The impact of testosterone replacement therapy on glycemic control,vascular function,and components of the metabolic syndrome in obese hypogonadal men with type 2 diabetes

Objective: This study set out to assess effects of testosterone replacement therapy (TRT) on parameters of metabolic syndrome and vascular function in obese hypogonadal males with type 2 diabetes mellitus (DM2).

Study design: Fifty-five obese hypogonadal diabetic males on oral hypoglycemic treatment were enrolled into this one-year, double-blind, randomized, placebo-controlled clinical study. Group T (n?=?28) was treated with testosterone undecanoate (1000?mg i.m. every 10?weeks) while group P (n?=?27) received placebo.

Methods: Anthropometrical and vascular measurements – flow-mediated dilatation (FMD) and intima media thickness (IMT) – biochemical and hormonal blood sample analyses were performed at the start of the study and after one year. Derived parameters (BMI, HOMA-IR, calculated free testosterone (cFT) and bioavailable testosterone (BT)) were calculated.

Results: TRT resulted in reduction of HOMA-IR by 4.64?±?4.25 (p?p?p?=?.005).

Conclusion: TRT normalized serum testosterone levels, improved glycemic control and endothelial function while exerting no ill effects on the study population.     

Effects of testosterone replacement therapy on hypogonadal men with osteopenia or osteoporosis: a subanalysis of a prospective randomized controlled study in Japan (EARTH study)

Objective: We investigated the effects of testosterone replacement therapy (TRT) on bone mineral density (BMD) among hypogonadal men with osteopenia/osteoporosis.

Methods: From our previous EARTH study population, 74 patients with a clinical diagnosis of osteopenia or osteoporosis and hypogonadism were included in this study, as the TRT (n?=?35) and control (n?=?34) groups. The TRT group was administered 250?mg of testosterone enanthate injection every 4 weeks for 12 months. The BMD, waist circumference, body mass index, body fat percentage, and muscle volume were measured at baseline and at 12 months. Blood biochemical data, including total cholesterol, triglycerides, HDL-cholesterol, hemoglobin A1c, and adiponectin values were also evaluated.

Results: At the 12-month visit, BMD significantly increased in both groups. However, comparisons on changes of parameter values from baseline to the 12-month visit between the TRT and control groups were significantly different in BMD (5.0?±?5.0 vs. 3.0?±?3.2; p?=?.0434) and in adiponectin value (?0.90?±?3.33 vs. 0.10?±?2.04; p?=?.0192). There were no significant changes in other parameters.

Conclusions: TRT for 12 months could improve BMD with a decrease in adiponectin levels among hypogonadal men with osteopenia/osteoporosis.     

Effects of long-term testosterone replacement therapy,with a temporary intermission,on glycemic control of nine hypogonadal men with type 1 diabetes mellitus – a series of case reports

Abstract

Type 2 diabetes mellitus (T2DM) is often associated with obesity and subnormal serum testosterone (T) levels. Until 5 years ago there was no indication that men with type 1 diabetes mellitus (T1DM) had subnormal serum T. But recent studies indicate that about 10% of men with T1DM suffer from hypogonadism, as a rule aged men and men with obesity. While hypogonadal men with T2DM benefit from normalization of their serum T, this has not been investigated in men with T1DM. Nine men with T1DM, erectile dysfunction and hypogonadism (total testosterone?≤?12?nmol/L) received testosterone replacement therapy (TRT). In seven men TRT was intermitted: one man with prostate malignancy and six men because of problems of reimbursement. Incidentally, this provided an opportunity to monitor the effects of withdrawal and of the reinstatement of TRT. In all men, glycemic control (serum glucose and HbA_1c), weight, waist circumference, lipid profiles and erectile function improved upon TRT. The seven men whose TRT was intermitted showed a deterioration which improved again upon reinstatement of TRT. The data suggest that aging and obese men with T1DM might have subnormal T levels and that their glycemic control, lipid profiles and erectile function might benefit from TRT.     

