Reduced Testosterone Levels Research Articles

Exploring the link between comorbid insomnia and sleep apnea (COMISA) and erectile dysfunction: implications for male sexual health.

This review explores the interplay between comorbid insomnia and sleep apnea (COMISA) and erectile dysfunction (ED), 2 conditions that significantly impact men's health. COMISA, a recently recognized condition characterized by the coexistence of insomnia and obstructive sleep apnea, has been shown to disrupt sleep architecture and cause intermittent hypoxia. These disturbances are increasingly linked to the exacerbation of ED, a prevalent issue among men. Understanding the connection between COMISA and ED is crucial for developing integrated treatment approaches that address both sleep and sexual health. We aim to explore the epidemiological, physiological, and potential therapeutic intersections of COMISA and ED. This review sets out to develop a better understanding of the relationship between these conditions and to emphasize the need for an integrated diagnostic and therapeutic approach that addresses both sleep and sexual health. Through a comprehensive analysis, including a detailed examination of extant studies, we address the hormonal imbalances and alterations in neural pathways that collectively contribute to the complex pathophysiology of ED and how these are particularly susceptible to the concurrent presence of COMISA. Our analysis indicates that disruptions in sleep architecture and intermittent hypoxia associated with COMISA can exacerbate ED. Hormonal imbalances, endothelial dysfunction, autonomic imbalance, and increased inflammation and oxidative stress are key mechanisms through which COMISA influences ED. These factors collectively impair vascular health, reduce testosterone levels, disrupt neural control of erections, and contribute to the severity of ED. This review underscores the necessity for an integrated approach to diagnosis and therapy that considers both sleep and sexual health to improve overall outcomes. These insights should foster a deeper understanding of the relationship between COMISA and ED, encourage further research in this area, and potentially lead to the development of innovative treatment strategies to manage these closely intertwined health concerns.

Efficacy of silver-doped Carbon dots in Chemical Castration: a rat model study

This study evaluates silver-doped carbon dots (AgCDs) as a novel agent for chemical castration using a rat model. Six groups of rats (five males and ten females each, except for the surgical group which had only males) were utilized to compare the effects of different concentrations of AgCDs. The groups included control, sham, and three experimental groups injected with 1.25, 50, and 200 µg/mL AgCDs, respectively, along with a surgical castration group. Testosterone levels, sperm parameters, fertility index, oxidative damage, histopathological parameters, and gene expression of P53, Bax, Bcl-2, caspase-3, AKT, and PI3K were analyzed. Results demonstrated that the high-dose AgCDs group significantly reduced testosterone levels, sperm concentration, and motility, resulting in a decreased fertility index. MDA and NO significantly increased, while CAT, SOD, GPx, and TAC significantly reduced in the chemically castrated groups. Histological and genes expression analysis also revealed apoptosis and testicular damage in the AgCDs groups, indicated by significant increases in P53, Bax, and Caspase-3 levels, and significant reductions in AKT, PI3K, and Bcl-2. Based on these findings, AgCDs could be considered a potent and efficient agent for chemical castration, offering a less invasive, cost-effective solution with potential applications for population control.

ATRAZINE AS AN ENDOCRINE DISRUPTOR AND ITS EFFECTS ON MALE REPRODUCTIVE HEALTH

Atrazine has been widely used in Brazilian agriculture, especially in corn and soybean crops. Due to its widespread use, this literature review is relevant to systematize the main studies that evaluate the impact of atrazine as an endocrine disruptor leading to changes in fertility quality, especially in males. In several tests and studies carried out with the exposure of animals to atrazine, negative effects related to changes in factors that are essential for male fertility were observed. Therefore, inhibition of the hypothalamic-pituitary-testicular axis, decreased reproductive cells’s metabolic activity, reduced testosterone levels, reduced lactate dehydrogenase (LDH) enzyme, negative effects on spermatogenesis and morphological changes in the gonads and sperm are results of atrazine toxicity on the male reproductive system that contribute to infertility. In general, it is concluded that atrazine has a potential endocrine disruptor effect, leading to changes in the form of hormone production, especially in hormones related to male sexual reproduction. For this reason, assessing the risks of exposure to this toxin at different stages of life and over several generations, combined with knowledge of its pathophysiological mechanism on the male reproductive system, is essential to preserve the reproductive health of future generations.

