Benign prostatic hyperplasia (BPH) refers to the nonmalignant growth or hyperplasia of prostate tissue and is a common cause of lower urinary tract symptoms in men. Disease prevalence has been shown to increase with advancing age. Indeed the histological prevalence of BPH at autopsy is as high as 50% to 60% for males in their 60's, increasing to 80% to 90% of those over 70 years of age.
Several definitions exist in the literature when describing BPH. These include bladder outlet obstruction (BOO), lower urinary tract symptoms (LUTS), and benign prostatic enlargement (BPE). BPH describes the histological changes, benign prostatic enlargement (BPE) describes the increased size of the gland (usually secondary to BPH) and bladder outlet obstruction (BOO) describes the obstruction to flow. Those with BPE who present with BOO are termed benign prostatic obstruction. Lower urinary tract symptoms (LUTS) simply describe urinary symptoms shared by disorders affecting the bladder and prostate (when in reference to men). LUTS can be subdivided into storage and voiding symptoms. These terms have largely replaced those historically termed "prostatism."
The development of benign prostatic hyperplasia is characterized by stromal and epithelial cell proliferation in the prostate transition zone (surrounding the urethra), this leads to compression of the urethra and development of bladder outflow obstruction (BOO) which can result in clinical manifestations of lower urinary tract symptoms (LUTS), urinary retention or infections due to incomplete bladder emptying. Long-term, untreated disease can lead to the development of chronic high-pressure retention (a potentially life-threatening emergency) and long-term changes to the bladder detrusor (both overactivity and reduced contractility).
Treatment options for BPH range from watchful waiting, to medical and surgical intervention. Risk factors may be divided into non-modifiable and modifiable, with factors such as age, genetics, geographical location, and obesity, all shown to influence the development of BPH. It is, therefore, important to be able to identify those at risk of disease progression and those who can be managed more conservatively to reduce associated morbidity and health care burden.
This review provides an overview of the etiology, pathophysiology, recognition, and management of benign prostatic hyperplasia as well as interprofessional aspects that may enhance patient care.
The etiology of BPH is influenced by a wide variety of risk factors in addition to direct hormonal effects of testosterone on prostate tissue.
Although they do not cause BPH directly, testicular androgens are required in the development of BPH with dihydrotestosterone (DHT) interacting directly with prostatic epithelium and stroma. Testosterone produced in the testes is converted to dihydrotestosterone (DHT) by 5-alpha-reductase 2 in prostate stromal cells and accounts for 90% of total prostatic androgens. DHT has direct effects on stromal cells in the prostate, paracrine effects in adjacent prostatic cells, and endocrine effects in the bloodstream, which influences both cellular proliferation and apoptosis (cell death).
BPH arises as a result of the loss of homeostasis between cellular proliferation and cell death, resulting in an imbalance favoring cellular proliferation. This results in increased numbers of epithelial and stromal cells in the periurethral area of the prostate and can be seen histopathologically.
Non-modifiable and modifiable risk factors also contribute to the development of BPH. These have been shown to include metabolic syndrome, obesity, hypertension, and genetic factors.
Differences in case definitions make interpretation of population-based studies regarding BPH difficult. Whereas BPH can refer to histology, benign prostate enlargement, and physician-diagnosis of BPH, LUTS refers to the urinary symptoms shared by disorders affecting the prostate and bladder.
Age is a significant predictor of both development of BPH and subsequent LUTS, with 50% of men over the age of 50 shown to have evidence of BPH and the association with the development of LUTS shown to increase with age in a linear fashion. This is supported by studies that have demonstrated increases in prostate volume with age (2% to 2.5% increase in size per year). In the US, studies have shown BPH prevalence to be as high as 70% in those between 60 and 69 years of age and more than 80% in those over 70 years. The prevalence of male LUTS alone demonstrated a significant increase with age from 8% (30 to 39yrs) to 35% (60 to 69yrs) in the Boston area community health survey, other US population-based studies have shown 56% of men between 50-79yrs reported symptoms.