The role of parental emotional validation and invalidation on children’s clinical symptoms: A study with children exposed to intimate partner violence

Abstract

Parental emotional validation has been proposed of as a major explanatory mechanism of the association between intimate partner violence (IPV) and children’s psychological problems. The present study examined the effect of parental emotional validation and invalidation on the relationship between exposure to IPV, and both post-traumatic stress disorder (PTSD) and depression symptoms. Sample was composed of Portuguese children exposed to IPV and an age- and gender-matched control group. Structural equation modeling was conducted. Children who were exposed to IPV presented higher scores on PTSD (p?<?.001, d?=?.99) and depression symptoms (p?<?.01, d?=?.63), and paternal (p?<?.05, d?=?.67) and maternal (p?<?.01, d?=?.81) emotional invalidation. Children who were exposed to IPV presented lower scores on paternal emotional validation (p?<?.001, d?=?1.23). Exposure to IPV directly predicts both PTSD and depression symptoms but the indirect effect was stronger. Paternal emotional validation moderated the impact of exposure to IPV on clinical symptoms; the relationship between exposure to IPV and both PTSD and depression symptoms was mediated by maternal emotional invalidation. Findings suggest the potential usefulness of parental emotional validation and invalidation as treatment goals in clinical intervention with this population. Interventions to improve the therapist-patient alliance recommend that therapists use emotional validation. Training of emotional validation skills in parenting training may prevent the deleterious effects of exposure to IPV.     

The effect of testosterone treatment on prostate histology and apoptosis in men with late-onset hypogonadism

Objectives: To investigate the effect of testosterone replacement therapy (TRT) on prostate histology and apoptosis in men with late-onset hypogonadism (LOH).

Methods: The study included 25 men, having LOH with prostate-specific antigen (PSA) level of 4?ng/ml or less. All patients underwent transrectal ultrasound guided prostate biopsy at baseline, and received testosterone undecanoate treatment for 1 year. Prostate biopsy was repeated at the end of 1 year of testosterone therapy. In addition to clinical and biochemical parameters, prostate histology and apoptotic index (AI) were compared before and after the TRT.

Results: The mean serum total testosterone significantly increased from 178.04?±?51.92 to 496.28?±?103.73?ng/dl (p?=?0.001). No significant differences were observed in serum total and free PSA level, prostate volume and maximal urinary flow rate. There were also no significant differences in AI, stroma/epithelial cells ratio, Ki-67 positive cells and atrophy score of prostate tissue before and after the TRT.

Conclusions: This study demonstrated that TRT did not affect serum PSA level, prostate volume and maximal urinary flow rate. This study also suggests that TRT does not cause the risk for prostate cancer development, because of no significant differences in prostate histology after TRT.     

Association between serum levels of testosterone and biomarkers of subclinical atherosclerosis

Objective: To investigate the association between serum levels of testosterone and biomarkers of subclinical atherosclerosis based on data from 119 middle-aged men of the general population.

Methods: Testosterone, Apolipoprotein A-1 (ApoA-1), Apolipoprotein B (ApoB), Apolipoprotein B-to-Apolipoprotein A-1 ratio (ApoB-to-ApoA-1), high-sensitive C-reactive protein (hsCRP), and fibrinogen levels were measured. Data were also gathered based on age, BMI, waist circumference, smoking, alcohol consumption, and family history of cardiovascular diseases. Men were classified into two groups based on testosterone levels: hypogonadal (testosterone ≤12?nmol/L) and eugonadal men (testosterone >12?nmol/L).

Results: When compared to eugonadal, the hypogonadal men were significantly older (56?years vs. 55?years, p?=?.03), had greater BMI (28?kg/cm² vs. 26?kg/cm², p?=?.01), and higher waist circumference (104?cm vs. 100?cm, p?=?.01). Moreover, ApoB, ApoB-to-ApoA-1 ratio, and hsCRP were significantly higher in hypogonadal men compared to eugonadal men (1.1?g/L vs. 1.0?g/L, p?=?.03), (0.8 vs. 0.7, p?=?.03), (3.3?mg/L vs. 2.0?mg/L, p?=?.01), respectively. On the other hand, ApoA-1 and fibrinogen levels did not differ significantly between groups (p?>?.05). In an adjusted multivariate regression analysis model, only ApoB showed a significant negative association with testosterone levels (β?=??0.01; 95% CI?=??0.02, ?1.50; p?=?.04).

