The hormone that is responsible for the development and progression of benign prostatic hyperplasia (BPH) is dihydrotestosterone. BPH occurs within the prostate following the conversion of testosterone to dihydrotestosterone by 5-alpha reductase. Dihydrotestosterone is a hormone that is five times more potent than its pro-hormone, testosterone. It is responsible for the stimulation of growth factors that influence cell division and lead to enlargement and hyperplasia of the prostate.

Symptoms of BPH can be divided into irritative and obstructive. Irritative symptoms involve urine stores failing and those that are obstructive are associated with failure to empty the bladder. As such, the symptoms of BPH are:

  • Irritative: Frequency, nocturia, urgency
  • Obstructive: Poor flow, hesitancy, sensation of incomplete emptying, post-micturition dribble

Prostate size is the main consideration in choosing treatments for BPH. The two most common treatment options are selective alpha-1 adrenergic blockers and 5-alpha reductase inhibitors. Selective alpha-1 blockers relax smooth muscle in the bladder neck and prostate and thus can improve symptoms within 48 hours as well as increase urinary flow. Selective alpha-1 blockers seem to be effective regardless of prostate size. Meanwhile, 5-alpha reductase inhibitors are used when the prostate size is greater than 30-40 cm3. They improve symptoms and urinary flow, as well as reduce prostate size. However, it takes six months for improvement of symptoms to be observed.

Alpha Adrenergic Blockers

BPH occurs because the prostate is susceptible to stimulation by an increase in sympathetic tone, caused predominantly by adrenergic receptors. Dihydrotestosterone stimulates adrenergic receptors leading to a disruption in homeostasis which, in turn, leads to the development of BPH. However this stimulation can be reversed with drugs. The search for drugs which inhibit adrenergic receptors has led to the introduction of new agents over recent years.

One such example is tamsulosin which is a selective inhibitor at the alpha1A,1B adrenergic receptor. Tamsulosin does not require titration from its initial dose, and the elimination half-life of ten hours allows it to have once daily dosing. The drug is mostly well-tolerated however it does have several adverse effects such as dizziness, headache, asthenia and syncope. Its adverse effects increase at higher doses. Tamsulosin interacts with other medications such as frusemide, which reduces the plasma concentration of tamsulosin. Moreover, tamsulosin (like all adrenergic antagonists) enhances hypotension when administered with other hypotensive agents, such as prazosin.

5-alpha Reductase Inhibitors

5-alpha reductase inhibitors prevent the conversion of testosterone to dihydrotestosterone. There are two isoenzymes of 5-alpha reductase. Type 1 is found in tissues such as liver, skin and hair. Type 2 is found in genital tissues and the prostate. Finasteride is a type 2 5-alpha reductase inhibitor and is shown to reduce prostate size by 30%, improve symptoms, and increase urinary flow. It may take six months for symptom improvement to be observed, but once obtained continual symptom relief will be present for several years with ongoing treatment.

Adverse effects of finasteride include reduced libido, impotence, and reduced ejaculatory volume. Male sexual dysfunction is also commonly associated with patients who have BPH. Therefore, one of the main considerations of treatment of BPH is to restore sexual function. Adrenergic antagonists can restore male sexual function however the efficacy is variable between drugs and patients.

Phytotherapy is a possible alternative option to the above pharmacotherapies. For example, plant extracts such as saw palmetto berry, African plum tree, and stinging nettle. The studies regarding these plant extracts have been short and in uncontrolled environments making it difficult to measure the efficacy of phytotherapy treatment at this stage. The proposed mechanism of action is anti-inflammatory (by inhibiting of prostanoid formation), and inhibition of 5-alpha reductase.

In conclusion, adrenergic antagonists are effective in managing acute symptoms but have no effect on managing acute urinary retention or reducing rates of prostate surgery. On the other hand, 5-alpha reductase inhibitors do not show much improvement in acute symptoms but are effective in reducing the risk of acute urinary retention and delaying the progression of BPH. Furthermore, the Medical Therapy of Prostatic Symptoms Study found that using a combination of both therapies “significantly reduced the risk of overall clinical progression of benign prostatic hyperplasia more than did either drug alone.”

References:

  1. McConnell JD, Roehrborn CG, Bautista OM, Andriole GL Jr, Dixon CM, Kusek JW, et al. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med. 2003 ; 349(25): 2387-98.
  2. O’Leary MP. Tamsulosin: current clinical experience. Urology 2001; (58): 42-8.
  3. Revision 2073, Benign Prostatic Hyperplasia. In: Australian Medicines Handbook 2011 (CD-ROM). Adelaide: Australian Medicines Handbook Pty Ltd; 2011 Jan.
  4. Roehrborn CG, Bruskewitz R, Nickel GC, Glickman S, Cox C, Anderson R, et al. Urinary retention in patients with BPH treated with finasteride or placebo over 4 years. Characterization of patients and ultimate outcomes. Eur Urol 2000; (37): 528-36.
  5. van Dijk MM, de la Rosette JJ, Michel MC. Effects of alpha(1)-adrenoceptor antagonists on male sexual function. Drugs 2006; (66): 287-301.
  6. Walker R, Whittlesea C, editors. Clinical Pharmacy and Therapeutics. 4th ed. London: Churchill Livingstone; 2007. p. 691-8.

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