Serum Total Testosterone and Premature Mortality Among Men in the USA.
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ABSTRACT: Patient summary
We explored the relationship between testosterone levels and premature death in a large US population. We found that low testosterone is associated with both premature death and related disease processes such as obesity, both of which can be initially treated with diet and exercise.
SUBMITTER: Fantus RJ
PROVIDER: S-EPMC8317905 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectivesThis study examines the associations between total testosterone levels and dialysis mortality.MethodsElderly men who initiate hemodialysis in Taoyuan General Hospital from January 2012 to June 2017 were enrolled. We reviewed clinical characteristics and biochemical data from start of dialysis and followed over a 5-year period after dialysis. Body composition parameters were assessed 3-6 months after dialysis. Skeletal muscle mass index (SMMI) was defined by skeletal muscle mass divided by squared height. We defined those with lowest tertile of testosterone values as low testosterone group. Adjusted hazard ratios (aHRs) and 95% confidence interval (95% CI) for mortality and cumulative survival curves were evaluated by Cox hazards model and Kaplan-Meier method. The discriminative power of SMMI and testosterone levels was calculated according to the area under the curve and the receiver operating characteristic curve (AUROC).ResultsFrom a total of 137 elderly hemodialysis patients, the range of lowest, middle, and highest tertile of testosterone values was <6.25 nmol/L, 6.25-10.5 nmol/L, and >10.5 nmol/L. After multivariate adjustment other than SMMI, total testosterone levels at baseline were a significant predictor for mortality aHR(95% CI): 0.79 (0.70-0.91). The unadjusted and adjusted c-statistics of SMMI vs testosterone values to predict overall were 770 (0.688-0.852) vs 0.779 (0.691-0.866) and 855 (0.812-0.886) vs 0.812 (0.744-0.856) (Ps < .05), whereas the capacity of c-statistics was similar (?2 = 0.143 and 2.709, Ps > .05).ConclusionsTotal testosterone value was a predictor for mortality. It was noninferior to SMMI in predicting dialysis mortality.
| S-EPMC6817078 | biostudies-literature
Project description:BackgroundHypogonadism in men (total testosterone <350 ng/dL) is associated with higher risk of cardiovascular disease and mortality in men on dialysis therapy. We evaluated the association of hypogonadism with all-cause mortality in men with non-dialysis-dependent chronic kidney disease (CKD).Study designRetrospective, cohort study.Setting & participants2,419 men with CKD stages 3-4 (estimated glomerular filtration rate, 15-59 mL/min/1.73 m2) who had total testosterone measured for cause between January 1, 2005, and October 31, 2011, at a tertiary-care center in Cleveland, OH.PredictorsTotal testosterone measured using an immunoassay measurement in 3 forms: (1) categorized as low or testosterone replacement therapy versus normal, (2) continuous log testosterone, and (3) quintiles (100-226, 227-305, 306-392, 393-511, and 512-3,153 ng/dL).OutcomesFactors associated with low total testosterone level and the association between low total testosterone level and all-cause mortality were evaluated using logistic regression, Cox proportional hazard models, and Kaplan-Meier survival curves.ResultsHypogonadism was found in 1,288 of 2,419 (53%) men. In a multivariable logistic regression analysis, African American ethnicity and higher estimated glomerular filtration rate were associated with lower odds of having hypogonadism. Diabetes and higher body mass index were associated with higher odds of having hypogonadism. 357 of 2,419 (15%) patients died during a median follow-up of 2.3 years. In the multivariate Cox model, testosterone level <350 ng/dL or testosterone replacement therapy was not associated with mortality. In a multivariable model also adjusted for testosterone supplementation, higher log testosterone was associated with significantly lower mortality (HR per 1 log unit, 0.70; 95% CI, 0.55-0.89). When compared to the highest quintile, the second lowest quintile of testosterone was associated with higher mortality (HR, 1.53; 95% CI, 1.09-2.16).LimitationsSingle-center study, timing of testosterone testing, lack of adjustment for proteinuria, and sampling bias.ConclusionsLow total testosterone level may be associated with higher mortality in men with CKD stages 3-4, but more studies are needed.
