The Relationship between Selected Bioelements and Depressiveness Associated with Testosterone Deficiency Syndrome in Aging Men.

Background and Objectives: Abnormal concentrations of bioelements (magnesium, manganese, chromium, copper, zinc) have been associated with physical and emotional dysfunctions, including depression. This association, however, has not been analyzed in testosterone deficiency syndrome (TDS) or patients with depressiveness, i.e., when individual symptoms do not form the picture of a full-syndrome depressive disorder. This study aimed to assess the relationship between concentrations of selected bioelements and the incidence of depressive symptoms in men aged 50 years and older with a concurrent testosterone deficiency syndrome. Material and Methods: Blood samples were taken from 314 men; the mean age of the population was 61.36 ± 6.38 years. Spectrophotometric method for biochemical analysis of magnesium (Mg), manganese (Mn), chromium (Cr), copper (Cu), and zinc (Zn) was used. The diagnosis of testosterone deficiency syndrome (TDS) was based on the total testosterone (TT), free testosterone (FT), estradiol (E2), and dehydroepiandrosterone sulfate (DHEAS) levels by ELISA. Each participant completed the Androgen Deficiency in Aging Male (ADAM) questionnaire, as well as the Beck Depression Inventory (BDI-Ia) measuring the severity of depressive symptoms. Results: Emotional disturbances manifested as depressive symptoms were diagnosed in 28.7% of all participants and testosterone deficiency syndrome in 49.3%. In the TDS group, the analysis showed a significant correlation between the level of manganese (R = 0.225, p = 0.005) and chromium (R = 0.185, p = 0.021) with the incidence of depression. Conclusions: The results of our study demonstrated a relationship between manganese and chromium concentrations with the incidence of depression in men aged 50 years and older with a concurrent testosterone deficiency syndrome. This may indicate that there is a correlation between these bioelements, as well as emotional disorders manifested as depressive symptoms in aging men with a diagnosed testosterone deficiency.

The effect of long term testosterone replacement therapy on bone mineral density.

OBJECTIVE: Long-term results of testosterone replacement therapy (TRT) on bone mineral density (BMD) in literature are still missing. MATERIALS AND METHODS: Totally, 45 males with testosterone deficiency syndrome (TDS) underwent TRT. The mean age was 57.84 years and the follow-up period was 94.62 months. Males were treated with three-month intramuscular injections of 1000 mg testosterone undecanoate. BMD was check at beginning of treatment, after two years and after 5 years. For a statistic evaluation, nonparametric Wilcoxon test was used. RESULTS: Mean BMD of lumbar spine was 1.067 at beginning, 1.122 after two years and 1.667 and after 5 years. The results after two and also 5 years showed a significant improvement (p < 0.001). CONCLUSION: Authors proved a positive effect of long-term TRT on BMD of the lumbar spine. Densitometry of the whole hip showed also an improvement, but only after 5 years. Densitometry of the femoral neck was relatively stable. Important is that despite the fact that males became older, BMD values of the lumbar spine were improved (Fig. 6, Ref. 18).

Results of long term testosterone replacement therapy in men with abdominal obesity, erectile dysfunction and testosterone deficiency.

INTRODUCTION: In this article, the authors evaluate subjective and objective results of long testosterone replacement therapy (TRT) and possible risk. METHODS: In a single center study, the authors treated 69 men with testosterone deficiency syndrome (TDS). The average age was 57.84 years and the follow-up period was 94.62 months. All men had at beginning a complete urological and internal examination. All the men were treated with three-month i.m. injections of 1000 mg testosterone undecanoate. The men were regularly checked according to the EAU guidelines. RESULTS: All of the men on treatment felt much better. Weight and waist circumference during monitoring showed a mild improvement. Excellent results were on red blood cells. Glucose, HDL cholesterol, triglycerides had stable values. PSA slightly increased and testosterone was within the normal range. In two men during treatment, we found a prostate cancer (low risk). Bone mineral density (BMD) of lumbar spine revealed a significant improvement. CONCLUSION: TRT had multiple positive effect on affected men with TDS. Our long-term results showed a long mild improvement during the time. Authors concluded that long term treatment had multiple benefit for affected men (Fig. 11, Ref. 13).

Testosterone undecanoate improves sexual function in men with type 2 diabetes and severe hypogonadism: results from a 30-week randomized placebo-controlled study.

