Prostate adenoma (benign prostatic hyperplasia, BPH)

Definition of the disease. Causes of the condition
Prostate adenoma, or prostate (benign prostatic hyperplasia) is the benign enlargement of the prostate gland. Adenoma occurs due to the proliferation of glands of the prostate located near the urethra. Hyperplasia of the prostate gland leads to urinary disorders and acute urinary retention.

Benign prostatic hyperplasia (BPH) is an age-related progressive condition that significantly affects the quality of life of elderly men. BPH is a common term for a condition that affects more than half of men over 60 years of age. Therefore, the longer men live, the more frequently cases of prostate adenoma occur.

Physiology
The prostate gland secretes a complex secretion consisting of acidic phosphatase, citric acid, fibrinolysin, prostate-specific antigen, and various proteins. This secretion is released into the urethra during ejaculation and enhances sperm motility. After sexual intercourse, it alters the pH in the female vagina to maintain the viability of sperm.

The prostate is the only internal organ in humans that continues to grow throughout life. It is covered by a thin vascularized capsule externally. As the prostate gland enlarges, the surrounding capsule begins to compress the urethra.
Under the influence of estrogen, whose concentration increases with age, the activity of the specific enzyme – 5-alpha reductase increases. Under the influence of this enzyme, testosterone in the tissues of the prostate gland is converted into its metabolite – dihydrotestosterone (DHT). DHT, in turn, is an active androgen that enhances the division of prostate gland cells. During hyperplasia, nodules form from the periurethral glands (glands located near the urethra), which push the prostate tissue to the periphery.

The development of BPH is based on two main mechanisms:

enlargement of the prostate gland with gradual narrowing of the urethral lumen;
increased tone of smooth muscle fibers in the stroma of the prostate gland and posterior urethra, leading to additional narrowing of the urethral lumen.
All cellular elements of the prostate may be involved in the development of nodular hyperplasia of the prostate gland.
The term “adenoma” has been known for about 100 years, yet it does not fully reflect the essence of the pathological process in the prostate gland. In this case, it is appropriate to speak of hyperplasia in the form of nodules of the glandular and stromal (body) tissue of the prostate gland.

Epidemiology:

According to statistics, nearly one in three men over the age of 50 has an enlarged prostate due to benign prostatic hyperplasia. By age 40, histological signs of prostate hyperplasia are present in 10% of men, increasing to 80% by age 80. It is known that benign prostatic hyperplasia occurs in one-third of men over 60 years old.
BPH is the main cause of pathological symptoms of lower urinary tract in men aged 50 and older.
Prostate hyperplasia is less common among residents of Southeast Asia (Korea, Japan, China, Thailand, India), with a predominance of the fibromuscular form of hyperplasia over the glandular variety typical in “white” regions.
Risk factors:
Confirmed risk factors for the development of BPH include age and hormonal status. Men who are castrated before reaching sexual maturity do not develop the disease. Patients whose fathers suffered from BPH have a higher risk of developing the disease early compared to others. Infections of the urogenital tract, prostate, and seminal vesicles do not lead to BPH.
Differences from cancer. Can prostate adenoma be malignant?
Prostate adenoma is a benign enlargement of the prostate. Unlike prostate cancer, it does not contain cancer cells and does not invade the rectum or the lumen of the bladder. The idea that untreated prostate hyperplasia leads to cancer has not been scientifically proven.
Difference from prostatitis:
Prostatitis is an inflammatory process of the prostate tissue, whereas hormonal factors play a leading role in the development of prostate hyperplasia. However, without adequate treatment, prostatitis can develop as a complication of BPH. Benign hyperplasia is more commonly detected in elderly patients, while prostatitis affects men of all ages, although the disease most commonly occurs in patients of reproductive age.

Symptoms of prostate adenoma:

Benign prostatic hyperplasia (BPH) is one of the most common causes of urinary disorders in men. The term “lower urinary tract symptoms” (LUTS) is used to define these urinary disorders. This collective term includes disturbances in bladder filling and emptying, as well as symptoms occurring after urination.

