Histologically, the incidence of BPH increases as men age. Histologic prostatic hyperplasia generally occurs in men over the age of 35 years, with no evidence that men younger than 30 years will still have BPH. By age 60 years approximately 50% of men have histologic prostatic hyperplasia, and by age 80 years, this percentage is as high as 83%.
Complications of benign prostatic hyperplasia
The main complications of BPH are bladder stones, urinary tract infections, urinary incontinence, ureteral reflux and impaired kidney function, and urinary retention.
Research data show that the incidence of bladder stones in patients with prostatic hyperplasia is 3.4%, compared to 0.4% in normal controls, and that the incidence in patients with BPH is about 9 times that of the normal population; however, the incidence of upper urinary tract stones in patients with BPH is not significantly increased compared to the normal population.
Urinary incontinence affects the quality of life of many patients with BPH. The most recent MTOPS study showed that the incidence of incontinence in patients with BPH that exceeds the patient’s acceptable capacity is 0.3%. BPH leads to urinary retention due to mechanisms such as bladder overfilling or bladder forceps instability due to bladder outlet obstruction.
Ureteral reflux and impaired renal function. Previous studies have shown that approximately 13.6% of patients underwent transurethral resection of the prostate because of renal failure. However, no patients with BPH were found to have renal insufficiency in the recent MTOPS study, but this finding warrants further study, as patients with impaired renal function may be excluded.
Urinary retention. Patients with BPH have both acute and chronic urinary retention. If there is recurrent urinary retention (inability to urinate after at least one extubation or two), the patient is advised to opt for surgical treatment. Acute urinary retention is one of the most significant complications in patients with BPH. Data show that 25-30% of patients with BPH undergo transurethral resection of the prostate for acute urinary retention; the recurrence rate within one week of the first occurrence of acute urinary retention is 56-64%, and this rate is as high as 76-83% in patients diagnosed with BPH. The cause of acute urinary retention is not clear, but it may be related to infection, overdistension of the bladder, alcohol consumption, sexual intercourse, and physical weakness. In addition, prostate infarction may also be a potential causative factor for acute urinary retention. Chronic urinary retention due to bladder outlet obstruction can lead to hydronephrosis and even impaired renal function. Transurethral electrodesis of the prostate is feasible for patients with chronic urinary retention if their renal function is normal; if the renal function is not complete, the urinary catheter should be left in place to drain the urine and then transurethral electrodesis of the prostate should be performed when the renal function returns to normal or near normal.
Clinical progressiveness of benign prostatic hyperplasia
The clinical progression of BPH is slow, and there is still no uniformity in the evaluation of clinical progression, but the more consistent opinions to date are: worsening of lower urinary tract symptoms and consequent decrease in the patient’s quality of life, progressive decrease in maximum urinary flow rate, acute urinary retention, recurrent hematuria, recurrent urinary tract infections, and impaired renal function, etc. And patients with BPH undergoing surgical treatment are the clinical manifestation of their lesions. The final manifestation of the progressive nature of the disease is surgery.
Current data suggest that the risk factors for clinical progressiveness of BPH are age, serum PSA, prostate volume, maximum urinary flow rate, residual urine volume and I-PSS score.
Age. The risk of acute urinary retention and the need for surgical intervention in patients with BPH increases with age; BPH patients ≥62 years of age are more likely to experience clinical progression.
The MTOPS study showed that patients with BPH with a serum PSA greater than 1.6 ng/ml were at greater risk of clinical progression.
Prostate volume. Prostate volume predicts the risk of acute urinary retention and the likelihood of undergoing surgical procedures in patients with BPH. The most recent MTOPS study showed that patients with BPH with a prostate volume ≥31 ml were at significantly increased risk of clinical progressivity.
Maximum urinary flow rate. The maximum urinary flow rate predicts the risk of acute urinary retention in patients with BPH. The most recent MTOPS study showed that patients with BPH with a maximum urinary flow rate <10.6 ml/s were at significantly increased risk of clinical progressivity.
Residual urine volume. The recent MTOPS study demonstrated a significantly increased risk of clinical progressivity in patients with BPH with a residual urine volume ≥39 ml.