7472 Estrogen Monotherapy for Testosterone Suppression in Gender Diverse Patients

Abstract Disclosure: C. Zhou: None. Q. Jones: None. S. Kokosa: None. C. Kelley: None. Background: For gender diverse individuals assigned male at birth (AMAB), gender-affirming hormone therapy consists of estrogen in combination with anti-androgen medications. Exogenous estrogen use results in the development of feminine secondary sex characteristics while indirectly decreasing testosterone. Anti-androgens such as spironolactone, leuprolide, finasteride, or dutasteride work to further suppress testosterone with successful suppression levels <50ng/dL. However, use of these agents increases the risk of adverse side effects like hyperkalemia, polyuria, and orthostatic hypotension, thus is not suitable for everyone. Anecdotally, estrogen monotherapy has been sufficient in reducing testosterone levels to goal in some patients, however at this time there are no known studies which evaluate estrogen monotherapy and suppression of testosterone. The purpose of this study is to retrospectively review estrogen formulations and dosages in patients who have adequate testosterone suppression in the absence of anti-androgen medications. Methods: The study was a retrospective chart review of adult patients ages 18- 84.99 AMAB receiving gender-affirming estrogen between 9/2020 and 12/2023 seen within an endocrine clinic at a single academic institution. Patients younger than 18, those receiving anti-androgen medications, and those with history of orchiectomy were excluded from the study. Charts were reviewed for estrogen formulations and dosages and total serum testosterone levels. Retrospective chart review will continue with additional data expected in 2024. Results: Ten patients between the ages of 19-81 met the inclusion criteria. Of these, 7 patients identified as transfeminine and 3 identified as nonbinary. The 3 patients who identified as non-binary were not included in analysis as their treatment goals may not align with full feminization or testosterone suppression (total serum testosterone <50ng/dL). Testosterone suppression from estrogen monotherapy was achieved in 100% (n=7) of the transfeminine patients when serum estradiol was >100pg/mL. In those who achieved testosterone suppression, 5 used injectable formulations (estradiol valerate 4-6mg weekly) and 2 used transdermal patches (range of estradiol from 0.2mg twice weekly to 0.3mg three times weekly). Conclusions: Estrogen monotherapy may be effective in suppressing testosterone without the need for anti-androgen medications. So far, this was noted most commonly with use of injectable estrogen formulations. A limitation of the study is the small sample size, however ongoing data collection is anticipated. Additional research evaluating estrogen monotherapy and testosterone suppression is needed and has potentially significant implications for simplified treatment protocols for transfeminine patients. Presentation: 6/2/2024

7472 Estrogen Monotherapy for Testosterone Suppression in Gender Diverse Patients

Abstract Disclosure: C. Zhou: None. Q. Jones: None. S. Kokosa: None. C. Kelley: None. Background: For gender diverse individuals assigned male at birth (AMAB), gender-affirming hormone therapy consists of estrogen in combination with anti-androgen medications. Exogenous estrogen use results in the development of feminine secondary sex characteristics while indirectly decreasing testosterone. Anti-androgens such as spironolactone, leuprolide, finasteride, or dutasteride work to further suppress testosterone with successful suppression levels <50ng/dL. However, use of these agents increases the risk of adverse side effects like hyperkalemia, polyuria, and orthostatic hypotension, thus is not suitable for everyone. Anecdotally, estrogen monotherapy has been sufficient in reducing testosterone levels to goal in some patients, however at this time there are no known studies which evaluate estrogen monotherapy and suppression of testosterone. The purpose of this study is to retrospectively review estrogen formulations and dosages in patients who have adequate testosterone suppression in the absence of anti-androgen medications. Methods: The study was a retrospective chart review of adult patients ages 18- 84.99 AMAB receiving gender-affirming estrogen between 9/2020 and 12/2023 seen within an endocrine clinic at a single academic institution. Patients younger than 18, those receiving anti-androgen medications, and those with history of orchiectomy were excluded from the study. Charts were reviewed for estrogen formulations and dosages and total serum testosterone levels. Retrospective chart review will continue with additional data expected in 2024. Results: Ten patients between the ages of 19-81 met the inclusion criteria. Of these, 7 patients identified as transfeminine and 3 identified as nonbinary. The 3 patients who identified as non-binary were not included in analysis as their treatment goals may not align with full feminization or testosterone suppression (total serum testosterone <50ng/dL). Testosterone suppression from estrogen monotherapy was achieved in 100% (n=7) of the transfeminine patients when serum estradiol was >100pg/mL. In those who achieved testosterone suppression, 5 used injectable formulations (estradiol valerate 4-6mg weekly) and 2 used transdermal patches (range of estradiol from 0.2mg twice weekly to 0.3mg three times weekly). Conclusions: Estrogen monotherapy may be effective in suppressing testosterone without the need for anti-androgen medications. So far, this was noted most commonly with use of injectable estrogen formulations. A limitation of the study is the small sample size, however ongoing data collection is anticipated. Additional research evaluating estrogen monotherapy and testosterone suppression is needed and has potentially significant implications for simplified treatment protocols for transfeminine patients. Presentation: 6/2/2024

