The causes of lower urinary tract symptoms (LUTS) are multifactorial and can be systemic, neurological, pharmacological and urological. Therefore, the term "lower urinary tract symptoms" is preferred to other terms used in the past, such as "prostatism" or "clinical benign prostatic hyperplasia (BPH)," as it does not presuppose a diagnosis.
LUTS can be subdivided into storage, evacuation and post-void symptoms . Although voiding symptoms are more common, they are the ones that bother patients the least. Storage symptoms, particularly urinary urgency and nocturia, are more bothersome. However, it is rare for patients to present with a group of symptoms in isolation; most have mixed symptoms. Although LUTS do not usually cause disease, they can significantly reduce the quality of life in men and may indicate serious urinary tract pathology. The Epidemiology of LUTS (EpiLUTS) study was an investigation of more than 14,000 men, 71% of whom complained of LUTS, which showed that the majority had mixed LUTS.
| Types of urinary symptoms |
Storage symptoms Frequency Nocturia Urgency Incontinence Disturbed bladder sensation Symptoms of emptying (evacuation) slow flow intermittent jet Hesitation Tight Split stream or spray terminal loss Symptoms after urination Incomplete emptying Post-void drip |
| Evaluation of lower urinary tract symptoms |
The latest guideline from the National Institute for Health and Care Excellence (NICE) from 2015 and updated in 2019 allows general practitioners to make the initial assessment before referring the patient to a urologist (for specific tests, or if necessary). is complicated or after failed medical treatment).
| Initial evaluation of lower urinary tract symptoms |
For men with LUTS, you should:
- Perform a complete history and physical examination, including digital rectal examination and evaluation of the urethral meatus
- Use urine test strips to check for blood, glucose, protein, leukocytes, and nitrites
- Use a validated symptom score (e.g., the International Prostate Syontom Score (IPSS)
- Make a urinary volume/frequency (GVFU) graph.
The 2015 NICE guidance suggests prostate-specific antigen (PSA) testing for men who have LUTS suggestive of prostate enlargement; have an abnormal prostate on digital rectal examination, or are particularly concerned about prostate cancer. However, there is evidence that PSA may also be a good indicator of progression risk. Marberger et al. demonstrated that, in men with LUTS, a PSA measurement >104 mg/mL was associated with a 9-fold increased risk of acute urinary retention. Patients should be fully informed and counseled before undergoing PSA testing.
> Renal function tests (serum creatinine, estimated glomerular filtration rate): indicated (according to the latest NICE guidance) only when there is clinical suspicion of renal impairment based on medical history, for example, patients with nocturnal enuresis, palpable bladder , recurrent urinary tract infections or stones in the urinary tree. Renal function should also be evaluated in the presence of hydronephrosis or when surgical treatment is being considered; This is recommended by the European Association of Urology in 2018.
> Urinary volume/frequency charts and bladder diaries: are useful in formulating a diagnosis and monitoring response to treatment. Also to identify urinary frequency, nocturnal polyuria and polyuria caused by excessive fluid intake.
GVFUs record the timing and volume of each void, while bladder diaries also include measurement of fluid intake. However, GVFUs and bladder diaries are not standardized, and some capture additional information, such as pad use or bladder sensation. The consensus is to record for at least 3 full days, so they are accurate enough for diagnosis or follow-up.
> International Prostate Symptom Score : is a 9-item questionnaire for the assessment of LUTS that allows stratification of the severity of symptoms into mild (1-7), moderate (8-19) or severe (20+). It is particularly valuable if used again after treatment, to measure its effectiveness. Quality of life is evaluated in the eighth question; This question is the most valuable in practice and is also sensitive to the change generated by the treatment.
> Flow velocity testing, postvoid residual volume (PRV) and urodynamic testing : Flow testing and postvoid residual measurement are not indicated in the first-line treatment of LUTS (according to the latest NICE guidance). Flow volumes can give a probability of obstruction, but cannot discriminate between poor detrusor function and bladder outflow tract obstruction. Flow volume testing is recommended for specialized evaluation of LUTS along with measurement of PRV, which also has a poor correlation with obstruction.
