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.     

Effects of oral testosterone undecanoate therapy on bone mineral density and body composition in 322 aging men with symptomatic testosterone deficiency: a 1-year,randomized, placebo-controlled,dose-ranging study

Abstract

Objective: We investigated the effects of oral testosterone undecanoate (TU) on bone mineral density (BMD), lean body mass (LBM) and body fat mass (BFM) in aging men with symptomatic testosterone deficiency (TD).

Methods: Three hundred twenty-two men ≥50 years with TD symptoms and calculated free testosterone <0.26?nmol/L participated in a multicenter, double-blind, placebo-controlled trial. Patients were randomized to placebo, oral TU 80?mg/d, oral TU 160?mg/d, or oral TU 240?mg/d, administered as divided doses with normal meals. BMD of the hip and lumbar spine were evaluated by dual energy X-ray absorptiometry (DEXA), and body composition (LBM and BFM) by whole body DEXA.

Results: Oral TU significantly increased BMD at Month 12 at the lumbar spine (240?mg/d), total hip (240?mg/d), and trochanter and intertrochanter (160 and 240?mg/d) compared with placebo. Oral TU significantly increased LBM at Months 6 and 12 for all oral TU groups compared with placebo. BFM significantly decreased at Month 6 (all oral TU groups) and Month 12 (160?mg/d) compared with placebo. The effects on BMD and body composition showed a clear dose response.

Conclusions: Treatment with oral TU led to improvement in BMD, LBM and BFM in aging men with symptomatic TD.     

Effects of testosterone treatment on body composition in males with testosterone deficiency syndrome

Abstract

Objective: We evaluated the safety of testosterone treatment and its efficacy on body composition in males with testosterone deficiency syndrome (TDS) over 24 months.

Methods: 50 males aged 50–65 years with TDS (Aging Males Symptoms Scale [AMS]?>?26 and calculated free testosterone [cFT] 250?pmol/l) were administered 50?mg testosterone gel daily for one year. During the second year, patients received 1000?mg of testosterone undecanoate every 2–3 months. Outcome measures were clinical chemistry values and total testosterone; sex hormone-binding globulin and cFT, changes in AMS and International Prostate Symptom Score; and changes in body composition measured by dual-energy-x-ray absorptiometry.

Results: There were no clinically significant changes in clinical chemistry safety parameters. There were significant improvements in both total and cFT and in AMS scores after three months (p?<?0.001). Lean mass increased 2.35% at 12 months and 4.5% at 24 months, but proportionally more muscle mass was gained in arms and legs than in the trunk. Fat mass decreased 4.2% at 12 months and 9.1% at 24 months.

Conclusions: Testosterone treatment in males with TDS leads to body changes affecting lean and fat mass with significant improvement in AMS scores, and has an excellent safety profile.     

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.     

Soy protein based supplementation supports metabolic effects of resistance training in previously untrained middle aged males

Abstract

Objective.?To determine changes in body composition, physical performance, metabolic and hormonal parameters induced by lifestyle counselling, resistance training and resistance training with soy protein based supplemention in middle aged males.

Design.?Randomised controlled study consisting of resistance training without (RT-G) or with (RTS-G) a soy protein based supplement and a control group with lifestyle education only (LE-G).

Subjects.?Forty healthy middle aged men (50–65 years, BMI 25–29.9 kg/m²).

Measurements.?Changes in body weight (BW) and waist circumference (WC) were measured and body composition (BC), fat mass (FM), lean body mass (LBM) were measured by skin fold anthropometry at baseline and after 12 weeks of intervention. In addition, changes in physical fitness, metabolic and hormonal parameters (lipids, glucose, fructosamines, insulin, insulin-like growth factor-1, Leptin, human growth hormone, dehydroepiandrosterone, testosterone, hs-CRP, Il-6) were evaluated.

Results.?Thirty-five participants completed the 12 week study. No significant changes in BW were noted although RM and WC dropped and LBM increased after training, particularly in the RTS group (FM 22.6?±?5.5?kg to 21.2?±?4.7?kg; LBM 68.5?±?7.2?kg to 70.1?±?7.4; p?<?0.01). Subjects in the RTS group experienced more pronounced improvements in the strength measurements than the RT group. After the training intervention there were significant changes in hormonal and metabolic parameters as well as in glycemic control, particularly in the RTS group.