I-PSS score. Data suggest that patients with an I-PSS score >7 have four times the risk of acute urinary retention than patients with an I-PSS score <7.
Physical examination of patients with benign prostatic hyperplasia
Digital rectal examination (DRE) is very important for middle-aged and older men. DRE can reveal the size, shape and texture of the prostate, whether there are nodules and pressure pain, whether the central sulcus is shallow or absent, and the tone of the anal sphincter; the entire rectum should be carefully palpated during DRE to rule out other abnormalities. However, rectal auscultation is only a rough assessment of the prostate volume, while transrectal prostate ultrasound can accurately assess the prostate volume.
Ancillary tests for benign prostatic hyperplasia
Serum PSA level test
The important purpose of serum PSA testing in BPH patients is to rule out prostate cancer. Serum PSA is closely related to the patient’s age and race, and increases with age in men after the age of 40.
Because prostate disease and operations involving the prostate may affect the determination of PSA, PSA testing should be performed one week after prostate massage, 48 hours after rectal examination, cystoscopy, catheterization and other operations, 24 hours after ejaculation, and one month after prostate puncture; and the test should be free of acute prostatitis and urinary retention and other diseases.
Determination of serum PSA results: serum total PSA <4.0ng/ml is normal; when total PSA is between 4 and 10ng/ml, then reference should be made to PSA related variables such as free PSA (ratio of free PSA to total PSA, if the ratio is normal, then it is considered normal; if the ratio is abnormal, then it is considered abnormal), PSA density and PSA rate; serum total PSA <10ng /ml, then it is abnormal. If serum PSA is abnormal, ultrasound-guided prostate puncture biopsy is recommended to rule out prostate cancer.
Transrectal Prostate Ultrasound
Transrectal prostate ultrasound can provide information on the size, shape, presence of abnormal echogenicity and residual urine volume of the prostate; and can accurately assess the volume of the prostate.
In addition, urodynamic testing and cystoscopy are also options if necessary.
Treatment of benign prostatic hyperplasia
In patients with BPH, the lower urinary tract symptoms caused by prostate enlargement and the resulting decrease in quality of life are an important basis for the choice of treatment measures. Currently, the main treatments for BPH are watchful waiting, medication and surgery.
1.Watch and wait
For BPH patients, watchful waiting is a non-pharmaceutical, non-surgical treatment measure, but it is not the same as not taking any measures. In fact, watchful waiting includes a wealth of content such as patient health education, lifestyle guidance and close follow-up.
The indications for watchful waiting can be adopted: patients with BPH who have mild lower urinary tract symptoms (I-PSS score ≤ 7) and moderate or more lower urinary tract symptoms (I-PSS score ≥ 8) while their quality of life has not yet been significantly affected can adopt watchful waiting. However, patients should undergo a thorough examination to rule out complications of BPH before taking watchful waiting treatment measures.
Health education about the patient. Influence patients taking watchful waiting treatment to understand the clinical features of BPH; and to undergo regular PSA, transrectal prostate ultrasound and rectal examinations to rule out prostate cancer.
About patient lifestyle guidance. Patients should limit water consumption appropriately at night or during social activities, which can significantly reduce urinary frequency symptoms, but daily water consumption should be at least 1500 ml; limit the intake of stimulating beverages such as alcohol and coffee; perform bladder training methods such as appropriate urine holding to increase bladder capacity and thus reduce urinary frequency symptoms; mental relaxation training, etc.
Patients with benign prostatic hyperplasia should be followed up closely. The main purpose is to understand the progress of the disease, whether there are comorbidities and whether there are indications for surgery, and also to exclude prostate cancer.
2. Drug treatment
Receptor blockers
(1) Mechanism of action and urinary tract selectivity of alpha-blockers: Alpha-blockers are used to relieve bladder outlet obstruction by blocking adrenergic receptors distributed on the smooth muscle surface of the prostate and bladder neck and relaxing smooth muscle. According to the urinary tract selectivity α-blockers can be divided into non-selective α-blockers (phenoxybenzamine, phenoxybenzamine), selective α1-blockers (doxazosin doxazosin, alfuzosin, terazosin terazosin) and highly selective α1-blockers (tamsulosin tamsulosin-α1A>α1D. naftifadil naftopidil-α1D>α1A).