Conclusion: Testosterone levels showed an inverse relation to ApoB, a biomarker implicated in subclinical atherosclerosis. These findings support the hypothesis that low testosterone levels play a role in atherosclerosis.     

Effects of testosterone replacement therapy on nocturia and quality of life in men with hypogonadism: a subanalysis of a previous prospective randomized controlled study in Japan

Abstract

Objective: We investigated the effects of testosterone replacement therapy (TRT) on nocturia and general health among men with hypogonadism and nocturia.

Methods: From our previous EARTH study population, 64 patients with a clinical diagnosis of nocturia (two or more times per one night) and hypogonadism, comprising the TRT group (n?=?31) and controls (n?=?33), were included in this analysis. The TRT group was administered 250?mg of testosterone enanthate as an intramuscular injection every 4 weeks for 6 months. All patients responded to the following questionnaires: International Prostatic Symptoms Score (IPSS), Aging Male Symptoms (AMS) score and Short Form-36 health survey at baseline and 6-month visit. These categories were compared based on changes from baseline to the 6-month visit between TRT and control groups.

Results: At the 6-month visit, the TRT group had a significant decrease in IPSS question no. 7 and AMS question no. 4, whereas no significant changes were observed in the control group. Additionally, role limitation because of health program, vitality and mental health domains were significantly improved in the TRT group.

Conclusions: Six-month TRT may improve nocturia, sleep conditions and quality of life among men with hypogonadism and nocturia.     

Interleukin-18 and testosterone levels in men with metabolic syndrome

Objective: Interleukin 18 (IL-18) is an adipokine associated with obesity. Data about the relationship of IL-18 to the metabolic syndrome (MS) are still scarce. Low testosterone (T) levels are common in men with MS, but we did not find data about the levels of IL-18 in men with low T. The aim of this study was to determine the levels of IL-18 in men with MS with or without low T.

Patients and methods: A total of 251 men were included in the study. Of them 218 had MS (IDF 2005) and they were divided according to their morning total testosterone (TT) level (cutoff 10.4?nmol/l) into two groups: MS-low T (N?=?84) and MS-normal T (N?=?134). The control group consisted of 33 men without MS and low T. IL-18 was determined in serum using enzyme-linked immunosorbent assay. A small group of eight men with MS and low T levels received testosterone therapy for three months and physical and laboratory parameters were monitored at the end of that period.

Results: MS men were at mean age (±SD)?=?53.77?±?9.59 years; body mass index (BMI)?=?34.0?±?6.3?kg/m²; and TT?=?12.59?±?5.66?nmol/l. The control group was at age?=?52.12?±?5.2 years (NS); BMI?=?25.6?±?2.4?kg/m² (p?p?p?p?p?p?Conclusions: In this study, higher IL-18 levels were found in the presence of MS compared to healthy men, but they did not differ between men having MS with or without LOH.     

Association between testosterone levels and the metabolic syndrome in adult men

Abstract

Objective: To evaluate the relationship between testosterone levels and the metabolic syndrome (MS) in men older than 45 years.

Methods: Six hundred and sixty men (45–70 years) selected from 2906 participants of a population screening for prostate cancer were included in this study. Testosterone and the components of MS were assessed in all men. MS was diagnosed according to NCEP-ATP III criteria. Triglycerides (TG)/HDL-cholesterol (chol) index was calculated.

Results: The presence of MS was inversely associated with testosterone (χ², p?<?0.001), independently of age (OR 0.802, CI 95%: 0.724–0.887, p?<?0.0001). Hypertension was the most frequent abnormality observed followed by elevated TG and waist circumference (WC). Testosterone correlated positively with HDL-chol (r: 0.14, p?<?0.0001) and negatively with body mass index (BMI)(r: ?0.29, p?<?0.0001), WC (r: ?0.26, p?<?0.0001), TG (r: ?0.20, p?<?0.0001), TG/HDL-chol (r: ?0.20, p?<?0.0001), glucose (r: ?0.11, p?=?0.005) and MS score (r: ?0.23, p?<?0.0001).

