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Immunosenescence, Prostate health, and Reverse glaucoma

September 2017

Prostate health

Male lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH).

Male lower urinary tract symptoms, benign prostatic hyperplasia, enlargement of the prostate, and bladder outlet obstruction are common among aging men and will increase in socioeconomic and medical importance at a time of increased life expectancy and aging of the baby boomer generation. This article reviews the epidemiology, management, and therapeutic options for these conditions. In patients bothered by moderate to severe symptoms, providers can make educated and differential choices between several classes of drugs, alone or in combination, to treat effectively and improve the symptoms in most men. Despite the efficacy of medical therapy, there will be patients who require referral to a urologist either early, to rule out prostate cancer and other conditions, or later, after initial medical therapy and lifestyle management has failed. Perhaps as many as 30% of patients fail to achieve sufficient symptom improvement with medication, lifestyle adjustment, and fluid management, and may require more invasive or surgical treatment options.

Med Clin North Am. 2011 Jan;95(1):87-100

Management of the complications of BPH/BOO.

Most men will develop histological BPH if they live long enough. Approximately, half will develop benign prostatic enlargement (BPE) and about half of these will get BOO with high bladder pressures and low flow, this in turn leads to detrusor wall hypertrophy. Many of these men will only have lower urinary tract symptoms (LUTS) but a significant number will also suffer the other complications of BPH. These include urinary retention (acute and chronic), haematuria, urinary tract infection, bladder stones, bladder wall damage, renal dysfunction, incontinence and erectile dysfunction. Recognition of the complications of BPH/BOO early allows more effective management of these complications. This is particularly important for the more serious urinary infections and also for high-pressure chronic retention (HPCR). Complications of LUTS/BPH are very rare in clinical trials because of their strict inclusion and exclusion criteria but are more common in real life practice.

Indian J Urol. 2014 Apr;30(2):208-13

The effect of short sleep duration on coronary heart disease risk is greatest among those with sleep disturbance: a prospective study from the Whitehall II cohort.

STUDY OBJECTIVES: Short sleep duration is associated with increased CHD (coronary heart disease) mortality and morbidity, although some evidence suggests that sleep disturbance is just as important. We investigated whether a combination of short sleep duration and sleep disturbance is associated with a higher risk of CHD than their additive effects. SETTING: The Whitehall II study. PATIENTS OR PARTICIPANTS: The Whitehall II study recruited 10,308 participants from 20 civil service departments in London, England. Participants were between the ages of 35 and 55 years at baseline (1985-1988) and were followed up for an average of 15 years. INTERVENTIONS: N/A.MEASUREMENTS: Sleep hours and sleep disturbance (from the General Heath Questionnaire-30) were obtained from the baseline survey. CHD events included fatal CHD deaths or incident nonfatal myocardial infarction or angina (ICD-9 codes 410-414 or ICD-10 120-25). RESULTS: Short sleep duration and sleep disturbance were both associated with increased hazards for CHD in women as well as in men, although, after we adjusted for confounders, only those reporting sleep disturbance had a raised risk. There was some evidence for an interaction between sleep duration and sleep disturbance. Participants with short sleep duration and restless disturbed nights had the highest hazard ratios (HR) of CHD (relative risk:1.55, 95% confidence interval:1.33-1.81). Among participants who did not report any sleep disturbance, there was little evidence that short sleep hours increased CHD risk. CONCLUSION: The effect of short sleep (< or = 6 hours) on increasing CHD risk is greatest among those who reported some sleep disturbance. However, among participants who did not report any sleep disturbance, there was little evidence that short sleep hours increased CHD risk.

Sleep. 2010 Jun;33(6):739-44

Sleep duration as a risk factor for cardiovascular disease- a review of the recent literature.

