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.     

Prevalence,incidence and risk factors of testosterone deficiency in a population-based cohort of men: results from the study of health in Pomerania

Objective.?Low total testosterone levels (TT) have been associated with increased morbidity and mortality. However, the prevalence and incidence of testosterone deficiency (TD) in association with its risk has not been assessed systematically to date.

Methods.?Data from the prospective population-based Study of Health in Pomerania were used. From the 2117 men aged 20–79 years at baseline, 1490 men with complete TT data were analysed. Crude and age-specific prevalence and incidence rates of TD were estimated by TT levels below the age-specific 10th percentile. Analysis of covariance and Poisson regression models were used to assess the association of socio-demographic characteristics, health-related lifestyle, as well as somatometric, medical and laboratory measures with risk of incident TD.

Results.?TD baseline prevalence was 10.4% (N?=?155) and incidence 11.7 per 1000 person-years. TT levels showed a significant age-related decline with an unadjusted rate of 0.05 nmol/l per year. Obesity, metabolic syndrome, diabetes and dyslipidaemia were identified as risk factors of incident TD. Subpopulations of men without the revealed risk factors at both examinations maintained constant TT levels over time.

Conclusions.?Besides aging alone, lifestyle and different comorbidities were associated with TT level decline, suggesting that the age-related TT decline may be at least partly prevented through the management of potentially modifiable risk factors and health related behaviour.     

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.     

Low total testosterone is associated with increased risk of incident type 2 diabetes mellitus in men: results from the Study of Health in Pomerania (SHIP)

Objective.?There is increasing evidence suggesting that low total testosterone concentration is associated with incident type 2 diabetes mellitus (T2DM) in men. The aim of this study was to evaluate the association between total testosterone and incident T2DM in a large population-based cohort.

Methods.?Of 2117 men at baseline, 1589 were followed up 5 years later. Low total testosterone concentration at baseline determined by <10th percentile (10-year age-strata) were used as a risk factor for incident T2DM at follow-up. To evaluate for potential non-response bias, drop out weights were used in sensitivity analysis.

Results.?From 1339 men eligible for analyses, 68 (5.1%) developed T2DM. Men with low total testosterone concentration had an increased risk of developing T2DM (odds ratio [OR] 3.4, 95% CI 1.9–6.1), even after adjustment for age, waist circumference and smoking, OR 3.0; (95% CI 1.6–5.7). Recalculated weighted models revealed almost identical estimates indicating no relevant non-response bias.

Discussion.?Our prospective findings suggest that low total testosterone concentration is associated with incident T2DM in men and might represent a biomarker that might causally be involved in the risk of T2DM. This underlines the importance of measuring total testosterone in men as the predominant male sex hormone.     

RigiScan data under long-term testosterone therapy: improving long-term blood circulation of penile arteries,penile length and girth,erectile function,and nocturnal penile tumescence and duration

Background: Late-onset hypogonadism (LOH) presents with low serum testosterone (TT) levels and sexual and nonsexual symptoms. Erectile dysfunction affects a man’s self-esteem and as a result partner relationship and quality of life.

Objectives: To investigate the andrological clinical profile outcomes of testosterone therapy (TTh) in men (n?=?88) with symptomatic LOH complaints and symptoms.

Main outcome measures: Erectile function was assessed using the International Index of Erectile Function-5 questionnaire at baseline and at 6 and 12 months of TTh. In addition, penile length was measured at baseline and 12 months. We also evaluated nocturnal penile tumescence (NPT, using RigiScan) and blood flow of cavernous arteries (penile Doppler ultrasonography) at baseline and 12 months of TT.

Materials and methods: Eighty-eight LOH men (M_age 51.1 years) with erectile dysfunction, all with serum TT?<10.4?nmol/L before TTh. Patients received intramuscular long-acting testosterone undecanoate for 12 months.

Results: Following TTh, in all patients, serum TT levels were restored within 3 months to normal levels. Compared with baseline values, erectile function significantly improved at 6 (mean score increase 1.95) and 12 months (mean score increase 2.16). No significant changes in penile length were observed. NPT significantly improved at 12 months in terms of both the frequency (mean increase 1.27 times) and duration of rigidity (mean increase 5.12?min). As regards the blood flow of the cavernous arteries, we observed a significant improvement (decrease of 1.16?cm/s) and end diastolic velocity of the penile arteries.

Conclusion: TTh in men with LOH resulted in improvement of the erectile function, NPT, and to some extent the blood flow of the cavernous arteries.     

Mission Statement

Aim.?To investigate sex hormone and androgen receptor (AR) levels and to evaluate their relationship with diabetes mellitus (DM) in senile men.

