Benign Hyperplasia of Prostate (BPH) is a degenerative disorder of Prostate in aging men, which takes effect variously in the masses. Histologically the changes of BPH start occurring as early as fourth decade of life. The incidence of Histological BPH has been found to be 8%, 50% and 80% in 4th, 6th and 9th decades of life.(1). Histologically there is hyperplasia of stromal component (Fibro muscular Component) and that of the glandular component in the form of acini and ducts (Glandular component)(2). The combined effects of these two give rise to various effects on the bladder outlet termed as Lower urinary tract symptoms (LUTS) (3). The obstruction at the bladder outlet caused by the enlargement of prostate is one of the causes of Bladder outlet obstruction (BOO)(4). The BOO caused by BPH has two components.
1. The static component. This is purely due to the bulk of prostate tissue located at the bladder neck and prostatic urethra but may not as simply related to the size of prostate as one may expect.
2. The dynamic component. This occurs as the smooth muscle bulk of the bladder neck and the adjoining base of prostate causes increased bladder outflow resistance due to contraction under the influence of adrenergic alpha-receptors in these circular muscle fibers.
Even though the prostate increases in volume in many men, all men do not get symptoms due to enlarging prostate (5). Furthermore the severity of symptoms of enlarged prostate can never be correlated with the size of prostate. Following are the various clinical presentations of enlarged prostate.(6,7,8)
1. Asymptomatic BPH. This is a very common presentation in today’s context. The culture of routine medical checkups brings out the sonographically discernible increase in the size of prostate. The normal size of prostate is accepted as up to 20 grams. Therefore any prostate estimated to be larger than this is reported as BPH. All sonographically detected enlarged prostates may not require treatment.
2. Irritative BPH .The enlargement of prostate, especially in early stages causes elongation of prostatic urethra, giving rise to increased micturition reflex. This presents as frequency, nocturia and urgency. This can also be classified as Overactive bladder (OAB)
3. Obstructive BPH. The prostate may enlarge and cause compression on the prostatic urethra and bladder neck and cause, slowing down of stream of urine. The patient may report as difficulty in initiating the stream of urine, prolonged act of urination, sense of incomplete evacuation of bladder. The stream can be so poor that the patient may report it as dribbling only. If the stream of urine improves after straining, it is likely to be due to stricture urethra rather than BPH.
4. Acute retention of urine (AUR). Some patients do not report any prior obstructive symptoms but may present as retention of urine needing catheterization. Many of these patients may start passing urine after brief period of catheterization coupled with alpha-blocker agents.
Clinical approach to presentation of a suspected case of BPH
Carefully eliciting history of the symptoms and their duration is essential in attempting to differentiate BPH from conditions mimicking it closely like urinary tract infection, stricture urethra, bladder stone, or bladder papilloma. Usually, BPH gives symptoms without burning or pain. If any of these is reported, one must consider another or additional diagnosis. Hematuria should never be attributed to BPH unless other causes have been adequately excluded. Bladder stone and stricture urethra can coexist with BPH. History of associated medical comorbidities is extremely important before planning the management. History of neurological event in past may influence the diagnosis of lower urinary symptoms and prognosticating the outcome of treatment.
Examination begins with the general physical examination and the performance status of the individual and makes an impact on the choice of treatment. Abdomen should be examined for percussable or palpable bladder. The external genitalia must be examined for any condition contributing to the cause of symptoms. Examination of spine and hernial sites is imperative. Digital rectal examination (DRE) is the most important clinical sign of enlarged prostate. Not only does it gives an idea of the presence of an enlarged prostate but also is important to exclude clinically identifiable cancer of prostate. The presence of nodularity and effacement of median sulcus should alert the clinician towards the possibility of malignancy arising out of prostate.
Investigations in a patient presenting with LUTS and likely to be BPH start with
1. Urine routine and microscopic examination,
3. Ultrasound examination of Urinary tract including post void residual urine and
Usually these are sufficient to make a confident diagnosis of BPH along with a firm treatment plan. If there is hematuria, extensive investigation must be carried out to exclude urothelial malignancy. If there is any doubt about the contractility of urinary bladder, as occurs in long standing diabetes or any history of neurological event in past, a detailed urodynamic assessment in the form of Cystometrogram must be done.
Treatment of BPH
Asymptomatic BPH does not require any treatment and needs only reassurance.
1. Medical management
This is the first line of treatment in most cases that present to the outpatient department (9). The early cases usually have irritative BPH and require medical management. The patients presenting with obstructive symptoms need to be carefully evaluated for need for surgical intervention. Medical management is classified into following categories
- Alpha 1 adrenergic antagonists. These act on the dynamic component of BOO by relaxing the circularly oriented smooth muscles around the bladder neck and prostatic urethra. However they are effective in most cases with differing efficacy. Most of these agents have effects on cardiovascular and consequent central nervous systems there by causing postural hypotension, palpitations, light-headedness and nasal stuffiness. In sexually active males these agents can cause retrograde ejaculation there by causing concern and anxiety if not educated about at the time of prescription of these agents. Using the agents beyond standard recommended dosages does not increase their efficacy but increase the incidence and severity of adverse effects. Following are the practical aspects of some of these agents as available in India.
a) Tamsulosin (0.4 mg once daily). Incidence of palpitations, postural hypotension, nasal stuffiness and retrograde ejaculation are fairly common with use of this drug.
b) Alfuzosin (10 mg once daily). Is similar to Tamsulosin but rarely causes retrograde ejaculation. Therefore it is the drug of choice for sexually active males with BPH.
c) Silodosin (4,8 mg, once daily). This has the least cardiovascular and nervous system side effects and therefore should be prescribed to patients with symptomatic BPH patients with coexistent cardiac/neurological ailments and elderly men.