Sleep loss is a common condition in developed countries, with evidence showing that people in Western countries are sleeping on average only 6.8 hour (hr) per night, 1.5 hr less than a century ago. Although the effects of sleep deprivation on our organs have been obscure, recent epidemiological studies have revealed relationships between sleep deprivation and hypertension (HT), coronary heart disease (CHD), and diabetes mellitus (DM). This review article summarizes the literature on these relationships. Because sleep deprivation increases sympathetic nervous system activity, this increased activity serves as a common pathophysiology for HT and DM. Adequate sleep duration may be important for preventing cardiovascular diseases in modern society.

Curr Cardiol Rev. 2010 Feb;6(1):54-61

Identification, pharmacologic considerations, and management of prostatitis.

BACKGROUND: Prostatitis is a collection of signs and symptoms that occur as a result of inflammation or swelling of the prostate gland. There are many different causes for prostatitis, including infection; occasionally no clear etiology for the inflammation is found. Effective treatment often depends on identification of the cause, but a microbiologic organism is not always detectable, especially in cases of chronic prostatitis. OBJECTIVE: The aim of this article was to review identification and treatment options for prostatitis, including pharmacologic and nonpharmacologic interventions. METHODS: Relevant information was identified through a search of MEDLINE (1966-June 2010), International Pharmaceutical Abstracts (1970-June 2010), and EMBASE (1947-June 2010). Randomized, controlled trials that examined prostate cancer, benign prostatic hypertrophy, or procedures related to the prostate (ie, biopsies) were excluded. RESULTS: A working classification system for prostatitis was developed in 1999, but there are few randomized controlled trials that distinguish between the various treatment options. Bacterial prostatitis can be acute or chronic but always requires some degree of antimicrobial therapy. Pharmacologic features of fluoroquinolones make them the preferred agents for most patients. These antibiotics can become trapped in a chronically inflamed prostate due to pH differences between prostatic tissue and serum. Many fluoroquinolones have penetration ratios (prostate level:serum level) of up to 4:1. A study in European men (N = 117) who received levofloxacin 500 mg/d with a diagnosis of chronic bacterial prostatitis demonstrated clinical success rates of 92% (95% CI 84.8%-96.5%), 77.4% (95% CI, 68.2-84.9%), 66.0% (95% CI, 56.2%-75.0%), and 61.9% (95% CI, 51.9%-71.2%) at 5-12 days, 1 month, 3 months, and 6 months after treatment. Additionally, there have been numerous randomized, placebo-controlled trials in patients with chronic prostatitis that have studied a-blockers, steroid inhibitors, anti-inflammatory agents, and bioflavonoids. Treatment responses to a-blockers appear to be greater with longer durations of therapy in a-blocker-naïve patients (National Institutes of Health-Chronic Prostatitis Symptom Index [NIH-CPSI] score reduction of at least 3.6 points after 6 weeks of tamsulosin therapy [P = 0.04] and up to 14.3 and 9.9 point NIH-CPSI score reductions with 14 weeks of terazosin and 24 weeks of alfuzosin therapy, respectively [P = 0.01 for both]). Combination therapy with an a-blocker, an anti-inflammatory, and a muscle relaxant does not appear to offer significant advantages over monotherapy (12.7 vs 12.4 point reduction in NIH-CPSI scores) and a stepwise approach to therapy involving antibiotics followed by bioflavonoids and then a-blockers appears to effectively reduce symptoms for up to 1 year in patients with chronic prostatitis (mean NIH-CPSI point reduction of 9.5 points compared with baseline, P < 0.0001). Patients who have had multiple unsuccessful treatment regimens may benefit from direct stimulation of the pelvic muscles through electromagnetic or electroacupuncture therapy. CONCLUSIONS: Prostatitis can resemble various other medical conditions but proper classification and an understanding of the pharmacologic features and expectations of the medications used to treat it can help identify effective treatment strategies. Fluoroquinolones are the preferred agents for treating bacterial causes of prostatitis and have demonstrated efficacy in some cases of chronic prostatitis when an organism has not been identified. However, the use of agents with anti-inflammatory or antiadrenergic properties may be necessary in combination with or after trying antimicrobial agents.

