Risk Of Testosterone Deficiency Research Articles

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.

Association between life's essential 8 and testosterone deficiency in US men: findings from national health and nutrition examination survey (NHANES) 2011-2016.

Testosterone deficiency (TD) is closely associated with cardiovascular diseases (CVD). We intended to explore the association of Life's Essential 8 (LE8), the recently updated measurement of cardiovascular health, with the prevalence of TD among US male adults. The population-based cross-sectional study selected male adults aged 20 years or older from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2016. According to the American Heart Association definitions, the LE8 score was measured on a scale of 0-100, and divided into health behavior and health factor scores, simultaneously. Furthermore, these scores were categorized into low (0-49), moderate (50-79), and high (80-100) classifications. TD is defined as a total testosterone level below 300ng/dL. Correlations were investigated by weighted multivariable logistic regression, and the robustness of the results were verified by subgroup analysis. A total of 4971 male adults with an average age of 47.46 ± 0.41 years were eligible for the final analyses, of whom 1372 were determined to have TD. The weighted mean LE8 score of the study population was 68.11 ± 0.41. After fully adjusting potential confounders, higher LE8 scores were significantly associated with low risk of TD (odd ratio [OR] for each 10-point increase, 0.79; 95% CI, 0.71-0.88) in a linear dose-response relationship. Similar patterns were also identified in the association of health factor scores with TD (OR for each 10-point increase, 0.74; 95% CI, 0.66-0.83). These results persisted when LE8 and health factor scores was categorized into low, moderate, and high groups. The inversed association of LE8 classifications and TD remained statistically significant among older, obese, and men without CVD. LE8 and its health factor subscales scores were negatively associated with the presence of TD in linear fashions. Promoting adherence to optimal cardiovascular health levels may be advantageous to alleviate the burden of TD.

Dose-response association between 24-hour total movement activity and testosterone deficiency in adult males.

Previous studies on the relationship between physical activity and testosterone are limited and controversial. Hence we investigated whether high level of physical activity is associated with a low risk of testosterone deficiency (TD). This cross-sectional analysis was conducted in a representative sample of US adult males who participated in the 2011-2014 cycle of the National Health and Nutrition Examination Survey (NHANES). We used the monitor independent movement summary (MIMS) to assess activity intensity, a novel physical activity metrics developed using raw data collected by accelerometers. Multivariable regression and smooth curve fitting was used to describe the relationships between physical activity and TD, and segmented regression model were used to analyze the threshold effect between them. Sensitivity analysis was conducted using interaction and stratified analysis. A U-shaped relationship between daily MIMS units and risk of TD was observed. The optimal value of daily MIMS units for the lowest risk of TD was 14.77 (×103), the risk of TD decreased by 5% in patients per unit increase of daily MIMS units when daily MIMS units <14.77 (×103) (adjusted OR = 0.95, 95%CI: 0.91, 0.99), but increased by 12% per unit increase of daily MIMS units when daily MIMS units ≥14.77 (×103) (adjusted OR = 1.12, 95%CI: 1.01, 1.23). In sensitivity analyses, the threshold effect was also similar according to baseline characteristics (P-interaction >0.05). In a nationally representative sample of US adult males, light to moderate intensity physical activity is associated with a lower odds of TD, while high-intensity physical activity is associated with a higher risk of TD.

Metabolic dysfunction-associated fatty liver disease is an early predictor for testosterone deficiency in aging men without metabolic syndrome.

Metabolic dysfunction-associated fatty liver disease (MAFLD) has emerged as a valuable marker for identifying individuals at increased risk of metabolic dysfunction, liver-related complications, and cardiovascular disease. However, the association between MAFLD and testosterone deficiency (TD) in aging men remains poorly understood. This study aimed to investigate the association between MAFLD and the risk of TD in aging Taiwanese men, with a specific focus on those without metabolic syndrome (MetS). A free health screening program was conducted for Taiwanese men aged over 40 years in Kaohsiung, Taiwan. Participants underwent physical examinations, completed questionnaires regarding demographics, medical history, and clinical symptoms of TD, and provided 20-mL whole blood samples for biochemical, adipocytokine, and hormonal evaluations. Fatty liver index was used to evaluate the risk of fatty liver. Diagnostic criteria for MAFLD included fatty liver along with overweight/obesity, type 2 diabetes, or evidence of metabolic dysregulation. A total of 631 men (mean age: 54.4 ± 8.4 years) were enrolled. The prevalence rates of TD and MetS were significantly higher in men with MAFLD compared to those without (both p < 0.001). Additionally, the presence of MAFLD showed a significant correlation with adipocytokines associated with insulin resistance, such as adiponectin, leptin, and retinol-binding protein-4 (RBP-4) levels (all p < 0.001). Among men without MetS, those with MAFLD had a 3.89- and 4.74-fold higher risk of total testosterone < 300 ng/dL and TD, respectively, after adjusting for potential covariates. MAFLD is associated with an elevated risk of TD in aging Taiwanese men, particularly in the absence of MetS. This finding suggests that MAFLD could serve as an early predictor of TD, facilitating the identification of high-risk individuals and enabling timely interventions. Further research is needed to validate these findings and explore the underlying mechanisms linking MAFLD, TD, and MetS in diverse populations.

