Partial androgen deficiency, depression, and testosterone supplementation in aging men.
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ABSTRACT:
SUBMITTER: Amore M
PROVIDER: S-EPMC3376477 | biostudies-literature | 2012
REPOSITORIES: biostudies-literature
Publications
Partial androgen deficiency, depression, and testosterone supplementation in aging men.
Amore Mario M Innamorati Marco M Costi Sara S Sher Leo L Girardi Paolo P Pompili Maurizio M
International journal of endocrinology 20120607
The aim of this review was to summarize current knowledge on the correlation between depressive symptoms with a syndrome called partial androgen deficiency of the aging male (PADAM) and on the potential benefits of testosterone (T) treatment on mood. Despite, the causative nature of the relationship between low T levels and depression is uncertain, many hypogonadal men suffer from depression and vice versa several depressed patients are affected by hypogonadism. Supplementation with testosterone ...[more]
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Project description:ObjectiveTo assess whether the receipt of androgen therapy is associated with a reduced 30-day rehospitalization rate among older men with testosterone deficiency.Patients and methodsWe conducted a retrospective cohort study using a 5% national sample of Medicare beneficiaries. We identified 6372 nonsurgical hospitalizations between January 1, 2007, and December 31, 2012, for male patients aged 66 years and older with a previous diagnosis of testosterone deficiency. Patients who died or lost Medicare coverage in the 30 days after hospital discharge or who were discharged to another inpatient setting were excluded from the analysis. Logistic regression was used to calculate odds ratios (ORs) and 95% CIs for the risk of 30-day hospital readmissions associated with receipt of androgen therapy.ResultsIn older men with testosterone deficiency, receipt of androgen therapy was associated with a reduced risk of rehospitalization (91 of 929 androgen users [9.8%] vs 708 of 5443 non-androgen users [13.0%]; OR, 0.73; 95% CI, 0.58-0.92) in the 30 days after hospital discharge. In a logistic regression analysis adjusting for multiple demographic, clinical, and health service variables, the OR was similar (OR, 0.75; 95% CI, 0.59-0.95). The adjusted OR for unplanned 30-day hospital readmissions was 0.62 (95% CI, 0.47-0.83). Each of these findings persisted across a range of propensity score analyses-including adjustment, stratification, and inverse probability treatment weighting-and several sensitivity analyses.ConclusionAndrogen therapy may reduce the risk of rehospitalization in older men with testosterone deficiency. Given the high rates of early hospital readmission among older adults, further exploration of this intervention holds broad clinical and public health relevance.
| S-EPMC4860086 | biostudies-literature
Project description:Symptomatic androgen deficiency is common in patients taking opioid analgesics, as these drugs potently suppress the hypothalamic-pituitary-gonadal axis. However, the efficacy of testosterone replacement in this setting remains unclear. The objective of this trial was to evaluate the efficacy of testosterone replacement on pain perception and other androgen-dependent outcomes in men with opioid-induced androgen deficiency. We conducted a randomized, double-blind, parallel placebo-controlled trial at an outpatient academic research center. Participants were men aged 18 to 64 years on opioid analgesics for chronic noncancer pain, and total testosterone levels were <350 ng/dL. Participants were randomly assigned to 14 weeks of daily transdermal gel that contained 5 g of testosterone or placebo. Primary outcomes were changes in self-reported clinical pain and objectively assessed pain sensitivity. Sexual function, quality of life, and body composition were also assessed. The mean age was 49 years. The median total and free testosterone levels at baseline were 243 ng/dL and 47 pg/mL and 251 ng/dL and 43 pg/mL in the testosterone and placebo arm, respectively. Of the 84 randomized participants, 65 had follow-up data on efficacy outcomes. Compared with men assigned to the placebo arm, those assigned to testosterone replacement experienced greater improvements in pressure and mechanical hyperalgesia, sexual desire, and role limitation due to emotional problems. Testosterone administration was also associated with an improvement in body composition. There were no between-group differences in changes in self-reported pain. In conclusion, in men with opioid-induced androgen deficiency, testosterone administration improved pain sensitivity, sexual desire, body composition, and aspects of quality of life.
