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MEDICAL MANAGEMENT OF BPH
R K Garg
Consultant Urologist, Bombay Hospital Institute of Medical Sciences, Mumbai 20.
BPH is the commonest disorder of advancing age of men with associated morbidity and mortality. 10.15% men need surgical intervention for one of the following indications.
- Acute retention of urine.
- Chronic retention of urine with or without renal failure.
- Recurrent urinary tract infection.
- Haematuria
- Secondary bladder stone due to BPH.
- Significant obstructive symptom.
However, majority of patients, if given a choice would like to avoid surgery. In the past prostate surgery was associated with high incidence of morbidity and mortality. But today the scenario has changed.
With increase in awareness and elderly people wanting to live better quality of life there was a search for alternative treatment by pharmaceutical companies and biotechnologists. Today we have alternatives available in the form of medical treatment of BPH in selected group of patients. The advantages are
- Easily available
- Minimal side effects.
- Side effects are reversible.
- Comparatively affordable.
- Effective
- Gives symptomatic relief and also arrests the disease process.
Indications
- Mild to moderate symptom of outflow obstruction.
- More irritative than obstructive symptoms.
- Medically patient is unfit for anaesthesia and surgery.
- Patient is unwilling for surgery.
- When definitive treatment is to be delayed temporarily.
Pathogenesis of BPH
The aetiology of BPH is multifactorial and as yet not fully understood. However, ageing and the presence of androgens are definite requirements for its development.
Prostate basically consist of epithelial tissue 25%, connective tissue 50% and smooth muscles 25%. Urethral obstruction due to BPH can be either due to epithelial or stromal component requiring selective medical treatment for each component. Usually we get mixture of both in different proportion requiring combination of drugs for optimal effect.
Satisfactory voiding of urine depends on two factors (i) static (ii) dynamic. Static factor depends on the mechanical obstruction caused by increase in volume of prostate which blocks the urinary passage. Whereas dynamic component depends on the adrenergic receptors in the bladder muscle an at bladder neck level.
The medical treatment depends on drugs controlling these factors.
Treatment of Dynamic Obstruction
Prostate is innervated by autonomic nervous system (mainly sympathetic) and hyperplastic portion is rich in alpha adrenergic receptor (both Alpha1 and Alpha2)Sympathetic stimulation increases the tone of this area giving urethral obstruction. Multiple agents that exert Alpha adrenergic blockage have been studied clinically.
Phenoxibenzamine which has properties of both Alpha1 and Alpha2 as first such agent used clinically many studies showed subjective and objective improvement by this agent but because of side effects due to non selective blockade of both receptors. This drug is no more used for this purpose.
It was found that beneficial effect were due to blockage of Alpha1 and unwanted effect due to blockage of Alpha2 receptors. It was with this in mind that efforts were made to study selective Alpha blocker.
Even in Alpha1 blockers we have short acting like prazosin and Alfuzocin (2-3 time a day). Long acting selective Alpha blockers like terazocin, doxazocin, allow once a day dosing though they are selective Alpha1 blocker. Some side effects are seen in the form of (1) Dizziness (2) Tachy cardia (3) Palpitation (4) Tiredness (5) Weakness (6) Nasal Congestion (7) Retrograde Ejaculation. Fortunately very few people get these side effects and can be reduced considerably by adjusting the dosage.
Treatment of Adynamic Obstruction
Human BPH is endocrine dependent. Nearly 100 years ago 100 patients underwent bilateril orchidectomy, for symptoms due to bladder outlet obstruction with good results. In 1940 Huggins got Noble prize for proving androgen dependency of prostate and BPH.
In 1946 various drugs were tried to achieve same goal. LHRH - analogue were tried, but in 1963 role of DHT. (dehydro testosterone) became more clear, for pathogenesis of BPH, and in 1965 enzyme responsible for such conversion from testosterone to dehydro testosterone, (5 Alpha reductase) was found. Now it was much easy to block this enzyme which did not lower the testosterone level in blood, maintaining libido.
Since 1990 various trials have been carried out which sums up like this. In epithelial component it works, it has to be given for long time (6 months to one year) for optimal result.
It should be started early in disease process. 5 Alpha reductase inhibitor (5 mg daily) works only in big juicy gland with epithelial prominent component. In certain cases it gives rash and certain cases impotency has also been reported.
This drug also reduces PSA which is the marker in blood for prostate carcinoma and prostate cancer may be missed if patient is already on this drug so one should be extra cautious in interpreting results of PSA on this group of patients. Medical management is not easy as it sounds because it needs proper evaluation of patient to make a proper diagnosis, to exclude more sinister problems which may mimic BPH, like, carcinoma of bladder, carcinoma of prostate, stricture urethra. They also need proper follow up to see whether they tolerate the medicine and symptoms are not getting worse to decide whether they need alternative therapy.
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