Conclusions: Our results show that in men older than 45 years, as long as testosterone levels decline, the prevalence of MS increases, independently of age. The correlations found between testosterone and four of the five components of MS, as well as with BMI and TG/HDL-chol ratio, a surrogate marker of insulin resistance, suggest considering male hypogonadism as a determinant of developmental abnormalities typical of MS.     

Association between dietary phytoestrogens intakes and prostate cancer risk in Sicily

Objective: In this study we aimed to investigate the association between dietary phytoestrogen consumption and prostate cancer in a sample of southern Italian individuals.

Methods: A population-based case-control study on the association between prostate cancer and dietary factors was conducted from January 2015 to December 2016 in a single institution of the municipality of Catania, southern Italy (Registration number: 41/2015). A total of 118 histopathological-verified prostate cancer (PCa) cases and a total of 222 controls were collected. Dietary data was collected by using two food frequency questionnaires.

Results: Patients with PCa consumed significantly higher levels of phytoestrogens. Multivariate logistic regression showed that lignans (Q[quartile]4 vs. Q1, OR [odds ratio]?=?4.72; p?p?p?p?p?p?p?Conclusion: We found of an inverse association between dietary isoflavone intake and PCa, while a positive association was found with lignans intake.     

Visceral adiposity index is associated with premature ejaculation inversely: a cross-sectional study

Objective: Visceral adiposity index (VAI) is a novel indicator for the assessment of visceral obesity. In this study, we aimed to evaluate the relationship between VAI and premature ejaculation (PE).

Materials and method: A total of 300 men were included in the study. Hundred and fifty men with PE and 150 men without PE (control). All men were evaluated for PE by premature ejaculation diagnostic tool (PEDT). VAI levels were calculated using body mass index (BMI), high density lipoprotein and triglyceride (TG) levels.

Results: Mean age of the study groups was 34.3?±?5.2 (30–60) years and the mean age of the controls were 35.9?±?5.3 (30–60) years. The men with PE had lower BMI, TG levels, waist circumference (WC) and higher high-density lipoprotein-cholesterol (HDL-C) levels. Mean VAI level was 4.13?±?0.7 in study group and 5.72?±?1.6 in control group, respectively. VAI levels were statistically higher in men without PE (p?Discussion: Our cross-sectional study demonstrated a negative correlation between VAI and PE. VAI is superior index for the evaluation and calculation the relationship between obesity and PE.     

Change in testosterone concentrations over time is a better predictor than the actual concentrations for symptoms of late onset hypogonadism

Abstract

Background. Symptoms of late-onset hypogonadism (LOH) and concentrations of testosterone (T) and bioavailable testosterone (BT) were studied in relation to the data from the same men 5 years earlier.

Methods.?In 2008, 282 men, aged 60–82 years, answered a questionnaire regarding demographic data, medical history, different symptoms of LOH and the 10 questions from the ‘Androgen Decline in Aging Males (ADAM)-questionnaire’. Blood samples were analysed for concentrations of T and calculations were made for BT.

Results.?A total of 87.2% of the questionnaires were returned and analysed, and 75.2% of the responders gave blood samples. The oldest third of the men were most affected by LOH symptoms (p?<?0.05). Both T and BT concentrations decreased during the 5 years (p?<?0.05) but only the symptom ‘less strong erections’ changed significantly (p?<?0.05). Men reporting one of the four specific symptoms from the ‘ADAM-questionnaire’ for the first time in 2008 had a higher loss of T and BT than men who had unchanged or fewer symptoms than that reported in 2003.

Conclusions.?The magnitude of the decrease in concentrations is a better predictor of LOH than are the actual concentrations of T and BT. A combination of symptoms predicts LOH better than any single symptom.     

Increased visceral adiposity index associated with sexual dysfunction in men

Objective: Visceral adipose index (VAI) is a novel parameter for the evaluation of visceral obesity. As we know that obesity is a risk factor for erectile dysfunction (ED). So, in this study, we compared the VAI levels between the men with ED and without ED.

