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Medication for Benign Prostatic Hyperplasia (BPH)

• Benign prostatic hyperplasia (1/6): definitions, epidemiology and etiology
• Benign prostatic hyperplasia (2/6): signs and symptoms
• Benign prostatic hyperplasia (3/6): diagnosis
• Benign prostatic hyperplasia (4/6): treatment algorithm
• Benign prostatic hyperplasia (5/6): medical treatment
• Benign prostatic hyperplasia (6/6): surgical treatment

Review literature: (Burnett und Wein, 2006) (DGU-Guideline: diagnostic workup, 2009) (DGU-Guideline: treatment, 2009) (EAU-Guideline: Oelke et al., 2010)

Contraindications for Medical Treatment of BPH

Surgery is the treatment of first choice in the following situations:

• Postrenal kidney failure
• Recurrent Urinary retention
• Recurrent Urinary tract infections
• Recurrent Hematuria
• Huge bladder diverticula

Alpha Blocker for Benign Prostatic Hhyperplasia (BPH)

Alpha blocker are the drugs of first choice to treat LUTS due to BPH. Numerous randomized trials have demonstrated the efficacy and safety of the alpha blocker listed below. Furthermore, alpha blocker should be given to support a trial without a catheter after urinary retention. For details see section pharmacology and side effects of alpha blocker.

Tamsulosin:

The dosage of tamsulosin is 0.4 mg 1-0-0 p.o. A low starting dosage is not necessary. The OCAS galenic (Oral Controlled Absorption System) enables dosing independent from meals.

Alfuzosin:

The dosage of alfuzosin is 2.5 mg 1-1-1 or 5 mg 1-0-1 p.o. A low starting dosage is not necessary. The sustained-release galenic enables a single dose of 5–10 mg 1-0-0 p.o.

Silodosin:

Silodosin is a new selective alpha blocker with little side effects on the cardiovascular system. Dosage 8 mg 1-0-0 p.o. Dose reduction to 4 mg is necessary in chronic kidney disease. A low starting dosage is not necessary.

Terazosin:

The dosage of terazosin must start with a low dose in the evening before bed time (1 mg 0-0-1 p.o.) to avoid side effects on the arterial blood pressure. The dose may be increased weekly to 2 mg, 5 mg, or 10 mg once daily to achieve the desired improvement of symptoms. Terazosin is a drug of second choice because of the side effects, but it may be beneficial in patients with arterial hypertension.

Doxazosin:

The dosage of doxazosin must start with a low dose in the evening before bed time (1 mg 0-0-1 p.o.) to avoid side effects on the arterial blood pressure. The dose may be increased weekly to 2 mg, 5 mg, or 10 mg once daily to achieve the desired improvement of symptoms. Doxazosin is a drug of second choice because of the side effects, but it may be beneficial in patients with arterial hypertension.

Comparison of Alpha Blocker:

The analysis of placebo-controlled trials shows that terazosin and doxazosin are more effective, but this leads to a higher rate of side effects (e.g., dizziness, weakness, postural hypotension). The advantages of alfuzosin and tamsulosin are reduced side effects and the lack of necessity for dose titration.

BPH and Accompanying Arterial Hypertension:

Alpha blocker for arterial hypertension proved inferior to beta-blocker and ACE inhibitors in current cardiology studies (ALLHAT, 2000). Therefore, alpha blocker are no longer recommended as first-line treatment for arterial hypertension. This also applies for patients with arterial hypertension and BPH: it is more useful to treat arterial hypertension with a drug of first choice and to treat BPH with selective alpha _1A-blocker.

5α-Reductase Inhibitors for Benign Prostatic Hyperplasia (BPH)

Dihydrotestosterone (DHT) is the main androgen for the prostate, it is converted from testosterone by the 5α-reductase. Finasteride is a competitive inhibitor of the 5α-reductase type 2 and leads to lower concentration of dihydrotestosterone (DHT) in the prostate. DHT is the only effective androgen on the prostate, thus a selective androgen deprivation of prostate is possible. Dutasteride is a new 5α-reductase inhibitor and acts on type 1 and type 2 isoenzyme of the 5α-reductase.

