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author:("hera, moit")
1.  Physiological normal levels of androgen inhibit proliferation of prostate cancer cells in vitro 
Asian Journal of Andrology  2014;16(6):864-868.
For more than 70 years, it has been believed that a severe reduction of serum androgen levels caused regression of prostate cancer (PCa) and that increasing androgen levels enhanced growth of PCa. However, numerous recent studies have questioned this traditional belief. In our study, LNCaP and MDA PCa 2b PCa cells were treated with various levels of androgens for 10 or 20 days, and the cell growth was measured with crystal violet mitogenic assay. The results indicated that the effect of androgens on the proliferation of PCa cells occurs in a biphasic pattern, with the androgen levels promoting optimal cell growth at approximately 0.23 ng ml−1 for LNCaP cells and between 1 and 2 ng ml−1 for MDA PCa 2b cells. Both of the optimal androgen levels are within the adult men's physiological low range (<2.4 ng ml−1). At lower concentrations than the optimal androgen level, increasing androgen concentration promoted the proliferation of PCa cells. However, at the higher concentrations, increasing androgen concentration resulted in a dose-dependent proliferative inhibition. We conclude that physiologically normal levels of androgen inhibit the proliferation of PCa cells in vitro. However, at very low levels androgens are essential for initial growth of PCa cells.
doi:10.4103/1008-682X.129132
PMCID: PMC4236330  PMID: 24923459
androgen; proliferation; prostate cancer; testosterone
2.  Erectile dysfunction 
Clinical Evidence  2011;2011:1803.
Introduction
Erectile dysfunction may affect 30% to 50% of men aged 40 to 70 years, with age, smoking, and obesity being the main risk factors, although 20% of cases have psychological causes.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of phosphodiesterase inhibitors in men with erectile dysfunction of any cause? What are the effects of phosphodiesterase inhibitors on erectile dysfunction in men with diabetes, with cardiovascular disease, with spinal cord injury, and with prostate cancer or undergoing prostatectomy? What are the effects of drug treatments other than phosphodiesterase inhibitors in men with erectile dysfunction of any cause? What are the effects of devices, psychological/behavioural treatments, and alternative treatments in men with erectile dysfunction of any cause? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 81 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: alprostadil (intracavernosal, intraurethral, topical), cognitive behavioural therapy, ginseng, papaverine, papaverine plus phentolamine (bimix), papaverine plus phentolamine plus alprostadil (trimix), penile prostheses, phosphodiesterase inhibitors (sildenafil, tadalafil, vardenafil), psychosexual counselling, vacuum devices, and yohimbine.
Key Points
Erectile dysfunction may affect 30% to 50% of men aged 40 to 70 years, with age, smoking, and obesity being the main risk factors, although 20% of cases have psychological causes.
Sildenafil improves erections and increases the likelihood of successful intercourse in men with erectile dysfunction (any cause) and in specific populations of men with erectile dysfunction and diabetes mellitus, heart disease, spinal cord injury, prostate cancer, or after radical prostatectomy. Tadalafil and vardenafil also improve erections in men with erectile dysfunction (any cause). They are also effective in specific populations of men with erectile dysfunction, for example in those with diabetes, or in men with prostate cancer or after radical prostatectomy; however, fewer studies were found than with sildenafil, and no high-quality evidence was found in other specific populations such as in men with cardiovascular disease.
CAUTION: sildenafil, tadalafil, and vardenafil are contraindicated in men who are taking nitrates, as combined treatment has been associated with severe hypotension and death.
Intracavernosal, intraurethral, and topical alprostadil improve erections compared with placebo, but can cause penile pain in up to 40% of men. Intracavernosal alprostadil may improve erections compared with intraurethral alprostadil and intracavernosal papaverine.Intracavernosal alprostadil may be as effective as sildenafil and bimix.Adding phentolamine to intracavernosal papaverine (bimix) may increase effectiveness compared with papaverine alone, and adding alprostadil to bimix (trimix) may be more effective again. However, papaverine injections may cause altered liver function, and penile bruising and fibrosis.
Ginseng and yohimbine may increase successful erections and intercourse compared with placebo.
Vacuum devices may be as effective as intracavernosal papaverine, phentolamine, and alprostadil (trimix) at increasing rigidity, but less effective for orgasm, and may block ejaculation. There is consensus that penile prostheses may be beneficial, but they can cause infections and are only used if less invasive treatments have failed.
Psychosexual counselling and cognitive behavioural therapy may improve sexual functioning in men with psychological erectile dysfunction, but we found few good-quality studies. Several studies have demonstrated benefit of combination therapy (i.e., sex therapy and sildenafil or sex therapy and vacuum erection device) compared with monotherapy without sex therapy.