A Pharmacological Overview of Degarelix and Relugolix in Advanced Prostate Cancer

Prostate cancer (PCa) ranks the second most diagnosed cancers among men globally and the sixth leading cause of cancer-related deaths. Advanced prostate cancer can be defined as the recurrence after definitive therapies (radical prostatectomy or external beam radiotherapy) and de novo metastasis (metastasis without prior treatment). Advanced PCa can be categorized as metastatic hormone sensitive prostate cancer (mHSPC), non-metastatic castration resistant prostate cancer (nmCRPC), and metastatic castration resistant prostate cancer (mCRPC). Management of advanced PCa often involves castration to reduce testosterone levels, which can be achieved by gonadotropin releasing hormone antagonists such as degarelix and relugolix. Degarelix is injectable while relugolix is an orally administered form of GnRH antagonist. This review aims to explore the latest pharmacological aspects of these drugs to inform treatment decisions for advanced PCa.

SARS-CoV-2 impairs male fertility by targeting semen quality and testosterone level: A systematic review and meta-analysis.

Since the discovery of COVID-19 in December 2019, the novel virus has spread globally causing significant medical and socio-economic burden. Although the pandemic has been curtailed, the virus and its attendant complication live on. A major global concern is its adverse impact on male fertility. This study was aimed to give an up to date and robust data regarding the effect of COVID-19 on semen variables and male reproductive hormones. Literature search was performed according to the recommendations of PRISMA. Out of the 852 studies collected, only 40 were eligible for inclusion in assessing the effect SARS-CoV-2 exerts on semen quality and androgens. More so, a SWOT analysis was conducted. The present study demonstrated that SARS-CoV-2 significantly reduced ejaculate volume, sperm count, concentration, viability, normal morphology, and total and progressive motility. Furthermore, SARS-CoV-2 led to a reduction in circulating testosterone level, but a rise in oestrogen, prolactin, and luteinizing hormone levels. These findings were associated with a decline in testosterone/luteinizing hormone ratio. The current study provides compelling evidence that SARS-CoV-2 may lower male fertility by reducing semen quality through a hormone-dependent mechanism; reduction in testosterone level and increase in oestrogen and prolactin levels.

Metformin reduces testosterone level in type 2 diabetes mellitus patients and its therapy by traditional medicine

BackgroundType 2 Diabetes Mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance and hyperglycemia. Metformin, a commonly prescribed treatment for T2DM, is known for its effectiveness in improving glycemic control. Recent studies suggest that metformin may also influence testosterone levels in male patients, a hormone crucial for male reproductive health, muscle mass maintenance, and overall quality of life. Medicinal plants were traditionally used for influencing the testosterone level in the body which may be given as a therapy for the side – effects of metformin tablet. ObjectiveTo assess the impact of metformin treatment on testosterone levels in male patients with T2DM compared to non-diabetic males, and to evaluate the potential implications of traditional medical treatments in managing the consequences of reduced testosterone levels. MethodsThis study is a prospective observational investigation conducted among a total of 60 patients,divided into two groups: 30 males taking metformin as a hyperglycaemic agent with T2DM and 30 males without any diabetic treatment. This study was be carried out in different outpatient department of Shri Mahant Indiresh Hospital, Patel Nagar, Dehradun to assess the level of testosterone in male patients with T2DM taking metformin and in non-Diabetic participants. Based on these findings, potential traditional medicines methods for reducing testosterone levels were summarized. ResultsIt was demonstrated that male patients with T2DM undergoing metformin treatment exhibited significant reduction in testosterone serum levels compared to non-diabetic patients. Several plants were examinedand, and clinical studies were conducted on them. It was discovered that these plants have been effective in increasingtestosterone level, suggesting their potential use as therapy for patients. ConclusionThis study shows reduction in the testosterone levels, which may lead to low sex drives and induction of low testosterone induced erectile dysfunction. While metformin is used to treat T2DM, it decreases testosterone levels, which negatively impacts the patients' quality of life. So, there is essential need to further study the effect of metformin on testosterone levels in patients with T2DM. Additionally, plants that may be useful in increasing the testosterone levels should be studied further for their beneficial characteristics and potential therapeutic applications.

