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• There is evidence of a strong and independent association between obesity/metabolic syndrome and BPH/LUTS; one of their common denominators is hypogonadism
• As the prevalence of this condition increases the management of metabolic syndrome is considered a major challenge to global public health. An effective way to combat metabolic syndrome and its related consequences is through primary prevention. However, examination of metabolic syndrome molecular pathways and prostatic diseases may offer new therapeutic perspectives for these conditions
• In a rabbit model of metabolic syndrome overt hypogonadism was induced and characterized by low testosterone along with prostate, seminal vesicle, and testis hypotrophy when compared with controls. In this model, prostatic mRNA levels of several inflammatory markers (e.g., IL-8, IL-1β, TNF-α and IL-6) were upregulated as was the expression of fibrotic and myofibroblast activation markers (including TGFβ1, αSMA, RhoA, ROCK1 and ROCK2)
• Testosterone prevented (and did not induce) prostatic diseases and normalized markers of metabolic syndrome in HFD-treated rabbits. In addition, oral treatment with INT-747 also significantly (p<0.05) normalized fasting glucose, glucose tolerance, and decreased visceral fat in HFD-treated rabbits
• Whereas testosterone treatment normalized prostate fibrosis and levels of HFD-upregulated mRNA of all the prostatic inflammatory markers plus expression of fibrotic and myofibroblast activation markers, INT-747 treatment had no effect on these parameters suggesting that the positive effect of testosterone on the prostate gland is not via a metabolic syndrome component
• It is evident that testosterone protects rabbit prostate from metabolic syndrome-induced prostatic hypoxia, fibrosis and inflammation, thus providing new insights and perspectives for prevention and intervention in BPH/LUTS

• T is an important factor in the etiology of obesity, MetS, T2DM and CVD, with sub-normal T levels increasing the accumulation of fat deposits, particularly abdominal (visceral) fat
• Lifestyle changes (diet and exercise) are typically recommended by physicians to combat obesity but the often transient effects are only marginally successful and of limited clinical benefit
• T treatment in hypogonadal men reverses fat accumulation with a significant improvement in lean body mass, insulin sensitivity and markers of cardiovascular risk
• Medical professionals are largely unaware of the potential benefit and contribution of T in combating obesity and managing MetS in hypogonadal men, with many physicians fearing an increased risk of PCa and CVD (despite the lack of supportive evidence)
• Combined with lifestyle changes, T may be a useful tool for the treatment of obesity in hypogonadal men; it also improves mood levels and vitality, while reducing fatigue, and may motivate men to adhere to diet and exercise regimens designed to combat obesity

• TU was well tolerated in men with hypogonadism. Adverse drug reactions (ADRs) related to TU therapy were rare (5.8%)
• Only 1 patient (0.1%) reported an ADR that was considered serious (prostate enlargement and urinary retention)
• The number of men who discontinued from the study was relatively low (17.5%)
• Overall, ADRs were associated with treatment discontinuation in 31 patients
• No cases of prostate cancer were observed with TU treatment
• Hematocrit levels increased slightly from a baseline level of 42.8 ± 6.6% to 44.5 ± 6.1% after the last TU injection (Visit 5; p < 0.0001) but remained below 50% (the recommended limit for testosterone treatment in men with androgen deficiency)
• Adverse cardiac events were reported in seven patients, all of whom had preexisting cardiovascular impairment

• The majority of physicians surveyed (82%) would regularly use laboratory measurements of total testosterone to diagnose testosterone deficiency
• Physicians consider the main symptoms of testosterone deficiency to be erectile dysfunction, lack of libido, fatigue, loss of power, depression, weight gain and loss of hair/reduced body hair
  
  
  • There was an increased awareness among physicians of depression and weight gain as clinical symptoms of low testosterone
• For 70% of the physicians surveyed, the severity of the symptoms experienced was considered a more significant reason to start testosterone treatment than the laboratory value of testosterone
• In 2010, significantly more physicians expressed concern about the adverse effects of testosterone treatment compared with 2006 (78% vs 54%)
  
  
  • Eleven percent of patients eligible for testosterone therapy did not receive treatment due to these concerns
• The proportion of patients diagnosed with erectile dysfunction who have testosterone deficiency ranged from 41% to 63% depending on the country
  
  
  • These patients were more likely in 2010 to be treated with phosphodiesterase type 5 (PDE5) inhibitor monotherapy or testosterone plus PDE5 inhibitors than in 2006.