Materials and method: A total of 177 men were included in the study. Ninety-five men with ED and 82 men without ED (control). All men were evaluated for ED by Index of Erectile Function-5 items (IIEF-5). VAI levels were calculated using body mass index, high density lipoprotein and tryglyceride levels.

Results: Mean age was 53.5 (38–69) in men who have ED and 53.1 (34–69) in control. The men with ED had higher body mass index (BMI), triglyceride (TG) levels, higher waist circumference (WC) and lower high-density lipoprotein-cholesterol (HDL-C) levels. Mean VAI level was 5.18?±?2.50 in study group and 3.47?±?1.76 in control goup, respectively. VAI levels were statistically higher in men with ED (p?Discussion: The simplicity of WC and BMI measurement and TG and HDL assessment, make VAI an easily applicable index for the evaluation of visceral fat dysfunction. VAI can be useful index for the evaluation and calculation of erectile dysfunction risk.     

Elevated high sensitivity C-reactive protein levels in aging men with low testosterone

Objective.?We examined baseline data from a lipid treatment study to assess the relationship between testosterone (T) and the cardiovascular inflammatory marker, high sensitivity C-reactive protein (hsCRP).

Methods.?The baseline T, hsCRP, lipid, glycemic, and anthropometric data were obtained from 467 men (mean age: 52 years). Inclusion criteria included low-density lipoprotein cholesterol ≥?3.4 to 4.9?mmol/l and triglycerides?≤?4.0?mmol/l. The baseline hsCRP levels were examined across the following T subgroups: <6.9?nmol/l (moderate to severe hypogonadism), 6.9 to <10.4?nmol/l (mild to moderate hypogonadism), 10.4 to <15?nmol/l (low-normal T), and?≥?15?nmol/l (normal T).

Results.?The median hsCRP levels were significantly (p?=?0.041) different across the four T subgroups; patients in the lower T subgroups had higher median hsCRP levels than patients in the higher T subgroups. The percentage of men with elevated hsCRP (>2?mg/l) was also significantly (p?=?0.038) different across the four T subgroups; 83% of men with T < 6.9?nmol/l had elevated hsCRP compared with 40% with T ≥ 15?nmol/l.

Conclusions.?This analysis demonstrated an inverse relationship between serum T and hsCRP in aging men. Urologists need to be aware that low T levels may not only adversely affect sexual function but also may worsen cardiovascular risk in aging, hypogonadal men.     

Electronic cigarette and combustible cigarette use following a campus-wide ban: Prevalence of use and harm perceptions

Abstract

The current study examined changes in prevalence of e-cigarette use and perceptions of the harmfulness of e-cigarette and combustible cigarettes following a campus-wide tobacco ban. Undergraduate students completed surveys of tobacco use and perceived product harmfulness. Four samples were collected: in 2013 prior to the ban (n?=?792) and in fall 2014 (n?=?310), 2015 (n?=?208), and 2016 (n?=?417). E-cigarette use increased in the years following the ban (p?=?.01) while combustible cigarette use decreased from 2013 to 2016 (p?=?.02). Men were more likely than women to use both products (ps?<?.05). Students’ perceptions of the harmfulness of combustible and electronic cigarettes remained stable in the years following the ban (p?>?.05). This study is the first to examine the impact of including e-cigarettes in tobacco free policies. Combustible cigarette use declined, but e-cigarette use increased in the years following the e-cigarette ban. Prospective research is needed to understand the long-term impacts of e-cigarette bans.     

Eating disorders and academic performance among college students

Abstract

Objective: There is a paucity of research exploring eating disorders (EDs) and academic performance (AP). This study aimed to understand the effect of ED treatment on AP, hypothesizing that students receiving treatment for EDs would have a higher GPA. Participants: The Spring 2010 – Spring 2011 National College Health Assessment data (N?=?231,586) was utilized. Methods: Ordinal logistic regressions, controlling for key confounders, analyzed the association between those diagnosed with anorexia or bulimia and GPA. Results: Students diagnosed with anorexia or bulimia and treated with medication and psychotherapy were respectively 1.49 (1.24, 1.80; p?<?.0001) or 1.35 (1.13, 1.61; p?=?.0009) times more likely to have a higher GPA (p?<?.0001) compared to students without EDs. Conclusion: Findings expand the literature on EDs and AP among college students. Additional research is needed to determine whether the combination of medication and psychotherapy is the most effective way to improve AP among students with EDs.     