| S-EPMC6036339 | biostudies-literature
Project description:Background and Objectives: Abnormal concentrations of bioelements (magnesium, manganese, chromium, copper, zinc) have been associated with physical and emotional dysfunctions, including depression. This association, however, has not been analyzed in testosterone deficiency syndrome (TDS) or patients with depressiveness, i.e., when individual symptoms do not form the picture of a full-syndrome depressive disorder. This study aimed to assess the relationship between concentrations of selected bioelements and the incidence of depressive symptoms in men aged 50 years and older with a concurrent testosterone deficiency syndrome. Material and Methods: Blood samples were taken from 314 men; the mean age of the population was 61.36 ± 6.38 years. Spectrophotometric method for biochemical analysis of magnesium (Mg), manganese (Mn), chromium (Cr), copper (Cu), and zinc (Zn) was used. The diagnosis of testosterone deficiency syndrome (TDS) was based on the total testosterone (TT), free testosterone (FT), estradiol (E2), and dehydroepiandrosterone sulfate (DHEAS) levels by ELISA. Each participant completed the Androgen Deficiency in Aging Male (ADAM) questionnaire, as well as the Beck Depression Inventory (BDI-Ia) measuring the severity of depressive symptoms. Results: Emotional disturbances manifested as depressive symptoms were diagnosed in 28.7% of all participants and testosterone deficiency syndrome in 49.3%. In the TDS group, the analysis showed a significant correlation between the level of manganese (R = 0.225, p = 0.005) and chromium (R = 0.185, p = 0.021) with the incidence of depression. Conclusions: The results of our study demonstrated a relationship between manganese and chromium concentrations with the incidence of depression in men aged 50 years and older with a concurrent testosterone deficiency syndrome. This may indicate that there is a correlation between these bioelements, as well as emotional disorders manifested as depressive symptoms in aging men with a diagnosed testosterone deficiency.
| S-EPMC7143167 | biostudies-literature
Project description:The prevalence of cardiovascular mortality is higher in men than in age-matched premenopausal women. Gender differences are linked to circulating sex-related steroid hormone levels and their cardio-specific actions, which are critical factors involved in the prevalence and features of age-associated cardiovascular disease. In women, estrogens have been described as cardioprotective agents, while in men, testosterone is the main sex steroid hormone. The effects of testosterone as a metabolic regulator and cardioprotective agent in aging men are poorly understood. With advancing age, testosterone levels gradually decrease in men, an effect associated with increasing fat mass, decrease in lean body mass, dyslipidemia, insulin resistance and adjustment in energy substrate metabolism. Aging is associated with a decline in metabolism, characterized by modifications in cardiac function, excitation-contraction coupling, and lower efficacy to generate energy. Testosterone deficiency -as found in elderly men- rapidly becomes an epidemic condition, associated with prominent cardiometabolic disorders. Therefore, it is highly probable that senior men showing low testosterone levels will display symptoms of androgen deficiency, presenting an unfavorable metabolic profile and increased cardiovascular risk. Moreover, recent reports establish that testosterone replacement improves cardiomyocyte bioenergetics, increases glucose metabolism and reduces insulin resistance in elderly men. Thus, testosterone-related metabolic signaling and gene expression may constitute relevant therapeutic target for preventing, or treating, age- and gender-related cardiometabolic diseases in men. Here, we will discuss the impact of current evidence showing how cardiac metabolism is regulated by androgen levels in aging men.
| S-EPMC7243157 | 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:Platelets have been long postulated to play a critical role in the pathogenesis of prostate cancer, although relatively little is known regarding the precise mechanisms involved. Androgen deprivation therapy (ADT) for prostate cancer eventually fails with relapse occurring in the form of castration-resistant prostate cancer (CRPC). CRPC tumors typically overexpress androgen receptor (AR), demonstrating continued dependence upon AR signaling. Platelets have been previously demonstrated to contain androgens, and we sought to explore the contribution of platelet-derived androgens in CRPC. In this study, we examined the role of platelet-derived androgens in vitro using platelets from men with CRPC, men with high-risk prostate cancer, and healthy male donors. A series of in vitro assays was performed to elucidate the impact of platelet-derived androgens on androgen-sensitive prostate tumor cells. By examining platelet-derived androgen effects on AR signaling in prostate tumor cells, we found that platelets, from men with CRPC and on ADT, strongly induce AR target genes and tumor cell proliferation. Moreover, we show a fully intact testosterone (T) biosynthetic pathway within platelets from its precursor cholesterol and demonstrate that platelets of CRPC patients with ADT resistance are able to generate T. Overall, our findings reveal an unknown capacity of platelets to synthesize T at functionally relevant levels in patients with lethal prostate cancer. Importantly, it suggests a novel paracrine mechanism of T production that may act to sustain CRPC state and potentiate therapeutic resistance.
| S-EPMC4719002 | biostudies-literature
Project description:Reduction in testosterone levels in men during aging is associated with cognitive decline and risk of dementia. Animal studies have shown benefits for testosterone supplementation in improving cognition and reducing Alzheimer's disease pathology. In a randomized, placebo-controlled, crossover study of men with subjective memory complaint and low testosterone levels, we investigated whether testosterone treatment significantly improved performance on various measures of cognitive functioning. Forty-four men were administered a battery of neuropsychological tests to establish the baseline prior to being randomly divided into two groups. The first group (Group A) received 24 weeks of testosterone treatment (T treatment) followed by 4 weeks washout, and then 24 weeks of placebo (P); the second group (Group B) received the same treatments, in reverse order (Placebo, washout, and then T treatment). In group A (TèP), compared to baseline, there was a modest (1 point) but significant improvement in general cognitive functioning as measured by the Mini Mental State Examination (MMSE) following testosterone treatment. This improvement from baseline was sustained following the washout period and crossover to placebo treatment. Similar Mini Mental State Examination (MMSE) scores were observed when comparing testosterone treatment with placebo. In group B (PèT) a significant increase was observed from baseline following testosterone treatment and a trend towards an increase when compared to placebo treatment. Improvements in baseline depression scores (assessed by Geriatric Depression Scale) were observed following testosterone/placebo treatment in both groups, and no difference was observed when comparing testosterone with placebo treatment. Our findings indicate a modest improvement on global cognition with testosterone treatment. Larger clinical trials with a longer follow- up and with the inclusion of blood and brain imaging markers are now needed to conclusively determine the significance of testosterone treatment.
