Testosterone therapy in erectile dysfunction

Studies in animals have indicated that the nitric oxide erectile pathway is testosterone-dependent. Castration induces erectile dysfunction and a reduction in nitric oxide synthase-stained nerves in erectile tissue. Furthermore, castration adversely affects penile hemodynamics and smooth muscle content, leading to veno-occlusive dysfunction. Testosterone replenishment reverses these physiological, biochemical and structural changes. Several clinical studies have demonstrated the benefits of a combination of testosterone and sildenafil. A recently published, multicenter study evaluated the safety and efficacy of testosterone gel 1% (Testogel®; Schering AG, Germany/AndroGel®; Solvay Pharmaceuticals) vs. placebo gel in conjunction with sildenafil, in producing an erectile response in hypogonadal men who did not respond to treatment with sildenafil alone for erectile dysfunction. The selection criteria required subjects to have had erectile dysfunction for at least 3 months, to be non-responsive to 100 mg sildenafil and to have low testosterone levels (<?400 ng/dl). The primary efficacy measurement was the mean change from baseline in the Erectile Function domain of the International Index of Erectile Function (IIEF). Secondary outcome measures included the mean change from baseline in the other domains and the total sum of the IIEF. Subjects were randomized to receive either testosterone gel + sildenafil, or placebo gel + sildenafil for 12 weeks. Testosterone therapy with testosterone gel improved the erectile response to sildenafil. Therefore, testosterone therapy may be considered for the treatment of erectile dysfunction in men with low to low-normal testosterone levels, who have failed prior treatment with sildenafil alone. Consequently, it is important to screen for hypogonadism in men who fail PDE5 inhibitors.     

Early weight loss predicts the reduction of obesity in men with erectile dysfunction and hypogonadism undergoing long-term testosterone replacement therapy

We and others have previously shown that testosterone replacement therapy (TRT) results in sustained weight loss in the majority of middle-aged hypogonadal men. Previously, however, a small proportion failed to lose at least 5% of their baseline weight. The reason for this is not yet understood. In the present study, we sought to identify early indicators that may predict successful long-term weight loss, defined as a reduction of at least 5% of total body weight relative to baseline weight (T0), in men with hypogonadism undergoing TRT. Eight parameters measured were assessed as potential predictors of sustained weight loss: loss of 3% or more of baseline weight after 1 year of TU treatment, severe hypogonadism, BMI, waist circumference, International Prostate Symptom Score (IPSS), glycated hemoglobin (HbA_1C), age and use of vardenafil. Among the eight measured parameters, three factors were significantly associated with sustained weight loss over the entire period of TU treatment: (1) a loss of 3% of the baseline body weight after 1 year of TRT; (2) baseline BMI over 30; and (3) a waist circumference >102?cm. Age was not a predictor of weight loss.     

Inverse association of testosterone and sex hormone binding globulin levels with leukocyte count in middle-aged and elderly men

Objective: The inverse associations of testosterone and sex hormone-binding globulin (SHBG) levels with cardiometabolic diseases are well established and are increasingly viewed as inflammatory diseases. This study aimed to examine the associations of testosterone and SHBG levels with leukocyte count in 451 Korean men aged ≥50 years.

Methods: Serum testosterone and SHBG levels were categorized into tertiles. High leukocyte count was defined as ≥7340 cells/μl, which corresponded to the 75th percentile of the current sample. The odds ratios (ORs) and 95% confidence intervals (95% CIs) for high leukocyte count were calculated across testosterone and SHBG tertiles using multiple logistic regression analysis.

Results: The mean leukocyte counts significantly decreased with increasing testosterone and SHBG tertiles. The ORs (95% CIs) of high leukocyte count for the first tertile of testosterone and SHBG were 3.27 (1.34–7.95) and 2.38 (1.05–5.96), respectively, compared with the referent third tertile, after adjusting for age, smoking status, alcohol drinking, regular exercise, body mass index, blood pressure, fasting plasma glucose, triglyceride, and high-density lipoprotein (HDL) cholesterol level.

Conclusion: We found inversely graded associations of low testosterone and SHBG levels with leukocyte count. These findings suggest that low testosterone and SHBG levels may be interpreted as a state of low-grade inflammation.     

Testosterone is not associated with mortality in older African-American males

Introduction.?Although testosterone and its association with disease progression and mortality is a widely studied topic, no studies have evaluated mortality risks related to testosterone levels in an older African-American population. The mechanisms for known racial differences in mortality risk for certain cancers and cardiovascular risk factors are largely unknown. Elucidating a mortality risk associated with testosterone levels may give insight into the elevated risk for certain diseases in African-Americans.