At a population-level, the prevalence of BPH increased dramatically between 1998 and 2007 in the US, nearly doubling in the number of cases. These increases are suggested to be attributable to an aging population, with those over 80 years of age projected to be around 19.5 million in 2030 (from 9.3 million in 2003). As populations age, the number of cases can, therefore, be expected to rise.
International studies have suggested that Western populations have significantly higher prostate volumes compared to those from southeast Asia. Further studies looking at the correlation of prostate volume with LUTS, however, found that lower prostate volumes did not necessarily correlate with symptoms, with higher mean IPSS (international prostate symptom scores) observed in a cohort of Indian men compared to western populations.
Both the development of lower urinary tract symptoms and bladder outlet obstruction in men with BPH can be attributable to static and dynamic components. Static obstruction is a direct consequence of prostate enlargement resulting in periurethral compression and bladder outlet obstruction. Here, periurethral compression requires increasing voiding pressures to overcome resistance to flow; in addition, prostate enlargement distorts the bladder outlet causing obstruction to flow.
Dynamic components include the tension of prostate smooth muscle (hence the use of 5-alpha reductase inhibitors to reduce prostate volume and alpha-blockers to relax smooth muscle). This is explained by decreases in elasticity and collagen in the prostatic urethra in men with BPH, which may further exacerbate bladder outlet obstruction due to loss of compliance and increased resistance to flow and may explain why prostate size alone is not always a predictor of disease.
Histological examination demonstrates that BPH is a hyperplastic process with an increase in cell number on histology (hyperplasia); these occur both in the periurethral and transition zones. Histological studies have demonstrated both glandular and stromal proliferation. Specifically, periurethral zones demonstrate stromal nodules, whereas glandular nodular proliferation is seen within the transition zone.
In the elective setting, a focused medical history should include all aspects of symptomatology, and this includes onset, timing, exacerbating, and relieving factors.
Lower urinary tract symptoms can be divided into storage (frequency, nocturia, urgency) and voiding symptoms (stream, straining, hesitancy, prolonged micturition) and can help establish other causes of urinary symptoms such as urinary tract infections/overactive bladder, in addition to determining the site affected (bladder vs. prostate). Men with BPH are likely to report predominant symptoms of nocturia, poor stream, hesitancy, or prolonged micturition.
Red flags help point to more sinister causes of urinary symptoms such as bladder/prostate cancer, neurology such as cauda equina, or chronic high-pressure retention (which can lead to silent renal failure). The presence of these can be established by asking about visible haematuria/bone pain/weight loss, neurology, and nocturnal enuresis/incontinence, respectively.
Complete medication history should be taken, including any medications they have tried and use of anticoagulants or antiplatelets, which may increase the risk of intra-operative bleeding or need to be held before surgery.
The overall fitness of the patient should also be established to determine suitability for any future interventions (fitness for anesthesia, independence, exercise tolerance, ability to complete activities of daily living), and the symptom burden on quality of life should also be established.
In the elective setting, the examination should include abdominal examination (looking for a palpable bladder/loin pain) and examination of external genitalia (meatal stenosis or phimosis). The examination should then conclude with a digital rectal examination making a note in particular of the size, shape (how many lobes), and consistency (smooth/hard/nodular) of the prostate (BPH is characterized by a smooth enlarged prostate).
Further bedside evaluation includes
Both the American urological association symptom index and IPSS can be used to assess the impact of LUTS on quality of life. They are useful when quantifying the disease burden on the patient and can be used to stratify patients into disease categories for treatment. The IPSS stratifies patients into three groups on the basis of symptoms. They are mild (0-7), moderate (8-19), and severe (20-35). Those with more severe symptoms are less likely to benefit from conservative or medical measures.
Standard investigation of BPH may include bedside urine dipstick, post-void residual, IPSS, and urine flow studies to establish if there is evidence of obstructive voiding. Further tests may be indicated depending on the patient/history.
Blood tests, including renal function tests, are useful to establish baseline renal function and can help support the diagnosis of renal failure/acute kidney injury in someone with chronic high-pressure retention or acute retention, for example.