• Mean trough serum total T increased from 9.6 nmol/L at baseline to 17.3 nmol/L before the fifth injection (p<0.0001)
• The proportion of patients with a high/very high libido increased from 10% at baseline to 61% at injection 5 (overall p<0.0001)
• Significant improvements over each injection interval were seen in the overall levels of vigor/vitality, mood and ability to concentrate (p<0.0001 for each)
• The proportion of patients reporting moderate, severe or extremely severe ED was significantly decreased from baseline at the time of the fifth TU injection, from 65% to 19% (p<0.0001)
• Statistically significant reduction in waist circumference (Figure 1)
• Adverse drug reactions related to TU therapy were rare (5.8%).

• Serum total testosterone increased from 8.9 nmol/L (256.5 ng/dL) at baseline to 23.7 nmol/L (683.0 ng/dL) at week 48 in the testosterone group (p<0.001) and from 9.1 nmol/L (262.3 ng/dL) to 11.2 nmol/L (322.8) ng/dL in the placebo group (p<0.001; between group difference p<0.001)
• At week 48 unadjusted quality of life scores of men in the testosterone treatment group improved significantly in five out of the eight domains on the Short-Form-12 survey
  
  
  • Physical health composite scores improved 4.0 points in the treatment group compared to 0.8 points in the placebo group (F=3.652, p=0.027)
  • Mental health composite scores improved 4.4 points in the treatment group compared to 1.0 point in the placebo group (F=4.514, p=0.018)
• After adjusting for baseline differences, significant improvement was observed in vitality and social functioning domains and mental health composite scores, but not in physical health composite scores
• No significant adverse events were observed.

Key Points

• Bone mineral density (BMD) improved significantly (by approximately 5% per year) in men treated with testosterone undecanoate for 36 months, but there was no improvement in BMD in the control group
• At 36 months:
  • Lumbar BMD was 1.053±0.145 g/cm² in the testosterone replacement therapy (TRT) group versus 0.866±0.109 g/cm² in controls (p <0.002 vs testosterone undecanoate)
  • Femoral BMD was 0.989±0.109 g/cm² versus 0.823±0.126 g/cm² in controls (p <0.003 vs testosterone undecanoate)
• There was a direct correlation between change in total testosterone levels and change in BMD at the lumbar site (r² = 0.66, p<0.0001) and femoral site (r² = 0.52, p <0.0001)
• There was a significant reduction in high-sensitivity C-reactive protein (hs-CRP) levels in the TRT, but not the untreated control, group after 12, 24 and 36 months
• No relationship between improvement in BMD and estradiol levels was observed

Key Points

• The prevalence of hypogonadism among men with sexual dysfunction and common medical causes of ED ranged from 30.8−64.3%
• Hypogonadism was prevalent among men who used alcohol excessively or who smoked
• The prevalence of hypogonadism was also substantial among men receiving medication for anxiety or depression and in men with work-related stress
• The highest prevalence of hypogonadism was observed in men in their 50’s and 60’s
• A significant association between the medical or psychiatric causes of ED and hypogonadism was limited to hypertension, tobacco abuse, sleep apnea and work stress
• Sleep apnea and work stress in particular were positively associated with hypogonadism.

Key Points

• Testosterone (T) replacement therapy was started in 39% of 1031 men with low testosterone levels [≤8.7 nmol/L (250 ng/dL)] during routine clinical care at 7 Veteran Affairs medical centres in the US
• After a mean follow-up of 40.5 months, overall mortality in T-treated men was 10.3%, compared with 20.7% for untreated men (p<0.001)
• The mortality rate was 3.4 deaths/100 person-years in T-treated men, compared with 5.7/100 person years in untreated men
• T-treated men had longer a survival time than untreated men (p=0.029)
• There was a 39% reduction in mortality risk for T-treated compared with untreated men when data were adjusted for age, treatment site, BMI, baseline testosterone level, overall medical morbidity, hospitalisation, and for the presence of coronary heart disease and diabetes mellitus
• T treatment appeared to be associated with greater mortality reduction in younger men (age <60 years), diabetic men and men without coronary heart disease
• During the retrospective observational study, 1.6% of T-treated men and 2.0% of untreated men were diagnosed with incident prostate cancer (p=0.68).

