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.     

Testosterone deficiency and the metabolic syndrome

Evidence is presented to link components of the metabolic syndrome to testosterone deficiency and obesity. Testosterone deficiency in hypogonadism or testosterone deprivation in normo-gonadotropic men increases fat mass as well as fasting insulin levels. Testosterone supplementation (TS) in a dose dependent manner, increase lean body mass (LBM), reduces fat mass, body mass index (BMI) and waist hip ratio in both young and elderly hypogonadal men. A negative association between T and insulin resistance as well as impaired glucose intolerance has been demonstrated and in type 2 diabetic men TS improves metabolic parameters. TS improves most components of the metabolic syndrome and also reduces inflammatory cytokines.     

Total testosterone levels are correlated to metabolic syndrome components

Introduction: Metabolic syndrome (MetS) is a constellation of interrelated risk factors of metabolic origin. Some studies suggest a possible link between low total testosterone (TT) levels and the presence of MetS.

Aim: To analyze the strength and independence of associations between TT and MetS components in non-diabetic men.

Methods: In this cross-sectional study, 143 non-diabetic men older than 40 were analyzed.

Main outcomes measure: Blood samples were collected to evaluate metabolic profile and TT levels. MetS was defined as the presence of three or more of the following characteristics: fasting blood glucose levels?≥?100?mg/dL, triglyceride?≥?150?mg/dL, HDL-c??102?cm.

Results: Mean age of the study population was 61.5?±?8.61 years old. MetS was present in 47.9% of the individuals. Thirty-four men had low TT and MetS was observed in 23 (70%) against 50 (46%) in those with normal TT (≥?300?ng/dL) (OR 4.94, p?p?=?0.03) and HDL-c (Beta: 0.19; p?=?0.04) remained significantly correlated with TT levels.

Conclusions: Low TT levels were associated with MetS diagnosis. Abdominal obesity was the MetS component independently correlated to low TT levels.     

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.     

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.     

Endogenous testosterone and brachial artery endothelial function in middle-aged men with symptoms of late-onset hypogonadism

In aging men, serum endogenous testosterone is inversely associated with common carotid intima-media thickness (IMT) and directly with beneficial plasma lipid levels; however, the relationship to endothelial function is poorly characterized. We examined the association between serum testosterone and endothelium-dependent brachial artery flow-mediated dilatation (FMD) in middle-aged to elderly men. A group of 83 men aged 40–69 years (mean 55.9?±?7.5 [SD]) with andropausal symptoms were studied. We measured their serum lipids, testosterone, luteinizing hormone, mean carotid IMT and brachial artery FMD by high resolution B-mode ultrasound. Brachial FMD correlated inversely with vessel diameter (r?=??0.38, p?=?0.0004), alcohol consumption (r?=??0.22, p?=?0.047) and serum testosterone (r?=??0.27, p?=?0.01), but not with luteinizing hormone. In multivariate analysis, FMD was explained by testosterone (β?=??0.17, p?=?0.0226), high density lipoprotein cholesterol (β?=?4.17, p?=?0.0312) and vessel diameter (β?=??4.37, p?<?0.0001) when adjusted for age, body mass index, triglycerides, blood pressure, carotid IMT, smoking, alcohol consumption, cardiovascular diseases and use of lipid lowering medication (HMG-CoA reductase inhibitors). In middle-aged to elderly men, there is an inverse correlation between serum testosterone and brachial FMD. These data suggest that testosterone may have an adverse effect on systemic endothelial function.     

Increased prevalence of premature ejaculation in men with metabolic syndrome

This prospective study aimed to investigate the relationship between metabolic syndrome (Met S) and premature ejaculation (PE) among men. The study included 300 consecutive male patients (53.6 y?±?8.7) who attended the urology clinic (December 2013–September 2014), mostly complaining of renal/ureteric calculi. A diagnostic approach was undertaken to include demographics, clinical features and laboratory investigations of the study subjects. Both erectile function and PE were evaluated using the International Index of Erectile Function (abridged form, IIEF-5) and Premature Ejaculation Diagnostic Tool (PEDT) questionnaires, respectively. Results identified 182 (60.7%) men had Met S. Prevalence of PE was significantly higher in the subjects with Met S than the controls (35.2% vs 7.6%, p?< 0.001). Patients with Met S and PE had significantly higher PEDT scores (15.4 vs 6.7), smaller waist circumference (108.3?cm vs 111.5?cm) and higher fasting blood sugar (187?mg% vs 161?mg%) than those with no PE (p?p?=?0.047 and <0.001, respectively) with PE in Met S. In conclusion, PE has a high prevalence in Met S. Patients with Met S should be questioned about PE. Both ED and systolic hypertension may be associated with PE. Prevention of Met S should be considered, and this may be of help to decrease the prevalence of PE.     

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.     