Application of multivariate longitudinal models in SIRT6, FBS,and BMI analysis of the elderly

Abstract

Objective: SIRT6 is a main regulator of metabolism and lifespan and its importance has been implicated in the prevention against aging-related diseases. The objective of this study was to examine the application of multivariate longitudinal models in SIRT6, FBS, and BMI analysis in the elderly men after eight weeks concurrent training with supplementation of l-arginine (l-Arg).

Methods: Thirty two elderly men with mean age of 63.09?±?3.71 years were randomly divided into four equal-sized groups (each n?=?8); Exercise?+?supplement (ES) group; exercise?+?placebo (EP) group; supplement (S) group and control (C) group. The ES and EP groups performed the eight weeks of concurrent training, three sessions per week. Group ES and group S consumed 1000?mg of l-Arg per day at 8:00?pm. Measurements of biochemical variables were done by ELISA Reader method. For analytical purposes, we used the paired sample t-test and multivariate longitudinal modeling with generalized estimating equation (GEE) methodology. All analyses have been implemented in R-3.4.1. p Values less than .05 were considered statistically significant.

Results: With respect to significant association between sirt6, FBS, and BMI, this study showed that synergy effect of training and supplementation was greater than the sum of their individual effects on SIRT6 (β?=?0.79, p?<?.001), FBS (β?=??5.56, p?=?.022), and BMI (β?=??3.89; p?=?.041). Also exercise alone had a significantly larger effect than supplementation alone on responses.

Conclusions: It can be concluded that the joint usage of concurrent training and supplement of l-Arg for elderly men could improve the metabolism and body composition.     

Importance of Self-Forgiveness and Social Support in Potentially Reducing Loneliness in Men Who Have Sex with Men

Abstract

Higher levels of loneliness in men who have sex with men (MSM) are associated with negative outcomes such as depression, anxiety, and sexual impulsivity. By identifying what may reduce loneliness in MSM, counselors and public health professionals can alleviate the distress of their clients. A significant hierarchical multiple regression controlling for relationship status, F(9, 105)?=?16.36, p?<?0.001, R² = .62, indicated that higher levels of self-forgiveness (β?=??.19, p?=?.04) and perceived social support (β?=??.49, p?<?.001) predicted lower levels of loneliness in MSM. Implications and limitations are discussed.     

Androgen replacement therapy contributes to improving lower urinary tract symptoms in patients with hypogonadism and benign prostate hypertrophy: a randomised controlled study

Purpose.?We performed a randomised controlled study regarding the effects of androgen replacement therapy (ART) on lower urinary tract symptoms (LUTS) in hypogonadal men with benign prostate hypertrophy (BPH).

Methods.?Fifty-two patients with hypogonadism and BPH were randomly assigned to receive testosterone (ART group) as 250?mg of testosterone enanthate every 4 weeks or to the untreated control group. We compared International Prostate Symptom Score (IPSS), uroflowmetry data, post-voiding residual volume (PVR) and systemic muscle volume at baseline and 12 months after treatment.

Results.?Forty-six patients (ART group, n?=?23; control, n?=?23) were included in the analysis. At the 12-month visit, IPSS showed a significant decrease compared with baseline in the ART group (15.7?±?8.7 vs. 12.5?±?9.5; p?<?0.05). No significant changes were observed in the control group. The ART group also showed improvement in maximum flow rate and voided volume (p?<?0.05), whereas no significant improvements were observed in the controls. PVR showed no significant changes in either group. In addition, the ART group showed significant enhancement of mean muscle volume (p?<?0.05), whereas no significant changes were seen in the controls.

Conclusion.?ART improved LUTS in hypogonadal men with mild BPH.