Conclusions.?Our data suggest that resistance training, particularly in combination with a soy protein based supplement improves body composition and metabolic function in middle aged untrained and moderately overweight males.     

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.     

The relationship between serum total testosterone and free testosterone levels with serum hemoglobin and hematocrit levels: a study in 1221 men

Objective: To investigate the relationship between serum total testosterone (TT) and free testosterone (FT) levels in men with anemia.

Methods: We reviewed the records of 1221 subjects between March 2009 and December 2014. All the subjects’ blood samples were drawn for TT and FT assays. Their serum hemoglobin (Hb) and serum hematocrit (Hct) levels were measured. The primary objective of our study was to investigate the association between TT and FT levels with Hb and Hct levels.

Results: The mean age was 59.82?±?12.71 years. The mean TT and FT levels were 4.54?±?2.02?ng/mL and 10.63?±?3.69?pg/mL, respectively. The mean Hb and Hct levels were 14.72?±?1.34?g/dL and 43.11?±?3.75%, respectively. Subjects with low TT (<2.35?ng/mL) had low Hb and Hct levels (p?p?Conclusions: Subjects with low TT and FT levels had low Hb and Hct levels. This suggests that TT and FT play a significant role in erythropoiesis. Testosterone replacement therapy may be effective in men with hypogonadism to reduce the incidence of anemia.     

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.     

The efficacy and safety of short-acting testosterone ointment (Glowmin) for late-onset hypogonadism in accordance with testosterone circadian rhythm

Introduction: It is well known that there is a reduction of circadian rhythm in blood testosterone levels with aging. Our previous report revealed that 3?mg of short-acting testosterone ointment (Glowmin: GL) elevated serum testosterone levels to within the physiological range for 4–6?h. The aim of this study was to clarify the clinical efficacy and safety of GL used topically once every morning, to enhance the circadian rhythm of testosterone, for late-onset hypogonadism (LOH).

Methods: A total of 61 LOH patients received 3?mg of GL topically once a day in the morning on scrotal skin for 24 weeks. The clinical efficacy of GL was evaluated by the aging males symptoms (AMS) scale, and blood sampling tests were measured before and after GL treatment.

Results: Mean patients age was 55.3?±?9.2 years old. Total AMS scores at 4, 12, and 24 weeks after GL treatments significantly decreased. The results of sub-analysis of AMS, including psychological, physical, and sexual factors also significantly improved after GL treatments. No severe adverse reactions or abnormal laboratory data were reported.

Conclusions: This study shows that TRT for LOH with once daily GL treatment supports testosterone circadian rhythm and should be considered to be an effective and safe therapy for LOH.     

The impact of metabolic syndrome on serum total testosterone level in patients with erectile dysfunction

Abstract

Objectives: To determine the association between metabolic syndrome (MetS) and serum testosterone levels (TT) in patients with erectile dysfunction (ED).

Methods: This study included 280 ED patients above 40-years-of-age. Participants were divided into two groups according to 2005 criteria of International Diabetes Federation. The severity of ED was determined according to the International Index of Erectile Function-EF (IIEF-EF score; 0–10 severe ED, 11–25 mild to moderate ED). The severity of ED, serum TT levels and other MetS components were compared between the groups.

Results: The mean age of the patients was 55.7?±?8.2 years. One hundred eighteen patients (%42.1) had MetS. Sixty-eight patients with MetS (57.6%) and 71 patients without MetS (43.8%) had severe ED (p?=?0.031). A total of 46 (16.4%) patients had hypogonadism. Hypogonadism was seen more prevalent in patients with MetS (22.9% vs. 11.7%, p?=?0.013). Logistic regression analyses for ED risk factors demonstrated that abnormal FBG increased the relative risk of severe ED up to 10.7-fold (p?<?0.001) but not presence of hypogonadism (p?=?0.706).

Conclusion: Metabolic syndrome was seen in almost half of the patients with ED. ED was more severe among MetS patients. Hypogonadism alone is a not risk factor for severe ED.     