Urine specimen testing can help detect infection, non-visible haematuria, or metabolic disorders (glycosuria). Leucocytes and nitrites are common findings with infection; the presence of proteinuria may point towards nephrological conditions. The American urological association recommend urinalysis using a dipstick test, further tests may be requested based on abnormal dipstick findings (culture, etc.).
Prostate-Specific Antigen (PSA)
Prostate-specific antigen testing has been shown to predict prostate volume. Prostate-specific antigen (PSA) testing should be used with caution, however, and should not be done routinely in the investigation of BPH. Levels may be raised in a large range of conditions (large prostate, infection, catheterization, prostate cancer) and can cause undue anxiety or further unnecessary investigations for the patient. It is the author's preference to conduct PSA testing in specific circumstances, i.e., where cancer is suspected (malignant feeling prostate, metastatic disease suspected) or a previous baseline established.
Ultrasound scans are used to look for evidence of hydronephrosis and are indicated in patients with high residual volumes or renal impairment. Other indications include suspicion of urinary tract stones or the investigation of haematuria.
Urine flow studies are used to determine the volume of urine passed over time. This can help establish whether there is objective evidence for obstruction to flow. Urodynamic studies are used to see how the bladder empties and fills. They can help further assess patients where the diagnosis is not certain or where a neurogenic/overactive bladder is suspected (i.e., neurological conditions that may affect the bladder, flow studies equivocal, diagnosis not clear).
Flexible cystoscopy should be used to investigate red flag symptoms such as visible haematuria/suspected bladder cancer and can also be used to look for urethral strictures, which may also result in poor flow/decreased urinary flow studies.
Men with BPH may present acutely with urinary retention or may be seen in the clinic or primary care setting. Management of male urinary retention is covered in a separate topic.
In those with LUTS, treatment options range from watchful waiting to medical and surgical intervention and depend on the degree of "bother" or disease burden to the patient (as assessed by IPSS).
Watchful waiting is a process to manage patients by giving lifestyle advice. Examples include weight loss, reducing caffeine intake or reducing fluid intake in the evening, and avoiding constipation to try and reduce risk factors and improve LUTS. Patients should be involved in the discussion and informed of the risks of disease progression. Clinical progression has shown to be around 31% in one observational study, with 5% developing acute urinary retention. These measures may be trialed in those with mild symptoms (IPSS<7).
Both static and dynamic components contribute to the pathophysiology of BPH. Medical therapy aims to address both of these components.
Alpha 1-adrenoreceptors are present on prostate stromal smooth muscle and bladder neck. Alpha 1-adrenoreceptor blockage results in stromal smooth muscle relaxation addressing the dynamic component of BPH and thus improving flow. Examples include selective Alpha-blockers such as Tamsulosin (400mcg once daily) and Alfuzosin (10mg once daily).
5 alpha-reductase inhibitors:
Alpha-reductase inhibitors such as finasteride (5mg once daily) and dutasteride block conversion of testosterone to DHT.. This addresses the static component of BPH by causing shrinkage of the prostate and takes several weeks to show noticeable improvement, with six months needed for maximal effectiveness. As a result of treatment serum, PSA can be reduced by 50%, with prostate volume decreasing by up to 25%. This has been shown to alter the disease process and subsequent disease progression.
Bladder detrusor instability can develop in patients with worsening bladder outlet obstruction. This can result in increased urgency (overactive bladder) and frequency. Muscarinic receptor antagonists can help with these symptoms by blocking muscarinic receptors on detrusor muscle. This reduces smooth muscle tone and can improve symptoms in those with overactivity. Examples include solifenacin, tolterodine, and oxybutynin. Those who fail antimuscarinic treatment may be considered for mirabegron use (a Beta-3 adrenoreceptor agonist), which causes detrusor relaxation.
In practice, the combination of an alpha-blocker and alpha-reductase inhibitor is often used to achieve improvements in voiding symptoms. This is backed by studies confirming the effectiveness of combination therapy over monotherapy.