Key Points

• This double-blind, placebo-controlled study enrolled Malaysian men aged 40−70 years with low total testosterone levels (≤346 ng/dL) and at least mild symptoms on all Aging Male Symptoms (AMS) domain scores or total AMS score of ≥27
• Participants (n=120) were randomized 1:1 to receive either long-acting injectable testosterone undecanoate 1000 mg or placebo injection administered on weeks 0, 6, 18, 30 and 42
• Mean serum total testosterone increased from 256.5 ng/dL at baseline to 685.9 ng/dL at week 48 in the treatment arm and from to 262.3 ng/dL to 322.8 ng/dL in the placebo arm (p<0.001 vs testosterone)
• The improvement in total AMS score from baseline (assessed at 18 and 48 weeks) was significantly greater in the treatment arm than the placebo arm (p=0.017)
• In absolute terms, the mean change from baseline in total AMS score was -21.9% in the testosterone group and -12.6% in the placebo group
• There were significantly greater improvements in somatovegetative and psychological subdomain scores for testosterone recipients versus placebo recipients but the difference in improvements in sexual subdomain scores did not reach statistical significance.

Key Points

Testosterone plays a significant role in obesity, glucose homeostasis, and lipid metabolism:

• Although androgens appear to be involved in the deposition of visceral fat in males, continued androgen stimulation is not required once fat is stored, and low testosterone adversely affects fat storage and metabolism
• There is a direct correlation between plasma testosterone and insulin sensitivity, and low testosterone levels increase the risk of type 2 diabetes mellitus
• Lower total testosterone and sex hormone-binding globulin (SHBG) predict a higher incidence of the metabolic syndrome (MetS)
• Testosterone replacement therapy (TRT) reverses part of the unfavourable risk profile for the development of diabetes and atherosclerosis in hypogonadal men

There is a growing evidence and acceptance that testosterone is a pivotal hormone for many aspects of men’s health and the administration of TRT to elderly men with hypogonadism is a responsible strategy provided that accepted treatment guidelines are followed.

Key Points

• TT was measured using gold standard liquid chromatography tandem mass spectrometry in nonobese healthy men aged 19-40 years old enrolled in the third generation (G3) of the Framingham Heart Study; FT was calculated
• Values below the 2.5^th percentile of reference sample (348.3 ng/dL [12.1 nmol/L] for TT and 70.0 pg/mL [243 pmol/L] for FT) were classified as low

• Men with low TT and FT were more likely to have slow walking speed, difficulty climbing stairs or frailty, and diabetes than those with normal level
• Men with low TT and FT were more likely to report sexual symptoms than men with normal levels and were more likely to have at least one of the following:
  
  
  
  • Sexual symptoms
  • Physical dysfunction, or
  • Diabetes

Conclusions

• These reference ranges generated in a community-based sample of men provide a rational basis for categorizing testosterone levels as low or normal
• Men with low TT or FT had a higher prevalence of physical dysfunction, sexual dysfunction, and diabetes

Key Points

Time-course of effects of testosterone replacement therapy in hypogonadal men as shown in clinical studies:

• Effects on sexual interest appear after 3 weeks and plateau at 6 weeks
• Changes in erections/ejaculations occur within 6 months
• Effects on quality of life evident within 3–4 weeks and continue thereafter
• Effects on depressive mood noted after 3–6 weeks and reach a maximum after 18–30 weeks
• Effects on glycaemic control become evident after 3–12 months, although insulin sensitivity may improve within a few days
• Changes in body composition and muscle strength occur within 12–16 weeks and stabilize at 6–12 months
• Effects on bone mineral density are detectable after 6 months and continue for at least 3 years
• Beneficial effects on lipids appear after 4 weeks and reach a maximum after 6–12 months
• Prostate-specific antigen and prostate volume marginally rise, plateauing at 12 months.