| S-EPMC4143431 | biostudies-literature
Project description:Testosterone concentrations in men are associated with cardiovascular morbidity, osteoporosis, and mortality and are affected by age, smoking, and obesity. Because of serum testosterone's high heritability, we performed a meta-analysis of genome-wide association data in 8,938 men from seven cohorts and followed up the genome-wide significant findings in one in silico (n?=?871) and two de novo replication cohorts (n?=?4,620) to identify genetic loci significantly associated with serum testosterone concentration in men. All these loci were also associated with low serum testosterone concentration defined as <300 ng/dl. Two single-nucleotide polymorphisms at the sex hormone-binding globulin (SHBG) locus (17p13-p12) were identified as independently associated with serum testosterone concentration (rs12150660, p?=?1.2×10(-41) and rs6258, p?=?2.3×10(-22)). Subjects with ? 3 risk alleles of these variants had 6.5-fold higher risk of having low serum testosterone than subjects with no risk allele. The rs5934505 polymorphism near FAM9B on the X chromosome was also associated with testosterone concentrations (p?=?5.6×10(-16)). The rs6258 polymorphism in exon 4 of SHBG affected SHBG's affinity for binding testosterone and the measured free testosterone fraction (p<0.01). Genetic variants in the SHBG locus and on the X chromosome are associated with a substantial variation in testosterone concentrations and increased risk of low testosterone. rs6258 is the first reported SHBG polymorphism, which affects testosterone binding to SHBG and the free testosterone fraction and could therefore influence the calculation of free testosterone using law-of-mass-action equation.
| S-EPMC3188559 | biostudies-literature
Project description:Abstract BACKGROUND: In men, obesity is often associated with low testosterone (T) levels, but information is limited as to how body weight affects the pharmacokinetic profile or dosing of testosterone therapy (TTh) in men with T deficiency. Historically, men with body mass index (BMI) >32.4 kg/m2 required higher doses of T 2% gel to achieve physiological T levels than men with BMI ≤29.1 or 29.2–32.4 kg/m2.(1) In a phase 3 trial (N=150) of subcutaneous (SC) testosterone enanthate (TE) administered weekly, concentration-guided dosing raised T levels to within physiological range in 92.7% of patients.(2) Here, we report a post hoc analysis evaluating the association between body weight and serum T levels attained with SC TE. Methods: SC TE was evaluated in an open-label, single-arm, dose-blinded, 52-week phase 3 trial (NCT02159469). Patients self-administered 75 mg SC TE weekly during the titration phase; blinded dose-adjustments in 25 mg increments occurred at pre-defined time points beyond the sixth dose. The primary endpoint of this study was the percentage of patients achieving an average serum T concentration (Cavg0-168h) of 300 to 1,100 ng/dL at week 12. For this post hoc analysis, a linear regression model with weight and dose as independent variables was used to assess differences in mean minimum T concentration (Cmin) and Cavg0-168h at week 12. Results: For this analysis, 137 patients were included. Doses were 50 mg (n=25), 75 mg (n=93), and 100 mg (n=19). The mean weight was 84.4 kg, 102.2 kg, and 112.0 kg for the 50 mg, 75 mg, and 100 mg dose groups, respectively (range, 49.9–146.5 kg). The dose-normalized T Cmin was 9.2 ng/dL, 5.7 ng/dL, and 4.3 ng/dL per 1 mg of SC TE for the 50 mg, 75 mg, and 100 mg groups, respectively. The dose-normalized T Cavg0-168h was 12.0 ng/dL, 7.2 ng/dL, and 5.7 ng/dL per 1 mg of SC TE. In an overall linear regression model, 48.2% (P<0.0001) and 55.0% (P<0.0001) of the total variance in Cmin and Cavg0-168h, respectively, can be predicted from the independent weight and dose variables. Conclusion: Our results show an inverse relationship between body weight and T exposure. Men with higher mean body weights required higher doses of SC TE to achieve physiologic T levels compared with men with lower mean body weights. The available doses provide effective options to reach target exposures. These findings highlight the impact of weight and dose selection on SC TE exposure. References: (1) Dobs et al., J Sex Med 2014;11:857–864; (2) Kaminetsky et al., J Urol. 2019;201:587–94.