Guidelines for the indications for surgery in BPH as outlined by the European Association of Urology (EAU) are as follows:
Surgical management of BPH has broadened significantly over the years, with the development of further minimally invasive techniques. Recommended procedures include transurethral incision of the prostate, transurethral resection fo the prostate, in addition to newer techniques such as laser vaporization and holmium laser enucleation, which have largely replaced open prostatectomy. Surgical management options are outlined below.
Transurethral resection surgery focuses on debulking the prostate to produce an adequate channel for urine to flow. This is achieved using diathermy to produce a high-frequency current that allows the cutting of tissue. By resecting all obstructing prostatic tissue, an adequate channel can be created to allow urine to flow. Bipolar diathermy has largely replaced monopolar diathermy techniques for TURP, with increased benefits such as resection in saline and reduced risk of "TUR syndrome."
Previously, open prostatectomy allowed adenoma to be removed or enucleated off its capsule. This can now be achieved with laser enucleation, referred to as HoLEP (Holmium laser enucleation of the prostate). Meta-analysis has shown improved Qmax (flow rate), reduction in post-void residual, and IPSS compared to TURP.
Benefits include a lower transfusion rate with no increase in complications compared to TURP. However, limitations include specialized equipment required making it less readily available.
Tissue-sparing approaches, such as Urolift, have also been developed. This can help minimize the risk of bleeding in co-morbid patients and the associated risks of more invasive surgery (such as anesthesia risk, prolonged surgery time, etc.). By compressing prostate lobes, the channel can be widened in the prostatic urethra, improving LUTS. Studies have shown benefits, including the possibility of day-case surgery, preserved sexual function, and improved symptom scores (IPSS), and flow rates (QMax).
Differential diagnoses for lower urinary tract infections are broad and include the following:
Red flag conditions:
Deterioration in LUTS/increasingly problematic voiding symptoms is the most common indicator of disease progression. In addition to this, patients may present with complications, including acute retention, infections, or haematuria.
Observational studies have demonstrated that when left without treatment, clinical progression of BPH increased over a 48 month period, with 31% of the cohort requiring presentation at 48 months and 5% developing acute retention in the 48 month period.
The risk of acute urinary retention also increased with age, in the Olmsted County study, the incidence of retention in men increased over ten-fold, from 3/1000 (40-49yrs) to 34.7/1000 (70-79yrs). Left untreated, BPH, therefore, has a significant risk of progression and presentation. Indeed, up to 42% of men who presented with retention in 1 study, went on to have surgery. Men with significantly enlarged prostates (>30ml) have also been shown to be at an increased risk of disease progression.
Other complications may arise as a result of catheterization for management of LUTS in BPH and include:
International studies have demonstrated that BPH accounts for over two-thirds of cases of acute urinary retention. Further to this, 15% of those who experience acute urinary retention experience another episode in the future, with 75% requiring surgery compared to those with precipitating causes (only 26%).
Men with BPH can also develop chronic retention. This is usually chronic high-pressure retention due to high voiding detrusor pressures in the bladder as a result of outflow obstruction. Due to the inability to empty the bladder completely, the pressure within the bladder can increase, resulting in hydronephrosis and subsequent deterioration in renal function leading to renal failure. Management of these subsets of patients is, therefore, urgent catheterization and urgent surgery to relieve the obstruction (TURP) or long-term catheter (those with high-pressure retention should not undergo TWOC).
Urinary Tract Infections
This occurs due to incomplete bladder emptying resulting in incomplete bladder emptying and stagnant urine. Recurrent infections may indicate a need for treatment or long-term antibiotics to prevent associated co-morbidity (admissions with urosepsis).
This is a common complication in BPH and a common cause for referral for further investigation. Due to the increased vascularity of larger prostate vessels may be disrupted, causing bleeding. Finasteride has been shown to decrease the density of vessels and can help manage problematic BPH related haematuria.
