Bloodless management of benign prostatic hyperplasia: medical and minimally invasive treatment options

Benign prostatic hyperplasia (BPH) is a medical condition affecting a wide range of the aging male population resulting in various degrees of lower urinary tract symptoms (LUTS). Today, a variety of medical therapies and minimally invasive BPH treatment modalities are available. Medical therapy includes α₁ blockers, 5α reductase inhibitors and combination therapy. When these options fail, surgery is indicated. Transurethral resection of the prostate (TURP) is still considered the gold standard surgical treatment for BPH. Nevertheless, numerous minimally invasive treatment alternatives are available that are comparable in effectiveness to TURP, with significantly less morbidity. In this article, current treatment options for BPH are reviewed with respect to their indications, long-term safety and efficacy in relieving BPH related LUTS. The selection of the type of BPH treatment should be based on the physician's experience, patient's co-morbidities as well as the prostate size and clinical disease progression.     

Epidemiology and risk factors of lower urinary tract symptoms/benign prostatic hyperplasia and erectile dysfunction

Benign prostatic hyperplasia (BPH) is very common in aging men and causes lower urinary tract symptoms (LUTS), which decrease health-related quality of life. A number of evidence suggests that other than ageing, modifiable factors, such as increasing prostate volume, obesity, diet, dyslipidemia, hormonal imbalance, hypertension, metabolic syndrome, alcohol, and smoking, also contribute to the development of BPH and/or LUTS. More recently, erectile dysfunction (ED) has been linked to LUTS/BPH as a part of this syndrome, suggesting that patients with BPH or LUTS easily develop ED, and that LUTS/BPH symptoms often coexist with ED. This article focuses on the epidemiology and risk factors of the combined phenotype LUTS/BPH – ED.     

Treatment of lower urinary tract symptoms/benign prostatic hyperplasia and erectile dysfunction

Abstract

This article summarizes years of challenging research on erectile dysfunction (ED), a condition that has an important social and cultural relevance. Preclinical and clinical research progress has led to new therapeutic approaches to ED in patients with different comorbidities and particularly in those with low urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH). These goals were possible only by combined work of specialists and researchers of different and intertwined medical disciplines. Currently, tadalafil (5?mg/d) is the best choice; other phosphodiesterase-5 inhibitors (PDE5i) are not included among options, despite the growing evidence of therapeutic effects. Different regimens of tadalafil may be prescribed based on patient needs, severity of LUTS/BPH – ED profile, and clinical experience. An integrated approach is necessary to choose for a combined therapy with PDE5i and α-blockers following urological and cardiac counseling in terms of outcomes and adverse effects.     

Daily use of sildenafil 50mg at night effectively ameliorates nocturia in patients with lower urinary tract symptoms associated with benign prostatic hyperplasia: an exploratory multicenter,double-blind,randomized, placebo-controlled study

Purpose: To compare the efficacy and safety of sildenafil 25?mg qd, 25?mg bid or 50?mg qd – on treating lower urinary tract symptoms with benign prostatic hyperplasia (LUTS/BPH).

Materials and methods: Men aged?>?45 years with LUTS/BPH were randomly assigned to receive sildenafil 25?mg qd (n?=?42), bid (n?=?41), 50?mg qd (n?=?38) or placebo (n?=?41) for 8 weeks. Changes from baseline in International Prostate Symptom Score (I-PSS), maximum urinary flow rate (Qmax) and postvoid residual urine volume (PVR) were assessed at week 4 and week 8.

Results: Sildenafil 25?mg qd (-7.3?±?5.8) and 25?mg bid (-7.0?±?5.7) exhibited significant improvements of I-PSS compared to placebo (-5.2?±?6.4) (p?=?0.020, 0.025, respectively). In particular, voiding domain was more affected than storage domain. Only sildenafil 50?mg qd improved nocturia significantly (versus placebo, p?=?0.027). Quality of life score was improved in all treatment groups. Q_max and PVR did not change significantly in all groups. All regimens were well tolerated.

Conclusions: Sildenafil 25?mg qd, 25?mg bid and 50?mg qd are safe and effective to improve LUTS/BPH in long term, along with coexisting ED. In particular, nocturia is most well-controlled by 50?mg qd.     