Hexavalent chromium reduces testosterone levels by impairing lipophagy and disrupting lipid metabolism homeostasis: Based on a metabolomic analysis

Hexavalent chromium (Cr(VI)) causes testicular damage and reduces testosterone secretion. Testosterone synthesis relies on cholesterol as a raw material, and its availability can be affected by lipophagy. However, the role of lipophagy in Cr(VI)-induced testicular damage and reduced testosterone secretion remains unclear. In this study, we investigated the effect of Cr(VI) on lipid metabolism and lipophagy in the testes of ICR mice. Forty mice were randomly divided into four groups and exposed to different doses of Cr(VI) (0, 75, 100, 125 mg/kg) for thirty days. Cr(VI) increased the rate of sperm abnormalities, decreased testosterone level, and decreased the levels of testosterone synthesis-related proteins, namely steroidogenic acute regulatory (StAR) and 3β-hydroxysteroid dehydrogenase (3β-HSD) proteins. Through metabolomic analysis, Oil Red O staining, and biochemical indicator (triglyceride and total cholesterol) analysis, Cr(VI) was found to disrupt testicular lipid metabolism. Further investigation revealed that Cr(VI) inhibited the AMP-activated protein kinase (AMPK)/sterol regulatory element-binding protein 1 (SREBP1) pathway, elevated levels of the autophagy-related proteins microtubule-associated protein 1 light chain 3B (LC3B) and sequestosome 1 (SQSTM1)/P62 and lipophagy-related proteins Rab7 and Rab10, while increasing colocalization of LC3B and Perilipin2. These findings suggest that Cr(VI) exposure leads to abnormal lipid metabolism in the testes by suppressing the AMPK/SREBP1 pathway and disrupting lipophagy, ultimately reducing testosterone level and inducing testicular damage.

Local synthesis of estradiol in the rostral ventromedial medulla protects against widespread muscle pain in male mice.

Animal studies consistently demonstrate that testosterone is protective against pain in multiple models, including an animal model of activity-induced muscle pain. In this model, females develop widespread muscle hyperalgesia, and reducing testosterone levels in males results in widespread muscle hyperalgesia. Widespread pain is believed to be mediated by changes in the central nervous system, including the rostral ventromedial medulla (RVM). The enzyme that converts testosterone to estradiol, aromatase, is highly expressed in the RVM. Therefore, we hypothesized that testosterone is converted by aromatase to estradiol locally in the RVM to prevent development of widespread muscle hyperalgesia in male mice. This was tested through pharmacological inhibition of estrogen receptors (ER), aromatase, or ER-α in the RVM which resulted in contralateral hyperalgesia in male mice (C57BL/6J). ER inhibition in the RVM had no effect on hyperalgesia in female mice. As prior studies show modulation of estradiol signaling alters GABA receptor and transporter expression, we examined if removal of testosterone in males would decrease mRNA expression of GABA receptor subunits and vesicular GABA transporter (VGAT). However, there were no differences in mRNA expression of GABA receptor subunits of VGAT between gonadectomized and sham control males. Lastly, we used RNAscope to determine expression of ER-α in the RVM and show expression in inhibitory (VGAT+), serotonergic (tryptophan hydroxylase 2+), and μ-opioid receptor expressing (MOR+) cells. In conclusion, testosterone protects males from development of widespread hyperalgesia through aromatization to estradiol and activation of ER-α which is widely expressed in multiple cell types in the RVM.Significance Statement This study's findings reveal, for the first time, that testosterone protects males from development of widespread muscle hyperalgesia through aromatization to estradiol and activation of ER-α within the RVM. The findings also show, for the first time, ER-α expression in the RVM in male mice, and the distribution patterns of this expression among multiple cell types. Thus, together our data suggest a unique endogenous mechanism in the RVM for protection against widespread pain in males only.