OBJECTIVE: To evaluate the sexual function response to 30 weeks' treatment with long-acting testosterone undecanoate (TU) or placebo in 199 men with type 2 diabetes and either severe or mild hypogonadism (HG). PATIENTS AND METHODS: Men with HG were identified from seven primary care type 2 diabetes registers. A 30-week randomized placebo-controlled study of TU was carried out in 199 of these men (placebo, n = 107, TU, n = 92). The patient-reported outcome measure was the 15-item International Index of Erectile Function score. Men completing the study (n=189) were stratified, firstly, by baseline total testosterone (TT) or free testosterone (FT) into mild HG (TT 8.1-12 nmol/L or FT 0.18-0.25 nmol/L) and severe HG groups (TT ≤8 nmol/L and FT ≤0.18 nmol/L), and secondly, by intervention (placebo or TU), thereby creating four groups: mild HG/placebo; mild HG/TU; severe HG/placebo and severe HG/TU. STATISTICAL ANALYSIS: Changes in sexual function score (a secondary outcome of the study) at each visit within group (from baseline) and between groups (TU vs placebo) at each assessment (6, 18 and 30 weeks) were compared using a Wilcoxon signed-rank and Wilcoxon rank-sum test, respectively. RESULTS: Significant improvement in erectile function was evident only in the severe HG group after 30 weeks of TU treatment; this finding persisted when TU was compared with placebo. Intercourse satisfaction and sexual desire scores were also improved at 6, 18 and 30 weeks in the severe HG group after TU treatment; this increase in scores was also evident when compared with placebo. TU did not appear to alter orgasmic function significantly in any of the patient groups. CONCLUSIONS: The present study suggests that benefit in sexual symptoms after TU treatment is evident principally in patients with HG with TT levels ≤8 nmol/L and FT levels ≤0.18 nmol/L. We also suggest that 30 weeks of treatment is necessary before evaluating improvement in erectile function.

Prevalence of symptoms and associated comorbidities of testosterone deficiency syndrome in the Korean general population.

INTRODUCTION: Testosterone deficiency syndrome (TDS) is a prevalent disease of the aging male with much confusion to its associated presentation, diagnosis, and comorbidities. AIM: We investigated the overall prevalence of TDS and its putative symptoms and associated diseases in a nationwide study on participants recruited from routine checkup. METHODS: One thousand eight hundred seventy-five participants seeking biennial health checkup were enrolled from a nationwide distribution of randomly selected registry of primary clinics. Putative symptoms and comorbidities were assessed for serum testosterone-dependent prevalence change, independent of age. The identified symptoms were then assessed by multivariate backward stepwise binominal regression to determine the optimal reference level of testosterone and the strength of the associated comorbidities. MAIN OUTCOME MEASURES: TDS was assessed by serum testosterone, the Aging Males' Symptom scale, and the Androgen Deficiency in Aging Male questionnaire. Patient body habitus measurements and history of associated comorbidities were also described. The dependent variables included the age-specific prevalence of decreased testosterone and the probability of TDS-specific symptoms. RESULTS: Grossly 10.2% of the participants fell into the criteria for TDS. Testosterone was highly age dependent, and most putative symptoms of TDS showed significant age dependence but was not affected by serum testosterone levels. However, the symptoms of decreased libido and erectile dysfunction, and comorbidities such as hypertension, type 2 diabetes, and obesity showed relevant dependence on serum testosterone levels as well as age above 50 years of age. Furthermore, these symptoms were also affected at different serum testosterone thresholds. Decreased libido increased significantly at serum testosterone levels of 550 ng/dL (odds ratio [OR] = 1.295, 95% confidence interval [CI] = 1.047-1.601), and erectile dysfunction was affected by serum testosterone levels at 250 ng/dL (OR = 1.369, 95% CI = 1.005-1.866). CONCLUSIONS: Most symptoms and diseases thought to be associated with TDS are primarily age dependent. Few sexual symptoms and diseases such as hypertension, diabetes, and obesity show testosterone dependence only at older ages.

Coadministration of anastrozole sustains therapeutic testosterone levels in hypogonadal men undergoing testosterone pellet insertion.