Риск развития дефицита тестостерона у мужчин с сахарным диабетом 2 типа в зависимости от уровня гликированного гемоглобина

Риск развития дефицита тестостерона у мужчин с сахарным диабетом 2 типа в зависимости от уровня гликированного гемоглобина

Association of lipid accumulation products with testosterone deficiency in adult American men: A cross-sectional study.

Testosterone deficiency and changes in testosterone levels are important in men's health and may be associated with fat accumulation. In order to investigate the connection between testosterone and fat accumulation in adult males, we employed lipid accumulation product and compared it to triglyceride-glucose and Homeostasis Model Assessment of Insulin Resistance. An intersecting surface research of participators from 2013 to 2014 was carried out using National Health and Nutrition Examination Survey, in addition, participants from 2015 to 2016 were selected. Using multivariate adjusted logistic regression, the connection between lipid accumulation product, testosterone levels, and testosterone insufficiency was investigated, smoothed curve fitting was calculated to integrate non-linear relationships, and subgroup analysis was performed to identify sensitive populations. After removing all potential confounders, testosterone levels in 1651 subjects tended to decrease with increasing continuous variable lipid accumulation product (β = -0.49, 95% confidence interval [-0.77, -0.22], p = 0.0005) and adding the chance of testosterone deficiency (odds ratio = 1.01, 95% confidence interval [1.01, 1.01], p < 0.0001). In the lipid accumulation product quartile, testosterone levels decreased the most (β = -77.65, 95% confidence interval [-110.99, -44.31], p < 0.0001) and the risk of testosterone deficiency was highest (odds ratio = 2.76, 95% confidence interval [1.47, 5.20], p = 0.0016). The area under the curve values were 0.718 (95% confidence interval: 0.688-0.750) for lipid accumulation product, 0.723 (95% confidence interval: 0.689-0.756) for Homeostasis Model Assessment of Insulin Resistance, and 0.673 (95% confidence interval: 0.640-0.708) for triglyceride-glucose, with no statistical difference between lipid accumulation product and Homeostasis Model Assessment of Insulin Resistance comparisons. The cut-off value of lipid accumulation product ≥52.408 predicted testosterone deficiency with good sensitivity and specificity. Higher lipid accumulation product was linked to a higher incidence of testosterone loss and inadequate, especially in hypertensive and non-smoker. Lipid accumulation product is a better predictor of testosterone deficiency than triglyceride-glucose and does not differ significantly from the Homeostasis Model Assessment of Insulin Resistance phase.

Relationship between Alcohol Consumption and Testosterone Deficiency according to Facial Flushes among Middle-Aged and Older Korean Men.

This study examined the relationship between alcohol consumption and total testosterone deficiency based on facial flushing among Korean men. A total of 314 men were included in this study and divided into non-drinkers (n=78) and drinkers (n=236). Drinkers were also divided into flushers (n=96) and non-flushers (n=140). Flushers and non-flushers were separated into two groups based on the amount of alcohol consumed: moderate drinkers (≤8 standard drinks per week) and heavy drinkers (>8 standard drinks per week). Total testosterone <3.5 ng/mL was defined as testosterone deficiency. The risk of testosterone deficiency was significantly higher in heavy drinkers who flushed than in nondrinkers (odds ratio, 4.37; 95% confidence interval, 1.20-15.88; P=0.025). However, no significant difference was observed in the risk of testosterone deficiency in non-flushers, regardless of the amount of alcohol consumed. This study suggests that the risk of testosterone deficiency increases in heavy drinkers (>8 drinks per week) who flush compared to that in non-drinkers.