The most accurate evaluation of obstruction is done using urodynamic testing (pressure-flow testing). This is the only accurate way to discriminate between bladder outlet obstruction, detrusor overactivity, and reduced detrusor contractility, but it is an invasive study. It should be considered in very elderly (and younger) patients, in those with coexisting neurological disease or a combination of unusual symptoms, or when previous surgical treatment has failed.
| Causes of urinary symptoms in men |
Neurological diseases Parkinson’s disease Dementia Diabetic neuropathy Multiple sclerosis Other systemic diseases Mellitus diabetes Diabetes insipidus Heart failure Metabolic syndrome Drugs Opioids Antimuscarinics (including tricyclic antidepressants and ipratropium bromide) Diuretics Alcohol Caffeine Benzodiazepines Lithium Antipsychotics Other causes Prolapse Pelvic mass Urological causes Benign prostatic enlargement Urethral strictures calculations Bladder and prostate cancer Urinary tract infections Phimosis Metal stenosis interstitial cyst |
> Upper tract imaging and cystoscopy
Upper tract imaging or cystoscopy is not recommended in the initial evaluation of uncomplicated LUTS, but may have a place in specialized management.
| Treatment |
Several factors motivate the decision to treat. These include the severity of symptoms and their impact on quality of life, risk of disease progression, comorbidities and other complications of the disease. LUTS associated with any of the following "red flags" should prompt referral to a urologist:
- Rectal examination suggestive of prostate cancer
- Age-related elevated PSA
- Kidney dysfunction
- Hematuria
- bladder pain
- Recurrent infection
- Palpable or percussive bladder
- Very serious symptoms.
Instead, many patients can be reassured and/or treated conservatively with lifestyle modifications, such as avoiding caffeinated beverages and excess alcohol, or limiting fluid consumption. Patients with non-problematic LUTS can be reassured after baseline studies, and if progression and development of complications are relatively low.
| Identification of high-risk patients |
The Therapy of Prostatic Symptoms (MTOPS) trial identified the following baseline characteristics as risk factors for progression to acute urinary retention, need for surgery, or increase of at least 4 points on the IPSS:
- Age (8 times higher risk in people aged 70 to 79 years) compared to those aged 40-49 years)
- LUTS severity at baseline (3 times the risk if symptoms are moderate/severe rather than mild)
- Prostate volume (3 times the risk if prostate volume is >30 cm3)
- PSA level (9-fold increased risk if PSA is >1.4 ng/ml)
- Maximum flow (4 times the risk if <12 ml/second)
- PRV (3 times the risk if > 50 ml)
- Prostatic inflammation.
It has also been shown that 3 dynamic variables predict the progression of LUTS:
- Episodes of intercurrent retentions
- VRP increase over time
- Increased discomfort or worsening of symptoms while on treatment.
Risk stratification in patients with LUTS can help plan treatment.
| Urinary retention |
Acute urinary retention is a fairly simple clinical diagnosis and generally triggers urgent intervention with catheterization and referral to a specialist. A more insidious and difficult diagnosis is chronic retention, when a patient persistently retains substantial amounts of urine after urination. Patients with chronic retention may be asymptomatic or suffer from nocturnal enuresis. Some of them have highly compliant bladders with low detrusor pressures, a condition known as chronic low-pressure retention. Others have chronic high-pressure retention, with elevated end-empty pressures. This progresses to hydronephrosis and renal failure, and requires urgent referral to a ruologist.
| Metabolic syndrome and lower urinary tract symptoms |
Metabolic syndrome is defined by the presence of obesity and 2 of the following:
- elevated triglycerides
- Reduced high-density lipoprotein cholesterol
- High blood pressure and fasting hyperglycemia. It is accepted as a strong predictor of cardiovascular disease and overall mortality, and also appears to be associated with the development and progression of LUTS. Emerging histopathological evidence suggests that men with metabolic syndrome experience inflammation of the prostate, a key factor in the pathogenesis of BPH in this group.