The effects of orchidectomy and supraphysiological testosterone administration on trabecular bone structure and gene expression in rats

Abstract

Objective: This study aimed to determine the effects of orchidectomy and supraphysiological testosterone replacement on trabecular structure and gene expression in the bone.

Methods: Twenty-four 3-month old male rats were randomized into sham (SH), orchidectomized (ORX) and testosterone-treated (TE) groups. Orchidectomy was performed on the ORX and TE group. Weekly testosterone enanthate intramuscular injection at 7?mg/kg body weight was administered to the TE group for 8 weeks while the other groups received peanut oil as vehicle. Blood was collected before and after treatment for serum testosterone analysis. The femora and tibiae were harvested after the treatment period for trabecular structure and gene expression analysis.

Results: The trabecular bone volume decreased significantly and the porosity increased significantly in the ORX group compared to the SH group (p?<?0.05). Testosterone treatment prevented all these changes (p?<?0.05). The expression of osteogenic genes decreased significantly in the ORX group compared to the SH group (p?<?0.05). Testosterone treatment decreased the expressions of RANKL and OPG genes significantly (p?<?0.05).

Conclusion: Orchidectomy-induced degeneration in trabecular structure is caused by a decrease in the expressions of osteogenic genes. Supraphysiological testosterone replacement is able to prevent these degenerative changes in the bone despite the modest changes in gene expression.     

Evaluation of sex hormone levels and some metabolic factors in men with coronary atherosclerosis

Background Because of the great controversy over the role of androgens in the pathogenesis of atherosclerosis, we investigated the relationship between serum sex hormone levels and angiographically confirmed coronary artery disease in men.

Material and methods We investigated 86 men aged 40–60 years, 56 with coronary artery disease and 30 healthy men, matched by age, as a control group. Body mass index and waist to hip ratio were calculated and total body fat mass and percentage of abdominal deposit were investigated by dual-energy X-ray absorptiometry (Dpx (?+?) Lunar, USA). The serum levels of sex hormones and insulin were measured using commercial radioimmunoassay and IRMA (by SHBG) kits (DPC, USA). The serum levels of lipids and glucose were assessed by means of enzymatic methods.

Results Men with coronary artery disease had lower total testosterone levels (17.01?±?6.42 vs. 19.37?±?6.58?nmol/l; p?<?0.05), testosterone/estradiol ratio (228.5?±?88.5 vs. 289.8?±?120.1; p?<?0.05) and free androgen index (FAI) (59.49?±?14.79 vs. 83.03?±?25.81; p?<?0.0001), and higher levels of estrone (49.5?±?27.7 vs. 36.6?±?12.7?pg/ml) than men in the control group. Moreover, men with coronary artery disease were more insulin-resistant than controls and had an atherogenic lipid profile. There was an inverse correlation (p?<?0.05) between testosterone level and serum level of glucose (r?=??0.29), triglycerides (r?=??0.37), body mass index (r?=??0.55), waist (r?=??0.43), total body fat mass (r?=??0.3) and fasting insulin resistance index. A significant positive association (p?<?0.05) was found between testosterone and the quantitative insulin sensitivity check index and high density lipoprotein cholesterol level in serum (r?=?0.26).

Conclusions Low levels of total testosterone, testosterone/estradiol ratio and free androgen index and higher levels of estrone in men with coronary artery disease appear together with many features of metabolic syndrome and may be involved in the pathogenesis of coronary atherosclerosis.     

Effect of testosterone therapy on lumbar spine and hip mineral density in elderly men

Objective.?The aim of the present study was to analyse the effect of testosterone therapy on bone mineral density in healthy elderly men who had low levels of total testosterone.

Design.?Randomized, double-blind, placebo-controlled study.

Participants.?Forty-eight men over 60 years old with decreased testosterone levels (≤320 ng/dL) comprised the study. Twenty-five out of 48 received intramuscular injections of testosterone enanthate every three weeks during 12 months; the remaining 23 participants formed the control group. All participants had measurements of bone mineral density (BMD) in both lumbar spine and hip before and at the end of the study as well as testosterone and 17-β estradiol levels.

Results:?Testosterone treated group exhibited a significant (p < 0.05) increment (from 1.198 ± 0.153 to 1.240 ± 0.141 g/cm²) in lumbar BMD in parallel with a significant (p < 0.001) increment (from 301 ± 32 to 471 ± 107 ng/dL) in testosterone concentrations, whereas no significant change occurred in femoral neck BMD.