Fatty liver index is associated with the risk of testosterone deficiency in aging men without metabolic syndrome.

Non-alcoholic fatty liver disease (NAFLD) is suggested to be a precursor of metabolic syndrome (MetS) and could influence the risk of testosterone deficiency (TD). Fatty liver index (FLI) is a simple and useful screening tool for NAFLD. We determined the association between the risk of NAFLD assessed by FLI and TD in aging Taiwanese men, especially those without MetS. A free health screening program was conducted for men (age: >40years) in a medical center in Kaohsiung, Taiwan. All participants underwent a physical examination; answered a questionnaire assessing demographics, medical history, and clinical symptoms of TD; and provided 20-mL whole blood samples for biochemical, adipocytokine, and hormonal evaluations. The risk of NAFLD was evaluated using FLI. The presence of NAFLD was ruled out if FLI value was <25 and ruled in if FLI value was ≥35. A total of 552 men (mean age: 54.7±7.7years) were enrolled. The prevalence rates of TD and MetS were significantly higher among men with NAFLD than those without NAFLD (both p<0.001). FLI was significantly correlated with total testosterone (TT) and adipocytokines associated with insulin resistance, such as adiponectin, leptin, and retinol-binding protein-4 (RBP-4) levels, respectively (all p<0.001). Among men without MetS, those at risk of and with NAFLD had a 3.82 and 8.50 times higher risk of TD, respectively, than those without NAFLD after adjusting for potential covariates. The FLI is associated with the risk of TD in aging Taiwanese men, especially in those without MetS. Our findings also suggest that insulin resistance may be an important link among the inter-relationships of NAFLD, MetS, and TD. Further population-based studies with larger sample sizes of different ethnicities are warranted to confirm these preliminary results.

Guideline of guidelines: testosterone therapy for testosterone deficiency.

We analysed the guidelines for testosterone therapy (TTh) produced by major international medical societies including: the American Urological Association, European Association of Urology, American Association of Clinical Endocrinologists, British Society for Sexual Medicine, Endocrine Society, International Society for Sexual Medicine, and the International Society for the Study of the Aging Male, and compared their recommendations. All the organisations were in general agreement concerning the following key points: Only men meeting the criteria for testosterone deficiency (TD) should be treated. Consider screening asymptomatic men with certain conditions that increase the risk of TD. Exogenous TTh causes impairment of spermatogenesis. There is no evidence that TTh causes prostate cancer. Men on TTh require careful laboratory monitoring.

Hepatocyte Nuclear Factor-4α P2 Promoter Variants Are Associated With the Risk of Metabolic Syndrome and Testosterone Deficiency in Aging Taiwanese Men

BackgroundHepatocyte nuclear factor-4α (HNF4A) can influence the risk of insulin resistance that is postulated to be an important link between metabolic syndrome (MetS) and testosterone deficiency (TD) in men. AimTo investigate the relationship between single-nucleotide polymorphisms (SNPs) of HNF4A and the risk of developing MetS and TD in a population of aging Taiwanese men. MethodsA free health screening of men over 40 years of age was conducted in a medical center in Kaohsiung City, Taiwan. All participants underwent a physical examination, answered a questionnaire on demographics and medical history, completed the Androgen Deficiency in The Aging Male questionnaire to assess clinical symptoms of TD, and provided 20-mL whole blood samples for biochemical, hormonal, and genetic evaluation. Main Outcome Measure3 common SNPs (rs11574736, rs1884613, and rs2144908) of HNF4A were selected and identified using a TaqMan 5’ allelic discrimination assay. Results559 men were enrolled for this study (mean age, 55.8± 4.9 years). Prevalence of TD was significantly higher (P = .031) in subjects with MetS (16.8%) than those without MetS (10.1%). In SNP rs1884613 of HNF4A, subjects with the C allele carried a 1.31- and 1.50-times higher risk of developing MetS and TD, respectively, compared to those with the G allele, after adjusting for potential covariates. In addition, subjects with the CC genotype were exposed to a 1.91- and 2.20-times higher risk of developing MetS and TD, respectively, compared to those with the GG genotype. Clinical ImplicationsOur findings may point to the importance of the role played by insulin resistance in the link between MetS and TD. Strength & LimitationsOur current work is the first report with adequate sample size to evaluate the role of genetic variants of HNF4A on the risk of both MetS and TD in men. The limitations included subjects enrolled from a free health screening and single measurement of serum testosterone levels. ConclusionThe rs1884613 SNP marker of HNF4A is significantly associated with an increased risk for developing both MetS and TD in aging Taiwanese men. Further population-based studies utilizing larger samples of different ethnicities may be needed to confirm these preliminary results.Liu C-C, Lee Y-C, Hung S-P. Hepatocyte Nuclear Factor-4α P2 Promoter Variants Are Associated With the Risk of Metabolic Syndrome and Testosterone Deficiency in Aging Taiwanese Men. J Sex Med 2018;15:1527–1536.

