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:Hypogonadism 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).Retrospective, cohort study.2,419 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.Total 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).Factors 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.Hypogonadism 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).Single-center study, timing of testosterone testing, lack of adjustment for proteinuria, and sampling bias.Low 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: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: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: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:Previous studies on the prognostic significance of serum levels of androgens in patients with chronic heart failure (CHF) have yielded conflicting results. The aim of this study was to examine the relationship between serum concentration of testosterone and mortality in men with systolic CHF. A total of 175 elderly men (age ≥ 60 years) with CHF were recruited. Total testosterone (TT) and sex hormone-binding globulin (SHBG) were measured, and estimated free testosterone (eFT) was calculated. The median follow-up time was 3.46 years. Of these patients, 17 had a TT level below 8 nmol l⁻¹ (230 ng dl⁻¹), 27 had an eFT level below 0.225 nmol l⁻¹ (65 pg ml⁻¹) and 12 had both. Using the age-specific tenth percentiles of TT and eFT in healthy men in our laboratory as cutoff points, the prevalences of TT and eFT deficiency was 21.7% (38/175) and 27.4% (48/175), respectively. Both TT and eFT were inversely associated with left ventricular ejection fraction (LVEF) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) (all P<0.01). Kaplan-Meier curves for patients in low, medium and high tertiles according to TT and eFT level showed significantly different cumulative survival rate (both P<0.01 by log-rank test). However, after adjustment for clinical variables, there were no significant associations of either TT or eFT levels with survival time (OR=0.97, 95% CI: 0.84-1.12, P=0.28 and OR=0.92, 95% CI: 0.82-1.06, P=0.14, respectively). Our study showed that levels of TT and eFT are commonly decreased in elderly patients with systolic CHF and related to disease severity, but they are not independent predictors for mortality.
| S-EPMC3739581 | biostudies-other
Project description:ContextTestosterone (T) plus progestin combinations are the most promising hormonal male contraceptives. Nestorone (NES), a progestin without estrogenic or androgenic activity, when combined with T may be an excellent candidate for male contraception.ObjectiveOur objective was to determine the effect of transdermal NES gel alone or with T gel on gonadotropin suppression.Design and settingThe randomized, unblinded clinical trial was conducted at two academic medical centers.ParticipantsA total of 140 healthy male volunteers participated.InterventionsOne hundred subjects were randomized initially (20 per group) to apply NES gel 2 or 4 mg, T gel 10 g, or T gel 10 g plus NES gel 2 or 4 mg daily for 20 d. Because only about half of the subjects in T plus NES 4 mg group suppressed serum gonadotropins to 0.5 IU/liter or less (suboptimal suppression), two additional groups of 20 men were randomized to apply daily T gel 10 g plus NES gel 6 or 8 mg.Main outcome variableSuppression of serum LH and FSH concentrations to 0.5 IU/liter or less after treatment was the main outcome variable.ResultsA total of 119 subjects were compliant with gel applications with few study-related adverse events. NES alone reduced gonadotropins significantly but less than T gel alone. Combined T gel 10g plus NES gel 6 or 8 mg suppressed both serum gonadotropins to 0.5 IU/liter or less in significantly more men than either gel alone.ConclusionTransdermal NES gel alone had gonadotropin suppression activity. Combined transdermal NES (6 or 8 mg) plus T gel demonstrated safe and effective suppression of gonadotropins, justifying a longer-term study of this combination for suppression of spermatogenesis.
| S-EPMC2708961 | biostudies-literature
Project description:Purpose:To investigate how pretreatment testosterone levels correlate with progression-free survival, metastasis-free survival, and overall survival in a propensity-adjusted localized prostate cancer population. Methods:Men diagnosed with clinical NCCN-risk stratified very-low, low, intermediate, high, and/or very-high risk prostate cancer who had a baseline total serum testosterone level?100?ng/dl measured within the 100?days preceding the first definitive therapy were identified from our prospectively gathered institutional database. Cohorts below (100-239?ng/dl), within (240-593?ng/dl), or above (594?+?ng/dl) one standard deviation from the mean testosterone level (416?ng/dl) were used for comparison. Progression-free, metastasis-free, and overall survival were evaluated. A separate cohort of men not receiving ADT was used to evaluate testosterone recovery after various treatment modalities (surgery, external beam radiation, brachytherapy, or combined EBRT?+?Brachy). Results:There was no statistically significant difference between the low, average, and high testosterone cohorts for PFS, MFS, or OS. In men not using ADT, there were no statistically significant changes in testosterone levels 1 year after therapy, regardless of therapy type. Conclusion:In men with serum testosterone levels >=100?ng/dl at diagnosis, baseline testosterone does not impact PFS, MFS, or OS. Recovery of testosterone back to baseline is expected for men undergoing either surgery, external beam or brachytherapy, or combined modality radiation when not using ADT.
| S-EPMC7201500 | biostudies-literature
Project description:Previous studies have shown controversial results about the role of testosterone in all-cause mortality in elderly men. We hypothesized that metabolic syndrome (MetS) could partly explain this discrepancy. We therefore examined the association of all-cause mortality with total and bioavailable testosterone, taking into account the MetS. We used data from the Three-City Cohort (3C) study with 12-year follow-up. The 3C study included 3650 men aged >65 years in three French cities. Hormone was measured in a random subsample of 444 men, and MetS was determined as stated by the International Diabetes Federation criteria. We used inverse-probability-weighted Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs). Of 444 men included in the analysis, 106 (23.9%) had MetS at baseline, and 166 died over the follow-up. There was a significant interaction between testosterone level and MetS for all-cause mortality (P = 0.002 and P = 0.008 for total and bioavailable testosterone, respectively). Among men with MetS, a decrease in one standard deviation of testosterone was associated with higher mortality risk [HR 1.78 (95% CI 1.13 to 2.78) and HR 1.83 (95% CI 1.17 to 2.86) for total and bioavailable testosterone, respectively]. By contrast, there was no association of testosterone with mortality risk among men without MetS. Our results suggest that MetS modifies the association between testosterone and mortality in older men. If confirmed, these findings could contribute to improve risk stratification and better manage the health of older men.
| S-EPMC5848820 | biostudies-other