Am J Geriatr Pharmacother. 2011 Feb;9(1):37-48

Symptomatic diagnosis of prostate cancer in primary care: a structured review.

BACKGROUND: Prostate cancer has the second highest cancer incidence and mortality in European men. Most prostate cancers are diagnosed after lower urinary tract symptoms (LUTS) are presented to primary care, but such symptoms more often have a benign cause. A general practitioner (GP) has to try and identify which of these patients have prostate cancer. AIMS: To review the presenting features of symptomatic prostate cancer. DESIGN OF STUDY: Structured review. METHOD: We searched Medline from 1980 to 2003 for symptoms, signs, and investigations reported in prostate cancer. This list was then expanded by secondary searches of reference lists. We excluded studies on post-diagnostic topics, such as staging, treatment, and prognosis; studies on non-Western patients; and studies on investigations that are not available in primary care. A second cycle of exclusions removed studies whose results would not guide a GP in deciding whether a patient has prostate cancer. RESULTS: No studies from primary care compared prostate cancer patients directly with controls. Two secondary care studies had enough information to allow a comparison of symptoms in cases compared with controls. In these studies, symptoms were generally more prevalent in cases, but the differences were small. Screening and secondary care studies suggest that early prostate cancer is symptomless, and that locally advanced cancer has LUTS that are similar to those for benign prostatic hypertrophy. CONCLUSION: There is a very weak evidence base for the primary care diagnosis of prostate cancer in men with lower urinary tract symptoms.

Br J Gen Pract. 2004 Aug;54(505):617-21

With alpha blockers, finasteride and nettle root against benign prostatic hyperplasia. Which patients are helped by conservative therapy?

Symptomatic benign prostatic hyperplasia (BPH), which a man has a 50% chance of developing during the course of his lifetime, should receive stage-related treatment. While Vahlensieck stage I disease requires no therapy, stages II and III are indications for medication. Established medications for the treatment of BPH in current use are alpha-blockers, finasteride, and the phytotherapeutic agents pumpkin seed (cucurbitae semen), nettle root (urticae radix), the phytosterols contained in Hypoxis rooperi, rye pollen and the fruits of saw palmetto (sabalis serrulati fructus). If the patient responds, these medicaments can be given life-long, or intermittently. The hard criterion for the rational use of drug treatment of BPH is, over the long term, the reduction in the number of prostate operations. In stage IV disease surgical measures--after prior compensation of renal function--are to the fore.

MMW Fortschr Med. 2002 Apr 18;144(16):33-6

Epidemiology of benign prostatic syndrome. Associated risks and management data in German men over age 50.

In Germany, the condition of lower urinary tract symptoms (LUTS)/benign prostatic hypertrophy (BPH) is referred to as benign prostatic syndrome (BPS), reflecting the vast variation and interdependency of symptom severity, prostate volume, and micturition parameters. BPS is a progredient disease with distinguished risk factors for progression: age, symptom severity, prostate volume, and degree of obstruction. Therapy in Germany is provided by general practitioners and urologists. From a representative survey in Germany (the Herner BPS study), it can be calculated that among 11,674,900 men over 50 years of age, 3,230,000 have an enlarged prostate (benign prostatic enlargement, with prostate volume >25 ml). Moreover, 1,500,000 men with significant symptoms [International Prostate Symptom Score (IPSS) >7] have a prostate volume >40 ml, representing BPS with a high risk of progression, and 2,080,000 men show signs of obstruction (defined as Qmax <10 ml/s). Thirty percent of men with significant symptoms (IPSS >7) are treated medically, and an additional 20% have been prescribed medication for LUTS at least once. Ten percent of men in Germany are treated without evidence of symptoms. Based on published parameters of progression, 18.5% of men over 50 years of age will experience symptomatic progression (IPSS increase above four score points). Overall progression (symptomatic, surgery, or urinary retention) was 27% in 5 years. These findings show that BPS is a disease with substantial future effects on the German healthcare system.