(2) Recommendation: α-blockers are indicated for patients with BPH with lower urinary tract symptoms. Tamsulosin, doxazosin, alfuzosin and terazosin are recommended for the pharmacological treatment of BPH. Napridil and other applications can be chosen for the treatment of BPH.
(3) Clinical efficacy: The clinical use of α-blockers for the treatment of lower urinary tract symptoms caused by BPH began in the 1970s. the results of the Meta-analysis by Djavan and Marberger showed that various α1-blockers significantly improved patients’ symptoms compared with placebo, resulting in an average improvement of 30% to 40% in symptom scores and an increase of 16% to 25% in the maximum urinary flow rate. Phenobarbital, which was initially used, had significant side effects and was therefore difficult for patients to accept.
Symptom improvement can be seen 48 hours after α-blocker treatment, but assessment of symptom improvement using the I-PSS should be done after 4 to 6 weeks of drug use. Continuous use of α-blockers for 1 month without significant symptom improvement should not be continued. The results of a clinical study of tamsulosin for BPH for up to 6 years showed that long-term use of alpha blockers maintained a stable efficacy. The MTOPS study also confirmed the long-term efficacy of alpha blockers alone. baseline prostate volume and serum PSA levels in patients with BPH did not affect the efficacy of alpha blockers, nor did alpha blockers affect prostate volume and serum PSA levels. The results summarized by the American Urological Association BPH Guidelines Development Committee using a special Bayesian technique showed that the clinical efficacy of various alpha blockers is similar, with some differences in side effects. For example, tamsulosin has a lower incidence of cardiovascular side effects, but a higher incidence of retrograde ejaculation.
(4) Alpha blockers for acute urinary retention: The results of clinical studies show that patients with acute urinary retention BPH treated with alpha blockers have a significantly higher chance of successful removal of the urinary catheter than placebo treatment.
(5) Side effects: Common side effects include dizziness, headache, weakness, sleepiness, upright hypotension, retrograde ejaculation, etc. Upright hypotension is more likely to occur in elderly and hypertensive patients.
5α-reductase inhibitors
(1) Mechanism of action: 5α-reductase inhibitors inhibit the transformation of testosterone to dihydrotestosterone in the body, which in turn reduces the content of dihydrotestosterone in the prostate, achieving the therapeutic purpose of reducing the volume of the prostate and improving urinary difficulties. The 5α-reductase inhibitors that are currently used in China include finasteride and epristeride.
(2) Recommendation: Finasteride is indicated for the treatment of BPH patients with enlarged prostate volume with lower urinary tract symptoms. For patients at high risk for clinical progression of BPH, finasteride may be used to prevent clinical progression of BPH, such as the development of urinary retention or surgical treatment. Patients should be informed of the risk of clinical progression of BPH if they do not receive treatment, and the side effects and longer duration of finasteride treatment should be fully considered.
(3) Clinical efficacy: The results of several large-scale randomized clinical trials have confirmed the effectiveness of finasteride, reducing prostate volume by 20% to 30%, improving patients’ symptom scores by about 15%, increasing urinary flow rates by about 1.3 to 1.6 ml/s, and reducing the risk of acute urinary retention and the need for surgical intervention in patients with BPH by about 50%. Studies have shown that finasteride is more effective in treating patients with larger prostate volumes and/or higher serum PSA levels. The long-term efficacy of finasteride has been demonstrated, with results from randomized controlled trials showing maximum efficacy after 6 months of finasteride use. The efficacy of continuous drug treatment for 6 years has remained stable. Several studies have shown that finasteride reduces the incidence of hematuria in patients with BPH. Data from studies have shown that finasteride (5 mg/d for more than 4 weeks) applied prior to transurethral resection of the prostate reduces intraoperative bleeding in patients with BPH with large prostate volumes.
(4) Side effects: The most common side effects of finasteride include erectile dysfunction, abnormal ejaculation, low libido and others, such as gynecomastia feminization and mastalgia.