INTRODUCTION: Current U.S. Food and Drug Administration-approved therapies for hypogonadism involve testosterone (T) replacement. Testosterone pellets (TP) require a minor office procedure every 3 to 4 months. The need for repeated insertions increases the likelihood of a complication. Anastrozole (AZ) is an aromatase inhibitor that has been used off-label for the treatment of male hypogonadism. AZ increases T levels by lowering serum estradiol (E2) levels and increasing gonadotropin (GTP) levels. AIM: We hypothesized that the concomitant use of AZ with TP insertions would sustain therapeutic T levels and increase the interval between TP insertions. METHODS: Men treated with TP for hypogonadism at an academic center were offered AZ (1 mg/day) at the time of TP reinsertion as a way of potentially decreasing the frequency of TP insertions. Total T (TT), free T (FT), sex hormone binding globulin, E2, luteinizing hormone (LH), and follicle-stimulating hormone FSH levels were obtained prior to T replacement and at 6 and 15 weeks from TP insertion. Men were re-implanted at 16 weeks if their TT levels were less than 350 ng/dL and their symptoms recurred. We retrospectively reviewed our records of men who underwent TP, TP, and AZ from 2011 to 2012. Demographics, TT, FT, LH, FSH, and E2 levels were recorded. Data were analyzed with anova and a Tukey's test. MAIN OUTCOME MEASURE: TT level at 6, 15, or >15 weeks from TP insertion. RESULTS: Thirty-eight men with 65 insertions were analyzed. The TP AZ group had significantly higher TT and FT levels than the TP group at >120 days (P < 0.05). The TP group had significantly higher E2 levels at all time points (P < 0.01). GTP levels remained stable in the TP AZ group. Average time to reinsertion in TP AZ was 198 days vs. 128 days in the TP group. CONCLUSION: Men on TP AZ maintain therapeutic T levels longer than men on TP alone and have significantly less GTP suppression.

Retrospective investigation of testosterone undecanoate depot for the long-term treatment of male hypogonadism in clinical practice.

INTRODUCTION: Testosterone undecanoate depot (TUD) administered intramuscularly is an effective form of testosterone replacement therapy (TRT) for male hypogonadism. Because of the ease of administration, TUD therapy may be preferable to subcutaneously implanted extended release T pellet implants (TI). AIM: The primary objective was to retrospectively assess the efficacy and safety of long-term (≥ 2 years therapy) TUD therapy in the clinical setting. The secondary objective was to retrospectively compare TUD with TI therapy. METHODS: Retrospective data were collected from the Waikato Hospital Endocrine Database for 179 hypogonadal men treated with TUD for ≥ 2 years from 1998-2011, with 124 of these men receiving previous TI therapy. MAIN OUTCOME MEASURES: The main outcome measure for efficacy was serum trough total testosterone (TT), and for safety an increase in hemoglobin (Hb) and/or hematocrit (Hct), rise in prostate-specific antigen (PSA) and/or prostatic biopsy and alteration in body mass index and lipid profile. Additional outcome measures were changes in the dosing and/or interval regimens for TUD therapy. RESULTS: Overall, 72% of trough TT levels were in the normal range for TUD therapy compared with 53% of trough TT levels during TI therapy. TUD therapy was well tolerated with 162 men (90.5%) completing 2 years of treatment, and only seven men (3.9%) stopping TUD because of adverse effects. A rise in Hb and/or Hct occurred in 25 men (14%), and a significant rise in PSA in 20 men (13%) at some stage during TUD therapy. At 2 years, 91% of men received the standard 1,000 mg TUD dose with 66% at the standard dosing interval of 10-14 weekly. CONCLUSIONS: TUD is an efficacious, safe, and well tolerated form of TRT, and individual optimisation of the dose and/or interval is only required in the minority of men. Particularly given the ease of administration, TUD was the preferred TRT for both patients and clinicians.

Comparability of single measurements of serum testosterone to the 24-hour C(avg) in patients using testosterone 2% solution.