In BPH, men often experience the need to wake up at night to empty the bladder, and the force of the urine stream decreases. Patients also feel a sensation of incomplete bladder emptying after urination. Symptoms of prostate adenoma usually do not threaten the patient’s life but significantly affect its quality.

However, prostate enlargement does not always lead to the development of clinical manifestations.

The urinary disorders associated with BPH in men include:

Urgency: the sudden and uncontrollable urge to urinate.
Pollakiuria: increased frequency of urination during the day (normally limited to eight urinations per day).
Reduced urine volume.
Dribbling of urine after urination.
Nocturia: the need for a man to wake up two or more times at night to urinate.
Various types of urinary incontinence.
Enuresis: any involuntary urination, usually during sleep.
Weakened urine stream.
Intermittent urine stream: involuntary interruption of the urine stream one or more times during urination.
Straining during urination: the need to strain the muscles of the abdominal wall to initiate urination.
Post-micturition dribble: dribbling of urine at the end of urination.
Sensation of incomplete bladder emptying.

All these symptoms of prostate adenoma can progress, persist, or decrease over time.

In the early stages of BPH development, the bladder is not completely emptied, but at this stage, there is no kidney damage. In the late stages, patients with BPH may have residual urine in the bladder after urination, which can contribute to the formation of bladder stones.

As the prostate gland enlarges, the flow of urine from the bladder is obstructed, leading to dilation of the ureters and renal pelvis, which can cause chronic inflammation called pyelonephritis. Without adequate treatment, these processes can lead to complete obstruction of the bladder, acute urinary retention, and the development of chronic kidney failure. These conditions are life-threatening for the patient.

Classification and stages of development of prostate adenoma:

There are three stages of clinical manifestations in benign prostatic hyperplasia (BPH), based on the amount of urine remaining in the bladder after urination:

Stage I: residual urine up to 40 ml.
Stage II: residual urine up to 100 ml.
Stage III: residual urine more than 1.5 liters. Paradoxical ischuria may develop, which is urinary incontinence due to overflow, when urine involuntarily leaks from a distended bladder through an atonic (lacking normal tone) external urethral sphincter.

In Russia, an outdated classification by Guyon is sometimes used, which distinguishes three stages:

Compensated stage: minor urinary disturbances with no residual urine.
Subcompensated stage: residual urine is present, complications of the disease arise.
Decompensated stage: paradoxical ischuria develops, accompanied by pronounced ureterohydronephrosis (dilation of the ureter and renal collecting system) and chronic kidney failure.

Complications of prostate adenoma:

Without adequate treatment, the risk of acute urinary retention sharply increases in the later stages of BPH. Other common complications associated with BPH include:

Chronic urinary retention.
Infectious-inflammatory diseases of the genitourinary system (prostatitis, epididymitis, pyelonephritis, urethritis, cystitis).
Bilateral ureterohydronephrosis.
Vesicoureteral reflux.
Urinary tract stones.
Chronic kidney failure.

Infectious complications in the third stage of BPH include:

Chronic prostatitis.
Chronic pyelonephritis in remission with the development of kidney failure.
Chronic cystitis and urethritis.
Acute and chronic epididymitis.

Acute urinary retention is the most serious complication and a medical emergency, in which the enlarged prostate completely obstructs the urinary tract.

Without timely cystostomy (urine diversion by inserting a tube into the bladder through the abdominal wall), the following complications may develop:

Uremic coma.
Ascending pyelonephritis.
Prostatitis.
Urethritis (inflammation of the urethra).
Urolithiasis.
Hematuria (blood in the urine).
“Neurogenic bladder” (uncontrolled frequent urination).
Urine leakage.
Sleep disturbances.
Erectile dysfunction.
Psychological disorders.