Key Points

• Testosterone (T) deficiency (TD; hypogonadism) is a common and under-diagnosed condition associated with aging and with common medical comorbidities
• Significantly increased risk of TD associated with obesity, metabolic syndrome (MetS), type 2 diabetes mellitus (T2DM) and hypertension
• Significant associations exist between T levels and all-cause and cardiovascular death in men ≥40 years
• There is rigorous evidence supporting T replacement therapy (TRT) in reducing fat mass, a key component in treating individuals with MetS or T2DM
• TRT reduces fasting plasma glucose, homeostasis model assessment index of insulin resistance (HOMA-IR), triglycerides and waist circumference, and increases high-density lipoprotein cholesterol in patients with TD and MetS
• Consistent support for the benefits of TRT in improving sexual desire, erectile function and performance
• Current commercial formulations for TRT include short-acting IM injections, topical gels or patches, subcutaneous T pellets and long-acting intramuscular T undecanoate
• Current treatment modalities appear relatively safe, and adverse events definitively associated with treatment are reversible on withdrawal of treatment
• Lack of a clearly-defined serum threshold for distinguishing T deficiency –published consensus guidelines recommend arbitrary thresholds, generally ranging from 200 to 350 ng/dL
• Physicians managing patients with TD should use their clinical judgment and experience in determining which patients require diagnosis and treatment, based on low T and the presence of symptoms.

Key Points

In elderly men:

• Testosterone (T) is important as a regulator of body composition and for maintaining bone mineral density
  
  
  • Low T is associated with frailty
• Low T is associated with higher mortality
  
  
  • Increased risk of type 2 diabetes, depression, cardiovascular disease, chronic obstructive pulmonary disease, metabolic syndrome, chronic renal disease, and a higher incidence of mortality
• Low T is common in men with heart failure
  
  
  • Low T and dehydroepiandrosterone level appear to be independent predictors of death in men with heart failure

T replacement therapy has been shown to be beneficial in elderly frail men, including those with cardiac dysfunction and/or heart failure

• Improves lean body mass and reduces fat mass
• Ameliorates a number of cardiovascular risk factors
• Improves strength, physical and metabolic function

Key Points

After 6 and 12 months, IM testosterone undecanoate (TU) significantly:

• Improved metabolic parameters by reducing homeostasis model assessment index of insulin resistance (HOMA-IR) (p<0.001), decreasing waist circumference (p<0.0001), decreasing fat mass (p<0.001) and increasing fat-free mass (p<0.001)
• Improved International Index of Erectile Function (IIEF-5) and Aging Males’ Symptoms (AMS) scores

In contrast 6 months of oral TU did not significantly improve any parameters studied

In patients who crossed over from oral TU, 6 months of IM TU:

• Increased TT and FT (p<0.0001)
• Improved metabolic parameters (p<0.001)
• Improved IIEF-5 and AMS scores (p<0.01)

Haemoglobin and haematocrit values increased with oral and IM TU, but remained stable and within the normal range during treatment.

Key Points

Key evidence-based recommendations included:

• Clinical and biochemical diagnosis
• Testosterone (T) deficiency (TD) and metabolic diseases
• T and cardiovascular (CV) diseases
• T therapy and CV health
• Questionnaires to screen for TD
• Indications for T treatment
• Age and T treatment
• Indications for T treatment in men with sexual dysfunction
• Combination therapy with T and phosphodiesterase type 5 inhibitors
• Commercial T formulations
• Serum T levels to be achieved with T treatment
• Prostate safety
• Cautions in the use of T therapy
• Monitoring

Key Points

• Testosterone replacement therapy (TRT) significantly increased serum total T and free T by week 12 in Korean men with ED and hypogonadism
• TRT also significantly improved:
  
  
  • total IIEF score and all 5 domain scores
  • total AMS scale and all three domain scores of AMS
• 77% of men reported improved erectile function
• Improvements in lipid profile and some metabolic components were seen
• Serum glucose levels tended to improve with treatment, reaching statistical significance in men with elevated initial glucose levels
• TRT was effective, safe and well tolerated in hypogonadal Asian men.

