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Testosterone Level and Cause-Specific Mortality in Older Men without Metabolic Syndrome.

ABSTRACT: Purpose:Previous studies yielded controversial findings on the association of testosterone with mortality in older men. Heterogeneity might be partially explained by comorbidities and the presence of metabolic syndrome, and differential associations according to causes of death. Methods:We used data from a random subsample of the Three-City study (3C) in which hormones were measured in 338 men ?65 years without metabolic syndrome, followed-up during 12 years. Vital status was determined for all participants from different sources. We used inverse-probability-weighted Cox regression to estimate hazard ratios (HRs) of cause-specific mortality and 95% confidence intervals (95% CIs). Results:Over the follow-up, 130 men died (30 from cardiovascular disease, 45 from cancer, 55 from other causes). The association of testosterone with mortality showed significant heterogeneity across causes of death (p=0.027 and p=0.022, for total and bioavailable testosterone, respectively). Higher testosterone level was associated with increased cardiovascular mortality (HR for 1-SD increase: 1.86, 95% CI: 1.28-2.71, and 1.50, 95% CI: 1.04-2.17, for total and bioavailable testosterone, respectively). By contrast, there was no significant association of testosterone with mortality from cancer and other causes. Conclusion:Our data suggest that the association of testosterone with mortality in men without metabolic syndrome might be differential according to the cause of death. These findings may explain part of the heterogeneity across studies on the relation between testosterone and mortality.

SUBMITTER: Laouali N

PROVIDER: S-EPMC7644941 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Testosterone levels and cause-specific mortality in the older French men without metabolic syndrome.

Laouali Nasser N Brailly-Tabard Sylvie S Helmer Catherine C Ancelin Marie-Laure ML Tzourio Christophe C Elbaz Alexis A Guiochon-Mantel Anne A Canonico Marianne M

Epidemiology and health 20200601

<h4>Objectives</h4>Previous studies have reported controversial findings regarding the association of testosterone with mortality in older men. This heterogeneity might be partially explained by comorbidities and the presence of metabolic syndrome, as well as differential associations according to causes of death.<h4>Methods</h4>We used data from a random subsample of the Three-City study, in which hormone levels were measured in 338 men ≥65 years without metabolic syndrome who were followed-up ...[more]

PMID: 32512663

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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.

Project description:Background Several recent journal articles report that d-chiro-inositol (DCI), primarily known as insulin second messenger, influences steroidogenesis. In particular, new evidence is arising on DCI ability to regulate aromatase expression and testosterone biosynthesis. In this regard, DCI administration could represent a good therapeutic opportunity in case of reduced levels of testosterone. Older men generally have lower testosterone concentrations than younger men, and recent randomized controlled trials have examined whether testosterone treatment might improve health outcomes in this age group. There is limited information about the safety of testosterone replacement therapy in these men, hence DCI could represent an interesting alternative for future trials. Therefore, this study aims to evaluate the effect of DCI treatment on testosterone levels in older male patient. Results Ten older men with basal low testosterone levels were enrolled in this study. Patients took 600 mg of DCI, two-times per day, for 30 days. We evaluated hormonal and glycaemic parameters, weight, waist circumference, and Body-Mass Index at baseline (T0) and after 30 days (T1). Finally, all patients also filled in the standardized International Index of Erectile Function questionnaire and performed the Handgrip test at T0 and T1. Men receiving DCI showed increased androgen and reduced oestrogen concentrations, and improved glycaemic profiles. DCI was also associated with reduced weight, Body-Mass Index, waist circumference, and improved grip strength and self-reported sexual function. All these effects led to the improvement of sexual function and physical strength. Conclusions In this pilot study, DCI treatment improved the levels of testosterone and androstenedione at the expense of oestrogens in elder men with low basal levels of these hormones without adverse effects. Trial registration Clinicaltrials.gov: D-chiroinositol Administration in Hypogonadal Males, NCT04708249