Methods and results.?Study data were derived from a cohort 622 African-Americans (age 80.05?±?6.4, range 68–102) from Saint Louis, Missouri that includes 190 males (age 79.38?±?6.2, range 70–102). The eligible sample for this report includes 56 of the 190 males (age 78.89?±?6.9, range 70–102) who donated blood at baseline in 1992–1994 and subsequently tested for total testosterone and bioavailable testosterone. Covariates for adjusted analyses were lower body functional limitations, physician visits and comorbidities, also collected at baseline. Males' mean bioavailable testosterone levels (ng/dl) were 33.33?±?24.4 (n above 70?ng/dl?=?5) and mean total testosterone levels (ng/dl) were 246.63?±?118.7 (n above 300?ng/dl?=?20). Vital status was determined through 2002; 41 males (73%) were deceased and 15 were alive. Mortality did not differ among males with testosterone levels?<300 versus 300+ (p?=?0.42) or with bioavailable testosterone levels?<70 versus > 70 (p?=?0.34). Total testosterone levels did not predict mortality when adjusted for age (Adjusted Hazard Ratio [AHR]?=?0.998; 95% confidence interval [CI] 0.995–1.001; p?=?0.28) or adjusted for age and other covariates (AHR?=?0.099; 95% CI 0.996, 1.002; p?=?0.35). Bioavailable testosterone levels did not predict mortality when adjusted for age (AHR?=?0.992; 95% CI .977–1.007; p?=?0.30) or when adjusted for age and other covariates (AHR 0.991; 95% CI .976–1.006; p?=?0.261).

Conclusion.?In older African-American males, total and bioavailable testosterone levels, with and without adjustment for covariates, are not independently associated with mortality risk.     

Androgens and sexual function: a placebo-controlled,randomized, double-blind study of testosterone vs. dehydroepiandrosterone in men with sexual dysfunction and androgen deficiency

Purpose.?Supplemental administration of androgens has been advocated for men with sexual dysfunction (SD) and hypoandrogenism. The preponderance of evidence indicates that most delivery forms of testosterone (T) are effective but the role of dehydroepiandrosterone (DHEA) is controversial. A placebo-controlled, randomized trial of oral androgen (T versus DHEA) supplementation was carried out to determine their efficacy.

Materials and methods.?Eighty-six men with SD and decreased levels of serum T and/or DHEA, participated in a study receiving oral T undecanoate (OTU) (n?=?29) 80?mg twice daily, DHEA (n?=?28) 50?mg twice daily, or placebo (n?=?29). Outcomes included evaluation of sexual performance by the International Index of Erectile Function (IIEF), the Androgen Deficiency in the Aging Male (ADAM), Aging Male Symtom Scale (AMS), and Global Assessment Questionnaire (GAQ) questionnaires. Biochemical evaluations included measurement of T and DHEA, prolactin, gonadotropins, and PSA.

Results.?Seventy-nine men completed the study. There were no significant differences in outcomes as assessed by four different instruments: the ADAM, IIEF, AMS, and GAQ in regard to sexual interest or erectile function. Biochemically, a significant increase in serum DHEA between baseline and final visit was documented in the group receiving DHEA. The levels of T, on the other hand, increased insignificantly between entry and final visit in the T cohort. No biochemical changes were observed in the placebo group. Levels of PSA remained stable in all three groups.

Conclusions.?This study did not suggest a clinical benefit of OTU or DHEA supplementation in men with hypoandrogenism and SD. The recommended dose of OTU may have been inadequate or poorly absorbed. Increased doses or an alternative T delivery form may result in a different response.     

Timetable of effects of testosterone administration to hypogonadal men on variables of sex and mood

Introduction.?The effects of testosterone have been extensively characterized, but little attention has been given to the timetable of occurrence of the various effects of testosterone.

Methods.?The timetables of effects on sexual and psychological variables in 40 hypogonadal men receiving treatment with either parenteral testosterone enanthate (TE) or undecanoate (TU).

Results.?Sexual thoughts/fantasies and sexual interest/desire/spontaneous morning erections emerged quickly and plateaued after 3 weeks. Total erections rose to a maximum over 9 weeks and then plateaued. Ejaculations per week/satisfaction with sex life rose over the first 3 weeks, increasing steadily to a plateau at 12 weeks. Depression scores decreased to reach a plateau after 6 weeks. Aggressiveness did not change. Scores of concentration improved and reached a plateau after 3 weeks in the group treated with TE and after 9 weeks in the group treated with TU. Good mood improved after 6–9 weeks. Positive effects on self-confidence appeared between 3–6 weeks and on fatigue after 9–12 weeks.

Conclusion.?Insight into the emergence of effects may be useful information for the patient and for the attending physician in monitoring clinical effects of testosterone treatment of hypogonadal men.     

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

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

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

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

Clinical experience with the new long-acting injectable testosterone undecanoate. Report on the educational symposium on the occasion of the 5th World Congress on the Aging Male, 9–12 February 2006, Salzburg,Austria

This symposium report summarizes first extensive clinical findings with injectable testosterone undecanoate (Nebido®) in hypogonadal patients showing clinical symptoms of androgen deficiency with or without erectile dysfunction (ED). This new testosterone formulation (1000 mg testosterone undecanoate in 4 ml castor oil) possesses nearly ideal long-term kinetics, i.e. sustained close mimicking of eugonadal testosterone serum levels without supra- or sub-physiological serum concentrations. The generally accepted administration scheme recommends the second injection 6 weeks after the first one followed by further injections every 12 weeks. Applying this regimen, administration intervals are drastically reduced in comparison to conventional i.m. testosterone preparations (e.g. about 16 injections of testosterone enanthate vs. 4–5 injections of testosterone undecanoate per year). Depending on the testosterone serum levels, individualized therapy is possible by shortening (every 10 weeks) or prolonging (every 14 weeks) the injection intervals. In hypogonadal patients with ED 58% respond to testosterone undecanoate alone. Best results are seen in diabetic hypogonadal patients. The regimen of injectable testosterone undecanoate administration ideally fits recommendations regarding pharmacokinetics, efficacy and safety monitoring.