Urologe A. 2008 Feb;47(2):141-8

Risk factors for lower urinary tract symptoms suggestive of benign prostatic hyperplasia in a community based population of healthy aging men: the Krimpen Study.

PURPOSE: We explored risk factors for lower urinary tract symptoms suggestive of benign prostatic hyperplasia in the open population. MATERIALS AND METHODS: A longitudinal, population based study with a followup of 6.5 years was done in 1,688 men who were 50 to 78 years old. Data were collected on transrectal ultrasound of prostate volume, urinary flow rate, ultrasound estimated post-void residual urine volume, generic and disease specific quality of life, and symptom severity based on the International Prostate Symptom Score. Lower urinary tract symptoms suggestive of benign prostatic hyperplasia were defined as an International Prostate Symptom Score of greater than 7 after a report of a score of less than 7 in the previous round. A multivariate Cox proportional hazard model was constructed to determine risk factors for clinical benign prostatic hyperplasia after correcting for patient age. RESULTS: Total followup was 4,353 person-years. During followup 180 events of attaining an International Prostate Symptoms Score of greater than 7 occurred. Multivariate analysis showed that functional bladder capacity, post-void residual urine volume, treatment for cardiac diseases, education level, antidepressant use, calcium antagonist use, erectile function or dysfunction, prostate specific antigen and a family history of prostate cancer were determinants with a significant HR. CONCLUSIONS: In addition to age, we established 9 significant determinants for lower urinary tract symptoms suggestive of benign prostatic hyperplasia. However, not all risk factors for lower urinary tract symptoms suggestive of benign prostatic hyperplasia are accounted for since we can conclude that 1 of 3 men without these risk factors will still be diagnosed with lower urinary tract symptoms suggestive of benign prostatic hyperplasia between ages 50 and 80 years.

J Urol. 2009 Feb;181(2):710-6

Pathogenic mechanisms linking benign prostatic hyperplasia, lower urinary tract symptoms and erectile dysfunction.

INTRODUCTION: Erectile dysfunction (ED) and lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH) are clinical entities very prevalent in men aged over 50 years. There is evidence that both may have a common pathophysiology. OBJECTIVE: The objective of this study was to conduct a literature review aiming to show theories and hypotheses that justify a single pathophysiology for ED and LUTS/BPH. METHODS: A search in Medline using the keywords of the Medical Subject Headings (MESH) 'erectile dysfunction' and 'lower urinary tract symptoms' in all fields of the database up to 15 December 2012. This search found 198 relevant articles that were analyzed. RESULTS: The data and articles were divided according to the type of evidence found. There are strong epidemiological data showing that LUTS/BPH is a risk factor for developing ED. Several experimental models demonstrated partial obstruction of the bladder in animals causes voiding disorders as well as a negative impact on erectile function of the operated animals. The increased adrenergic tonus in animals leads to prostate growth and urodynamic conditions similar to those found in men with LUTS and ED. Arteriosclerosis may lead to loss of vesical complacency, urinary tract obstruction and fibrosis of the cavernous bodies. The use of phosphodiesterase type 5 inhibitors (PDE-5i) and/or alpha-adrenergic blockers to treat ED and LUTS/BPH reinforces the hypothesis that, at least in some patients, both clinical pictures may have the same pathophysiology.

Ther Adv Urol. 2013 Aug;5(4):211-8

A comparative randomized prospective study to evaluate efficacy and safety of combination of tamsulosin and tadalafil vs. tamsulosin or tadalafil alone in patients with lower urinary tract symptoms due to benign prostatic hyperplasia.