(5) Finasteride affects serum PSA level: Finasteride can reduce serum PSA level. Taking Finasteride 5mg daily for 1 year can reduce PSA level by 50%. For patients who applied finasteride, doubling their serum PSA level did not affect its efficacy in detecting prostate cancer.
(6) Epristeride: Epristeride is a non-competitive 5α-reductase inhibitor. A 4-month multicenter open clinical trial in China containing 2006 cases showed that epristeride reduced I-PSS score, increased urinary flow rate, reduced prostate volume and decreased residual urine volume. There is no evidence derived from randomized clinical trials.
Combination therapy Combination therapy refers to the combined application of alpha-blockers and 5α-reductase inhibitors for the treatment of BPH.
(1) Recommendation: Combination therapy is indicated for patients with BPH with enlarged prostate volume and lower urinary tract symptoms. patients at greater risk of clinical progression of BPH are more suitable for combination therapy. The risk of clinical progression of BPH in a specific patient, the patient’s wishes, economic status, and the increase in costs associated with combination therapy should be fully considered before using combination therapy.
(2) Clinical efficacy: The current study results confirm the long-term clinical efficacy of combination therapy. the MTOPS study showed that both doxazosin and finasteride significantly reduced the risk of clinical progression of BPH compared to placebo; and the combination of doxazosin and finasteride further reduced the risk of clinical progression of BPH. Further analysis of the results revealed that when the prostate volume was greater than or equal to 25 ml, the combination therapy was significantly better than doxazosin or finasteride monotherapy in reducing the risk of clinical progression of BPH.
Chinese medicine and botanical preparations Chinese medicine has made an indelible contribution to the development of medicine and health in China as well as to the health of the Chinese nation. There are many types of herbal medicines applied in the clinical treatment of BPH, please refer to the recommendations of the Society of Traditional Chinese Medicine or Integrative Chinese and Western Medicine to carry out the treatment.
3.Surgical treatment
(1) The purpose of surgical treatment BPH is a progressive disease, and some patients eventually need surgical treatment to relieve lower urinary tract symptoms and their impact on quality of life and complications.
(2) Indications for surgical treatment Patients with severe BPH or those whose lower urinary tract symptoms have significantly affected their quality of life can choose surgical treatment, especially for those who have failed or refused to receive drug treatment.
Surgical treatment is recommended when BPH leads to the following complications: (i) recurrent urinary retention (inability to urinate after at least one extubation or two); (ii) recurrent hematuria and ineffective treatment with 5α-reductase inhibitors; (iii) recurrent urinary tract infections; (iv) bladder stones; (v) secondary upper urinary tract hydrocele (with or without renal impairment) in patients with BPH combined with large bladder diverticula, inguinal hernia, severe hemorrhoids or prolapse, and those who are clinically judged to have difficulty achieving therapeutic results without relieving lower urinary tract obstruction should be considered for surgical treatment. The measurement of residual urine volume has some reference value for the degree of lower urinary tract obstruction due to BPH, but because of the instability of repeated measurements, interindividual variability, and the inability to distinguish lower urinary tract obstruction from bladder contractile weakness, it is not considered possible to determine the upper limit of residual urine volume that can be used as an indication for surgery. However, surgical treatment should be considered in patients with BPH who have significantly increased residual urine to the point of overflow incontinence.
The choice of treatment by the urologist should respect the patient’s wishes. The choice of surgical treatment should take into account the surgeon’s personal experience, the patient’s opinion, the size of the prostate, and the patient’s concomitant disease and general condition.
(3) Surgical treatment of BPH includes general surgery, laser treatment, and other treatment modalities, and the effectiveness of BPH treatment is reflected in changes in subjective symptoms (e.g., I-PSS scores) and objective indicators (e.g., maximum urinary flow rate). The evaluation of treatment methods should take into account a combination of factors such as treatment effects, complications, and socioeconomic conditions.