| S-EPMC7208516 | biostudies-literature
Project description:Background and Objectives: Male hypogonadism is a clinical disorder characterized by reduced serum testosterone in men. Although treatment using herbal medicines, including Eurycoma longifolia, has been investigated, the benefits remain unclear. This study aims to investigate the efficacy of E. longifolia as a sole intervention to increase testosterone levels in males. Materials and Methods: We conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) according to the PRISMA guidelines. Relevant articles were retrieved from the databases PubMed, Scopus, Web of Science, Cochrane, Ovid/Embase, and Google Scholar. Results: After literature screening, a total of nine studies was included in the systematic review. Five RCTs were included in the meta-analysis. A significant improvement in total testosterone levels after E. longifolia treatment was mostly reported in both healthy volunteers and hypogonadal men. The random model effect revealed a significant increase (SMD = 1.352, 95% CI 0.565 to 2.138, p = 0.001) in the total testosterone levels in men receiving E. longifolia supplementation, which was confirmed in the hypogonadism subgroup. Conclusions: This systematic review and meta-analysis of the literature supports the possible use of E. longifolia supplementation for enhancing testosterone production. Although more research is required before its use in clinical practice, this may represent a safe and promising therapeutic option, particularly in hypogonadal men.
| S-EPMC9415500 | biostudies-literature
Project description:BackgroundNon-alcoholic fatty liver disease (NAFLD) is highly prevalent in people with diabetes with no available treatment.AimTo explore the effect of testosterone treatment on liver. Testosterone therapy improves insulin resistance and reduces total body fat, but its impact on the liver remains poorly studied.MethodsThis secondary analysis of a 40 wk, randomised, double-blinded, placebo-controlled trial of intramuscular testosterone undecanoate in men with type 2 diabetes and lowered serum testosterone concentrations evaluated the change in hepatic steatosis as measured by liver fat fraction on magnetic resonance imaging (MRI).ResultsOf 88 patients enrolled in the index study, 39 had liver MRIs of whom 20 received testosterone therapy and 19 received placebo. All patients had > 5% hepatic steatosis at baseline and 38 of 39 patients met diagnostic criteria for NAFLD. Median liver fat at baseline was 15.0% (IQR 11.5%-21.1%) in the testosterone and 18.4% (15.0%-28.9%) in the placebo group. Median ALT was 34units/L (26-38) in the testosterone and 32units/L (25-52) in the placebo group. At week 40, patients receiving testosterone had a median reduction in absolute liver fat of 3.5% (IQR 2.9%-6.4%) compared with an increase of 1.2% in the placebo arm (between-group difference 4.7% P < 0.001). After controlling for baseline liver fat, testosterone therapy was associated with a relative reduction in liver fat of 38.3% (95% confidence interval 25.4%-49.0%, P < 0.001).ConclusionTestosterone therapy was associated with a reduction in hepatic steatosis in men with diabetes and low serum testosterone. Future randomised studies of testosterone therapy in men with NAFLD focusing on liver-related endpoints are therefore justified.
| S-EPMC9099110 | biostudies-literature
Project description:BackgroundTo improve symptoms associated with testosterone deficiency, many testosterone therapies are available that aim to restore serum testosterone (T) levels to the normal physiologic range. The magnitude, frequency, and duration between peak and trough T concentrations vary with route of administration, and none reflect normal endogenous daily diurnal T variations.ObjectiveTo compare pharmacokinetic profiles of serum T from approved T formulations with endogenous diurnal T variations in young and older men, and to consider whether there may be value in mimicking the diurnal T rhythmicity with exogenous testosterone therapies as men age.Materials and methodsA literature search of studies examining the diurnal variation of endogenous T in healthy men and men with testosterone deficiency was performed using PubMed in January 2020. Additional searches for serum T pharmacokinetic profiles of various testosterone therapy formulations were also conducted. Prescribing information for various T formulations was also reviewed.Discussion and conclusionEndogenous diurnal T variation is well described and appears to be blunted naturally as men age. Men with testosterone deficiency lack diurnal T variation and exhibit a flatter T profile compared with eugonadal men. Some T replacement options provide intraday T level variations similar to normal circadian secretion, and others provide a flatter exposure profile reflective of depot release. Others provide profiles that exceed the frequency and physiologic range of the natural diurnal variation of T. All exogenous T replacement dosing targets an increase in average T levels to within the normal physiologic range and improves symptoms associated with low T, but no single testosterone therapy can exactly mimic the normal diurnal T patterns seen in younger men and the blunted circadian T secretion of older men.