Key Points

Nine symptoms were confirmed to be significantly related to total or freetestosterone (T) level

• Three sexual symptoms
• Three physical symptoms
• Three psychological symptoms
• The probability of symptoms increased with decreased levels of T and the presence of the three sexual symptoms correlated most closely with low T
• Total T <317 ng/dL (11 nmol/L) + free T levels <64 pg/mL (220 pmol/L) + all 3 sexual symptoms were diagnostic of late-onset hypogonadism.

Key Points

• Total and bioavailable testosterone (T) levels increased significantly following administration of the testosterone gel
• T gel was significantly superior to placebo in improving the Erectile Function Domain score in men with baseline T ≤300 ng/dL (10.4 nmol/L), a widely accepted definition of hypogonadism
• The increase in successful intercourse rate increased correspondingly by 33.1% vs 13.4% (p<0.038)
• The lower the baseline level of T, the lower the improvement in sexual function obtained by tadalafil alone in the placebo group
• Hypogonadal men with baseline T ≤300 ng/dL may benefit from the addition of T replacement therapy to optimal ED therapy with tadalafil.

Key Points

• Men with MetS had significantly lower levels of total plasma testosterone compared with healthy subjects
• This was also true when men with or without erectile dysfunction were analysed separately and when different definitions of MetS were used
• The presence of type 2 diabetes mellitus (T2DM) further enhanced the MetS-related decline in testosterone levels
• Adjusted for age and body mass index, both T2DM and MetS independently predicted low testosterone (p<0.001 and p<0.05, respectively)
• Data from longitudinal studies showed that baseline testosterone was significantly lower among patients with MetS than in controls (mean -2.17 nmol/L; p<0.0001)
• Testosterone replacement therapy significantly reduced metabolic risk factors, including fasting plasma glucose, homeostasis model assessment index of insulin resistance (HOMA-IR), triglycerides and waist circumference, and increased HDL-cholesterol.

Key Points

• After 12 months, there was a significant difference in homeostasis model assessment index of insulin resistance (HOMA-IR), carotid intima media thickness (CIMT) and high-sensitivity C-reactive protein (hsCRP) between the TU and placebo groups (p<0.01)
• No modification of metabolic factors occurred during treatment with placebo
• Consequently, all patients received TU for the remaining 12 months of the study
• TU markedly improved insulin sensitivity from baseline to 12 months (p<0.0001), and maintained the improvement after 24 months
• HOMA-IR significantly improved in patients shifted from placebo to testosterone undecanoate (p<0.001) due to a reduction in fasting glucose and fasting insulin levels
• TU also significantly reduced hsCRP levels (p<0.0001) and CIMT values (p<0.001)
• Overall at 24 months, only 35% and 58% of patients still met NCEP-ATPIII and IDF criteria, respectively, for a diagnosis of MetS
• The main determinants of improvement in MetS were reduction in waist circumference (p<0.0001), visceral fat mass (p<0.0001) and improvement in HOMA-IR (Figure 1).

Key Points

The nested case-control study showed:

• At baseline, over 20% of men were hypogonadal, according to a widely accepted lower limit for normal total testosterone levels
• Hypogonadism ranged from 5.2% to 13.8% and 22.4% depending on the threshold used (total testosterone less than 8, 10.4 and 12 nmol/L, respectively
• During follow-up, 139 of the patients had a major cardiac event, such as ischaemic heart disease, cerebrovascular events (stroke or transient ischaemic attack) or peripheral artery disease
• MACE were fatal in 15 men
• Although low testosterone in itself was not associated with MACE, those patients with total testosterone levels below 10.4 nmol/L who had a major cardiac event were significantly more likely to die than those with higher testosterone levels
• When adjusted for Chronic Diseases Score (an index of comorbidities) the risk of death was increased by a factor of seven (hazard ratio [HR] 7.1) in men with testosterone below 8 nmol/L
• Of interest, fatal MACE were associated with a higher ANDROTEST score measuring hypogonadal-related symptoms and signs (HR = 1.2 for each ANDROTEST score increment; P = 0.05).