Chronic Polystyrene Microplastic Exposure Reduces Testosterone Levels in Mice through Mitochondrial Oxidative Stress and BAX/BCL2-Mediated Apoptosis.

Microplastics (MPs) have emerged as a major environmental issue. They have been found to cause significant reproductive toxicity and lower testosterone levels in adult males, though the exact mechanisms remain unclear. In this study, C57bl/6 mice were orally exposed to saline or varying doses (0.25, 0.5, and 1 mg/day) of 5 μm polystyrene MPs (PS-MPs) for 4 weeks, and TM3 mouse Leydig cells were treated with different concentrations of PS-MPs. Our results found that exposure to PS-MPs significantly reduced testosterone levels and impaired the synthesis function of testicular steroids. In vitro, PS-MPs reduced steroid synthesis in Leydig cells. Treatment with PS-MPs significantly increased the apoptosis rate and BAX/BCL2 ratio in Leydig cells. Additionally, GSH-px and SOD activities decreased, while MDA levels increased, along with a rise in mitochondrial ROS. In conclusion, chronic PS-MP exposure reduced testosterone levels in mice through mitochondrial oxidative stress and BAX/BCL2-mediated apoptosis. This study offers new insights into the health risks posed by MPs.

Characteristics of depression treatment in men with testosterone deficiency

BACKGROUND: Treatment of depression in men with testosterone deficiency is particularly challenging because of the overlap between the symptoms of depression itself and those associated with testosterone deficiency, which requires the development of additional diagnostic and therapeutic approaches. AIM: To enhance the effectiveness of comprehensive treatment of depression in men with testosterone deficiency. MATERIALS AND METHODS: The study involved 140 male participants (aged 18–65 years) diagnosed with depressive episodes and recurrent depressive disorder according to the International Classification of Diseases, 10th revision. Patients were divided into the main group (testosterone levels below 12.1 nmol/l) and the control group (normal testosterone levels). The main group (n=90) was further divided into three therapeutic subgroups of 30 patients each: receiving sertraline monotherapy, testosterone monotherapy, and combined sertraline and testosterone treatment. The control group included men with depression and normal testosterone levels (n=50), who received sertraline only. RESULTS: Depression in men in the context of testosterone deficiency has distinct clinical features, both phenomenologically and syndromally. The severity of the depressive syndrome in men with testosterone deficiency is lower (17.0 [16.0; 18.75] points on the HDRS scale) than in patients with normal testosterone levels (19.0 [18.0; 22.0] points on the HDRS scale), and the depressive episode tends to occur later in life (47.0 [42.0; 55.0] years) compared to those with normal levels of testosterone (29.5 [24.25; 40.0] years) and is less likely to be recurrent than in those with normal testosterone levels (29.5 [24.25; 40.0] years). The study of the efficacy and safety of depression therapy in the context of testosterone deficiency shows that a combined approach to the treatment of depression in men with testosterone deficiency has both advantages (considering the specifics of patients by normalizing testosterone levels and erectile function) and disadvantages (relatively higher risk of adverse events) compared to sertraline monotherapy. CONCLUSION: The identified characteristics of the course and treatment of depression in the context of reduced testosterone levels allowed for the development of a more effective therapeutic and diagnostic algorithm.

Chronic exposure to polystyrene microplastics induced LHR reduction and decreased testosterone levels through NF-κB pathway