Alternative drug therapies for dementia

Drugs currently approved by the U.S. Food and Drug Administration (FDA) for the treatment of Alzheimer's disease include acetylcholinesterase inhibitor (i.e., tacrine, donepezil, rivastigmine, and galantamine) and glutamate-modulating (i.e., memantine) drugs. Because these drugs have modest benefits, various alternative drug therapies have been of interest. Drugs with vasodilator activity were originally tried in dementia when it was hypothesized that the condition was due to cerebrovascular insufficiency. Isoxsuprine and ergoloid mesylates are FDA approved for the treatment of dementia, although they have limited evidence of benefit and are rarely used. The hypothesis that free radicals may initiate and maintain mechanisms responsible for neurodegeneration in dementia has stimulated interest in investigating various antioxidant and anti-inflammatory drugs. There is no evidence that other drug therapies, including vitamin E, selegiline, nonsteroidal anti-inflammatory drugs, statin drugs, omega-3 fatty acids, estrogen or combined estrogen plus progestin therapy, or B vitamins, are sufficiently effective and safe to justify their clinical use for the treatment of dementing disorders.     

Publication bias and outcome reporting bias: agomelatine as a case example

Publication bias and outcome reporting bias contribute to distorted perceptions of drug efficacy and the underreporting of adverse events. To demonstrate these biases, this article describes how the clinical profile of the antidepressant agent agomelatine (Valdoxan(?)) has been presented in the literature. Agomelatine has been systematically assessed in 10 short-term placebo-controlled studies and three long-term placebo-controlled relapse prevention studies. Five published trials demonstrated clinically modest but statistically significant benefits over placebo. Five unpublished trials did not find agomelatine more effective than placebo, but in two of these studies the active comparison drug (fluoxetine [Prozac(?)] or paroxetine [Paxil(?)]) was more effective than placebo. Agomelatine was more effective than placebo in one of three relapse prevention studies, but only the positive study was published. Based on what is evident in the entire published and unpublished dataset, agomelatine does not have a tremendously superior sleep and sexual effects profile. The risk of liver toxicity is also not prominently highlighted in the published literature.     

Efficacy and safety of orally disintegrating tamsulosin tablets in Taiwanese patients with benign prostatic hyperplasia

Objectives: Tamsulosin is an alpha-1 adrenoceptor antagonist applied in treating lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH). This study aimed to evaluate safety, efficacy and acceptance of newly formulated orally disintegrating tamsulosin tablets in Taiwanese patients with LUTS/BPH. Methods: This single center, non-comparative, observational study enrolled 45 male patients over age 50 years. All patients received 0.2?mg tamsulosin orally disintegrating tablets daily and were evaluated at weeks 0, 4, 8, 12 of the 12-week treatment period. Tamsulosin efficacy was evaluated by International Prostate Symptom Score (I-PSS) with 7 questions on urinary symptoms and one disease-specific quality-of-life question, with scores ranging from 0 (no symptoms) to 35 (highly symptomatic). Maximum flow rate (ml/s), voided volume (ml), flow time (s), and mean flow rate (ml/s) were measured. Danish prostatic symptom sexual function scale rated severity and associated concerns of erection quality, ejaculatory function and pain/discomfort were also assessed. Results: Patients’ mean ± SD age was 62.47?±?7.77 (range: 50–89) and mean ± SD I-PSS was 13.98?±?5.50. Statistically significant changes from baseline were found in post-test I-PSS and quality of life (both P < 0.001). Mean ± SD I-PSS decreased from 14.30?±?9.34 to 6.73?±?0.88 at patients’ final visit. Statistically significant increases in mean maximum flow rate and mean flow rate were found over 12-week study period (P < 0.05). No adverse events were reported. No significant differences were found in pulse, SBP/DBP or sexual function. Conclusion: Orally disintegrating tamsulosin tablets demonstrate acceptable safety and efficacy for acceptance and well tolerance by Taiwanese LUTS/BPH patients.     