Diagnosis of prostate adenoma:

The mandatory diagnostic minimum includes:

Medical history taking.
Keeping a voiding diary and completing the International Prostate Symptom Score (IPSS) and Quality of Life (QOL) questionnaire (assessing the impact of symptoms on quality of life).
Digital rectal examination of the prostate.
Urinalysis.
Urine culture.
Assessment of kidney function.
Prostate-specific antigen (PSA) determination.
Identification of concomitant diseases affecting urination: chronic prostatitis, pyelonephritis, kidney failure, erectile dysfunction, prostate cancer, diabetes mellitus, bladder tumor, pelvic organ tumors, urethral strictures.

Medical history taking:
Medical history is a crucial part of patient examination. When assessing urination disorders caused by benign prostatic hyperplasia (BPH), the International Prostate Symptom Score (IPSS) questionnaire is used. This scale is also supplemented with an assessment of the impact on quality of life due to urination disturbances.

The IPSS questionnaire is included in Russian, European, and American clinical guidelines. To further clarify the patient’s complaints, voiding diaries are used to assess:

Frequency of urination.
Distribution of urination throughout the day.
Volume of each urination.
Total urine volume per day and its comparison with fluid intake.

Physical examination:

Digital rectal examination allows assessing the size of the prostate and identifying suspicious areas suggestive of prostate cancer.

PSA norms in prostate adenoma:

Total prostate-specific antigen (PSA) values are used in the differential diagnosis of BPH and prostate cancer. PSA level is also a prognostic factor that allows assessing the risk of developing benign prostatic hyperplasia. PSA levels can increase to 50–100 ng/mL in concurrent BPH and acute prostatitis and partly in chronic bacterial prostatitis, remaining elevated for 6–8 weeks after the disappearance of disease symptoms.

Assessment of urination:

A simple test to assess urination is measuring the average urine flow rate. For this, a measuring container and a stopwatch are needed. Starting urination into the measuring container, the patient starts the stopwatch, and upon finishing, stops it. Dividing the volume of urine voided by the time taken, one can obtain the average urine flow rate. A rate of more than 8–9 mL/s indicates normal urination.

Uroflowmetry and Transrectal Ultrasound (TRUS):

Uroflowmetry is a test that evaluates the maximum urine flow rate. It is important for the results of this method to be reliable that the patient experiences an adequate urge to urinate. They urinate into a special device called a uroflowmeter. A urine flow rate of more than 15 mL/s indicates adequate urination.

TRUS is performed through the rectum using ultrasound equipment. The procedure is conducted with a full bladder. The volume of the prostate is considered normal when it is up to 25–30 cm^3, small from 30 to 40 cm^3, medium from 40 to 80 cm^3, large over 80 cm^3, and exceeding 250 cm^3 is considered gigantic.

Ultrasound of the urinary system:

In addition to examining the prostate gland, ultrasound of the kidneys and urinary bladder is mandatory. Ultrasound examination allows detecting complications of BPH, such as bladder stones and hydronephrosis, and also ruling out tumors of the kidney parenchyma and urinary bladder.

Treatment of Benign Prostatic Hyperplasia (BPH)

Overview:
The treatment of benign prostatic hyperplasia aims to improve quality of life, prevent disease progression, and avoid complications.

Methods of Treatment:
The doctor selects treatment methods based on various factors:

Patient’s age
Coexisting conditions
Size, location, and characteristics of nodules
Prostate volume
Presence and volume of residual urine
Severity of voiding dysfunction
Frequency of nocturnal voiding and sleep disturbance
Presence of comorbidities

After analyzing the patient’s data, the doctor may choose a dynamic observation approach, prescribe medication therapy, or recommend surgical intervention.

Non-surgical Treatment Options:
Dynamic observation involves periodic patient evaluations, information provision, and lifestyle recommendations, such as limiting fluid intake (especially at night), reducing alcohol and caffeine consumption, relaxation techniques during voiding, double voiding, and distraction techniques or bladder training for urgent symptoms.