| S-EPMC5078598 | biostudies-literature
Project description:Cognitive impairment and dementia are predicted to undergo a dramatic increase in the following years with more than 131.5 million people being affected by 2030. Although vascular diseases play the most important role in the pathogenesis of memory impairment in aging men, some pre-clinical and clinical evidence has suggested a possible contribution of the age-dependent reduction of testosterone (T). In this paper we have summarized and discussed all the information derived from available animal and experimental studies. In addition, we meta-analyzed data rising from all randomized placebo controlled trials (RCTs) published so far. Only limited preclinical and clinical evidence can support a possible contribution of T in the pathogenesis of the age-dependent impairment of cognitive functions. In addition, our meta-analysis did not support the use of T replacement therapy for the improvement of several cognitive domains analyzed including attention/working memory, executive function, language, verbal memory, visual memory, visuomotor ability, and visuospatial ability. However, it is important to recognize that the vast majority of available RCTs included mixed populations of subjects with eugonadism and hypogonadism preventing any final conclusion being drawn on these issues.
| S-EPMC7752509 | biostudies-literature
Project description:Testosterone supplementation during energy deficit promotes whole body lean mass accretion, but the mechanisms underlying that effect remain unclear. To elucidate those mechanisms, skeletal muscle molecular adaptations were assessed from muscle biopsies collected before, 1 h, and 6 h after exercise and a mixed meal (40 g protein, 1 h postexercise) following 14 days of weight maintenance (WM) and 28 days of an exercise- and diet-induced 55% energy deficit (ED) in 50 physically active nonobese men treated with 200 mg testosterone enanthate/wk (TEST) or placebo (PLA) during the ED. Participants (n = 10/group) exhibiting substantial increases in leg lean mass and total testosterone (TEST) were compared with those exhibiting decreases in both of these measures (PLA). Resting androgen receptor (AR) protein content was higher and fibroblast growth factor-inducible 14 (Fn14), IL-6 receptor (IL-6R), and muscle ring-finger protein-1 gene expression was lower in TEST vs. PLA during ED relative to WM (P < 0.05). Changes in inflammatory, myogenic, and proteolytic gene expression did not differ between groups after exercise and recovery feeding. Mechanistic target of rapamycin signaling (i.e., translational efficiency) was also similar between groups at rest and after exercise and the mixed meal. Muscle total RNA content (i.e., translational capacity) increased more during ED in TEST than PLA (P < 0.05). These findings indicate that attenuated proteolysis at rest, possibly downstream of AR, Fn14, and IL-6R signaling, and increased translational capacity, not efficiency, may drive lean mass accretion with testosterone administration during energy deficit.
| S-EPMC7750513 | biostudies-literature
Project description:The indication for testosterone therapy in aging hypogonadal men without hypothalamic, pituitary, or testicular disease remains to be elucidated. The aim of this study was to investigate the effect of testosterone therapy on insulin sensitivity, substrate metabolism, body composition, and lipids in aging men with low normal bioavailable testosterone levels using a predefined cutoff level for bioavailable testosterone. A randomized, double-blinded, placebo-controlled study of testosterone treatment (gel) was done on 38 men, aged 60-78 years, with bioavailable testosterone <7.3 nmol/l and a waist circumference >94 cm. Insulin-stimulated glucose disposal (Rd) and substrate oxidation were assessed by euglycemic hyperinsulinemic clamps combined with indirect calorimetry. Lean body mass (LBM) and total fat mass (TFM) were measured by dual x-ray absorptiometry, and serum total testosterone was measured by tandem mass spectrometry. Bioavailable testosterone was calculated. Coefficients (b) represent the placebo-controlled mean effect of intervention. LBM (b?=?1.9 kg, p?=?0.003) increased while HDL-cholesterol (b?=?-0.12 mmol/l, p?=?0.043) and TFM decreased (b?=?-1.2 kg, p?=?0.038) in the testosterone group compared to placebo. Basal lipid oxidation (b?=?5.65 mg/min/m(2), p?=?0.045) increased and basal glucose oxidation (b?=?-9.71 mg/min/m(2), p?=?0.046) decreased in response to testosterone therapy even when corrected for changes in LBM. No significant changes in insulin-stimulated Rd was observed (b?=?-0.01mg/min/m(2), p?=?0.92). Testosterone therapy increased muscle mass and lipid oxidation in aging men with low normal bioavailable testosterone levels; however, our data did not support an effect of testosterone on whole-body insulin sensitivity using the euglycemic hyperinsulinemic clamp technique.
| S-EPMC3260358 | biostudies-literature