Administration of daily 5 mg tadalafil improves endothelial function in patients with benign prostatic hyperplasia

Introduction: Tadalafil is a promising phosphodiesterase (PDE) 5 inhibitor prescribed for erectile dysfunction (ED). Daily low dose (5?mg) of tadalafil has also been used for the treatment of male lower urinary tract symptoms (LUTS) associated with benign prostate hyperplasia (BPH). PDE5 inhibitors induce relaxation of smooth muscle cells in the urethra, prostate, bladder neck, and blood vessels. The aim of this study was to investigate the efficacy of tadalafil on vessels endothelial function, in patients with male LUTS symptoms associated with BPH.

Methods: The Institutional Review Board (IRB) approved this clinical study and informed consents had been obtained from 81 BPH patients.

The following male LUTS parameters: international prostate symptom score (IPSS), overactive bladder symptom score (OABSS), voiding volume, max and mean voiding flow on voiding flowmetry examination and post-voiding residual urine (RU) were compared at 0, 1, 3, 6, and 12 months after a daily dose of 5?mg tadalafil.

In addition, erectile function was evaluated by the sexual health inventory for men (SHIM) score and vessels endothelial function and peripheral neuropathy were assessed by the brachial-ankle pulse wave velocity (baPWV), ankle brachial index (ABI), and vibration perception threshold (VPT) at 0, 3, 6, and 12 months after treatment.

Results: The mean age of 81 patients was 66.4?±?11.4 years old. Their prostate size was 30.2?±?22.1?ml.

Male LUTS parameters including IPSS, OABSS, and RU showed significant improvement from 1 to 12 months after tadalafil administration. Max and mean voiding flow was significantly increased at 6 months after tadalafil treatment.

The SHIM score showed significant improvement after 3 months. Whilst, the results of baPWV also showed significant improvement from 3 to 12 months. ABI was also significantly improved at 6 months. However, there was no change in the VPT at any time point.

Conclusions: Tadalafil is effective for both male LUTS and ED. It is also shown that tadalafil improves baPWV, which we can conclude that higher vessels elasticity has been obtained. This major finding of this study shows that tadalafil has the potency to improve vessels endothelial dysfunction in patients with BPH.     

Briefly Noted

Last month, the federal Food and Drug Administration (FDA) warned that combining gabapentin or pregabalin with central nervous system (CNS) depressants such as opioids could result in serious breathing problems for patients with underlying respiratory problems, or in the elderly. New labeling will be required on gabapentin and pregabalin, the FDA said. There is less evidence supporting such a risk in otherwise healthy people, the FDA said in the Dec. 19, 2019, warning. Gabapentin, first approved in 1993, is not a controlled substance. It is approved to treat various conditions, including seizures, nerve pain, fibromyalgia and restless legs syndrome. Pregabalin, first approved in 2004, is Schedule V on the Controlled Substances Act, the lowest‐risk category of controlled substance. “With the evolution of the opioid crisis, getting ahead of new concerns or addressing those that are already evident requires examining signs of misuse and abuse as soon as any signal emerges,” said Douglas Throckmorton, M.D., deputy director for regulatory programs in the FDA's Center for Drug Evaluation and Research, in announcing the warning. “Reports of gabapentinoid abuse alone, and with opioids, have emerged and there are serious consequences of this co‐use, including respiratory depression and increased risk of opioid overdose death. In response to these concerns, we are requiring updates to labeling of gabapentinoids to include new warnings of potential respiratory depressant effects.” Drug manufacturers are also being required to conduct clinical trials to evaluate the abuse potential of all gabapentinoids, particularly when combined with opioids, said Throckmorton. The downside is that prescribers could inadvertently increase opioid use by not using these medications, Throckmorton acknowledged, saying “we do not want to unintentionally increase opioid use by turning prescribers away from this class of pain medications.” For more information, go to https://www.fda.gov/drugs/drug‐safety‐and‐availability/fda‐warns‐about‐serious‐breathing‐problems‐seizure‐and‐nerve‐pain‐medicines‐gabapentin‐neurontin .     