Key Points

• 20.9% of men had biochemical testosterone deficiency defined as bioavailable testosterone <2.6 nmol/L, 16.91% using testosterone <8.1 nmol/L and 24% using either
• There was excess mortality in testosterone-deficient men; 21% versus 12% in those with testosterone levels in the normal range (>2.6 nmol/L), p=0.002 (Figure 1)
• Low serum testosterone was one of only four variables found to influence the time to all-cause mortality in multivariate analysis (hazard ratio [HR] 2.27)
• The other variables significantly influencing time to all-cause mortality were presence of left ventricular dysfunction (HR 3.85), aspirin therapy (HR 0.63) and β-blocker therapy (HR 0.45)
• Low bioavailable testosterone more than doubled adjusted all-cause and vascular mortality (HR 2.2, p<0.0001 for all-cause mortality and HR 2.2, p=0.007 for vascular mortality) compared with those with normal levels of testosterone
• Overall, serum total testosterone was inversely associated with mortality (HR 0.96), with a baseline level of <15.1 nmol/L associated with an all-cause HR of 1.86 and vascular mortality with a HR of 2.5.

Key Points

The nested case-control study showed:

• No difference in Fat Free Mass (FFM) beween the two groups (low and normal T), but Fat Mass (FM) percentage was significantly higher in the low T group (32.2% vs 25.9%; P<0.001) compared with controls – this group also had higher weight, waist circumference, and total abdominal adipose tissue (TAT)
• Muscle strength was similar between the groups, but the control group performed significantly better in two of the three functional tests. Bone Mineral Density (BMD) measured in both the lumbar spine and hip showed no significant difference between the groups
• At the Oral Glucose Tolerance Test men with low T had significantly higher fasting and two hour glucose levels compared with the control group. Likewise, the HbA1c, insulin, C-peptide and triglycerides levels and insulin resistance (HOMA) values were significantly higher in men with subnormal testosterone levels
• Men in the control group reported better overall and somatic Quality of Life (QoL) scores (AMS) although the scores in the sexual domain were not significantly different. In the Beck Depression Inventory the control group reported a significantly better total and second subscale score
• There were no differences between groups in the General Health Questionnaire or World Health Organisation quality of life old score (WHOQOL-OLD)

The intervention study showed that:

• Total and free T increased significantly in the T group. Luteinizing hormone (LH) and follicle stimulating hormone (FSH) decreased in the T group and at the end of the study were significantly lower in the T group compared with placebo
• FFM increased and FM reduced significantly during T treatment compared to the placebo group at the end of the study (FFM: +4.2 kg in T group, +0.4 kg in placebo; FM: -5.3kg in T group, -0.6 kg in placebo) while weight, BMI and waist circumference did not change significantly
• BMD in the hip increased significantly in the T group and there was a significant difference between the groups at the end of the study
• T did not increase strength in knee extension or handgrip strength, but in the placebo group handgrip strength was reduced in both the dominant and non-dominant hand such that at the end of the study there were significant differences between the groups
• There was no significant difference in QoL, cognitive function or emotional function between the groups at the end of the study
• Serum PSA, hematocrit and hemoglobin increased in the T group and by the end of the study were significantly higher than in the placebo group; two men in the T group (and one in the placebo group) had PSA levels >4.0µg/l by the end of the study

Key Points

• Serum testosterone, glycosylated haemoglobin (HbA1c), fasting plasma glucose, high-density lipoprotein cholesterol, triglyceride concentrations, and waist circumference improved in both groups after 52 weeks of treatment
• The addition of testosterone significantly further improved these measures compared with D&E alone
• All D&E and testosterone treated patients reached the HbA1c glycemic control goal of less than 7.0%, and 87.5% achieved HbA1c of less than 6.5%. In comparison, only 40.4% of the D&E alone participants reached HbA1c less than 7.0%, and none reached less than 6.5%
• Based on Adult Treatment Panel III criteria, 81.3% of the D&E with testosterone patients no longer met the criteria of MetS compared with 31.3% of those receiving D&E alone
• Testosterone treatment improved insulin sensitivity (HOMA model), adiponectin, and high-sensitivity C-reactive protein
• Serum PSA concentrations did not differ between the two treatment groups indicating that 52 weeks of testosterone replacement does not appear to increase risks of prostate problems.

