.2 nmol/l vs. 10.61 ± 4.7 nmol/l (p &lt; 0.0007), respectively, at 15 years of age – 21.45 ± 9.57 nmol/l vs. 13.60 ± 5.64 nmol/l (p &lt; 0.0001), respectively, at 16 years of age – 20.02 ± 5.84 nmol/l vs. 16.65 ± 6.44 nmol/l (p &lt; 0.0268), respectively. The FSH level in infertile males and adolescents with varicocele was 5.16 ± 2.67 IU/L and 4.1 ±2.63 IU/L (p &lt; 0.0081), whereas LH level was 5.01 ± 2.69 IU/L and 2.76 ± 1.65 IU/L (p &lt; 0.04), respectively. In adolescents with varicocele and infertile males, estradiol level was 177.45 ± 70.63 pmol/l and 136.51 ± 92.79 pmol/l (p &lt; 0.001), respectively. While comparing hormone levels in fertile males and adolescents lacking varicocele, a significantly higher estradiol level was found in adolescents 181,87 ± 27.14 pmol/l vs. 82.49 ± 48.33 pmol/l (p &lt; 0.001).Conclusion. A study of the hormonal status in infertile vs. fertile males revealed decreased testosterone production accompanied with higher levels of LH and estradiol. Due to profound changes in LH and testosterone levels detected in adolescents with varicocele as well as in infertile males, it is plausible that such hormones may serve as predictors of hypogonadism in the pubertal period. Adolescents with varicocele taking into consideration progressive course of the disease and verified lower testosterone level require further monitoring of hormone level to prevent endocrine infertility.

Testicular steroidogenesis is suppressed during experimental autoimmune encephalomyelitis in rats

Multiple sclerosis (MS) is an autoimmune disease that usually occurs during the reproductive years in both sexes. Many male patients with MS show lower blood testosterone levels, which was also observed in male rats during experimental autoimmune encephalomyelitis (EAE), an animal model of MS. To better understand the causes of decreased testosterone production during EAE, we investigated the expression status of genes and proteins associated with steroidogenesis in the testes. No changes in the number of interstitial cells were observed in EAE animals, but the expression of the insulin-like 3 gene was reduced at the peak of the disease, implying that the Leydig cell functional capacity was affected. Consistent with this finding, the expression of most steroidogenic enzyme genes and proteins was reduced during EAE, including StAR, CYP11A1, CYP17A1 and HSD3B. No signs of testicular inflammation were observed. Recovery of steroidogenesis was observed after injection of hCG, the placental gonadotropin, or buserelin acetate, a gonadotropin-releasing hormone analogue, at the peak of EAE. Together, our results are consistent with the hypothesis that impaired testicular steroidogenesis originates upstream of the testes and that low serum LH is the main cause of decreased testosterone levels during EAE.

Meta-analysis and experimental validation identified atrazine as a toxicant in the male reproductive system.

Atrazine (ATZ), as a widely used triazine herbicide, is an environmental endocrine disruptor (EDC) that can cause many health problems. Therefore, we conducted this study based on the evidence of rats and mice to figure out the characteristics of ATZ damage to the reproductive system and further evaluate its health effects on the human. PRISMA's guidelines were followed according to the principles recommended by the Cochrane Handbook for Systematic Review. Health assessment was performed using the OHAT approach. Our new data were obtained from randomized controlled trials in rats designed in accordance with toxicological guidelines. Exposure to ATZ was significantly associated with decreased testosterone production (SMD = - 0.90, 95% CI - 1.27 to - 0.53), and reduced absolute weights of testis (SMD = - 0.41, 95% CI - 0.61 to - 0.22) and other reproductive organs. The damaging effect of sperm quality was also observed clearly, which included reduction of sperm count both in epididymis (SMD = - 2.32, 95% CI - 2.83 to - 1.81) and testis (SMD = - 1.01, 95% CI - 1.37 to - 0.64), decrease in sperm motility (SMD = - 8.86, 95% CI - 10.88 to - 6.83), and increase in sperm abnormality. Subgroup analysis revealed consistency across different species, life stage, and dosage. In addition, we found that ATZ exposure at a daily dose of 120 mg/kg during adolescence could cause decrease in weight gain and histological damage to the testis. The gene expression levels of Nrf2/HO-1 and Bcl-2/caspase signaling pathways in testis tissues were changed significantly. The results of this SR indicated that exposure to ATZ was associated with impairment of male reproductive system in rodents regardless of species, exposure life stage, and dosage. It is believed that ATZ exposure may have similar effects on male reproductive system of human beings. Pathways related to oxidative stress and apoptosis may be the mechanism leading to testicular damage in rats treated with ATZ.