INTRODUCTION: Efficacy of testosterone replacement therapy is determined by the proportion of men with 24-hour average serum testosterone concentration (Cavg ) in the normal range. In clinical practice, monitoring and dose adjustments are based on single testosterone measurements; however, how single measurements reflect Cavg is unclear. AIM: This post-hoc analysis evaluated whether single serum testosterone measurements and Cavg from the same day are both in the normal range in men receiving testosterone replacement therapy. METHODS: In an open-label, multicenter, titration trial, androgen-deficient men (N = 155) were started on 60-mg daily morning dose of testosterone 2% solution (Axiron®, Eli Lilly and Company, Indianapolis, Indiana, USA) applied to axillae (30 mg/axilla). Serum testosterone Cavg was determined on Days 15, 60, and 120. If necessary, dose was adjusted to maintain Cavg in the normal range (300-1,050 ng/dL). This analysis included subjects (n = 105) whose Cavg was within the normal range on Days 15, 60, and 120. MAIN OUTCOME MEASURES: Proportion of men with normal serum testosterone levels at 2, 4, or 8 hours post-dose on Days 15, 60, and 120. RESULTS: Greater than 93% of subjects had testosterone serum levels within the normal range 2, 4, or 8 hours post-dose on at least 1 day. In subjects with blood samples available from Days 15 and 60 or Days 15 and 120, 71.1% to 79.8% had normal levels at 2, 4, or 8 hours post-dose on both days, and in subjects with blood samples available from Days 15, 60, and 120, 63.9% to 68.8% had normal levels at 2, 4, or 8 hours post-application on all 3 days. CONCLUSION: Less than 70% of single testosterone measurements made on 3 separate days were concordant with same-day Cavg for all 3 days. These findings, which are specific for testosterone 2% solution, indicate that single measurements do not always reflect the 24-hour Cavg , and may possibly lead to inappropriate dose adjustments.

Testosterone replacement therapy improves metabolic parameters in hypogonadal men with type 2 diabetes but not in men with coexisting depression: the BLAST study.

INTRODUCTION: The association between testosterone deficiency and insulin resistance in men with type 2 diabetes is well established and current endocrine society guidelines recommend the measurement of testosterone levels in all men with type 2 diabetes or erectile dysfunction. AIM: We report the first double-blind, placebo-controlled study conducted exclusively in a male type 2 diabetes population to assess metabolic changes with long-acting testosterone undecanoate (TU). METHODS: The type 2 diabetes registers of seven general practices identified 211 patients for a 30-week double-blind, placebo-controlled study of long-acting TU 1,000 mg followed by 52 weeks of open-label use. Because of the established impact of age, obesity, and depression on sexual function, these variables were also assessed for influence on metabolic parameters. MAIN OUTCOME MEASURE: Changes in glycated hemoglobin (HbA1c) and the level of testosterone at which response are achieved. RESULTS: Treatment with TU produced a statistically significant reduction in HbA1c at 6 and 18 weeks and after a further 52 weeks of open-label medication most marked in poorly controlled patients with baseline HbA1c greater than 7.5 where the reduction was 0.41% within 6 weeks, and a further 0.46% after 52 weeks of open-label use. There was significant reduction in waist circumference, weight, and body mass index in men without depression, and improvements were related to achieving adequate serum levels of testosterone. There were no significant safety issues. CONCLUSIONS: Testosterone replacement therapy significantly improved HbA1c, total cholesterol, and waist circumference in men with type 2 diabetes. Improvements were less marked in men with depression at baseline, and therapeutic responses were related to achieving adequate serum testosterone levels. Current advice on 3- to 6-month trials of therapy may be insufficient to achieve maximal response. Patients reported significant improvements in general health.

Testosterone replacement therapy following the diagnosis of prostate cancer: outcomes and utilization trends.

INTRODUCTION: Late-onset hypogonadism may impair quality of life and contribute to metabolic and cardiovascular comorbidity in aging men. Testosterone replacement therapy is effective in treating hypogonadism. However, for the millions of men with a history of prostate cancer, exogenous testosterone has long been considered contraindicated, even though little data in such men are available. Clarification of this safety issue could allow treatment to be considered for a sizeable segment of the aging male population. AIM: The aim of this study is to examine population-based utilization and impact of testosterone replacement therapy in men with prostate cancer. METHODS: Using linked Surveillance, Epidemiology, and End Results-Medicare data, we identified 149,354 men diagnosed with prostate cancer from 1992 to 2007. Of those, 1181 (0.79%) men received exogenous testosterone following their cancer diagnosis. We used propensity scoring analysis to examine the effect of testosterone replacement on the use of salvage hormone therapy and overall and prostate cancer-specific mortality. MAIN OUTCOME MEASURES: We assessed overall mortality, cancer-specific mortality, and the use of salvage hormone therapy. RESULTS: Following prostate cancer diagnosis, testosterone replacement was directly related to income and educational status and inversely related to age (all P < 0.001). Men undergoing radical prostatectomy and men with well-differentiated tumors were more likely to receive testosterone (all P < 0.001). On adjusted analysis, testosterone replacement therapy was not associated with overall or cancer-specific mortality or with the use of salvage hormone therapy. CONCLUSIONS: In this population-based observational study of testosterone replacement therapy in men with a history of prostate cancer, treatment was not associated with increased overall or cancer-specific mortality. These findings suggest testosterone replacement therapy may be considered in men with a history of prostate cancer, but confirmatory prospective studies are needed.