The consequence of 5α-reductase inhibition is the shrinkage of the prostate (7–13 ml in 12 months), improvement of BPH-symptoms (decreasing IPSS), improved urinary flow (maximum flow 0.6–1.6 ml/s better than placebo) and the risk reduction for urinary retention (3% vs. 7%), gross hematuria or the need for TURP (5% vs. 10%) (McConnell et al., 1998). The shrinking of the prostate also decreases the PSA concentration (up to 50%).

The mechanism of action is slow, a significant clinical effect can be expected after a treatment period of 1 year. The larger the prostate, the greater the therapeutic effect.

Pharmacokinetics and Side Effects of 5α-Reductase Inhibitors

5α-reductase inhibitors are well tolerated, the safety of the drugs was documented in several years of study, for details see sections finasteride and dutasteride. Both substances reduce the incidence of prostate cancer if given over several years (Andriole et al., 2004). This led to the initiation of prostate cancer prevention trials, such as the REDUCE trial [see section prevention of prostate cancer].

Phosphodiesterase Inhibitors

Smooth muscle cells of the prostate and urinary bladder also express type 4 and type 5 phosphodiesterase. Randomized trials show that treatment with tadalafil relieves BPH symptoms (Laydner et al., 2011). Compared with tamsulosin, the therapeutic effect with tadalafil is comparable; in addition, erectile function improves (Oelke et al., 2012). Tadalafil has been approved for the therapy of BPH since 2012, the dosage is 5 mg once daily.

Anticholinergics for Benign Prostatic Hyperplasia (BPH)

Irritative BPH-symptoms without any significant residual urine may be treated with anticholinergic drugs. Trials have shown that there is only a low risk for urinary retention. If there is significant obstruction, anticholinergic drugs may be combined with alpha blocker. The side effects are increased by the combination therapy.

Therapy of Nocturia

Nocturia is a distressing symptom that can be caused by BPH but also numerous other conditions, see nocturia. It is important to rule out internal medicine diseases causing nocturia before starting treatment: control of medication, exclusion of cardiac, pulmonary, neurological or metabolic causes of nocturia.

• Micturition diary: to diagnose nocturnal polyuria and bladder storage disorders.
• Behavioral therapy: refraining from evening fluids and alcohol is important. Optimization of sleep hygiene.
• Urological therapy: conservative or, if necessary, surgical therapy of BPH for voiding symptoms or residual urine. Therapy of overactive bladder in case of storage symptoms.
• Desmopressin: is an option if nocturia persists despite above mentioned measures. Dosage of desmopressin: 50 μg before sleep for men, 25 μg before sleep for women (Han et al., 2017). For pharmacology, contraindications, and side effects, see desmopressin.

Drug Combinations for the Treatment of Benign Prostatic Hyperplasia (BPH)

Alpha Blocker and 5α-reductase Inhibitors

Sound drug combinations are the administration of an alpha blocker for rapid symptom improvement and a 5α-reductase inhibitor for long-term shrinkage of the prostate. The efficiency of the combination was demonstrated in randomized trials, in the further course of the treatment, the alpha blocker could often be discontinued after 3–5 months.

Phytotherapeutic Drugs for Benign Prostatic Hyperplasia (BPH)

Mono extracts or combinations of plant extracts from Sabal serrulata (dwarf palm), Serenoa repens (saw palmetto), Pygeum africanum (African plum), beta-Sitosterone from Hypoxis rooperi (African grass), Secale cereale (rye) and many more are available over the counter. Suspected mechanisms of action include the inhibition of 5α-reductase (Serenoa repens), the inhibition of growth factors (Pygeum africanum), promotion of apoptosis (Serenoa repens), anti-inflammatory effects, placebo effects and many more. Only a few well-structured randomized trials indicate a moderate effect of plant extracts, the effect of Serenoa repens (Saw Palmetto) is documented best. Trials documenting the long-term efficiency and safety of plant extract are not available.

References

  Deutsche Version: Medikamentöse Therapie der benignen Prostatahyperplasie