Project description:ImportanceIn one-third of older men with anemia, no recognized cause can be found.ObjectiveTo determine if testosterone treatment of men 65 years or older with unequivocally low testosterone levels and unexplained anemia would increase their hemoglobin concentration.Design, setting, and participantsA double-blinded, placebo-controlled trial with treatment allocation by minimization using 788 men 65 years or older who have average testosterone levels of less than 275 ng/dL. Of 788 participants, 126 were anemic (hemoglobin ≤12.7 g/dL), 62 of whom had no known cause. The trial was conducted in 12 academic medical centers in the United States from June 2010 to June 2014.InterventionsTestosterone gel, the dose adjusted to maintain the testosterone levels normal for young men, or placebo gel for 12 months.Main outcomes and measuresThe percent of men with unexplained anemia whose hemoglobin levels increased by 1.0 g/dL or more in response to testosterone compared with placebo. The statistical analysis was intent-to-treat by a logistic mixed effects model adjusted for balancing factors.ResultsThe men had a mean age of 74.8 years and body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) of 30.7; 84.9% were white. Testosterone treatment resulted in a greater percentage of men with unexplained anemia whose month 12 hemoglobin levels had increased by 1.0 g/dL or more over baseline (54%) than did placebo (15%) (adjusted OR, 31.5; 95% CI, 3.7-277.8; P = .002) and a greater percentage of men who at month 12 were no longer anemic (58.3%) compared with placebo (22.2%) (adjusted OR, 17.0; 95% CI, 2.8-104.0; P = .002). Testosterone treatment also resulted in a greater percentage of men with anemia of known cause whose month 12 hemoglobin levels had increased by 1.0 g/dL or more (52%) than did placebo (19%) (adjusted OR, 8.2; 95% CI, 2.1-31.9; P = .003). Testosterone treatment resulted in a hemoglobin concentration of more than 17.5 g/dL in 6 men who had not been anemic at baseline.Conclusions and relevanceAmong older men with low testosterone levels, testosterone treatment significantly increased the hemoglobin levels of those with unexplained anemia as well as those with anemia from known causes. These increases may be of clinical value, as suggested by the magnitude of the changes and the correction of anemia in most men, but the overall health benefits remain to be established. Measurement of testosterone levels might be considered in men 65 years or older who have unexplained anemia and symptoms of low testosterone levels.Trial registrationclinicaltrials.gov Identifier: NCT00799617.

Project description:BACKGROUND:Serum testosterone concentrations decrease as men age, but benefits of raising testosterone levels in older men have not been established. METHODS:We assigned 790 men 65 years of age or older with a serum testosterone concentration of less than 275 ng per deciliter and symptoms suggesting hypoandrogenism to receive either testosterone gel or placebo gel for 1 year. Each man participated in one or more of three trials--the Sexual Function Trial, the Physical Function Trial, and the Vitality Trial. The primary outcome of each of the individual trials was also evaluated in all participants. RESULTS:Testosterone treatment increased serum testosterone levels to the mid-normal range for men 19 to 40 years of age. The increase in testosterone levels was associated with significantly increased sexual activity, as assessed by the Psychosexual Daily Questionnaire (P<0.001), as well as significantly increased sexual desire and erectile function. The percentage of men who had an increase of at least 50 m in the 6-minute walking distance did not differ significantly between the two study groups in the Physical Function Trial but did differ significantly when men in all three trials were included (20.5% of men who received testosterone vs. 12.6% of men who received placebo, P=0.003). Testosterone had no significant benefit with respect to vitality, as assessed by the Functional Assessment of Chronic Illness Therapy-Fatigue scale, but men who received testosterone reported slightly better mood and lower severity of depressive symptoms than those who received placebo. The rates of adverse events were similar in the two groups. CONCLUSIONS:In symptomatic men 65 years of age or older, raising testosterone concentrations for 1 year from moderately low to the mid-normal range for men 19 to 40 years of age had a moderate benefit with respect to sexual function and some benefit with respect to mood and depressive symptoms but no benefit with respect to vitality or walking distance. The number of participants was too few to draw conclusions about the risks of testosterone treatment. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT00799617.).

Dataset Information

Testosterone Level and Cause-Specific Mortality in Older Men without Metabolic Syndrome.

Publications

Testosterone levels and cause-specific mortality in the older French men without metabolic syndrome.

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