Clomiphene citrate: A potential alternative for testosterone therapy in hypogonadal males.

BACKGROUND: Hypogonadism is a worldwide problem among men causing sexual, physical and mental problems. Testosterone therapy is the first-choice treatment for male hypogonadism, with several side effects, that is, subfertility. Clomiphene citrate (CC) is an alternative off-label therapy for a certain group of hypogonadal males, especially for those with an active or future child wish. There is scarce literature in usage of CC for men with hypogonadism. The aim of this retrospective study was to evaluate the effectiveness and safety of CC for hypogonadal males. METHODS: In this single-centre study, men treated with CC for hypogonadism were evaluated retrospectively. Primary outcome was hormonal evaluation including total testosterone (TT), free testosterone (FT), luteinizing hormone (LH) and follicle stimulating hormone (FSH). Secondary outcomes were hypogonadal symptoms, metabolic and lipid parameters, haemoglobin (Hb), haematocrit (Ht), prostate specific antigen (PSA), side effects, the effect of a trial without medication and potential predictors for biochemical and clinical response. RESULTS: In total, 153 hypogonadal men were treated with CC. Mean TT, FT, LH and FSH increased during treatment. TT increased from 9 to 16 nmol/L, with a biochemical increase in 89% of the patients. In patients who continued CC treatment, an increased level of TT persisted after 8 years of treatment. With CC treatment, 74% of the patients experienced hypogonadal symptom improvement. LH at the lower normal range before CC treatment was predictive for better TT response. During CC therapy, few side effects were reported and no clinical important changes in PSA, Hb and Ht were found. CONCLUSION: Clomiphene citrate is an effective therapy on short and long term, improving both clinical symptoms and biochemical markers of male hypogonadism with few side effects and good safety aspects.

Testosterone deficiency syndrome among males with type 2 diabetes mellitus in East Malaysia.

Type 2 diabetes mellitus (T2DM) may be independently associated with testosterone deficiency syndrome (TDS). Both conditions are linked with reduced quality of life and cardiovascular comorbidities. The magnitude of TDS among T2DM men and its predictors has still not been well established in Malaysia. This study aimed to determine the prevalence of TDS and its predictors among men with T2DM attending a government health clinic in Kuching, Sarawak. TDS severity and level of serum total testosterone were also explored. A cross-sectional study was conducted involving 360 respondents. Aging Males Symptoms Scale (AMS) score > 26 and serum total testosterone ≤ 12 nmol/L were used to diagnose TDS. The prevalence of TDS in current study was 19.7%. Multivariate analysis showed that determinants for TDS included age (Adjusted OR 1.061: 95% CI 1.020; 1.103), Iban ethnicity (Adjusted OR 2.469: 95% CI 1.154; 5.283) and a waist circumference equal or greater than 90 cm (Adjusted OR 3.655: 95% CI 1.472; 9.081). However, there was no significant association between TDS and the level of serum total testosterone (p = 0.581). We concluded that the prevalence of TDS in this study was relatively low. The severity of this condition may not be influenced by testosterone level. Physicians might consider a diagnosis of TDS if elder diabetic men with abdominal obesity present to primary care clinics with clinical features of hypogonadism. Health care providers also might consider lowering their threshold to screen for TDS among Iban men with T2DM.

Efficacy of Nasal Testosterone Gel (Natesto®) Stratified by Baseline Endogenous Testosterone Levels.