①General surgery: The classic surgical methods are transurethral resectionoftheprostate (TURP), transurethralincisionoftheprostate (TUIP), and open prostate removal. Currently, TURP remains the “gold standard” of treatment for BPH. The results of various surgical procedures are close to or similar to those of TURP, but the scope of application and complications vary. As an alternative to TURP or TUIP, transurethralelectrovaporizationoftheprostate (TUVP) and transurethral plasma bipolarplasmapheresis (TUPP) are available. bipolartransurethralplasmaKineticprostatectomy (TUPKP) are now also used for surgical treatment. All of these treatments have been shown to improve lower urinary tract symptoms in more than 70% of patients with BPH.
②TURP: It is mainly applied to treat BPH patients with prostate volume below 80 ml, and the limit of prostate volume can be relaxed by skilled operators. The incidence of dilated blood volume and dilutional hyponatremia (transurethral resection syndrome, TUR-syndrome) due to excessive absorption of flushing fluid is about 2%. risk factors include high intraoperative bleeding, long operation time and large prostate volume. the risk of transurethral resection syndrome increases significantly with prolonged TURP operation time. The probability of needing blood transfusion is about 2% to 5%. The incidence of various postoperative complications: urinary incontinence about 1% to 2.2%, retrograde ejaculation about 65% to 70%, and bladder neck contracture about 4%. Urethral stricture is about 3.8%.
③TUIP: For patients with prostate volume less than 30 ml and without mesolimbic hyperplasia. the degree of improvement of patients’ lower urinary tract symptoms after TUIP treatment is similar to that of TURP. Compared with TURP, there are fewer complications, lower risk of bleeding and need for blood transfusion, lower incidence of retrograde ejaculation, shorter operative time and hospital stay. However, the long-term recurrence rate is higher than that of TURP
Open prostatectomy: It is mainly suitable for patients with prostate volume greater than 80ml, especially for those with combined bladder stones or combined bladder diverticula that need to be operated together. The commonly used procedures are suprapubic prostate removal and retropubic prostate removal. The incidence of postoperative complications is higher than that of TURP: about 1% for urinary incontinence, 80% for retrograde ejaculation, 1.8% for bladder neck contracture, and 2.6% for urethral stricture. The effect on erectile function may not be related to the procedure.
⑤ TUVP: For patients with BPH with poor coagulation and small prostate volume. It is an alternative to TUIP or TURP and has a better hemostatic effect compared to TURP. The long-term complications are similar to those of TURP.
Diet and prostate enlargement
Although there is no convincing evidence to date that dietary factors play a major role in BPH, a number of useful explorations have been made.
Studies have shown that men who consume vegetables, tofu, and red meat, for example, are significantly and negatively associated with the risk of BPH (with a ratio of 0.78 for men who consume more vegetables); however, the risk of BPH is not strongly associated with Western-style dietary habits.
The study showed that consumption of animal fat increased the risk ratio for BPH by about 31%, consumption of polyunsaturated fatty acids increased it by 27%, and protein intake decreased it by 15%; the risk ratio for daily consumption of red meat was 1.38, while the risk ratio for alcohol drinkers was 0.67 and the risk ratio for those who consumed more vegetables was 0.68; supporting the idea that consumption of lycopene, zinc and vitamin D supplementation decreased the risk of BPH. There is insufficient evidence to support that lycopene consumption, zinc and vitamin D supplementation reduce the risk of BPH and that antioxidant supplementation does not reduce the risk of its development.
Lycopene and benign prostatic hyperplasia. The study found a significant reduction in serum prostate-specific antigen, no continued increase in prostate volume, and a significant reduction in the International Prostate Symptom Score (I-PSS) in the trial group taking 15 mg of lycopene daily, so the authors concluded that lycopene halted the disease progression of BPH.
Green tea and benign prostatic hyperplasia. The study suggests that green tea tea polyphenols not only reduce the risk of prostate cancer, but also improve lower urinary tract symptoms and facilitate the treatment of BPH.
Selenium and benign prostatic hyperplasia. Selenium is one of the essential trace elements, although some people advocate that selenium supplementation can help in the prevention of BPH, but recent studies have shown that moderate supplementation of selenium cannot produce growth inhibition of BPH cells, nor can it cause apoptosis to occur.