High-pressure Chronic Retention
Chronic retention is commonly referred to as either high or low-pressure retention. High-pressure chronic retention commonly occurs in bladder outflow obstruction as a result of high detrusor pressures required to overcome the obstruction (BPH). Persistence of this high-pressure causes reflux and subsequent hydronephrosis. Over time this can result in an insidious deterioration in renal function, which may be missed. High-pressure retention is characterized by nocturnal enuresis - due to decreased resting pressure of the bladder neck overnight.
Management consists of catheterization to relieve the bladder pressure and definitive management to prevent retention and further renal dysfunction. Management options include TURP or long-term catheter/intermittent self-catheter. Following catheterization, the patient may undergo post-obstructive diuresis. This is characterized by increased urine output in the following 24 to 72 hours and may require IV fluid supplementation if exceeding >200 ml per hour. There is no evidence to suggest any benefit in gradual vs. rapid decompression, and so patients should be left on free drainage following catheterization for HPCR.
Lifestyle factors such as weight loss or improved diabetic control should be explained to the patient to allow modifiable risk factors to be addressed. This may also translate to reducing the risk of the surgery itself in the future, by reducing anesthetic and post-operative complication risks. Lifestyle measures such as reducing caffeine and timing of fluid intake can also be used as a measure to address specific problematic urinary symptoms.
Those managed with long-term catheters or intermittent self-catheterization should be taught the importance of hygiene and catheter care to prevent urinary tract infections. This may be done with the assistance of dedicated specialist nurses. The provision for managing the catheter in the community should also be made.
Patients with BPH should understand the risks of disease progression before committing to treatment options and should be counseled on alternative management options such as watchful waiting, medical therapy along with any other surgeries available in order to make an informed decision.
Healthcare outcomes can be optimized through the use of IPSS or AUA scoring systems. These can help stratify patients according to disease severity and guide physician decision making. Adherence to lifestyle factors affecting BPH may also be addressed through diet advice, weight loss, and glycaemic control. The role of primary care/endocrine/diabetic nurse specialists can help address these areas, and early referral to these areas can help ensure medical conditions are optimized. Optimizing these factors prior to surgery can also be beneficial in reducing the risk of co-morbidity and the risk of post-operative complications.
Catheter-care is an important process for those performing intermittent self-catheterization due to symptoms or with long-term catheters. This can be addressed by specialist nurses who can help educate the patient in order to ensure adequate training, support, and follow-up in the community. In the UK, the department of health advocates accesses to integrated continence services for those with long-term bladder problems. Those who are involved in catheter care and management in the community should be aware of the indications for catheterization, and when to refer to the hospital for intervention, implementation of a catheter passport can help assist this.
Pharmacists are of particular importance due to the increasing incidence of BPH with age and increasing polypharmacy associated (multiple medications) with these patients. It is therefore important that any drug interactions are identified, further to this, the use of concomitant anticoagulants should be recognized to ensure that they may be held before surgery or other treatments offered to the patient depending on co-morbidity.