Conservative treatment is considered optimal and aims to prevent or delay surgical intervention indefinitely. Surgical treatment is recommended for patients with severe symptoms and evident urinary obstruction, while non-surgical methods are preferred for those with moderately expressed voiding disturbances.

Medication Therapy:
Several types of medications are used in BPH treatment, but the basic therapy consists of three groups of drugs:

Alpha-1 adrenoreceptor antagonists
5-alpha-reductase inhibitors
Phosphodiesterase type 5 inhibitors (PDE5 inhibitors)

Given the progressive nature of the disease, BPH medication therapy is administered for a long time, sometimes throughout the patient’s life.

Alpha-1 Adrenoreceptor Antagonists: These drugs are considered first-line therapy and are used for moderate to severe symptoms. The effect begins within 48 hours after administration. Commonly used drugs in this group include alfuzosin, doxazosin, silodosin, tamsulosin, and terazosin. Side effects may include asthenia, dizziness, and orthostatic hypotension.

5-alpha-reductase Inhibitors: These drugs are indicated for moderate to severe LUTS and a prostate volume exceeding 40 cm3 and a PSA > 1.4 ng/ml. Clinical effects appear after 3-6 months. Dutasteride and finasteride are the two drugs commonly used in this group. Side effects may include decreased libido, erectile dysfunction, and rarely gynecomastia and ejaculatory disorders.

Phosphodiesterase Type 5 Inhibitors (PDE5 inhibitors): These drugs are indicated for moderate to severe voiding symptoms with or without erectile dysfunction. Common side effects include headaches, back pain, dizziness, and dyspepsia.

Muscarinic Receptor Antagonists: These drugs are indicated for moderate to severe LUTS, especially in cases of storage symptoms. However, they are less commonly used due to concerns about acute urinary retention.

In cases of multiple complaints, combination therapy with two or more drugs may be prescribed.

Surgical Treatment

Surgeries for benign prostatic hyperplasia (BPH) are among the most common surgical interventions in elderly men, with approximately 30% of men undergoing some form of surgery for this condition during their lifetime.

Indications for Surgical Treatment of Benign Prostatic Hyperplasia:

Severe infravesical obstruction (i.e., obstruction to urine flow at the level of the bladder neck and urethra)
Lack of response to previous medical therapy
Severe symptoms
Development of complications of BPH
Recurrent macrohematuria (blood in the urine)
Large amount of residual urine detected by ultrasound examination
Recurrent urinary retention

Before surgery, treatment of urinary tract infection is necessary.

Types of Operations:

Endo-Urethral Procedures Using Electrosurgery: These include monopolar and bipolar techniques.
Endo-Urethral Procedures Using Laser: These include thulium and holmium laser techniques.
Open Surgeries: These include transvesical and retropubic adenomectomy.
Laparoscopic and Robotic Adenomectomy: Minimally invasive techniques.
Prostate Artery Embolization: A less invasive procedure.
Implantation of Intraprostatic Stents: Another minimally invasive approach.
Experimental Methods: Various innovative techniques.

The main criterion for choosing between open surgeries and transurethral interventions is the volume of the prostate gland, the capabilities of the medical institution, and the surgeon’s expertise.

Consequences of Surgery for Benign Prostatic Hyperplasia (BPH)

During transurethral resection (TUR) and in the postoperative period, complications may arise, as with any surgical intervention. The most serious complication after TUR is massive bleeding during the operation, requiring blood transfusion. The average frequency of hemorrhagic complications after TUR for BPH is 7.2%.

Transurethral Electrovaporization (TUVP)

Electrovaporization involves vaporizing hyperplastic prostate tissue with a special electrode using high-frequency and high-power currents, with simultaneous coagulation of underlying layers. The vaporization effect prevents capillary bleeding, leaving large vessels and venous sinuses uncoagulated if they are opened, which improves visibility during surgery. Bipolar vaporization is considered the most promising method of surgical treatment for BPH.

