Dr. med. Dirk Manski



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Medication for Benign Prostatic Hyperplasia (BPH)


Review literature: (Burnett und Wein, 2006) (DGU-Guideline: diagnostic work-up, 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:


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 renal insufficiency. 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].

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.

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.

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 by trials. Trials documenting the long-term efficiency of plant extract are not available.







Index: 1–9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z



References

Andriole u.a. 2004 ANDRIOLE, G. L. ; ROEHRBORN, C. ; SCHULMAN, C. ; SLAWIN, K. M. ; SOMERVILLE, M. ; RITTMASTER, R. S.:
Effect of dutasteride on the detection of prostate cancer in men with benign prostatic hyperplasia.
In: Urology
64 (2004), Nr. 3, S. 537–41; discussion 542–3

Burnett und Wein 2006 BURNETT, A. L. ; WEIN, A. J.:
Benign prostatic hyperplasia in primary care: what you need to know.
In: J Urol
175 (2006), Nr. 3 Pt 2, S. S19–24

Chapple 2004 CHAPPLE, C. R.:
Pharmacological therapy of benign prostatic hyperplasia/lower urinary tract symptoms: an overview for the practising clinician.
In: BJU Int
94 (2004), Nr. 5, S. 738–44

DGU-Guidelines: diagnostic work-up
Leitlinien der Deutschen Urologen zur Diagnostik des benignen Prostatasyndroms (BPS).
In: Urologe A
48 (2009), S. 1356–60, 1362–4


DGU-Guidelines: treatment
Leitlinien der Deutschen Urologen zur Therapie des benignen Prostatasyndroms (BPS).
In: Urologe A
48 (2009), S. 1503–1516


Donovan u.a. 2000 DONOVAN, J. L. ; PETERS, T. J. ; NEAL, D. E. ; BROOKES, S. T. ; GUJRAL, S. ; CHACKO, K. N. ; WRIGHT, M. ; KENNEDY, L. G. ; ABRAMS, P.:
A randomized trial comparing transurethral resection of the prostate, laser therapy and conservative treatment of men with symptoms associated with benign prostatic enlargement: The CLasP study.
In: J Urol
164 (2000), Nr. 1, S. 65–70

McConnell, J. D.; Bruskewitz, R.; Walsh, P.; Andriole, G.; Lieber, M.; Holtgrewe, H. L.; Albertsen, P.; Roehrborn, C. G.; Nickel, J. C.; Wang, D. Z.; Taylor, A. M. & Waldstreicher, J.
The effect of finasteride on the risk of acute urinary retention and the need for surgical treatment among men with benign prostatic hyperplasia. Finasteride Long-Term Efficacy and Safety Study Group
N Engl J Med, 1998, 338, 557-63


Oelke, M.; Bachmann, A.; Descazeaud, A. & Emberton, M.
Guidelines on conservative treatment of non-neurogenic male LUTS
www.uroweb.org, 2010.


Reich u.a. 2006 REICH, O. ; GRATZKE, C. ; STIEF, C. G.:
Techniques and long-term results of surgical procedures for BPH.
In: Eur Urol
49 (2006), Nr. 6, S. 970–8; discussion 978


  Deutsche Version: Medikamentöse Therapie der benignen Prostatahyperplasie