INTRODUCTION: Lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) and erectile dysfunction are common disorders of advancing age. AIM: To evaluate the efficacy and safety of tamsulosin and tadalafil in patients with LUTS due to BPH. METHODS: In this prospective randomized study, 133 men complaining of LUTS due to BPH were included. Forty-five patients received tamsulosin 0.4 mg/day alone (Group A), 44 patients received tadalafil 10 mg/day (Group B), and combination therapy (tamsulosin and tadalafil both) was instituted in 44 patients (Group C). After a 2-week medication free run-in period, they were evaluated for International Prostatic Symptom Score (IPSS), International Index of Erectile Function score (IIEF5), quality of life (IPSS QoL), maximum urinary flow rate (Qmax), post-void residual urine (PVR) volume, and safety parameters before and at 3 months of treatment. MAIN OUTCOME MEASURES: There were primary (IPSS, IPSS QoL index, Qmax, and PVR) and secondary (erectile function [EF] domain scores from IIEF5) efficacy end points. Safety assessment included laboratory tests and patient's reporting of adverse event. RESULTS: A significant improvement in IPSS score was observed in all the 3 groups A, B, and C (-50.90%, P < 0.05; -33.50%, P < 0.05; and -53.90%, P < 0.05, respectively). IIEF5 score increased significantly in these three groups (+39.28%, P < 0.05; +45.96%, P < 0.05; and +60.23%, P < 0.05, respectively). A significant increase in Qmax and decrease in PVR were also observed (33.99%, P < 0.05; 29.78%, P < 0.05; and 37.04%, P < 0.05) and (-60.90%, P < 0.05; -49.45%, P < 0.05; and -62.97%, P < 0.05, respectively). The QoL scores improved significantly (-73.35%, P < 0.05; -70.26%, P < 0.05; and -79.65%, P < 0.05, respectively). Side effects were dyspepsia, heartburn, headache, flushing, myalgia, and backache. Adverse effect dropout was 3.7%. No participant experienced any severe or serious adverse events. CONCLUSIONS: In patients with LUTS due to BPH, tamsulosin and tadalafil alone or in combination cause a significant improvement in patients with LUTS. Their EF also improves with these medications. The improvement is better with combination therapy compared with single agent alone.

J Sex Med. 2014 Jan;11(1):187-96

The efficacy of PDE5 inhibitors alone or in combination with alpha-blockers for the treatment of erectile dysfunction and lower urinary tract symptoms due to benign prostatic hyperplasia: a systematic review and meta-analysis.

INTRODUCTION: Erectile dysfunction (ED) and lower urinary tract symptoms (LUTS) are both highly prevalent in aging men. Alpha-blockers and PDE-5 inhibitors are widely used for the treatment of LUTS/benign prostatic hyperplasia (BPH) and ED. AIM: The purpose of this meta-analysis was to evaluate the efficacy of phosphodiesterase type 5 (PDE5) inhibitors alone or in combination with alpha-blockers for the treatment of ED and LUTS. METHODS: The databases MEDLINE, EMBASE, PubMed, the Cochrane Controlled Trial Register of Controlled Trials, and the Chinese Biological Medical Database were searched to identify randomized controlled trials that referred to the use of a combination of PDE5 inhibitors and alpha-blockers for the treatment of ED and LUTS associated with BPH. A systematic review and meta-analysis was conducted. MAIN OUTCOME MEASURES: International Prostate Symptom Score (IPSS), the maximum flow rate (Qmax), and International Index of Erectile Function-Erectile Function (IIEF-EF) domain score were used in this meta-analysis. RESULTS: Seven publications involving 515 patients were included in the meta-analysis. In the analysis, we found significantly improved IIEF, IPSS, and Qmax values in the combination use group compared with the use of PDE5 inhibitors alone (P = 0.04, 0.004, 0.007, respectively). CONCLUSIONS: The combined use of PDE5 inhibitors and alpha-blockers results in additive favorable effects in men with ED and LUTS suggestive of BPH compared with PDE5 inhibitor monotherapy. The alpha-blockers may enhance the efficacy of the PDE5 inhibitors, which is beneficial for the treatment of ED and LUTS.

J Sex Med. 2014 Jun;11(6):1539-45