Pharmacotherapy for psychotropic drug-related weight gain

Weight gain is a significant problem for many patients taking various psychotropic medications. The U.S. Food and Drug Administration (FDA) has approved certain medications for the treatment of obesity. Other medications known to be associated with weight loss could be used for treating obesity, although they are not FDA approved for this indication. This article briefly describes the sympathomimetic, antidepressant, anticonvulsant, histamine-modulating, antidiabetic, and gastrointestinal drugs that have been found to cause weight loss and might be considered for adjunctive use in the overall management of psychotropic drug-related weight gain. However, even if such drugs are effective, all patients should receive ongoing dietary and physical activity counseling.     

Impact of metabolic syndrome on erectile dysfunction and lower urinary tract symptoms in benign prostatic hyperplasia patients

Introduction.?The aim of this study was to investigate the relationship among metabolic syndrome (MetS), erectile dysfunction (ED) and lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia (BPH).

Methods.?Our study included 106 patients with BPH, 33 (31.1%) of whom had MetS. Blood pressures, waist circumferences, serum levels of fasting blood glucose, high density lipoprotein and triglyceride of patients were recorded. Erectile functions of the patients were evaluated by International Index of Erectile Function (IIEF). Patients were divided into two groups according to IIEF scores, namely ‘mild/no ED’ and ‘moderate/severe ED’. IIEF scores of ED groups were between 17 and 30 and 6–16 in turn. LUTS severities were assessed by International Prostate Symptom Score (IPSS) and classified as mild (IPSS 0–7), moderate (IPSS 8–19) and severe (IPSS 20–35).

Results.?There was a significant difference between ED groups concerning MetS presence (p?=?0.032). MetS presence was not found to be associated with the severity of LUTS (p?=?0.144). There was no correlation between ED groups regarding LUTS severity (p?=?0.303).

Conclusion.?Results of the present study showed a correlation between MetS presence and ED. In the light of our results, MetS seems to play an important role in the etiopathogenesis of ED in patients with BPH.     

Now take a deep breath: inhaled loxapine for the treatment of acute agitation

Acute agitation in patients with schizophrenia or bipolar disorder is an important clinical management problem. Liquid concentrates, orally disintegrating tablets, and/or intramuscular formulations of several second-generation atypical antipsychotic drugs are available for treating acute agitation. Loxapine is an older first-generation antipsychotic drug that is approved for the treatment of schizophrenia. Staccato(?) loxapine is an investigational device system using a loxapine-coated heat source to administer loxapine by inhalation. Three multicenter, randomized, double-blind, placebo-controlled efficacy and safety studies of Staccato loxapine have been conducted in patients with acute agitation associated with schizophrenia or bipolar disorder. These studies found that inhaled loxapine was rapidly effective and generally well tolerated, although there are potential concerns about adverse pulmonary effects.     

Androgen replacement therapy contributes to improving lower urinary tract symptoms in patients with hypogonadism and benign prostate hypertrophy: a randomised controlled study

Purpose.?We performed a randomised controlled study regarding the effects of androgen replacement therapy (ART) on lower urinary tract symptoms (LUTS) in hypogonadal men with benign prostate hypertrophy (BPH).

Methods.?Fifty-two patients with hypogonadism and BPH were randomly assigned to receive testosterone (ART group) as 250?mg of testosterone enanthate every 4 weeks or to the untreated control group. We compared International Prostate Symptom Score (IPSS), uroflowmetry data, post-voiding residual volume (PVR) and systemic muscle volume at baseline and 12 months after treatment.

Results.?Forty-six patients (ART group, n?=?23; control, n?=?23) were included in the analysis. At the 12-month visit, IPSS showed a significant decrease compared with baseline in the ART group (15.7?±?8.7 vs. 12.5?±?9.5; p?<?0.05). No significant changes were observed in the control group. The ART group also showed improvement in maximum flow rate and voided volume (p?<?0.05), whereas no significant improvements were observed in the controls. PVR showed no significant changes in either group. In addition, the ART group showed significant enhancement of mean muscle volume (p?<?0.05), whereas no significant changes were seen in the controls.

Conclusion.?ART improved LUTS in hypogonadal men with mild BPH.     

