Benign prostatic hyperplasia

By Shane Moran & Johnny Blatchford

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Benign prostatic hyperplasia (BPH) is one of the most common urological conditions among males, with an estimated 3 million affected in the UK. The incidence of BPH is approximately 50% in males aged 60–70 years, increasing to 90% in males aged over 80 years​[1,2]​.

BPH is characterised by the non-malignant proliferation of glandular epithelial tissue and stromal components of the prostate. The main clinical manifestations of BPH are lower urinary tract symptoms, which considerably reduce men’s quality of life​[3,4]​. Patients with BPH commonly present in primary care to their GP or community pharmacist, but more complex cases can present in a hospital setting if red flag symptoms are present.

The role of the pharmacist is inextricably linked to the management of BPH, from initial presentation and diagnosis, to pharmacological management. The various treatment options available makes pharmacist involvement crucial to optimising treatment, ensuring positive outcomes and minimising adverse effects.

The prostate is a small, walnut-sized organ located under the bladder, through which the urethra runs. It is composed of epithelial cells, which are secretory, and stromal cells, which include smooth-muscle cells and connective tissue. The prostate’s main function is to produce prostatic fluid, which is combined with sperm to make semen​[5]​.

The prostate is intricately linked to the endocrine system and relies on androgens, such as testosterone, to maintain its secretory functions. Testosterone is converted to dihydrotestosterone (DHT) by the enzyme 5α-reductase​[5,6]​. DHT is ten times more potent than testosterone and, through intracellular effects on DNA transcription, is responsible for the normal development of the prostate. It is also thought to be responsible for the abnormal growth seen in BPH​[4,5]​. The aetiology of BPH also has a dynamic component owing to increased smooth muscle tone in the prostate​[4]​.

BPH is often asymptomatic but can lead to benign prostate enlargement. This causes the prostate to compress on the urethra and neck of the bladder, leading to lower urinary tract symptoms and bladder outflow obstruction​[3]​. However, not all males with lower urinary tract symptoms will have BPH, nor will all males with BPH have bladder outflow obstruction.

Lower urinary tract symptoms are divided into three categories: voiding symptoms, storage symptoms and post-micturition symptoms (see Table 1)​[3,5,6]​. Other symptoms of BPH include both acute and chronic urinary retention, renal impairment, haematuria (blood in urine) and frequent urinary tract infections (UTIs)​[6]​.

Red-flag symptoms that require referral or further investigation include​[1,7]​:

There are two main risk factors for developing BPH: age and the presence of circulating androgens​[8]​. Increasing age is the most significant risk factor. It is hypothesised that, as circulating levels of testosterone decrease with age, the enzymatic conversion of testosterone to DHT is upregulated [8]. Studies have shown that castrated patients do not develop the condition, indicating that circulating androgens are necessary to the development of BPH​[9]​. There is a genetic predisposition to developing BPH; there is a greater risk of developing the condition if there is a known family history[5,10]. Modifiable risk factors, such as poor diet, obesity and decreased physical activity, can substantially influence the development of BPH​[10]​. A link between BPH and erectile dysfunction has been observed, but it is unclear if one precedes the other​[10]​.

BPH is diagnosed using a combination of clinical examinations and investigations. A digital rectal exam should be carried out to gauge the size of the prostate. A thorough clinical history will be taken and an international prostate symptom score (IPSS) calculated​[3]​. The IPSS questionnaire comprises eight questions and is used to assess clinical severity and record lower urinary tract symptoms; 0–7 is mild, 8–19 is moderate and 20–35 is severe. Urinalysis is used to exclude infection and identify haematuria. A full blood count, urea and electrolyte panel are used to establish renal function and exclude differential diagnoses​[3,11]​. A prostate specific antibody (PSA) test can be useful for identifying elevated PSA levels (common in BPH) and estimating the size of the prostate.

The main differential diagnosis to consider when suspecting BPH is prostate cancer, which can present with overlapping symptoms. Other prostate cancer symptoms to be aware of are painless haematuria, lower back pain, weight loss and reduced appetite​[12]​. PSA is also raised in patients with prostate cancer; however, PSA levels naturally increase with age and false positive rates are as high as 75%​[12,13]​.

For many patients, lifestyle modifications can improve symptoms without the need for further intervention​[14]​:

Cognitive behavioural therapy and bladder training both include techniques to increase the time between feeling the urge to urinate and passing urine. For instance, in bladder training, patients learn to suppress the urgency for urination by contracting their pelvic muscles, hopping from one foot to another and distracting themselves. Evidence has shown the impact of bladder training on both incontinence and an overactive bladder, with up to 87% of patients demonstrating improvement​[20]​.

The aim of pharmacological treatment is to manage symptoms based on patient-related goals focusing on issues prioritised by the individual​[14]​.

Medication should be offered to patients with bothersome symptoms, as described in Table 1, for whom lifestyle changes have not been successful​[3]​. Symptoms, comorbidities, age, concurrent medication and recent observations (such as blood pressure) should be taken into consideration before starting treatment​[3]​.

An alpha blocker should be offered as first-line treatment for patients with moderate-to-severe symptoms​[14]​. By relaxing smooth muscle, they improve symptoms and urinary flow rates but do not reduce the risk of requiring subsequent surgery​[21]​. Dizziness, orthostatic hypotension, nasal congestion and retrograde ejaculation are common side effects​[22]​. The lower urinary tract is largely mediated by alpha-1A-adrenergic receptors. As a result, alpha-1A-selective alpha blockers, such as tamsulosin, have fewer systemic adverse effects​[23]​.

