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.     

Influence of testosterone substitution on glycemic control and endothelial markers in men with newly diagnosed functional hypogonadism and type 2 diabetes mellitus: a randomized controlled trial

Abstract

Effects of testosterone (T) on the cardiovascular system of men remain controversial. The impact of T-replacement therapy (TRT) in men with functional hypogonadism and type 2 diabetes mellitus (T2DM) has to be elucidated. This study included 80 men (mean age 51.5?±?6.3 years) with newly diagnosed T2DM (according to ADA criteria) and functional hypogonadism (according to EAU criteria). Randomization: Group1 (n?=?40): TRT using 1%-transdermal T-gel (50?mg/day), Group2 (n?=?40) no TRT (controls). Dietary treatment applied to both. Parameters at baseline/after 9?months: anthropometric parameters, lipids and indicators of carbohydrate metabolism (fasting glucose, insulin, HbA1c, HOMA-IR), markers of adipose tissue and EnD (leptin, resistin, p- and e-selectin, ICAM- 1, VCAM- 1 and CRP). ANCOVA for repeated measurements revealed TRT to cause a significant decrease in waist circumference (WC), HOMA-IR and HbA1c vs controls (p?<?.001, p?=?.002, p?=?.004, respectively). Leptin declined in subjects receiving TRT vs controls (p?=?.04). Concentrations of resistin, ICAM-1, p-selectin and CRP decreased significantly vs controls (all p?<?.001); no effects for e-selectin and VCAM-1. Advanced age attenuated effects, higher delta testosterone levels augmented effects. Decrement of WC was related to decreasing markers of adipose tissue secretion/EnD. TRT in men with functional hypogonadism and T2DM improved carbohydrate metabolism and markers of endothelial dysfunction.     

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.     

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.     

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.     

Dutasteride improves bone mineral density in male patients with lower urinary tract symptoms and prostatic enlargement: a preliminary study

Introduction: We studied the effect of dutasteride on bone mineral density (BMD) in aging male patients with lower urinary tract symptoms (LUTS) and prostatic enlargement.

Methods: We prospectively studied 17 patients with LUTS and prostatic enlargement. Before and 1 year after dutasteride (0.5?mg daily), we assessed International Prostate Symptom Score (IPSS), prostatic volume (PV), serum prostatic-specific antigen (PSA) and testosterone. BMD in the lumbar and femur was measured by DEXA method.

Results: Dutasteride significantly reduced PV (from 51?±?24 to 34?±?17?ml, p?p?p?2, p?2, p?2, p?Conclusions: Dutasteride has a potential to improve BMD with elevation of serum testosterone in aging male patients with LUTS and prostatic enlargement.     

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.     

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 long-acting testosterone undecanoate on bone mineral density in middle-aged men with late-onset hypogonadism and metabolic syndrome: results from a 36 months controlled study

We evaluated the effects of long-term testosterone replacement therapy (TRT) on the bone mineral density (BMD) in obese patients with metabolic syndrome (MS) and late-onset hypogonadism (LOH). Sixty men (mean age 57 ± 10) with low serum testosterone (T < 320 ng/dL) and MS regardless the presence of osteoporosis were enrolled. Forty men received intramuscular T-undecanoate (TU) four times/year for 36 months and 20 age-matched hypogonadal men with MS in whom T treatment was contraindicated were used as controls. Hormonal, biochemical markers, vertebral and femoral BMD by dual-energy x-ray absorptiometry were measured. At baseline, overall patients had mild osteopenia (lumbar BMD= 0.891 ± 0.097 g/cm(2); femoral BMD= 0.847 ± 0.117 g/cm(2)). TU induced a significant improvement of bone mass after 36 months (lumbar BMD=1.053 ± 0.145 g/cm(2); p < 0.002; femoral BMD=0.989 ± 0.109; p < 0.003 g/cm(2)) with a 5%/year increase and a significant reduction in hs-CRP without changes in body mass index. A direct relationship between serum T and BMD increments at the lumbar (r(2)?= 0.66, p < 0.0001) and femoral (r(2)?=0.52, p < 0.0001) sites was demonstrated. Study adherence was 50% without serious side effects. Long-term TRT in middle-aged men with LOH and MS determines a significant increase in both vertebral and femoral BMD related to increased serum T levels, probably independently from estradiol modifications.     

Cystatin C as a predictor of mortality in elderly patients with chronic kidney disease

Background: The prevalence of chronic kidney disease (CKD) in the elderly is high. Serum cystatin C is an accurate marker of kidney function and it also has prognostic utility in CKD patients. The aim of our study was to determine the prediction of serum cystatin C and other markers of kidney function on long-term survival in elderly CKD patients.

Methods: Fifty eight adult Caucasian patients, older than 65 years, without known malignancy, thyroid disease and/or not on steroid therapy were enrolled in the study. In each patient, ⁵¹CrEDTA clearance, serum creatinine, serum cystatin C, and estimated glomerular filtration rate using different equations were determined on the same day and patients were then followed for 11 years or until their death.