PMCID: PMC3217797  PMID: 21711956
3.  Testosterone replacement therapy among elderly males: the Testim Registry in the US (TRiUS) 
Background:
Testosterone levels naturally decline with age in men, often resulting in testosterone deficiency (hypogonadism). However, few studies have examined hypogonadal characteristics and treatment in older (≥65 years) men.
Objective:
To compare data at baseline and after 12 months of testosterone replacement therapy (TRT) in hypogonadal men ≥65 vs <65 years old. Data for participants 65–74 vs ≥75 years old were also compared.
Methods:
Data were from TRiUS (Testim Registry in the United States), which enrolled 849 hypogonadal men treated with Testim® 1% (50–100 mg testosterone gel/day) for the first time. Anthropometric, laboratory, and clinical measures were taken at baseline and 12 months, including primary outcomes of total testosterone (TT), free testosterone (FT), and prostate-specific antigen (PSA) levels. Comparisons of parameters were made using Fisher’s exact test or analysis of variance. Nonparametric Spearman’s ρ and first-order partial correlation coefficients adjusted for the effect of age were used to examine bivariate correlations among parameters.
Results:
Of the registry participants at baseline with available age information, 16% (133/845) were ≥65 years old. They were similar to men <65 years old in the duration of hypogonad-ism prior to enrollment (∼1 year), TT and FT levels at baseline, TT and FT levels at 12-month follow-up, and in reported compliance with treatment. Older patients were more likely to receive lower doses of TRT. PSA levels did not statistically differ between groups after 12 months of TRT (2.18 ± 2.18 ng/mL for ≥65 vs 1.14 ± 0.84 ng/mL for <65 years old, P = 0.1). Baseline values for the >75-year-old subcohort were not significantly different from subcohorts aged 65–74 years and <65 years.
Conclusion:
Hypogonadal men ≥65 years old showed significant benefit from TRT over 12 months, similar to that found for hypogonadal men <65 years old. TRT was well tolerated in older patients, successfully increased testosterone level regardless of age, and did not significantly increase PSA levels in older men.
doi:10.2147/CIA.S32036
PMCID: PMC3430096  PMID: 22956867
male hypogonadism; elderly; testosterone replacement therapy; testosterone gel; TRiUS registry; Testim
4.  Effect of 12 months of testosterone replacement therapy on metabolic syndrome components in hypogonadal men: data from the Testim Registry in the US (TRiUS) 
Background
Recent evidence suggests that there may be a bidirectional, physiological link between hypogonadism and metabolic syndrome (MetS), and testosterone replacement therapy (TRT) has been shown to improve some symptoms of MetS in small patient populations. We examined the effect of 12 months of TRT on MetS components in a large cohort of hypogonadal men.
Methods
Data were obtained from TRiUS (Testim® Registry in the United States), a 12-month, multicenter, prospective observational registry (N = 849) of hypogonadal men prescribed Testim 1% testosterone gel (5-10 g/day). Data analyzed included age, total testosterone (TT), free testosterone (FT), sex hormone-binding globulin (SHBG), and MetS components: waist circumference, blood pressure, fasting blood glucose, plasma triglycerides, and HDL cholesterol.
Results
Of evaluable patients (581/849) at baseline, 37% were MetS+ (n = 213) and 63% were MetS- (n = 368). MetS+ patients had significantly lower TT (p < 0.0001) and SHBG (p = 0.01) levels. Patients with the lowest quartile TT levels (<206 ng/dL [<7.1 nmol/L]) had a significantly increased risk of MetS+ classification vs those with highest quartile TT levels (≥331 ng/dL [≥11.5 nmol/L]) (odds ratio 2.66; 95% CI, 1.60 to 4.43). After 12 months of TRT, TT levels significantly increased in all patients (p < 0.005). Despite having similar TT levels after TRT, only MetS+ patients demonstrated significant decreases in waist circumference, fasting blood glucose levels, and blood pressure; lowest TT quartile patients demonstrated significant decreases in waist circumference and fasting blood glucose. Neither HDL cholesterol nor triglyceride levels changed significantly in either patient population.
Conclusion
Hypogonadal MetS+ patients were more likely than their MetS- counterparts to have lower baseline TT levels and present with more comorbid conditions. MetS+ patients and those in the lowest TT quartile showed improvement in some metabolic syndrome components after 12 months of TRT. While it is currently unclear if further cardiometabolic benefit can be seen with longer TRT use in this population, testing for low testosterone may be warranted in MetS+ men with hypogonadal symptoms.
doi:10.1186/1472-6823-11-18
PMCID: PMC3217857  PMID: 22044661
Testosterone; metabolic syndrome; obesity; testosterone gel; testosterone replacement; TRiUS registry; Testim; hypogonadism; testosterone deficiency; fasting glucose

Results 1-4 (4)