Functional outcomes and complications following B-TURP versus HoLEP for the treatment of benign prostatic hyperplasia: a review of the literature and Meta-analysis

Objective: To conduct a systematic review and Meta-analysis of the literature on the efficacy and safety of B-TURP versus HoLEP for the treatment of benign prostatic hyperplasia (BPH) in terms of demographic and clinical baseline characteristics, peri-operative variables, and postoperative outcomes and complications.

Methods: Trials comparing B-TURP and HoLEP were identified systematically using Pubmed, Embase, CNKI, Web of Science and the Cochrane Library. Primary outcomes were the peak urinary flow rate (Q_max), post-void residual volume (PVR) and international prostate symptom score (IPSS). Secondary outcomes were operation time, irrigation duration, catheterization duration, resected tissue and complications.

Results: Four trials assessing B-TURP and HoLEP were considered eligible for Meta-analysis, including three randomized controlled trials (RCTs) and one retrospective study. There was no statistically significant difference between B-TURP and HoLEP in terms of Q_max, IPSS, PVR at 3–6?months follow-up, operation duration, catheterization duration, resected tissue and complications (p?>?0.05). HoLEP was associated with a significantly shorter irrigation time as compared with B-TURP (p?Conclusion: Both B-TURP and HoLEP are safe and minimally invasive techniques that are similar in terms of symptomatic relief, although these findings need further validation in larger RCTs involving larger numbers of patients and over a longer follow-up duration for B-TURP or HoLEP before a new gold standard procedure emerges for surgical treatment of BPH.     

CBD may help prevent relapse in abstinent heroin addicts

Cannabidiol (CBD) has the potential to reduce craving and anxiety in people with opioid use disorder who have been opioid‐free for at least a week, a recent study using Epidiolex, the Food and Drug Administration–approved form of the marijuana‐derived drug, has found. The study compared CBD to placebo in subjects who were exposed to drug‐related and non‐drug‐related‐cues, and measured craving and anxiety. CBD administration was short‐term (three days), but beneficial effects lasted seven days afterward. There were no effects on cognition and no adverse effects.     

Can the UroLift prostatic implant device treat the symptoms of benign prostatic hypertrophy,avoid sexual dysfunction and reduce hospital TURP waiting times? A single centre,single surgeon experience and review of the literature

BPH associated with LUTS and sexual dysfunction is common. We performed UroLift on 11 patients, average age 71?years (range 56–90). IPSS improved by an average of 9 points post-procedure. Pre-operatively their post-void residuals were 306.3?ml (range 120–499?ml SD [120.6]) and their Q_MAX was 7?ml/s (range 4–14 SD [2.8] ml/s). Post-procedure the post-void residual decreased by 35.4% at 4?months (mean difference – 106.3?ml). Q_MAX improved by an average of 1.7?ml/s, which was not statistically significant. No patients suffered any sexual dysfunction side effects and all patients were satisfied with their result. Hospital stay and theatre time were significantly reduced. Average length of stay was just 10.6 (6–18) hours and average theatre time just 18.7 (12–30) min. This is significantly faster than other surgery for LUTS. We therefore feel that there are significant benefits for both the patients, who are able to go home much faster, and also the hospital, who are able to perform far more surgeries for their patients. Patients also do not require an inpatient bed so patients should not be cancelled on the day of theatre.     

Drug therapies for tardive dyskinesia: part 2

Tardive dyskinesia (TD) is a serious complication associated with the long-term use of dopamine receptor-blocking drugs. No drugs are approved by the U.S. Food and Drug Administration for treating TD. A number of drugs appear to have some benefit for its treatment, including branched-chain amino acids, piracetam (Nootropil(?), Nootrop(?), Nootropyl(?)), clonazepam (Klonopin(?)), levetiracetam (Keppra(?)), propranolol (Inderal(?)), and clonidine (Catapres(?)), and they would be clinically reasonable to try. Gabapentin (Neurontin(?) and others) has a good safety profile and would be appropriate to consider, although no controlled trials confirm its efficacy. The efficacy of ginkgo biloba should be balanced against its safety concerns. Essential fatty acids have not been shown to be effective. Antioxidant therapies, including vitamin E, melatonin, and vitamin B?, could conceivably be used together with other drug therapies for the treatment of TD.     