OBJECTIVE: Pharmacokinetic and efficacy data from a phase 3 testosterone nasal gel (TNG) study were stratified by baseline endogenous testosterone level in patients with testosterone deficiency. Total testosterone (TT), LH, and FSH levels, as well as erectile function, mood, and lean body mass for each group were compared. In a subset of patients with very low baseline endogenous testosterone levels (<100 ng/dL), we investigated whether TNG is a suitable treatment option. MATERIALS AND METHODS: Patients with testosterone deficiency (serum TT <300 ng/dL) were treated with TNG for 3 months, followed by safety extension periods of 90 and/or 180 days. Pharmacokinetic parameters were calculated from serum hormone levels on days 30 and 90, along with efficacy measurements, which were analyzed by comparison with baseline values. Baseline and/or predose TT values were used for patient stratification. RESULTS: Prestudy and predose endogenous testosterone concentrations correlated. The maximal concentration of TT was nearly identical across all cohorts at days 30 and 90, whereas the average concentration over 24 hours had a slight positive dependence relative to predose levels. LH levels remained in the normal range but were decreased more in patients with higher starting baseline levels. These findings indicate that TNG works with an active hypothalamic-pituitary-gonadal axis that responds to each dose of TNG throughout the treatment period. Patients with the lowest endogenous testosterone levels received maximum exposure impact from each TNG dose. Patients with severe testosterone deficiency had similar efficacy improvements as the remainder of the study population. CONCLUSION: All testosterone-deficient cohorts were successfully treated with TNG.

Importance of Different Grades of Abdominal Obesity on Testosterone Level, Erectile Dysfunction, and Clinical Coincidence.

The aim of the current study was to investigate the influence of different grades of abdominal obesity (AO) on the prevalence of testosterone deficiency syndrome (TDS), erectile dysfunction (ED), and metabolic syndrome (MetS). In a cross-sectional descriptive study, a total of 216 males underwent a complete urological, internal, and hormonal evaluation. Males were divided according to waist circumference into five groups: less than 94 cm (Grade [G] 0), 94 to 101 cm (G1), 102 to 109 cm (G2), 110 to 119 cm (G3), and more than 120 cm (G4). Incidence of ED, TDS, and MetS was compared in these groups and in participants without AO. Some degree of ED was identified in 74.7% of males with AO. In G1, there were 61% of males with ED, in G2 68%, in G3 83%, and in G4 87%. A strong correlation between testosterone (TST) level and AO was identified. Ninety-eight out of 198 (49.5%) males with AO and 1/18 (5.5%) males without AO had TDS. There were significant differences between individual groups. In the group of males with AO G4 (more than 120 cm), 87.1% had TDS. MetS was diagnosed in 105/198 (53.0%) males with AO, but in G4, 83.9% of males with AO had MetS. Males older than 40 years of age with AO have a higher incidence of ED, TDS, and MetS. Dividing males into five groups according to waist circumference seems to be reasonable. With growing AO, there were significantly more males with ED, TDS, and MetS.

Hormone concentration, metabolic disorders and immunoexpression of androgen and estrogen-alpha receptors in men with benign prostatic hyperplasia and testosterone deficiency syndrome.

INTRODUCTION: A slight decrease in blood testosterone level in men is a physiological state associated with the aging. The aim of our study was to evaluate the occurrence of hormone and metabolic disorders, as well as the immunolocalization and immunoexpression of androgen receptors (AR) and estrogen-alpha receptors (ERa) in the prostates of men with benign prostatic hyperplasia (BPH) and coexisting testosterone deficiency syndrome (TDS). MATERIAL AND METHODS: The study involved 150 men, diagnosed with and receiving pharmacological treatment for BPH. Concentrations of glucose, total cholesterol (TCh), high-density lipoproteins (HDL), low-density lipoproteins (LDL), and triglycerides (TG) were determined in blood serum. Serum concentrations of total testosterone (TT), free testosterone (FT), estradiol (E2), luteinizing hormone (LH), insulin (I), sex hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), and insulin-like growth factor 1 (IGF-1) were measured by ELISA. The number of AR-positive cells and ERa-positive cells were measured in prostate sections of men with BPH. RESULTS: Patients eligible for transurethral resection of the prostate and TDS were significantly more likely to have higher abdominal circumference and higher serum levels of insulin and IGF-1 as well as lower levels of FT and SHBG than control subjects with BPH and no TDS. Quantitative analysis revealed 35.8% AR-positive colum-nar epithelial cells and 24.3% AR-positive stromal cells in prostates of BPH patients with TDS and 30.5% and 23.0%, respectively, in BPH patients without TDS. However, the differences between the study and the control groups were statistically not significant. In prostates of BPH patients with TDS the immunoexpression of ERa was observed in 2.88% of the columnar epithelial cells and 0.39% of stromal cells. In BPH patients without TDS ERa-positive cells were only found in 0.04% of columnar epithelial cells and 0.62% of prostatic stromal cells. CONCLUSIONS: Considering the statistically significantly higher levels of I and IGF-1 and larger abdominal circumference of men with BPH and TT deficiency, it can be supposed that visceral obesity and carbohydrate disorders may contribute to the reduction of testosterone concentration. The results of our study indicate a relationship between TT concentration in the plasma of patients with BPH and the percentage of AR-positive cells in the prostate.