Tamsulosin has been classified as a pharmacy-only medicine since 2009​[24]​. See Table 2 for dosing information. It can be purchased over the counter by patients who meet stringent eligibility criteria (see Box). Eligible patients can be offered an initial two-week supply, followed by a further four-week supply if improvements in urinary symptoms are seen​[24]​. After six weeks, patients must be assessed by a doctor to determine suitability for further treatment or if additional investigations are needed​[24]​. Referral criteria is detailed in the box below​[24]​.

Men with symptoms of BPH who have prostates estimated to be greater than 30g or a PSA level more than 1.4ng/mL, and are deemed to be at high risk of progression, should be given a 5α-reductase inhibitor, such as finasteride or dutasteride​[3]​. By blocking the conversion of testosterone to dihydrotestosterone, finasteride and dutasteride reduce serum PSA, prostate volume, urinary symptoms and the need for surgery​[25]​. Although usually well tolerated, the side effects can be distressing for patients and can include impotence, gynecomastia and decreased libido​[24]​. Head-to-head comparison studies have not shown any significant difference between finasteride and dutasteride​[26]​.

Anticholinergics can be offered to patients with symptoms of an overactive bladder​[3]​. Muscarinic M3 receptors initiate bladder contraction and, therefore, antagonising these receptors causes relaxation. Traditional side effects include dry mouth, dizziness, constipation and blurred vision​[22]​. Furthermore, increasing focus on the long-term cognitive impact of anticholinergics has demonstrated an increased risk of dementia​[27]​. Anticholinergic burden is a scoring system describing the risk of adverse drug reactions and dementia with a higher score indicating a higher risk​[28]​. All anticholinergics used for the treatment of urinary symptoms have an anticholinergic burden of 3 — the highest possible individual score​[27]​.

Mirabegron is a novel, specific β3-adrenoceptor agonist with proven efficacy in the treatment of an overactive bladder​[29]​. Meta-analysis has shown similar efficacy in comparison with antimuscarinics (a subtype of anticholinergic drugs), but with fewer inconvenient side effects​[30]​. This is reflected by patients having greater adherence with mirabegron than more traditional therapies​[31]​. Blood pressure should be monitored and dose reductions are recommended for patients on concurrent enzymatic inhibitors or in the presence of renal and hepatic impairment​[22]​. It provides a valuable alternative for patients who cannot tolerate, or have a clinical contraindication to, anticholinergics; however, it is a relatively new drug with few long-term studies in this cohort and is significantly more expensive than anticholinergics.

A loop diuretic, taken in the afternoon, can be offered for patients with nocturnal polyuria; however, this is an unlicensed indication​[3,22]​. Desmopressin can be considered for the treatment of nocturnal polyuria after other medical causes have been rigorously excluded and patients have not benefitted from other treatments​[3]​. Phosphodiesterase-5 inhibitors should not be offered to males solely experiencing urinary symptoms​[3]​.

Herbal supplements have been proposed for the treatment of BPH​[32]​. The most widely used is saw palmetto (serena repens) extract, potentially owing to its mechanism as a mild 5α-reductase inhibitor; however, trials have demonstrated no benefit compared with placebo for improving symptoms or urinary flow rate​[33–35]​.

Botulinum toxin is a neurotoxin that inhibits the release of acetylcysteine​[36]​. A recent meta-analysis demonstrated that botulinum toxin did not differ from placebo in terms of efficacy or procedure-related side effects​[37]​. Clear recommendations for its use cannot be made owing to insufficient proof of clinical benefit​[38]​.

Surgery can be offered to patients who have not responded adequately to medical management​[3]​. Transurethral resection of the prostate (TURP) is considered the gold standard and involves removing a section of the gland using a heated metal wire​[39]​. In severe cases, complete removal may be necessary — known as a prostatectomy​[40]​. Given the typical age of presenting patients, surgery poses significant risks of mortality and morbidity. For example, retrograde ejaculation and erectile dysfunction can occur in up to 75% and 10% of men, respectively​[41]​.

Devices are increasingly being used to avoid the risks associated with medication and surgery​[42]​. Transurethral microwave thermotherapy, transurethral needle ablation, transrectal high-intensity focused ultrasound (HIFU) and use of the UroLift system are simple procedures that are often performed in an outpatient setting​[42]​. In March 2023, UroLift was recommended by the National Institute for Health and Care Excellence (NICE) as a cost-effective alternative to TURP​[43]​. Fewer side effects have been reported using these methods; however, concerns have been raised over their long-term efficacy​[42]​. For instance, 44% of patients treated with HIFU required BPH-related surgery within four years​[44]​.

Urinary catheterisation, either intermittent or indwelling, is recommended by NICE for select patients​[3]​. It can be conducted by patients, carers or healthcare professionals. Intermittent catheterisation can give patients control over their symptoms but requires training and dexterity to complete successfully​[14]​. Indwelling catheters can be offered to patients for whom medical management or surgery has failed and who are not able to manage intermittent self-catheterisation​[14]​. However, they increase the risk of urinary tract infection and can cause local trauma to the urethral area if placed incorrectly​[45]​.

Incontinence products can be used at any stage of management. They include pads, pants, sheaths and drainage systems. Toilet aids and containment products are occasionally available on the NHS, depending on local policy​[46]​.

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