The extensive utilization of plastic products in recent years has resulted in a significant contamination of microplastics (MPs). The ingestion of MPs by aquatic and terrestrial organisms facilitates their transmission to mammals through the food chain. Therefore, the toxicity of MPs has attracted widespread attention from researchers. Previous studies have shown a connection between being exposed to polystyrene MPs (PS-MPs) and issues with male reproductive function. Testosterone, a hormone essential for male reproductive function, is produced and secreted by specialized cells known as Leydig cells, which found in the testicular interstitium. In our prior research, we confirmed that exposure to PS-MPs caused a reduction in testosterone levels by interfering with the LH-mediated LHR/cAMP/PKA/StAR pathway, with LHR being pivotal in this mechanism. However, the molecular mechanism underlying PS-MPs-induced reduction of LHR remains unclear. In this study, mice were respectively given drinking water containing 1000 μg/L PS-MPs characterized by diameters of 0.5 μm, 4 μm, and 10 μm for a period of 180 days. Our findings indicated that exposure to PS-MPs resulted in the proliferation of macrophages as well as their polarization towards the M1 phenotype. Additionally, the presence of PS-MPs triggered the release of tumor necrosis factor alpha (TNF-α) from macrophages, thereby activating nuclear factor-κB (NF-κB) signaling pathway within Leydig cells. The translocation of NF-κB into nucleus facilitated its binding to the promoter region of LHR, which consequently led to the repression of LHR transcription. This transcriptional inhibition resulted in a subsequent suppression of testosterone synthesis and secretion. Overall, this study elucidates a theoretical basis for explaining the interference of PS-MPs on the testosterone synthesis and secretion in Leydig cells from the perspective of the interaction between cells in the testicular interstitium.

Apigenin improves testosterone synthesis by regulating endoplasmic reticulum stress

Obesity is a growing epidemic among reproductive-age men, which can cause and exacerbate male infertility by means of associated comorbidities, endocrine abnormalities, and direct effects on the fidelity and throughput of spermatogenesis. A prominent consequence of male obesity is a reduction in testosterone levels. Natural products have shown tremendous potential anti-obesity effects in metabolic diseases. This study aimed to investigate the potential of apigenin (AP) to alleviate testicular dysfunction induced by a high-fat diet (HFD) and to investigate the underlying mechanisms, focusing on endoplasmic reticulum stress (ERS) and testosterone synthesis. A murine model of obesity was established using HFD-fed mice. The effects of AP on obesity, lipid metabolism, testicular dysfunction, and ERS were assessed through various physiological, histological, and molecular techniques. Administration of AP (10 mg/kg) ameliorated HFD-induced obesity and testicular dysfunction in a mouse model, as evidenced by decreased body weight, improved lipid profiles and testicular pathology, and restored protein levels related to testosterone. Furthermore, in vitro studies demonstrated that AP relieved ERS and recovered testosterone synthesis in murine Leydig cells (TM3) treated with free fatty acids (FFAs). It was also observed that AP rescued testosterone synthesis enzymes in TM3 cells, similar to that observed with the inhibitor of the PERK pathway (GSK2606414). In addition, ChIP, qPCR, and gene silencing showed that the C/EBP homologous protein (CHOP) bound directly to the promoter region of steroidogenic STAR and negatively modulated its expression. Collectively, AP has remarkable potential to alleviate HFD-induced obesity and testicular dysfunction. Its protective effects are attributable partly to mitigating ERS and restoring testosterone synthesis in Leydig cells.

Hirsutella sinensis intensifies testicular function and spermatogenesis in male mice with high-fat diet-induced obesity.

Hirsutella sinensis (HS) is a mycelium isolated from the fruiting body of the medicinal mushroom Cordyceps sinensis . This study explored whether HS treatment affects reproductive dysfunction in a high-fat diet (HFD)-induced mouse model and regulates various mechanisms, focusing on oxidative stress, apoptosis, inflammation, and autophagy. Twenty-four C57BL/6J (B6) mice were randomly divided into a standard chow diet (NCD)- or HFD-fed group for 24 weeks. During the final 8 weeks, half of the HFD-fed mice were orally administered HS (HFD + HS). Biochemical markers, including glucose, insulin, triglycerides, and total cholesterol, were assessed, and hormones, including testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH), were analyzed. Liver and testicular histology, as well as sperm quality markers such as sperm motility, sperm count, and percentage of sperm with normal morphology, were observed. The activities of the testicular antioxidants superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx) and the products of lipid peroxidation, such as malondialdehyde (MDA), were measured. The protein expression levels of apoptosis-, autophagy- and inflammation-related markers were measured. The HFD-fed mice had abnormal sex hormone levels, poor sperm quality, and a destroyed testicular structure, with increased oxidative stress and apoptosis in the testis. HS supplementation in HFD-fed mice attenuated testicular apoptosis by suppressing the Bax/Bcl-xl ratio and cleaved caspase 3 protein expression. The HS-treated mice exhibited improved reproductive function, possibly due to reduced oxidative stress and apoptosis, suggesting that HS has a protective effect against HFD-induced testicular damage. Male mice supplemented with HS exhibited attenuated poor semen quality and reduced testosterone levels brought about by HFD-induced obesity by reducing oxidative stress.