- Naftopidil (50 mg once daily). This has been shown to reduce the incidence of Nocturia in some studies and therefore has been recommended in patients with bothersome nocturia.
B). 5 Alpha reductase inhibitors. These agents block the enzymatic action of 5 alpha reductase, which converts the testosterone molecule into its active form Dihydrotestosterone which is essential for the growth and perpetuation of the glandular component of BPH (10). They can reduce the size of prostate gland by a maximum of 30% over 6 months of use, as this is the contribution by the glandular component in the BPH tissue. The size of prostate rapidly returns to pretreatment size if the treatment by these agents is withdrawn. Therefore these must be continued lifelong. These agents can cause loss of libido (4.5%), erectile dysfunction (7%)and ejaculatory disturbances (2.3%) in men taking them in the long run (11). These are reversible after stopping the offending drug. Finasteride (5 mg once daily) and Dutasteride (0.5 mg once daily) are commonly used drugs in this class (12). They may be used alone or in combination with alpha-adrenergic antagonists. They are the drug of choice if the patients are unable to tolerate alpha-adrenergic blockers due to bothersome and life threatening adverse effects. However it must be kept in mind that these do not work as effectively if the size of the prostate is less than 30 grams.
C). Bladder sedatives. Patients with bothersome irritative symptoms like frequency and urgency need to be treated with additional drugs if they do not respond to the first line treatment agents as described above. These patients need to be treated with agents to reduce the bladder detrusor irritability. However if the bladder is hyper excitable due to a central nervous lesion then it doesn’t respond well to these agents.
a. Antimuscarinic agents. These are primarily antagonists to the muscarinic receptors in the bladder detrusor, which mediate the contraction of bladder. They increase the functional bladder capacity and may increase the post void residual urine. There have been incidences of precipitating acute urinary retention (AUR) following use of these agents in case of BPH with already a residual urine more than 150 ml, even though some clinical studies have not supported this fact. The other adverse effects commonly encountered along with use of these agents are dry mouth, constipation, abdominal bloating, forgetfulness, Blurred vision, changes in cognitive function especially in elderly (13). Tolterodine (4 mg once daily), Solifenacin (5,10 mg once daily), Darifenacin (7.5,15 mg once daily), Trospium Chloride (60 mg extended release, once daily) are commonly used antimuscarinic agents. Since Trospium is a quaternary ammonium compound, it doesn’t cross blood brain barrier and therefore is devoid of CNS side effects. Darifenacin also doesn’t cross blood brain barrier in sufficient concentration to cause CNS side effects. Thus these two agents are the drugs of choice for elderly persons.
b. Beta 3 adrenergic agonists (Mirabegron 25,50 mg once daily). Beta 3 adrenergic receptors mediate the relaxation of detrusor muscle without reducing its contractility (14). Thus these agents do not cause the increase in post void residual urine and consequently retention of urine is quite rare. Mirabegron is a well tolerated and has been shown to be effective in all groups of patients either alone or in combination with antimuscarinic agents like solifenacin. Commonly seen adverse effects include hypertension, palpitations, blurred vision and nervousness.
2. Surgical management.
Indications of surgical intervention include
a) Recurrent retention of urine
b) Severely symptomatic obstructive LUTS
c) Significant residual urine more than 200 ml
d) Obstructive uropathy jeopardizing the renal function
e) Concomitant bladder pathology like Vesical calculus, Bladder tumor etc.
It is to be noted that recurrent infections, frequency, urgency, nocturia are not indications of surgery for BPH. In fact surgery may aggravate these symptoms and make the person more miserable. Surgical options include the following.
a. Trans urethral Resection of Prostate (TURP). This is considered the gold standard for surgical treatment of BPH. It is cheap and can be performed with usually available technology even in peripheral centers. The cost of consumables is acceptable and all urology-training centers impart the basic training in TURP. However it has the disadvantages of hemorrhage, both intraoperative and secondary, limiting its use in prostate less than 100 grams. Large prostate glands more than 100 grams need to be judicially treated by this modality in centers with adequate backup to deal with complications. There is 7-10% incidence of recurrence of obstructive BPH following TURP after a median of 7 years.
b. Holmium Laser enucleation of prostate (HoLEP). This is a relatively newer technology in vogue since the beginning of 21st century. Holmium laser is used to enucleate the obstructing adenoma which is the retrieved as small bits after morcellation through the cystoscope. The procedure is associated with less blood loss as compared with TURP. The immediate postoperative operative period has minimal nursing events and the morbidity is much less. Large sized glands can be treated effectively using this technique. There is virtually no recurrence of obstructive BPH after this procedure. The specimen retrieved is available for histological examination.
c. Photo selective vaporization of prostate (PVP). This is performed by Potassium Titynyl Phosphate (KTP, Greenlight) laser. The red color in the blood pigment absorbs the green laser light and causes vaporization of prostate. This is good procedure for small and moderate sized prostate and utilizes a side firing fiber which gets worn out in one procedure. Thus there significant cost attached to the use of one fiber per treatment, which cost almost USD 1000. Some cases with large prostate may require two fibers per treatment especially in cases with large prostate. The disadvantage is the lack of specimen for histological examination.d. Open prostatectomy still has a role in surgical management of very large prostates.