Transurethral Enucleation (TUE)

With the development of laser technologies, doctors increasingly prefer new surgical methods for treating BPH, such as transurethral enucleation of the prostate using holmium or thulium laser. Laser enucleation involves anatomically justified excision of prostate lobes down to its surgical capsule. After enucleation, lobes are displaced into the bladder and subsequently removed. Indications for laser enucleation are almost identical to those for standard transurethral monopolar resection.

Holmium Laser Enucleation of the Prostate (HoLEP)

HoLEP is considered the standard surgical treatment for moderate to severe lower urinary tract symptoms with a prostate volume exceeding 80 cm3.

Advantages of Holmium Enucleation:

Safety with anticoagulant therapy
Reduction in duration of bladder catheterization after surgery
Decrease in blood loss and transfusion rate

Laser Vaporization

Thulium laser vaporization can be an alternative to TURP for small to medium-sized prostates. Unlike laser enucleation, the goal of vaporization is to reduce the gland volume focusing on individual areas affected by hyperplasia.

Other Methods

Interstitial laser coagulation, cryodestruction, transurethral microwave thermotherapy (TUMT), transurethral radiofrequency thermotherapy, balloon dilation, urethral stents for BPH treatment are not used. These methods are absent from clinical recommendations.

Open Prostatectomy

Open adenomectomy is considered the most invasive but also the most effective method of treating BPH with long-lasting effects. According to clinical recommendations, in the absence of endourological equipment, including holmium laser or bipolar systems, open adenomectomy remains the method of choice for treating patients with a prostate volume > 80 cm3.

Variants of Open Adenomectomy: Retropubic adenomectomy, transvesical adenomectomy, suprapubic adenomectomy. The choice of open adenomectomy variant mainly depends on surgical approaches.

Alternative Surgical Methods for Benign Prostatic Hyperplasia (BPH)

Suprapubic Adenomectomy

Suprapubic adenomectomy is characterized by accessibility, as there is no need for specific expensive equipment, and the operation can be performed regardless of the volume of the hyperplastic prostate gland. However, considering the high trauma of the operation and the prolonged hospital stay for patients, alternative options for surgical treatment are always considered.

Retropubic Adenomectomy

The advantages of this adenomectomy method over suprapubic access include a shorter and easier postoperative period (early removal of drainage and discharge of the patient), as well as fewer postoperative complications.

Laparoscopy

Laparoscopic modification of adenomectomy is a worthy minimally invasive alternative to open surgical treatment of BPH. Laparoscopic adenomectomy is preferred for patients with a prostate volume of 90–100 cm3 or more but is more invasive than transurethral methods. This surgical intervention minimally damages soft tissues and nerves. Access is made through small incisions (1–2 cm).

Robotic Surgery

Robotic surgery has been actively developing since the early 2000s, with urology being the main field of application. Robotic surgery significantly improves the effectiveness of surgical treatment for BPH by enhancing functional outcomes, eliminating postoperative complications, and enabling rapid rehabilitation, thus making the good outcomes even better.

Transurethral Incision of the Prostate (TUIP)

Transurethral incision of the prostate is indicated for patients with a prostate size of less than 30 cm3. Unlike TURP, electro-surgical tissue incision is performed using a resectoscope loop. With this method of surgical treatment, it is impossible to perform histological examination of prostate tissue.

Transurethral Needle Ablation (TUNA)

Transurethral needle ablation of the prostate is less effective than TURP but does not require hospitalization of the patient and general anesthesia during the operation. Special needles are inserted into the prostate via cystoscope. Radio waves are delivered through these needles, causing heating and destruction of prostate tissue. This method may be offered to patients with severe comorbidities.

As every surgery has its drawbacks, techniques are constantly being refined, and alternative surgical treatment options for BPH are being explored. The choice of treatment method should be made by the physician individually, taking into account all accompanying factors (medical and social) and with active participation of the patient.