Conclusions.?Testosterone therapy elicited a positive effect only in lumbar BMD in elderly men with diminished testosterone serum levels.     

Prevalence of low testosterone in aging men with benign prostatic hyperplasia: data from the Proscar Long-term Efficacy and Safety Study (PLESS)

Abstract

Objectives: We examined the prevalence of low testosterone (LT) in the subset of men in the Proscar Long-term Efficacy and Safety Study (PLESS) who had serum total testosterone (TT) measured at baseline.

Methods: PLESS enrolled 3040 men with benign prostatic hyperplasia (BPH). Of these men, 299 had TT and body mass index (BMI) measurements at baseline. Patients were classified as having LT if their baseline TT was <300?ng/dl.

Results: Of the 299 PLESS patients with baseline TT and BMI measurements, 65 (21.7%) had LT. The prevalence of LT increased with increasing BMI, occurring in 8/78 (10.3%) normal weight patients (baseline BMI <25?kg/m²), 35/160 (21.9%) overweight patients (baseline BMI ≥25–<30?kg/m²), and 22/61 (36.1%) obese patients (baseline BMI ≥30?kg/m²).

Conclusions: LT was observed in more than one in five PLESS patients with baseline TT and BMI measurements. The prevalence of LT increased with increasing BMI – more than one in three obese PLESS patients with baseline TT measurements had LT.     

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.     

Endogenous hydrogen sulfide insufficiency as a predictor of sexual dysfunction in aging rats

Objective: Our earlier studies showed that endogenous hydrogen sulfide (H₂S) pathway contributed significantly to erectile function. In this study, we tested the hypothesis that age-dependent changes in the bioavailability of H₂S increased the risk of erectile dysfunction (ED). Methods: Young, adult (3-month) and older (18-month) male Sprague-Dawley rats (n?=?6?8/group) were treated daily with sodium hydrosulfide hydrate (NaHS), DL-propargylglycine, sildenafil or l-NAME for 10 weeks. Subsequent to cavernous nerve electrical stimulation, intracavernosal pressure (ICP) responses were determined, and the samples were collected and processed for hormonal (plasma) and gaseous parameters (plasma and erectile corpus cavernosum [CC]) using standard assay protocols. Results: Aging significantly reduced the ICP response (35.9?±?2.0 mmHg vs. 45.2?±?1.9 mmHg in young controls), which was countered by NaHS (53.5?±?6.0) or sildenafil (52.8?±?9.8) treatment. In these rats, marked increments to testosterone (T) or estradiol resulted from NaHS supplementation. Similar to age-dependent decline in NO, the plasma and CC level of H₂S was significantly lower in senescent rats when compared with young animals (p?<?0.05). Conclusion: Our results confirm that ED with aging may be linked to a derangement in the H₂S pathway accompanied by low T levels. It is likely that a pharmacologic intervention delivering H₂S will provide additional benefits to sexual function from an improved T milieu.     

Prevalence of low testosterone and its relationship to body mass index in older men with lower urinary tract symptoms associated with benign prostatic hyperplasia

Abstract

Purpose: We examined the prevalence of low testosterone (LT) and its relationship with body mass index (BMI) in men with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH), who were enrolled in a clinical trial of drug therapy, the Medical Therapy of Prostatic Symptoms (MTOPS) Study.

Materials and methods: MTOPS enrolled 3047 men, and of these, 1896 had total testosterone (TT) measured at baseline. LT was defined as a single measurement of TT of <300?ng/dL.

Results: The overall prevalence of LT was 25.7%. Prevalence increased with increasing BMI; 14.7% among men who were normal weight (BMI <25?kg/m²) and 24.2% and 39.3% among overweight (BMI 25 to <30?kg/m²), and obese (baseline BMI ≥30?kg/m²) men, respectively.

Conclusions: LT was observed in about one in four MTOPS study participants with baseline TT measurements. The prevalence of LT increased markedly with increasing BMI. Our findings suggest a high prevalence of LT in obese men with LUTS/BPH. Physicians should be alert to the possibility of symptoms of hypogonadism in this population.