Overall close interplay is needed between primary care clinicians/urologists/nephrologists/nurses and pharmacists to ensure patients are managed and referred appropriately. The use of specialist urology/bladder care specialists can help improve patient compliance with both lifestyle modification, medications, and interventions such as catheters. This ensures the patient can be managed in a multi-disciplinary manner and achieve the best outcomes. [Level 5]
|||Roehrborn CG, Benign prostatic hyperplasia: an overview. Reviews in urology. 2005; [PubMed PMID: 16985902]|
|||Abrams P, LUTS, BPH, BPE, BPO: A Plea for the Logical Use of Correct Terms. Reviews in urology. 1999 Spring; [PubMed PMID: 16985774]|
|||Silverman WM, [PubMed PMID: 15038396]|
|||Abrams P, New words for old: lower urinary tract symptoms for [PubMed PMID: 8173393]|
|||Roehrborn CG, Pathology of benign prostatic hyperplasia. International journal of impotence research. 2008 Dec; [PubMed PMID: 19002119]|
|||Parsons JK, Benign Prostatic Hyperplasia and Male Lower Urinary Tract Symptoms: Epidemiology and Risk Factors. Current bladder dysfunction reports. 2010 Dec; [PubMed PMID: 21475707]|
|||Chughtai B,Forde JC,Thomas DD,Laor L,Hossack T,Woo HH,Te AE,Kaplan SA, Benign prostatic hyperplasia. Nature reviews. Disease primers. 2016 May 5; [PubMed PMID: 27147135]|
|||Foster CS, Pathology of benign prostatic hyperplasia. The Prostate. Supplement. 2000; [PubMed PMID: 11056496]|
|||Isaacs JT, Antagonistic effect of androgen on prostatic cell death. The Prostate. 1984; [PubMed PMID: 6483690]|
|||Gacci M,Corona G,Vignozzi L,Salvi M,Serni S,De Nunzio C,Tubaro A,Oelke M,Carini M,Maggi M, Metabolic syndrome and benign prostatic enlargement: a systematic review and meta-analysis. BJU international. 2015 Jan; [PubMed PMID: 24602293]|
|||Rohrmann S,Smit E,Giovannucci E,Platz EA, Association between markers of the metabolic syndrome and lower urinary tract symptoms in the Third National Health and Nutrition Examination Survey (NHANES III). International journal of obesity (2005). 2005 Mar; [PubMed PMID: 15672112]|
|||Golbidi S,Laher I, Bladder dysfunction in diabetes mellitus. Frontiers in pharmacology. 2010; [PubMed PMID: 21833175]|
|||Kristal AR,Arnold KB,Schenk JM,Neuhouser ML,Weiss N,Goodman P,Antvelink CM,Penson DF,Thompson IM, Race/ethnicity, obesity, health related behaviors and the risk of symptomatic benign prostatic hyperplasia: results from the prostate cancer prevention trial. The Journal of urology. 2007 Apr; [PubMed PMID: 17382740]|
|||Parsons JK,Carter HB,Partin AW,Windham BG,Metter EJ,Ferrucci L,Landis P,Platz EA, Metabolic factors associated with benign prostatic hyperplasia. The Journal of clinical endocrinology and metabolism. 2006 Jul; [PubMed PMID: 16608892]|
|||Furukawa S,Fujita T,Shimabukuro M,Iwaki M,Yamada Y,Nakajima Y,Nakayama O,Makishima M,Matsuda M,Shimomura I, Increased oxidative stress in obesity and its impact on metabolic syndrome. The Journal of clinical investigation. 2004 Dec; [PubMed PMID: 15599400]|
|||De Nunzio C,Aronson W,Freedland SJ,Giovannucci E,Parsons JK, The correlation between metabolic syndrome and prostatic diseases. European urology. 2012 Mar; [PubMed PMID: 22119157]|
|||Sanda MG,Beaty TH,Stutzman RE,Childs B,Walsh PC, Genetic susceptibility of benign prostatic hyperplasia. The Journal of urology. 1994 Jul; [PubMed PMID: 7515446]|
|||Meikle AW,Bansal A,Murray DK,Stephenson RA,Middleton RG, Heritability of the symptoms of benign prostatic hyperplasia and the roles of age and zonal prostate volumes in twins. Urology. 1999 Apr; [PubMed PMID: 10197844]|