Prostatic Artery Embolization

This method involves the selective occlusion (blockage) of blood vessels by intentionally introducing emboli into the prostate artery. In other words, the blood vessel that supplies blood to the prostate adenoma is intentionally blocked. The procedure is performed using special angiographic equipment by an endovascular surgeon.

Stenting Procedure

The placement of a prostatic stent is an alternative to catheterization for treating patients with contraindications to surgical intervention. However, they provide temporary relief, can migrate, and have a high frequency of side effects, so their use is limited.

Physiotherapeutic Methods for Treating Benign Prostatic Hyperplasia (BPH)

For patients with symptomatic BPH accompanied by chronic prostatitis in the early stages of the disease, physiotherapeutic methods may be used as part of comprehensive treatment. However, there is no mention of them in clinical recommendations.

Folk Remedies for Treating BPH

The most commonly used folk remedies include:

Cucurbita pepo (pumpkin seeds)
Hypoxis rooperi (South African plant)
Pygeum africanum (bark of the African plum tree)
Secale cereale (rye pollen)
Serenoa repens (synonym Sabal serrulata; fruits of American dwarf palm and saw palmetto)
Urtica dioica (root of stinging nettle)

According to the recommendations of the European Association of Urologists, plant extracts have no proven therapeutic effect and therefore cannot be recommended for BPH therapy.

Physical Exercises

Exercises to train the pelvic floor muscles, such as Kegel exercises, can be recommended.

Diet

Limit the consumption of caffeine and alcohol, as they stimulate urination urges.
Adhere to a low-fat diet.
Eat more vegetables.
Avoid consuming diuretic foods and beverages (tea, coffee, fruits, berries, alcohol, dairy products) three hours before bedtime.

Massage

Prostate massage for BPH is risky and can only be applied in the early stages of the disease, before tissue overgrowth becomes threatening. In most cases, direct manipulation of the prostate gland is not used.

Prognosis and Prevention

Despite the high prevalence of BPH among elderly men, preventive measures for the disease are insufficiently researched. Men over 50 often report urination disorders, so they should undergo screening for early detection of prostate enlargement.

Studies confirm the effectiveness of 5α-reductase inhibitors (5-ARI) for primary and secondary prevention of BPH. However, the use of these drugs solely for preventive purposes in wide clinical practice is not yet definitively justified.

An important risk factor for the development of BPH and its complications is lifestyle: diet, physical activity, and harmful habits. Symptoms of urinary dysfunction are often observed in men with improper nutrition and low physical activity.

Patients with BPH are recommended to:

Reduce fluid intake three hours before bedtime.
Empty the bladder before sleep.
Avoid using diuretics and anticholinesterase medications in the evening.

Follow-up examinations by a urologist should be conducted every 6-12 months.

The sources:

Pavlov, V. N., et al. “Symptoms of lower urinary tract and benign prostatic hyperplasia: a textbook.” Ufa: Publishing House of the Bashkir State Medical University, Ministry of Health of the Russian Federation, 2018. — 86 p.
“Urology. Clinical recommendations.” Ed. by N. A. Lopatkin. 2nd ed., revised. — Moscow: GEOTAR-Media, 2013. — 416 p.
“Urology. Russian clinical recommendations.” Ed. by Yu. G. Alyaev, P. V. Glybochko, D. Yu. Pushkar. — Moscow: GEOTAR-Media, 2016. — 480 p.
Mamoulakis, C., de la Rosette, J. J. “Bipolar transurethral resection of the prostate: Darwinian evolution of an instrumental technique.” Urology. 2015;85(5):1143-1150.
Michalak, J., Tzou, D., Funk, J. “HoLEP: the gold standard for the surgical management of BPH in the 21st Century.” Am J. Clin Exp Urol. 2015;3(1):36-42.
“Kegel exercises for men: Understand the benefits.” Mayoclinic, 2020.
“Enlarged prostate: Does diet play a role?” Mayoclinic, 2020.