Impact of combination therapy 5-alpha reductase inhibitors (5-ARI) plus alpha-blockers (AB) on erectile dysfunction and decrease of libido in patients with LUTS/BPH: a systematic review with meta-analysis

Lower urinary tract symptoms (LUTS) secondary to benign prostatic obstruction (BPO) represent one of the most common clinical complaints in adult men. Several drugs used for LUTS/BPO may strongly affect sexual function and bother. The aim of this systematic review and meta-analysis was to evaluate the impact of combination therapy with alpha-blockers (AB), 5-alpha reductase inhibitors (5-ARI) on the risk of erectile dysfunction(ED) and libido alterations (LA) from randomized clinical trial (RCT). Based on the inclusion and exclusion criteria, five RCTs involving 6131 patients were included in the analysis. According to the analysis, the overall prevalence of ED and LA were significantly greater in the combination treatment group than in the AB group (7.93% versus 4.66%; OR 1.81; p?p?=?0.003, respectively). The combination therapy increased the risk of ED compared to monotherapy with 5-ARI (7.93% versus 6.47%; OR 1.25; p?=?0.04) but not the risk of LA (3.51% versus 3.37; OR 1.03; p?=?0.84). In our systematic meta-analysis, we demonstrated that combination therapy with ABs and 5-ARIs was associated with significantly higher risk of ED and LA compared with single monotherapy. Combination therapy showed similar risk of LA compared with 5-ARI monotherapy.     

Impact of metabolic status on the association of serum vitamin D with hypogonadism and lower urinary tract symptoms/benign prostatic hyperplasia

Objective: The objective of this study is to investigate the impact of metabolic status on associations of serum vitamin D with hypogonadism and lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH).

Patients and methods: A total of 612 men underwent physical examination, biochemical/hormonal blood testing, and transrectal prostate ultrasound. Moreover, the subjects filled out standard questionnaires for identification and grading of LUTS and hypogonadism symptoms. Parameters were statistically compared with independent t-tests and correlation analyses.

Results: Vitamin D levels positively correlated with total testosterone (TT) but not with prostate volume or International Prostate Symptom Score (IPSS). Patients with metabolic syndrome had significantly lower vitamin D levels, which were not correlated with TT, prostate volume, or IPSS. However, vitamin D was positively correlated with TT, and negatively correlated with prostate volume and quality-of-life IPSS in subjects without metabolic syndrome.

Conclusion: The clinical usefulness of vitamin D for treatment of hypogonadism or LUTS/BPH varies according to metabolic status.     

Efficacy and safety of mirodenafil for patients with erectile dysfunction: a meta-analysis of three multicenter,randomized, double-blind,placebo-controlled clinical trials

Abstract

Aim: To systematically review evidence on the efficacy and safety of mirodenafil treatment in erectile dysfunction (ED) from randomised controlled trials.

Methods: We searched PubMed, Embase and the Cochrane Library database up to March 2013. Two authors independently assessed study quality and extracted data. All data were analyzed using RevMan 5.0. Outcome measures assessed were the International Index of Erectile Function (IIEF), erectile function domain (EFD) score (primary), the Sexual Encounter Profile questions 2 and 3, and the response to the Global Assessment Questionnaire and adverse effects (secondary).

Results: A total of 374 participants from three randomized controlled trials were identified in this meta-analysis. After 12 weeks treatment, mirodenafil was found to be more effective than placebo, and tolerability was good. The pooled results showed that the IIEF EFD score for 100?mg mirodenafil group was higher than placebo group (MD?=?8.13, 95%CI: 6.64–9.61, p?<?0.00001) and the mirodenafil group was also higher than placebo group in the changes from baseline for the IIEF EFD score (MD?=?7.32, 95%CI: 5.56–9.07, p?<?0.00001), respectively. The most common drug-related adverse events were flushing and headache (mirodenafil versus placebo: 15.8% versus 3.2%, 3.1% versus 0%; respectively).

Conclusion: This meta-analysis suggested that mirodenafil is effective and well-tolerated therapy for ED.