|||Rohrmann S,Fallin MD,Page WF,Reed T,Partin AW,Walsh PC,Platz EA, Concordance rates and modifiable risk factors for lower urinary tract symptoms in twins. Epidemiology (Cambridge, Mass.). 2006 Jul; [PubMed PMID: 16699472]|
|||Berry SJ,Coffey DS,Walsh PC,Ewing LL, The development of human benign prostatic hyperplasia with age. The Journal of urology. 1984 Sep; [PubMed PMID: 6206240]|
|||Platz EA,Joshu CE,Mondul AM,Peskoe SB,Willett WC,Giovannucci E, Incidence and progression of lower urinary tract symptoms in a large prospective cohort of United States men. The Journal of urology. 2012 Aug; [PubMed PMID: 22704110]|
|||Loeb S,Kettermann A,Carter HB,Ferrucci L,Metter EJ,Walsh PC, Prostate volume changes over time: results from the Baltimore Longitudinal Study of Aging. The Journal of urology. 2009 Oct; [PubMed PMID: 19683305]|
|||Wei JT,Calhoun E,Jacobsen SJ, Urologic diseases in America project: benign prostatic hyperplasia. The Journal of urology. 2005 Apr; [PubMed PMID: 15758764]|
|||Kupelian V,Wei JT,O'Leary MP,Kusek JW,Litman HJ,Link CL,McKinlay JB, Prevalence of lower urinary tract symptoms and effect on quality of life in a racially and ethnically diverse random sample: the Boston Area Community Health (BACH) Survey. Archives of internal medicine. 2006 Nov 27; [PubMed PMID: 17130393]|
|||Parsons JK,Bergstrom J,Silberstein J,Barrett-Connor E, Prevalence and characteristics of lower urinary tract symptoms in men aged > or = 80 years. Urology. 2008 Aug; [PubMed PMID: 18554695]|
|||Stroup SP,Palazzi-Churas K,Kopp RP,Parsons JK, Trends in adverse events of benign prostatic hyperplasia (BPH) in the USA, 1998 to 2008. BJU international. 2012 Jan; [PubMed PMID: 21615853]|
|||Trends in aging--United States and worldwide. MMWR. Morbidity and mortality weekly report. 2003 Feb 14; [PubMed PMID: 12645839]|
|||Jin B,Turner L,Zhou Z,Zhou EL,Handelsman DJ, Ethnicity and migration as determinants of human prostate size. The Journal of clinical endocrinology and metabolism. 1999 Oct; [PubMed PMID: 10523004]|
|||Ganpule AP,Desai MR,Desai MM,Wani KD,Bapat SD, Natural history of lower urinary tract symptoms: preliminary report from a community-based Indian study. BJU international. 2004 Aug; [PubMed PMID: 15291862]|
|||Caine M, The present role of alpha-adrenergic blockers in the treatment of benign prostatic hypertrophy. The Journal of urology. 1986 Jul; [PubMed PMID: 2423716]|
|||Foo KT, Pathophysiology of clinical benign prostatic hyperplasia. Asian journal of urology. 2017 Jul; [PubMed PMID: 29264224]|
|||Lepor H, Pathophysiology of benign prostatic hyperplasia in the aging male population. Reviews in urology. 2005; [PubMed PMID: 16986052]|
|||Babinski MA,Manaia JH,Cardoso GP,Costa WS,Sampaio FJ, Significant decrease of extracellular matrix in prostatic urethra of patients with benign prostatic hyperplasia. Histology and histopathology. 2014 Jan; [PubMed PMID: 23788026]|
|||McNeal J, Pathology of benign prostatic hyperplasia. Insight into etiology. The Urologic clinics of North America. 1990 Aug; [PubMed PMID: 1695776]|
|||Barry MJ,Fowler FJ Jr,O'leary MP,Bruskewitz RC,Holtgrewe HL,Mebust WK,Cockett AT, The American Urological Association Symptom Index for Benign Prostatic Hyperplasia. The Journal of urology. 2017 Feb; [PubMed PMID: 28012747]|
|||Bohnen AM,Groeneveld FP,Bosch JL, Serum prostate-specific antigen as a predictor of prostate volume in the community: the Krimpen study. European urology. 2007 Jun; [PubMed PMID: 17320271]|
|||Djavan B,Fong YK,Harik M,Milani S,Reissigl A,Chaudry A,Anagnostou T,Bagheri F,Waldert M,Kreuzer S,Fajkovic H,Marberger M, Longitudinal study of men with mild symptoms of bladder outlet obstruction treated with watchful waiting for four years. Urology. 2004 Dec; [PubMed PMID: 15596187]|