Results: The means are as follows: ⁵¹CrEDTA clearance 53.3?±?17.4?ml/min/1.73?m², serum creatinine 1.62?±?0.5?mg/dl, serum cystatin C 1.79?±?0.5?mg/l, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation 40.1?±?14?ml/min/1.73?m², Berlin Initiative Study 2 (BIS2) equation 38.9?±?10.7?ml/min/1.73?m², full age spectrum (FAS) creatinine equation 43.8?±?13.8?ml/min/1.73?m², FAS cystatin C equation 40.1?±?11.7?ml/min/1.73?m². In the follow up period, 47 (81%) patients died. Cox regression analysis showed different hazard ratios (HRs) for death: for ⁵¹CrEDTA clearance HR 1.022 (95% CI 1.004–1.042; p?=?.015), serum creatinine HR 1.013 (95% CI 1.006–1.019; p?=?.001), serum cystatin C HR 2.028 (95% CI 1.267–3.241; p?=?.003), CKD-EPI creatinine equation HR 1.048 (95% CI 1.019–1.076; p?=?.001), BIS2 equation HR 1.055 (95% CI 1.021–1.088; p?=?.001), FAS creatinine equation HR 1.046 (95% CI 1.017–1.074; p?=?.001), FAS cystatin C equation HR 1.039 (95% CI 1.010–1.071; p?=?.009).

Conclusions: Our results showed the highest HR for serum cystatin C among kidney function markers for prediction of outcome in elderly CKD patients.     

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.     

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.     

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.     

Bone mineral density at distal forearm in men over 40 years of age in Mae Chaem district,Chiang Mai Province,Thailand: a pilot study

Objective: To study the prevalence of bone mineral density (BMD) and osteoporosis in the distal forearm among Thai men over 40 years of age in Mae Chaem District, Chiang Mai Province, Thailand.

Methods: The subjects in this study were 194 Thai men, aged between 40 and 87 years who resided in Mae Chaem District, Chiang Mai Province, Thailand. Self-administered questionnaires were used for receiving the demographic characteristics information. BMD was measured by peripheral dual energy X-ray absorptiometry at the nondominant distal forearm in all men.

Results: The BMD was highest in the age-group 40–49 years and lowest in the age-group 70–87 years. The average T-score at the distal forearm was also highest in the age-group 40–49 years and lowest in the age-group 70–87 years. The BMD decreased as a function of age-group (p?p?p?>?.05). The percentage of osteopenia and osteoporosis are increased as a function of age-group in, while decreased in that of normal bone density.

Conclusions: We found the prevalence of osteoporosis in men who resided in Mae Chaem District, Chiang Mai Province, Thailand.     

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.     

Analysis of cardiovascular risk factors associated with serum testosterone levels according to the US 2011–2012 National Health and Nutrition Examination Survey

Objective: To investigate associations between cardiovascular disease risk factors, including fasting glucose, cholesterol, high density lipoprotein cholesterol (HDL-c), LDL-c, blood pressure, body mass index (BMI), C-peptide, creatinine kinase, smoking, alcohol use, physical activity, C-reactive protein as well as homocysteine levels and cardiovascular events.

Methods: Data from 1545 men aged ≥40?years, with testosterone deficiency (TD) (<300?ng/dL) and non-TD (≥300?ng/dL) which were extracted from the National Health and Nutrition Examination Survey database 2011–2012 and analyzed.

Results: Multivariate logistic regression analysis showed positive associations between TD and BMI (≥35 vs.?p?=?.016), HDL-c (<0.91 vs. ≥0.91: OR?=?1.60, 95% CI: 1.14–2.24, p?=?.006) and diabetes (diabetes vs. non-diabetes: OR?=?1.48, 95% CI: 1.14–1.92, p?=?.004) as well as negative associations between TD and metabolic equivalent scores (≥12 vs. <12: OR?=?0.69, 95% CI: 0.52–0.91, p?=?.009) and smoking (Ever vs. never: OR?=?0.69, 95% CI: 0.51–0.94, p?=?.018). Furthermore, total serum testosterone levels were lower in patients with heart failure (p?=?.04) and angina/angina pectoris (p?=?.001) compared with subjects without these cardiac problems.

Conclusion: Low serum testosterone was associated with multiple risk factors for CHD.     

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.     

A four-year efficacy and safety study of the long-acting parenteral testosterone undecanoate

Introduction. This is a four-year follow-up of 25 men who received parenteral testosterone undecanoate (TU), 1000 mg every 12 weeks for at least four years. This study was a continuation of a 30-week study wherein the effects of TU had been compared to those of parenteral testosterone enanthate.

Methods & Results. Plasma testosterone (T) trough values of the injection interval of 12 weeks): median 11.9 – 15.9 nmol/L (N 10.0–30.0). E2 and SHBG were stable. Body weight, BMI, waist-to-hip ratio remained stable. Total cholesterol, and triglycerides were unchanged but plasma LDL declined while HDL, after an initial reduction over the first 30 weeks, had increased significantly after three years. Leptin levels, bone mineral density, blood pressure, liver function tests, haemoglobin and haematocrit levels remained stable without values above the upper limit of normal. Over the first 12 months of the study there was an increase in prostate volume from 19.7 ± 8.8 mL to 22.0 ± 8.4 mL (p < 0.05) but thereafter volumes remained stable, paralleled by an increase in PSA from 0.67 ± 0.38 µg/dL to 0.75 ± 0.35 µg/dL (p < 0.05) without any further changes after 12 months.

Conclusion. TU appears to be a stable and safe treatment modality of hypogonadal men.