Key Points

• Restoring plasma testosterone levels to normal alleviated the symptoms of testosterone deficiency
• The percentage of patients who reported “low” or “very low” levels of sexual desire/libido decreased from 64% at baseline to 10% after four TU injection intervals
• At baseline, 67% of patients had moderate, severe or extremely severe erectile dysfunction (ED), this decreased to 19% after TU therapy. 61% of patients with some degree of ED reported a decrease in severity
• TU therapy markedly improved patients ability to concentrate and their reported mood
• 89% of patients were “satisfied” or “very satisfied” with TU therapy
• The mean waist circumference in patients decreased from 100 cm to 96 cm
• Intramuscular TU was well tolerated and safe for treatment of male hypogonadism in daily clinical practice, irrespective of ethnic background: adverse events and adverse drug reactions were recorded for 12% and 6% of patients respectively. These were mostly mild to moderate in severity
• The most commonly reported ADRs were increase in hematocrit, increase in PSA and injection site pain (all <1%)
• No case of prostate cancer was observed

Key Points

• This is the longest term study investigating testosterone in patients with stable chronic angina.
  (Angina is severe chest pain due to ischemia of the heart muscle, generally due to obstruction or spasm of the coronary arteries. Coronary artery disease, the main cause of angina, is due to atherosclerosis of the cardiac arteries)
• In the testosterone group, 'time to ST depression' is significantly prolonged, ie the time during exercise when severe chest pain occurs as a result of ischemia (which also becomes visible on the electrocardiogram). This reflects an increase in exercise capacity
• Peak metabolic equivalents (METS) also increased significantly in the testosterone treated patients indicating an improved exercise capability
• BMI and triglycerides were numerically, though significantly reduced in the treatment group
• There was a non-significant reduction in waist-to-hip ratio (a measure of visceral obesity) in the Nebido® group
• Carotid intima-media thickness (CIMT), a measure of atherosclerosis, improved in the Nebido group and did not change in the placebo group. However, the comparison between groups did not reach statistical significance.

Key Points

• This is the first publication from The Moscow Study, a placebo-controlled study in men with metabolic syndrome with a total duration of three years. The first 30 weeks are placebo-controlled, then all men are switched to Nebido®
• All three questionnaires, the Beck Depression Inventory (BDI-IA), the Aging Males' Symptoms (AMS) scale, and the International Index of Erectile Function 5-item (IIEF-5) scale improved significantly in the testosterone group
• These improvements persisted after correcting for smoking habits, BMI, and the presence or absence of type 2 diabetes
• These improvements correlated with improvements in BMI. This means that patients felt better and functioned better when they lost weight, and the more weight they lost, the more they improved

Key Points

• Testosterone treatment consistently reduces fat mass and increases muscle mass
• Body composition changes were similar between men with low testosterone (<10 nmol/L), intermediate testosterone (10-12 nmol/L) and low-normal testosterone (12-15 nmol/L). This questions the validity of the thresholds for deficiency discussed in current guidelines
• Men >65 years yielded the same benefit from testosterone therapy as those <65 years
• This is the largest placebo-controlled testosterone study to date

Key Points

• Long-acting testosterone treatment (Nebido) for 3 months in frail elderly patients was well tolerated
• Nebido significantly improved skeletal muscle function, cardiorespiratory parameters and metabolic parameters, including insulin resistance
• Patients with lower testosterone at baseline achieved the greatest improvements, but eugonadal patients also benefited

Key Points

• Testosterone treatment consistently reduces fat mass and increases muscle mass. This study confirms these findings in a healthy (non-obese and without hypogonadism) cohort
• Changes in visceral fat were more pronounced than changes in subcutaneous fat