Prevalence of Hypogonadism in Male Type 2 Diabetes Mellitus Patients: A Cross-Sectional Study

Background: Type 2 Diabetes Mellitus (T2DM) is a widespread metabolic disorder linked with various complications, including hypogonadism—a condition marked by reduced testosterone levels and symptoms such as erectile dysfunction, decreased libido, and increased fatigue. Hypogonadism remains underdiagnosed in diabetic populations, posing significant challenges to healthcare systems, especially in regions with high diabetic populations such as India. Methods: This cross-sectional study comprised 173 male T2DM patients aged 35 to 65. The study employed the Androgen Deficiency in Aging Males (ADAM) questionnaire to screen for hypogonadism, alongside physical examinations and biochemical tests to assess testosterone levels and other metabolic parameters. Results: The incidence of hypogonadism was found to be 27.2% among the study participants. Higher prevalence rates were related with older age, higher body mass index, greater waist circumference, and longer period of diabetes. Elevated fasting blood sugar and poor glycemic control (HbA1c ? 7%) were also significantly correlated with low testosterone levels. Conclusion: The significant association between T2DM and hypogonadism underscores the need for routine screening for testosterone deficiency in diabetic care, particularly given the condition’s impact on quality of life and metabolic health. Recommendations: Based on the findings, it is recommended that screening for hypogonadism be integrated into the regular management protocols for T2DM, particularly for patients presenting with metabolic syndrome features or those with poor glycemic control. Keywords: Type 2 Diabetes Mellitus, Hypogonadism, Testosterone, Metabolic Health, Indian Population

Mechanistic screening of reproductive toxicity in a novel 3D testicular co-culture model shows significant impairments following exposure to low-dibutyl phthalate concentrations

To improve the mechanistic screening of reproductive toxicants in chemical-risk assessment and drug development, we have developed a three-dimensional (3D) heterogenous testicular co-culture model from neonatal mice. Di-n-butyl phthalate (DBP), an environmental contaminant that can affect reproductive health negatively, was used as a model compound to illustrate the utility of the in vitro model. The cells were treated with DBP (1 nM to 100 µM) for 7 days. Automated high-content imaging confirmed the presence of cell-specific markers of Leydig cells (CYP11A1 +), Sertoli cells (SOX9 +), and germ cells (DAZL +). Steroidogenic activity of Leydig cells was demonstrated by analyzing testosterone levels in the culture medium. DBP induced a concentration-dependent reduction in testosterone levels and decreased the number of Leydig cells compared to vehicle control. The levels of steroidogenic regulator StAR and the steroidogenic enzyme CYP11A1 were decreased already at the lowest DBP concentration (1 nM), demonstrating upstream effects in the testosterone biosynthesis pathway. Furthermore, exposure to 10 nM DBP decreased the levels of the germ cell-specific RNA binding protein DAZL, central for the spermatogenesis. The 3D model also captured the development of the Sertoli cell junction proteins, N-cadherin and Zonula occludens protein 1 (ZO-1), critical for the blood–testis barrier. However, DBP exposure did not significantly alter the cadherin and ZO-1 levels. Altogether, this 3D in vitro system models testicular cellular signaling and function, making it a powerful tool for mechanistic screening of developmental testicular toxicity. This can open a new avenue for high throughput screening of chemically-induced reproductive toxicity during sensitive developmental phases.

Deoxynivalenol Inhibits Progenitor Leydig Cell Development by Stimulating Mitochondrial Fission in Rats.