Dynamics of hormonal disorders following unilateral orchiectomy for a testicular tumor

Testicular tumors and their treatment interfere with homeostasis, hormonal status included. The aim of the study was to evaluate hormonal disorders of the pituitary–gonadal axis in men treated for testicular tumors. One hundred twenty-eight men treated for a unilateral testicular tumor at our institution were included. The hormonal status was prospectively evaluated in 62 patients before orchiectomy, 120 patients 1 month after orchiectomy and 110 patients at least 1 year after the treatment. The concentrations of human chorionic gonadotropin (hCG), testosterone (T), estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin were measured. The clinically significant testosterone deficiency was defined either as testosterone <2.31 ng/mL or testosterone within the range of 2.31–3.46 ng/mL but simultaneous with T/LH ratio ≤1. Changes in hormone levels were significant: LH and FSH rose in the course of observation, and the concentration of hCG, testosterone, estradiol decreased. PRL concentration was the lowest at 1 month after orchiectomy. In multivariate analysis, the risk of the clinically significant testosterone deficiency was 0.2107 (95% CI 0.1206–0.3419) prior to orchiectomy, 0.3894 (95% CI 0.2983–0.4889) 1 month after surgery and 0.4972 (95% CI 0.3951–0.5995) 1 year after the treatment. The estradiol concentration was elevated in 40% of patients with recently diagnosed testicular cancer and that was correlated with a higher risk of testosterone deficiency after the treatment completion. Hormonal disorders of the pituitary–gonadal axis in men treated for testicular tumors are frequent. The malignant tissue triggers paraneoplastic disorders that additionally disturb the hormonal equilibrium.

Testosterone deficiency in testicular cancer survivors - a systematic review and meta-analysis.

Results concerning treatment of Testicular Germ Cell Cancer (TGCC) and subsequent risk of testosterone deficiency are conflicting. To systematically evaluate and estimate the risk of testosterone deficiency (TD) in TGCC-patients according to treatment to optimize follow-up and for prevention of late effects related to hypogonadism. We performed a critical review of PubMed in January 2015 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Twelve publications were selected for inclusion in this analysis. Eleven studies evaluated the risk of TD in TGCC-patients treated with standard chemotherapy (CT) and the odds ratio for TD was 1.8 (95% CI) (1.3-2.5), (p=0.0007). Seven studies evaluated the risk of TD in TGCC-patients treated with non-conventional therapy and the odds ratio for TD was 3.1 (95% CI) (2.0-4.8), (p<0.0001). Six studies evaluated the risk of TD in TGCC-patients treated with infradiaphragmatic radiotherapy (RT), and the odds ratio for TD was 1.6 (95% CI) (1.0-2.4), (p=0.03). In all treatment groups the risk of TD was compared with TGCC-patients treated with orchiectomy alone. There was no indication of heterogeneity between studies in the three treatment groups. Strong evidence exists that standard CT, non-conventional therapy and infradiaphragmatic RT are associated with an increased risk of TD in TGCC-patients when compared with orchiectomy alone. The risk of testosterone defficiency appears to be highest in patients treated with non-conventional therapy.

Age, Body Mass Index, and Frequency of Sexual Activity are Independent Predictors of Testosterone Deficiency in Men With Erectile Dysfunction