A randomized,double-blind,placebo-controlled trial of testosterone gel on body composition and health-related quality-of-life in men with hypogonadal to low-normal levels of serum testosterone and symptoms of androgen deficiency over 6 months with 12 months open-label follow-up

Introduction: The clinical significance of low to low-normal testosterone (T) levels in men remains debated. Aim: To analyze the effects of raising serum T on lean body mass (LBM), fat mass (FM), total body mass, and health-related quality-of-life (HRQoL). Methods: Randomized, double-blind, placebo-controlled study. Men, aged 50–80 years, with serum total T<15 nmol/L and bioavailable T < 6.68 nmol/L, and a Aging Males’ Symptoms (AMS) total score >36, received 6 months treatment with transdermal 1% T gel (5–7.5?mg/day; n =183) or placebo gel (n =179), followed by 12 months open-label with T in all. Results: After 6 months, LBM increased in T- treated patients by 1.28?±?0.15?kg (mean ± SE) and FM decreased by 1.16?±?0.16?kg, with minor changes with placebo (LBM +0.02?±?0.10?kg and FM ?0.14?±?0.12?kg; all p < 0.001, T group vs. placebo). Changes were largely similar across subgroups of age, baseline total testosterone, and baseline BMI. Total HRQoL improved compared with placebo (p < 0.05, T group vs. placebo). Conclusions: Six months 1% T gel improved body composition and HRQoL in symptomatic men with low to low-normal T, with further improvements over the following 12 months.     

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.     

Age-related testosterone decline is due to waning of both testicular and hypothalamic-pituitary function

Abstract

Hypogonadism is a condition in which the endogenous secretion of testosterone is either insufficient or inadequate to maintain serum testosterone levels within normal range, and may manifest as a variety of signs and symptoms. Age-related hypogonadism is due to a combination of primary hypogonadism (testicular failure) and secondary hypogonadism (hypothalamic-pituitary axis failure). This review provides insight into the mechanisms resulting in the multifactorial nature of acquired androgen-deficiency, and outlines the current controversy regarding testosterone-replacement therapy in aging males.     

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.     

Impact of metabolic status on the association of serum vitamin D with hypogonadism and lower urinary tract symptoms/benign prostatic hyperplasia

Objective: The objective of this study is to investigate the impact of metabolic status on associations of serum vitamin D with hypogonadism and lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH).

Patients and methods: A total of 612 men underwent physical examination, biochemical/hormonal blood testing, and transrectal prostate ultrasound. Moreover, the subjects filled out standard questionnaires for identification and grading of LUTS and hypogonadism symptoms. Parameters were statistically compared with independent t-tests and correlation analyses.

Results: Vitamin D levels positively correlated with total testosterone (TT) but not with prostate volume or International Prostate Symptom Score (IPSS). Patients with metabolic syndrome had significantly lower vitamin D levels, which were not correlated with TT, prostate volume, or IPSS. However, vitamin D was positively correlated with TT, and negatively correlated with prostate volume and quality-of-life IPSS in subjects without metabolic syndrome.

Conclusion: The clinical usefulness of vitamin D for treatment of hypogonadism or LUTS/BPH varies according to metabolic status.     

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.     

Transversal European survey on testosterone deficiency diagnosis

Background: Despite being one of the relevant public health threats among ageing men, testosterone deficiency syndrome (TDS) is under-recognized and under-diagnosed. Objective: To assess current clinical practices of European physicians regarding diagnosis and management of TDS compared with current guidelines. Methods: Postal survey conducted June–November 2008 in France, Germany, Italy and Spain among urologists, endocrinologists and general practitioners to collect information regarding knowledge of TDS. Results: Among 801 respondents, the majority of endocrinologists and urologists had received training on TDS, either initially or as part of continuous medical education. TDS was recognized by 86.5% of physicians as a true clinical entity, and estimated the prevalence at 10–15% of the male population; 73.5% considered that symptoms and a low level of testosterone were required for diagnosis. Treatment preferences were quarterly intramuscular injections (26.3% of physicians), percutaneous gels (23.9%), matrix patch (21.2%), semi-monthly injections (15.4%) and oral therapy (13.4%). Adverse effects of testosterone replacement therapy, such as benign prostatic hyperplasia and prostate cancer, were a concern for physicians. Conclusions: TDS management appeared to be close to that recommended in international guidelines. Signs and symptoms of testosterone deficiency were fairly well known, but some diagnostic and treatment variations were observed.     

Sleep disturbance as a clinical sign for severe hypogonadism: efficacy of testosterone replacement therapy on sleep disturbance among hypogonadal men without obstructive sleep apnea

Objective: The present subanalysis of the EARTH study investigates the effects of one year testosterone replacement therapy (TRT) on sleep disturbance among hypogonadal men without obstructive sleep apnea.

Methods: Sleep disturbance was defined as three or more points in question 4 of the aging males symptoms (AMS) questionnaire. All participants completed the AMS scale, International Prostatic Symptoms Score (IPSS), Sexual Health Inventory for Men (SHIM) and Short Form 36 (SF-36) health survey at baseline and after 12?months. Sexual symptoms were also evaluated based on three AMS subscores (Q15, 16 and 17).

Results: We identified 100 patients with sleep disturbance, of whom 48 (24 each in the TRT and control groups) were ultimately included for analysis. All SF-36 categories , AMS scale, IPSS and SHIM score subdomains were significantly worse in patients with sleep disturbance than in those without disturbance. Statistically significant differences in sleep disturbance, erectile symptoms, sexual desire and some domains of the SF-36 were observed between the TRT and control groups after 12?months.

Conclusion: Sleep disturbance may be one of the clinical signs for severe hypogonadism. Moreover, TRT improved sleep conditions, sexual function and quality of life among hypogonadal men with sleep disturbance.     

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.