Methods.?The cross-sectional study included 492 elderly men comprising 104 healthy subjects (mean age 71.4 ± 5.2 years), 259 subjects without DM (71.5 ± 5.0 years) and 129 DM patients (73.0 ± 6.3 years). Plasma concentrations of total testosterone (TT), free testosterone (FT), dehydroepiandrosterone sulphate, sex hormone-binding globulin (SHBG), estradiol (E₂), luteinising hormone) and follicle-stimulating hormone (FSH) were determined. AR-positive cells were measured by flow cytometry.

Results.?TT concentrations were significantly lower in the DM group (13.8 ± 4.7 nmol/l) than in the healthy (17.1 ± 6.1 nmol/l) and non-diabetes groups (15.8 ± 6.0 nmol/l; all P < 0.01). FT, SHBG, AR-positive proportion (AR%) and AR fluorescence intensity showed a decreasing trend among the healthy, non-DM and DM groups, but the differences were not significant. TT, E₂, E₂/testosterone and SHBG were negatively correlated with blood glucose. SHBG was positively correlated and TT and AR% were negatively correlated with the course of DM. Logistic multiple regression analysis revealed that age, waist/hip ratio, FSH, SHBG and AR% are potential risk factors for DM.

Conclusions.?Low levels of TT, SHBG and AR may be potential risk factors for DM in elderly men.     

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.     

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.     

Significant association between serum dihydrotestosterone level and prostate volume among Taiwanese men aged 40–79 years

Introduction.?We evaluated the association between serum sex hormone levels and prostate volume in Taiwanese men.

Methods.?A cross-sectional study was conducted in 505 men (aged 40–79 years, mean age 58 years). Serum total testosterone (TT), free testosterone (FT), dihydrotestosterone (DHT) and estradiol (E2) levels were measured. Total prostate volume (TPV) and transition zone volume (TZV) were measured by transrectal ultrasonography. Body mass index (BMI), DHT/TT and E2/TT were calculated. Correlations were determined using univariate and multivariate regression analyses.

Results.?Apart from DHT, an age-dependent change of sex hormone levels were observed. On univariate analyses, age, BMI, serum DHT level and DHT/TT ratio, as well as serum E2 level and E2/TT ratio, but not serum TT and FT levels showed a significant association with prostate volume. On multivariate analysis, however, only serum DHT level and DHT/TT ratio remained significant. Logistic regression analysis showed that the odds ratios (95% confidence interval) of the second, third, and fourth quartiles of serum DHT levels for benign prostatic hyperplasia (defined as TPV?≥20?ml) risk were 2.06 (1.21–3.51), 2.66(1.56–4.53) and 7.15(4.0–12.6), respectively (p?<?0.001).

Conclusions.?Higher serum DHT level and DHT/TT ratio were associated with larger prostate volume and higher prevalence of BPH in Taiwanese men.     

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.     

The influence of comorbidities on the aging males’ symptoms scale in patients with erectile dysfunction

Objectives: To investigate if certain common age-related comorbidities are related with a positive aging males’ symptoms (AMS) test outcome.

Methods: This was a multicentric, transversal, observational study carried out in a male population with erectile dysfunction. Comorbidities and testosterone levels were registered. The relationship between comorbidities, testosterone levels, and the AMS test outcomes was studied using the global score and the sub-scale score components.

Results: The study included 1112 patients. In the multivariate analysis the global score strongly correlated with TT?p?Conclusion: Although the AMS test is related to low levels of testosterone, it is also of some limited use for diagnosing hypogonadism because it has low specificity and is influenced by pathologies that are frequent during ageing.     

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.     

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.     

Functional testosterone: Biochemical assessment of hypogonadism in men – Report from a multidisciplinary workshop hosted by the Ontario Society of Clinical Chemists

Objectives. In 2004, the Ontario Society of Clinical Chemists (OSCC) held an invitational multidisciplinary workshop to establish the most reliable, cost-effective approach to the biochemical assessment of hypogonadism in men.

Methods. Specialists across Canada in clinical biochemistry, endocrinology, family medicine and urology were invited to participate in this workshop which included individual presentations and a consensus component addressing two challenge statements: 1) ‘Determinations for total testosterone (TT) are equivalent to those for bioavailable testosterone (BAT) or calculated BAT (cBAT) or free testosterone (FT) (by analogue radioimmunoassay or equilibrium dialysis) or calculated FT (cFT)’; 2) ‘There is no good evidence that borderline low testosterone concentrations in men should be treated’. The main outcomes were to identify what agreement exists in Canada, what issues were still controversial, and what research remains to be addressed.