Testosterone and the Prostate.

INTRODUCTION: Late-onset hypogonadism, lower urinary tract symptoms (LUTS) due to benign prostatic enlargement (BPE), and prostate cancer commonly coexist in the aging male. Due to a better understanding of the physiology and impact of testosterone on benign and malignant diseases of the prostate, the view toward testosterone replacement therapy (TRT) in these individuals has changed dramatically over time. AIM: This communication evaluates the effects of testosterone on benign prostatic growth and prostate cancer and reviews the evidence for TRT for men with BPE and prostate cancer. METHODS: A literature review was performed with regards to TRT in men with prostate cancer as well as the effect of testosterone on the growth of benign prostate tissue and prostate cancer carcinogenesis. MAIN OUTCOME MEASURE: To evaluate the evidence for an effect of testosterone on the growth of benign prostate tissue and the development of prostate cancer and TRT in men with prostate cancer. RESULTS: TRT does not exacerbate LUTS. Current evidence is lacking but suggests that TRT may not increase the risk of subsequent diagnosis of prostate cancer, and is unlikely to impact recurrence or progression for men with treated prostate cancer, but longer follow-up is needed. CONCLUSIONS: There is no evidence to suggest that TRT is contraindicated in men with BPE or effectively treated prostate cancer. Tan RBW, Silberstein JL, and Hellstrom WJG. Testosterone and the prostate. Sex Med Rev 2014;2:112-120.

Erectile Dysfunction as a Cardiovascular Risk Marker

Erectile dysfunction is a common problem affecting up to 30 percent of men above 40 years old. Cardiovascular risk factors are closely associated with the development of vasculogenic erectile dysfunction. This explains the keen interest in identifying erectile dysfunction as a cardiovascular risk marker. A review of the literature reveals that erectile dysfunction has been shown to precede the development of coronary artery disease, and a number of hypotheses has been generated to support this association. Hence, it appears paramount that a complete assessment of erectile dysfunction would invariably involve assessment of cardiovascular risk factors and cardiac risk stratification. The Princeton III Consensus recommendation provides a straightforward guide for this purpose. The cardiologist should be involved early in the management of all patients with high cardiovascular risk, and some patients in the intermediate risk group.

Hypogonadism, ADAM, and hormone replacement.

Male hypogonadism, or testosterone deficiency syndrome (TDS), results from a failure of the testes to produce adequate androgen. Patients have low circulating testosterone in combination with clinical symptoms such as fatigue, erectile dysfunction, and body composition changes. The cause may be primary (genetic anomaly, Klinefelter's syndrome) or secondary (defect in hypothalamus or pituitary), but often presents with the same symptomatology. In the older patient, androgen deficiency of the aging male (ADAM) is an important cause of secondary hypogonadism because testosterone levels decline progressively after age 40. Hypogonadal patients have alterations not only in sexual function and body composition, but also in cognition and metabolism. Regardless of etiology, hypogonadal patients who are both symptomatic and who have clinically significant alterations in laboratory values are candidates for treatment. The goal of hormone replacement therapy in these men is to restore hormone levels to the normal range and to alleviate symptoms suggestive of hormone deficiency. This can be accomplished in a variety of ways, although most commonly testosterone replacement therapy (TRT) is employed.