Deoxynivalenol (DON) is a common food contaminant that can impair male reproductive function. This study investigated the effects and mechanisms of DON exposure on progenitor Leydig cell (PLC) development in prepubertal male rats. Rats were orally administrated DON (0-4 mg/kg) from postnatal days 21-28. DON increased PLC proliferation but inhibited PLC maturation and function, including reducing testosterone levels and downregulating biomarkers like HSD11B1 and INSL3 at ≥2 mg/kg. DON also stimulated mitochondrial fission via upregulating DRP1 and FIS1 protein levels and increased oxidative stress by reducing antioxidant capacity (including NRF2, SOD1, SOD2, and CAT) in PLCs in vivo. In vitro, DON (2-4 μM) inhibited PLC androgen biosynthesis, increased reactive oxygen species production and protein levels of DRP1, FIS1, MFF, and pAMPK, decreased mitochondrial membrane potential and MFN1 protein levels, and caused mitochondrial fragmentation. The mitochondrial fission inhibitor mdivi-1 attenuated DON-induced impairments in PLCs. DON inhibited PLC steroidogenesis, increased oxidative stress, perturbed mitochondrial homeostasis, and impaired maturation. In conclusion, DON disrupts PLC development in prepubertal rats by stimulating mitochondrial fission.

Antifertility potential of the extracts of <i>Aloe barbadensis</i> Miller on the testes and reproductive hormones of male rats

There is a plethora of effective female contraceptives with varied efficacy, usability, and acceptability levels but not for males, who have condoms with a high failure rate and vasectomy with poor reversibility. This study was to determine the antifertility potential of the extracts of Aloe barbadensis as a herbal contraceptive for males. Gel and aqueous leaf extracts of Aloe barbadensis were administered orally to thirty-five sexually matured albino male rats for 30 days, to determine their effects on the reproductive hormones and histopathology of the testes. The animals were divided into 7 groups A, B, C, D, E, F, and G. Each group was for a treatment regimen having 5 rats. Group A, the Control, was given a normal ration and water. Groups B, C, and D were administered 10mg/kg, 30mg/kg, and 70mg/kg of fresh A. barbadensis gel daily for 30 days while groups E, F, and G were administered 10mg/kg, 30mg/kg, and 70mg/kg of aqueous leaf extract respectively. A significant reduction in testosterone levels (p<0.05), insignificant reduction in follicle-stimulating hormone levels, and an increase in luteinizing hormone levels that were also not significant (p>0.05) were observed. Histopathological alterations of disrupted cytoarchitecture, absence of Leydig cells, and scanty spermatozoa in the lumen of seminiferous tubules were observed in the tissues of the testes of the treated groups of rats, and as such the extracts may be possible effective natural antifertility agents for males although, toxic constituents of the plant extracts should be screened out before it is allowed for consumption.

Do statins decrease testosterone in men? Systematic review and meta-analysis.

Statins are one of the most prescribed classes of drugs worldwide to treat hypercholesterolemia and dyslipidemia. By lowering the level of cholesterol, the use of statin could cause a reduction in testosterone levels. The objective was to evaluate whether the continued use of statins in patients with hypercholesterolemia causes a deficiency in testosterone and other sex hormones. Systematic Review with Meta-analysis, performed in Embase, Medline and Cochrane databases, until May 2023; PROSPERO CRD42021270424protocol. Selection performed by two independent authors with subsequent conference in stages. Methodology based on PRISMA statement. There were selected comparative studies, prospective cohorts (CP), randomized clinical trials (RCT) and cross-sectional studies (CSS) with comparison of testosterone levels before and after statin administration and between groups. Bias analysis were evaluated with Cochrane Tool, The Newcastle-Ottawa Scale (NOS), and using the Assess the Quality of Cross-sectional studies (AXIS) tool. There were found on MedLine, Embase and Cochrane, after selected comparative studies, 10CP and 6RCT and 6CSS for the meta-analysis. In the Forrest plot with 6CSS, a correlation between patients with continuous use of statins and a reduction in total testosterone was evidenced with a statistically significant reduction of 55.02ng/dL (95%CI=[39.40,70.64],I²=91%,p<0.00001).In the analysis with 5RCT, a reduction in the mean total testosterone in patients who started continuous statin use was evidenced, with a statistical significance of 13.12ng/dL (95%CI=[1.16,25.08],I²=0%,p=0.03). Furthermore, the analysis of all prospective studies with 15 articles showed a statistically significant reduction in the mean total testosterone of 9.11 ng/dL (95%CI=[0.16,18.06],I²=37%,p=0.04). A reduction in total testosterone has been shown in most studies and in its accumulated analysis after statin use. However, this decrease was not enough to reach levels below normal. Statins use causes a decrease in total testosterone, not enough to cause a drop below the normal range and also determines increase in FSH levels. No differences were found in LH, Estradiol, SHBG and Free Testosterone analysis.