Results. Six recommendations based on expert opinion addressed these main themes: investigate with morning total testosterone (TT) followed by repetition and reflexive testing of sex hormone binding globulin (SHBG) if testosterone is 8–15 nmol/L with automatic calculation of cBAT; discontinue the use of analogue free testosterone assays; and definitive methods and standards must be available to ensure standardized results.

Conclusions. Total testosterone is a reliable marker for the initial investigation of men presenting with symptoms of hypogonadism; cBAT is a reasonable follow-up test in patients with equivocal biochemical or consistent symptomatic findings.     

Validation of an Arabic ADAM questionnaire for androgen deficiency screening in the Arab community

Background.?It is well documented that testosterone levels decline with age, this decline is associated with symptoms which could be assessed denoting androgen deficiency. We investigated the validity of an Arabic version of the Saint Louis University androgen deficiency in ageing men (ADAM) questionnaire to screen for androgen deficiency in Saudi and non Saudi Arabic speaking men.

Methods.?It was a cross sectional study of ambulatory community-based Arabic Saudi men recruited from Volunteers in Riyadh city, Capital of Saudi Arabia, aged 18–80 years. Seven hundred thirty men agreed to fill the Arabic ADAM questionnaire, they were invited to a morning blood sample for total testosterone and sex hormone binding globulin and those who agreed to complete the whole study were only 407 men. Low serum bioavailable testosterone (BT) levels (androgen deficiency) were defined as <10th percentile of serum BT levels in young healthy Saudi men (18–30 years).

Results.?Cronbach's Alpha of 0.71 (n?=?730) showed a good internal consistency of the Arabic ADAM questionnaire. Among participants, 18.2% and 77.6% had low serum BT levels and a positive ADAM questionnaire, respectively. The prevalence of positive ADAM and low serum BT is increasing with age. The Arabic ADAM questionnaire had a high sensitivity of 86.5%, a low specificity of 24.3%, and positive predictive values (+PVs) and negative (?PVs) of 20.3% and 89%, respectively.

Conclusion.?The Arabic ADAM questionnaire has a very good sensitivity but very low specificity for screening of androgen deficiency in Saudi men, therefore biological confirmation is needed especially when clinical symptoms of androgen deficiency are present.     

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.     

Voyage into our common future: from futurophobia to futurophilia

Aims.?To investigate the association between endogenous testosterone levels and psychological health symptoms in men from a general population.

Methods.?Total testosterone and sex hormone-binding globulin levels were analysed and free testosterone levels was calculated in 3413 men participating in the fifth Tromsø study in 2001. Self-administered questionnaires including information about education, marital status, smoking habits and the Hopkins Symptom Checklist-10 (SCL-10, a 10-item psychological health questionnaire) were completed. The cross-sectional data were analysed with partial association and analysis of variance and covariance.

Results.?The complete SCL-10 was not associated with total or free testosterone, but symptoms of anxiety were negatively associated with both total and free testosterone (p?p?=?0.021), before and after adjusting for age, waist circumference, marital status, education and smoking. There was an even stronger association between men presumed to be testosterone deficient and symptoms of anxiety (p?Conclusions.?Men presumed being testosterone deficient had a higher symptom score, in particularly regarding anxiety, but they did not have pathological symptoms. Thus, lower testosterone levels was only associated with subthreshold symptoms of anxiety and depression.     

Use of thermobalancing therapy in ageing male with benign prostatic hyperplasia with a focus on etiology and pathophysiology

Introduction: We investigated if “thermobalancing” therapy (TT), using Dr Allen’s therapeutic device (DATD) in men with benign prostatic hyperplasia (BPH), can aid in understanding the etiology and pathophysiology of BPH.

Methods: We compared urinary and other parameters of BPH patients who received TT over 6 months (treatment group) with those of healthy volunteers who had not received the treatment (control group). Dynamics of symptoms and indicators in each group were evaluated in comparison with their data at the beginning and end of the study. Parameters were the International Prostate Symptom Score (IPSS) for urinary symptoms and quality of life (QoL), ultrasound measurement of prostate volume (PV) and uroflowmetry (maximum flow rate, Q_max). TT effectiveness was examined in 124 men with BPH and PV?<60?mL. We also investigated the data of five patients with BPH and PV?>60?mL.

Results: TT decreased urinary symptoms and PV, increased Q_max and improved QoL in men with BPH, PV?<60?mL, and in men with BPH, PV?>60?mL.

Conclusions: The present study demonstrated that TT is effective for BPH, suggesting that blood circulation plays a crucial role in its cause. The continuous heat exposure that does not exceed the normal body temperature terminates the trigger of BPH development, “micro-focus” of hypothermia, and the following spontaneous expansion of capillaries. TT could be considered to be a useful tool in BPH treatment.