Two other possible mechanisms are: the direct action of insulin on the induction of prostate growth due to its structural similarity with insulin-like growth factor (IGF-I), and the increase in its bioavailability through the reduction of IGF-I binding protein 1; and insulin resistance linked to sympathetic activation, which can increase smooth muscle tone in both the bladder and prostate. The strong evidence that metabolic syndrome is associated with increased prostate size supports the involvement of metabolic disorders in the development and progression of BPH. There is also emerging evidence that dyslipidemia represents an independent risk factor associated with LUTS. Recently, elevated levels of low-density lipoproteins have been found to increase the secretion of growth factors (e.g., fibroblast growth factor β-basic) and proinflammatory factors (interleukin-6 (IL-6), IL-8 , IL-7) by stromal cells in BPH, isolated. Therefore, it can be speculated that dyslipidemia could induce the development of an inflammatory response within the prostate, leading to the progression of BPH and LUTS.
| Medical treatment |
Several classes of drugs are used, and the particular choice of each, or their combination, depends largely on the type of symptoms experienced by the patient and their risk of progression.
Selective α-adrenergic receptor blockers , such as tamsulosin, doxazosin and alfuzosin, act on α1 receptors in the neck of the bladder and prostatic urethra, causing relaxation of the smooth muscle and improvement of urinary flow. They act relatively quickly (within a few days) and are particularly effective in treating voiding symptoms, but in some patients they can cause postural hypotension and abnormal ejaculation. They are recommended for the first-line treatment of moderate to severe LUTS.
5α-reductase inhibitors , such as finasteride and dutasteride, block the conversion of testosterone to a more potent androgen, dihydrotestosterone, reducing prostate size and improving emptying symptoms. They take 6 months to reach their greatest effectiveness, and can cause decreased libido, erectile dysfunction, and gynecomastia.
5α-reductase inhibitors reduce the risk of LUTS progression, acute urinary retention, and need for surgery. Therefore, its use is recommended in men with a higher risk of progression and in men with prostate enlargement (>40 cm3). Patients with bothersome symptoms and increased risk of progression require combination treatment with an α-adrenoceptor blocker and a 5α-reductase inhibitor. This combination provides much greater improvement in symptoms and quality of life than monotherapy, in addition to reducing the risk of acute urinary retention and the need for surgery.
Antimuscarinics , such as oxybutynin, tolterodine, solifenacin festoteridine, and transpiro, are useful in the treatment of storage symptoms. They act on the muscarinic receptors of the delayed muscle and inhibit involuntary contraction; They also increase the storage capacity of the bladder. Adverse effects include dry eyes, dry mouth and gastrointestinal tract. They can be used effectively in patients with mixed storage and emptying symptoms, combined with α-adrenoceptor blockers, but should not be used in patients with high PVR.
The selective β3-adrenoceptor agonist mirabegron can be used when antimuscarinics are ineffective, contraindicated, or not tolerated for the treatment of storage symptoms. Mirabegron activates ß3 adrenoceptors in the bladder, improving its relaxation and increasing its storage capacity. The most commonly reported adverse effects are urinary infections and tachycardia.
Phosphodiesterase-5 inhibitors ( PDE5-I), such as sildenafil, tadalafil, and vardenafil, are widely used to treat erectile dysfunction, but may also have a role in the treatment of LUTS. Current evidence suggests that they significantly improve LUTS in men with or without erectile dysfunction, while the effect on flow volume is minor.
Several mechanisms of action have been proposed, including changes in prostate and bladder neck tone, mediated by nitric oxide, and a concomitant relaxation of the detrusor muscle, perhaps compensating for any change in urinary flow rate. PDE5-Is may be an option for men with LUTS, particularly if they have concomitant erectile dysfunction. Because LUTS and erectile dysfunction often coexist and are probably related, a significant improvement in overall quality of life can be achieved. The latest NICE guidelines do not recommend starting PDE5 inhibitors in patients without erectile dysfunction.
Some patients benefit from combinations of the aforementioned drugs. The effect of treatment on symptoms, quality of life and adverse effects should be monitored at 4-6 weeks and every 6-12 months thereafter. Patients who do not respond to conservative management or pharmacological treatment may be referred to urologists for evaluation and consideration of urologic surgery.