|||Gormley GJ,Stoner E,Bruskewitz RC,Imperato-McGinley J,Walsh PC,McConnell JD,Andriole GL,Geller J,Bracken BR,Tenover JS, The effect of finasteride in men with benign prostatic hyperplasia. The Finasteride Study Group. The New England journal of medicine. 1992 Oct 22; [PubMed PMID: 1383816]|
|||Emberton M,Cornel EB,Bassi PF,Fourcade RO,Gómez JM,Castro R, Benign prostatic hyperplasia as a progressive disease: a guide to the risk factors and options for medical management. International journal of clinical practice. 2008 Jul; [PubMed PMID: 18479366]|
|||Roehrborn CG,Siami P,Barkin J,Damião R,Major-Walker K,Nandy I,Morrill BB,Gagnier RP,Montorsi F, The effects of combination therapy with dutasteride and tamsulosin on clinical outcomes in men with symptomatic benign prostatic hyperplasia: 4-year results from the CombAT study. European urology. 2010 Jan; [PubMed PMID: 19825505]|
|||Regadas RP,Reges R,Cerqueira JB,Sucupira DG,Josino IR,Nogueira EA,Jamacaru FV,de Moraes MO,Silva LF, Urodynamic effects of the combination of tamsulosin and daily tadalafil in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia: a randomized, placebo-controlled clinical trial. International urology and nephrology. 2013 Feb; [PubMed PMID: 23108604]|
|||de la Rosette JJ,Alivizatos G,Madersbacher S,Perachino M,Thomas D,Desgrandchamps F,de Wildt M, EAU Guidelines on benign prostatic hyperplasia (BPH). European urology. 2001 Sep; [PubMed PMID: 11684840]|
|||Yin L,Teng J,Huang CJ,Zhang X,Xu D, Holmium laser enucleation of the prostate versus transurethral resection of the prostate: a systematic review and meta-analysis of randomized controlled trials. Journal of endourology. 2013 May; [PubMed PMID: 23167266]|
|||Garcia C,Chin P,Rashid P,Woo HH, Prostatic urethral lift: A minimally invasive treatment for benign prostatic hyperplasia. Prostate international. 2015 Mar; [PubMed PMID: 26157759]|
|||Jacobsen SJ,Jacobson DJ,Girman CJ,Roberts RO,Rhodes T,Guess HA,Lieber MM, Natural history of prostatism: risk factors for acute urinary retention. The Journal of urology. 1997 Aug; [PubMed PMID: 9224329]|
|||Pickard R,Emberton M,Neal DE, The management of men with acute urinary retention. National Prostatectomy Audit Steering Group. British journal of urology. 1998 May; [PubMed PMID: 9634047]|
|||Nickel JC, Benign prostatic hyperplasia: does prostate size matter? Reviews in urology. 2003; [PubMed PMID: 16985958]|
|||Speakman MJ,Cheng X, Management of the complications of BPH/BOO. Indian journal of urology : IJU : journal of the Urological Society of India. 2014 Apr; [PubMed PMID: 24744522]|
|||Roehrborn CG,Bruskewitz R,Nickel GC,Glickman S,Cox C,Anderson R,Kandzari S,Herlihy R,Kornitzer G,Brown BT,Holtgrewe HL,Taylor A,Wang D,Waldstreicher J, Urinary retention in patients with BPH treated with finasteride or placebo over 4 years. Characterization of patients and ultimate outcomes. The PLESS Study Group. European urology. 2000 May; [PubMed PMID: 10765090]|
|||Kashif KM,Foley SJ,Basketter V,Holmes SA, Haematuria associated with BPH-Natural history and a new treatment option. Prostate cancer and prostatic diseases. 1998 Mar; [PubMed PMID: 12496909]|
|||Boettcher S,Brandt AS,Roth S,Mathers MJ,Lazica DA, Urinary retention: benefit of gradual bladder decompression - myth or truth? A randomized controlled trial. Urologia internationalis. 2013; [PubMed PMID: 23859894]|
|||Thomas S, Good practice in continence services. Nursing standard (Royal College of Nursing (Great Britain) : 1987). 2000 Aug 9-15; [PubMed PMID: 11974377]|
|||Codd J, Implementation of a patient-held urinary catheter passport to improve catheter management, by prompting for early removal and enhancing patient compliance. Journal of infection prevention. 2014 May; [PubMed PMID: 28989364]|