| S-EPMC9293229 | biostudies-literature
Project description:Literature proves anti-mullerian hormone (AMH) and total testosterone (TT) as two important reproductive hormones in male development, however evidence regarding age variations of these hormones is lacking.To estimate the normal serum AMH values and to assess the age-specific TT levels in men aged 30-70, we conducted the present population-based study.A total of 831 healthy eligible men, aged 30-70 years, were recruited from Tehran Lipid and Glucose study cohort. Centiles for AMH were estimated according to the exponential normal 3-parameter model. The parametric method of Royston available in general software was applied for the first time to estimate the age-specific AMH and TT percentiles of 5th, 10th, 25th, 50th, 75th, 90th and 95th.Mean AMH level was 6.93, ranging from 0.1 to 40.1 ng/ml. Serum AMH concentrations followed a steady reduction with increasing age. Mean TT level was 4.8, ranging from 0.44 to 11.4 ng/ml.A measurable serum concentrations of AMH in healthy males throughout lifespan with variations, based on age, confirming a slight age-related AMH decline. Fractional polynomial (FP) regression models revealed that the mean and standard deviation (SD) of the TT were not associated with age, so the percentiles estimated were not age-specific.We presented a nomogram of age-specific AMH values in a healthy cohort of Iranian men. This finding might have clinical importance in dealing hormonal disorders in men.
| S-EPMC5513413 | biostudies-other
Project description:The present study aimed to evaluate the influence of serum vitamin D levels on semen quality and testosterone levels. This is a cross-sectional study conducted at Androscience, Science and Innovation Center in Andrology and High-Complex Clinical and Andrology Laboratory in Sao Paulo, Brazil, with 508 male patients, aged 18-60 years, from 2007 to 2017. Seminal parameters and serum sexual hormones were correlated with serum vitamin D concentrations in 260 men selected by strict selection criteria. Patients were divided into normozoospermic group (NZG, n = 124) and a group with seminal abnormalities (SAG, n = 136). Evaluation included complete physical examination, past medical history, habits and lifestyle factors, two complete seminal analysis with sperm functional tests, serum levels of 25-hydroxy-vitamin D3(25(OH)VD3), total and free testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone-binding globulin (SHBG), total cholesterol, homeostatic model assessment of insulin resistance (HOMA-IR) index, and karyotype. The mean concentration of 25(OH)VD3was significantly lower in the SAG (P < 0.001) and positively correlated with all baseline seminal parameters and total testosterone levels. In addition, serum vitamin D3concentration was found to be positively correlated with sperm concentration (β= 2.103; P < 0.001), total number of spermatozoa with progressive motility (β = 2.069; P = 0.003), total number of motile spermatozoa (β = 2.571; P = 0.015), and strict morphology (β = 0.056; P = 0.006), regardless of other variables. This is the first comparative study to address the issue of serum vitamin D3content between normozoospermic patients and those with sperm abnormalities. It clearly demonstrates a direct and positive relationship between serum vitamin D level and overall semen quality, male reproductive potential, and testosterone levels.
| S-EPMC7831823 | biostudies-literature
Project description:ObjectiveTo investigate whether serum total testosterone level is associated with knee pain and function in men and women with severe knee osteoarthritis (OA).MethodsWe enrolled 272 adults age ≥60 years (mean ± SD age 70.4 ± 4.4 years, 53% women) who underwent unilateral total knee replacement (TKR) due to severe knee OA. Serum testosterone levels and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function of the operated and contralateral knee were measured at 6-8 weeks after surgery. At the nonoperated knee, 56% of participants had radiographic knee OA with a Kellgren/Lawrence grade ≥2. Cross-sectional analyses were performed by sex and body mass index (BMI) subgroups, using multivariable regression adjusted for age, physical activity, and BMI.ResultsAt the operated knee, higher testosterone levels were associated with less WOMAC pain in men (B = -0.62, P = 0.046) and women (B = -3.79, P = 0.02), and less WOMAC disability scores in women (B = -3.62, P = 0.02) and obese men (B = -1.99, P = 0.02). At the nonoperated knee, testosterone levels were not associated with WOMAC pain in men or women, but higher testosterone levels were associated with less disability in women (B = -0.95, P = 0.02). Testosterone levels were inconsistently associated with pain and disability in BMI subgroups among men. Only among obese women, testosterone levels were inversely associated with radiographic knee OA (odds ratio = 0.10, P = 0.003).ConclusionHigher total testosterone levels were associated with less pain in the operated knee in men and women undergoing TKR and less disability in women. At the nonoperated knee, higher testosterone levels were inconsistently associated with less pain and disability.
| S-EPMC7702066 | biostudies-literature