To identify clinical predictors of testosterone deficiency (TD) in men with erectile dysfunction (ED), thereby identifying subgroups that are most likely to benefit from targeted testosterone screening. Retrospective review was conducted on 498 men evaluated for ED between January 2013 and July 2014. Testing for TD by early morning serum measurement was offered to all eligible men. Patients with history of prostate cancer or testosterone replacement were excluded. Univariable linear regression was conducted to analyze 19 clinical variables for associations with serum total testosterone (TT), calculated free testosterone (cFT), and TD (T <300 ng/dL or cFT <6.5 ng/dL). Variables significant on univariable analysis were included in multiple regression models. A total of 225 men met inclusion criteria. Lower TT levels were associated with greater body mass index (BMI), less frequent sexual activity, and absence of clinical depression on multiple regression analysis. TT decreased by 49.5 ng/dL for each 5-point increase in BMI. BMI and age were the only independent predictors of cFT levels on multivariable analysis. Overall, 62 subjects (27.6%) met criteria for TD. Older age, greater BMI, and less frequent sexual activity were the only independent predictors of TD on multiple regression. We observed a 2.2-fold increase in the odds of TD for every 5-point increase in BMI, and a 1.8-fold increase for every 10 year increase in age. Men with ED and elevated BMI, advanced age, or infrequent sexual activity appear to be at high risk of TD, and such patients represent excellent potential candidates for targeted testosterone screening.

Correction: Prediabetes Is Associated with an Increased Risk of Testosterone Deficiency, Independent of Obesity and Metabolic Syndrome

Correction: Prediabetes Is Associated with an Increased Risk of Testosterone Deficiency, Independent of Obesity and Metabolic Syndrome

No effects of n−3 fatty acid supplementation on serum total testosterone levels in older men: the Alpha Omega Trial

The intake of the n-3 fatty acids alpha-linolenic acid (ALA), acid (EPA) and docosahexaenoic acid (DHA) has been related to testosterone levels in epidemiological analyses. The aim of this study was to assess whether the n-3 fatty acids affects testosterone levels in post-myocardial infarction (MI) patients, who are at risk of testosterone deficiency. In a double-blind, placebo-controlled trial of low-dose supplementation of n-3 fatty acids, we included 1850 male post-MI patients aged 60-80 years who participated in the Alpha Omega Trial. Patients were randomly allocated to margarines that provided 400 mg/day of EPA-DHA (n = 453), 2 mg/day of ALA (n = 467), EPA-DHA plus ALA (n = 458), or placebo (n = 472). Serum testosterone levels were assessed at baseline and after 41 months using whole day blood samples obtained at the subjects' home or at the hospital. Subjects were on average age of 68.4 (SD 5.3) years old and had baseline mean serum total testosterone of 14.8 (SD 5.6) nmol/L. The four randomized groups did not differ for baseline characteristics. ALA, EPA-DHA, and EPA-DHA plus ALA supplementation did not affect serum total testosterone compared to placebo. Moreover, n-3 fatty acid supplementation did not affect the risk of incident testosterone deficiency (n = 76 with total testosterone <8.0 nmol/L). We conclude that n-3 fatty acids supplementation did not affect serum total testosterone in men who had had a MI.

Refractory nonmotor symptoms in male patients with Parkinson disease due to testosterone deficiency: a common unrecognized comorbidity.

Many patients with Parkinson disease (PD) suffer from nonmotor symptoms including depression, anxiety, sexual dysfunction, decreased energy level, and an overall decline in quality of life. Comorbid depression, hypothyroidism, and sleep disorders may account for some, but not all, of these problems. Testosterone deficiency affects 20% to 25% of males over the age of 60 years in the general population and may cause signs and symptoms of the nonmotor symptoms seen in PD. We observed numerous patients with PD whose nonmotor symptoms were refractory to treatment. To determine whether treatment of comorbid testosterone deficiency in male patients with PD can lead to improvements in refractory nonmotor symptoms. Case studies were reviewed of the first 5 male patients who had PD with symptoms of testosterone deficiency who were treated in our clinic. All patients had low serum testosterone levels. Screening for testosterone deficiency symptoms using the St Louis Testosterone Deficiency Questionnaire was performed for 4 of the 5 patients. Additionally, to assess the prevalence of PD, total testosterone levels in 68 patients in our PD registry were sent for evaluation. Following testosterone replacement therapy, all 5 patients experienced significant improvements in their refractory nonmotor symptoms. Of 68 male patients with PD enrolled in our PD registry, 24 (35%) had plasma evidence of testosterone deficiency. We also noted that the risk of testosterone deficiency per decade was found to increase 2.8-fold per decade (P<.001), paralleling that which is found in the general elderly male population. The findings from this study reveal the heretofore unrecognized high prevalence of testosterone deficiency in elderly male patients with PD similar to that found in the general population. These symptoms, which may be refractory to antidepressants, anxiolytics, and antiparkinsonian medications, may respond to treatment with testosterone. More rigorous controlled studies will need to be undertaken to examine the treatment of this common comorbidity in male patients with PD.