Testosterone replacement therapy and monitoring for the male patients with testosterone deficiency syndrome

Since the elderly population has been increasing recently in our country, old male patients with testosterone deficiency syndrome (TDS) with a significantly decreasing quality of life are becoming increasingly common. TDS in males is defined as a biochemical syndrome associated with advancing age and characterized by clinical manifestation and a deficiency in the serum testosterone level. These patients should be treated with extrinsic testosterone to improve quality of life. TDS in males should be diagnosed in the case of clinical manifestation with serum total testosterone 12 nmol/L (350 ng/dL). Products for testosterone replacement therapy (TRT) are administrated orally, transdermally, and through injectable preparations. Daily testosterone undecanoate is widely used for oral administration with good results and no hepatotoxicity. Short-acting intramuscular preparations are very effective but show wide swings in the resulting supra-physiological level of serum testosterone. Long-acting intramuscular preparations is also very effective and lasting for 3 months with normal physiologic levels. Many products for TRT on the market are effective and generally safe. However, those have a few significant adverse events each other. The ideal product should have notable effectsand few side effects, (such as selective androgen receptor modulators), be easy to administrate, maintain physiologic serum concentration, and be inexpensive. TDS in males can easily be correct by TRT. However, the advantages and disadvantages of the individual products and follow-up management of complicated adverse events should be understood before starting and maintaining TRT.

Análisis preliminar del cuestionario Potenziani para la validación diagnóstica del hipogonadismo de comienzo tardío y su concordancia con los cuestionarios de Heinemann (AMS) y de Morley (ADAM) / Preliminary analysis of the Potenziani questionnaire for the late onset hypogonadism diagnostic validation and its concordance with the Heinemann (AMS) and Morley (ADAM) questionnaires

Hipogonadismo de comienzo tardío, es una condición que afecta 6% al 12% de hombres entre 40 y 70 años y aun así, está subdiagnosticada, por lo que se propone un cuestionario de validación diagnóstica, con el objetivo de lograr mayor sensibilidad, especifidad y predictividad que los cuestionarios ya existentes. Se analizaron 107 hombres entre 45 y 70 años, con disminución del entusiasmo en actividad diaria, cansancio fácil, menor productividad en su trabajo, cambios del humor con propensión a la irritabilidad, disminución de su masa magra muscular, con tendencia al sobrepeso y afectación en actividades recreativas y deportivas. Se hizo interrogatorio exhaustivo, examen físico y pruebas de laboratorio (perfil 20, perfil hormonal urológico masculino, antígeno prostático específico total, libre y relación libre/total, examen de orina y urocultivo). Se solicitó contestar al paciente tres cuestionarios de validación diagnóstica del hipogonadismo de comienzo tardío: Heinemann AMS (Ageing Males Survey-1999, St. Louis University, Androgen Deficiency in Aging Male), Morley ADAM-2000 y el cuestionario de validadción diagnóstica del hipogonadismo de comienzo tardío-Potenziani-2007, para ser comparados y demostrar su validez con pruebas de especificidad y sensibilidad, índice de Youden, pruebas de concordancia con intervalos de confianza del 95%, en relación al diagnóstico bioquímico del hipogonadismo de comienzo tardío. Los resultados arrojaron que el cuestionario "Potenziani" fue más sensible (88,57%), fue más específico (41,67%), tuvo el índice de validez más alto (57,01%) y el valor predictivo positivo más alto de los tres cuestionarios con el 42,5%. Por tal motivo se ha demostrado que el cuestionario propuesto es más adecuado que Heineman-AMS y el Morley-ADAM en la aproximación diagnóstica del síndrome de hipogonadismo de comienzo tardio

Late onset hypogonadism a condition which affect 6%-12% of men between 40-70 years old, and still it is subdiagnosed for which we did a validation questionnaire with the objetive to be more sensitive, especific and predictive that old questionnaires. We analized 107 men with ages between 45-70 years old whom consulted for libido deterioration, erectile dysfunction, less enthusiasm of daily life, less work-productivity, easy tiredness, humor changes with irritability, less muscle mass, overweight, and deterioration of sexual life in general. We performed exhaustive interrogatory, physical examination, and laboratoty test (20 profile, hormonal-urologic profile, prostatic specific antigen, urine and urocultive). We ask them to complete three questionnaires of late onset hypogonadism diagnostic validation: Heinemann AMS, Morley ADAM, Potenziani 2007, to be compared and show its validity with specificity and sensibility tests, Youden Index, test of concordance with confidence interval of 95%, in relation to biochemical diagnosis of deficiency testosterone syndrome. The results were that the Potenziani`s cuestionary was more sensible (88.57%), more specific (41.67%), with the validation index more high (57.01%) and with the positive predictive value more high too (42.5%). For that reason we show that Potenziani`s validation questionnaire of late onset hypogonadism, is more adecuate in the diagnostic aproximation of this condition