Prostate adenoma treatment

Recently, the treatment of prostate adenoma has been rapidly developing. If 5 years ago there was practically no real alternative to surgical treatment of prostate adenoma (prostate gland), today a wide range of various methods of treating this disease is offered.

Treatment of prostate adenoma is an impressive list and can be represented by the following classification.

• Drug treatment of prostate adenoma (prostate gland).
• Surgical treatment of prostate adenoma (prostate gland).
  • Open adenomectomy.
  • TUR of the prostate.
    • Transurethral electroincision of the prostate.
    • Transurethral Electrovaporization of the Prostate
    • Methods of transurethral endoscopic laser surgery of the prostate ( vaporization, ablation, coagulation, incision).
  • Minimally invasive (alternative) methods of treating prostate adenoma (prostate gland).
    • Endoscopic thermal methods of prostate adenoma (prostate gland).
      • Interstitial laser coagulation.
      • Transurethral needle ablation.
    • Non-endoscopic thermal methods of prostate adenoma (prostate gland).
      • Transrectal microwave hyperthermia.
      • Transurethral microwave (radiofrequency) thermotherapy.
      • Transurethral radiofrequency thermal destruction.
      • Transrectal focused ultrasound thermal ablation.
      • Extracorporeal pyrotherapy.
    • Balloon dilation.
    • Prostatic stents.

The presence of a significant number of methods used to treat one disease indicates that none of them is ideal and requires determining its place in the structure of prostate adenoma treatment. At the same time, the method of treating prostate adenoma in a specific clinical case is determined by the balance of efficiency and safety factors, which together ensure the maintenance of the patient's required quality of life.

Clinical experience allows us to identify both individual and group criteria for selecting patients with prostate adenoma for treatment with a specific method:

• nature (irritative/obstructive) and severity of symptoms (IPSS/QOL);
• presence of complications of prostate adenoma;
• the nature and extent of urodynamic disturbances according to UFM data, determination of the amount of residual urine and complex UDI (cystomanometry, “pressure-flow”);
• size, echostructure and spatial geometry of the prostate;
• the presence of concomitant (including recurrent) infection of the genitourinary tract, primarily chronic prostatitis;
• condition and degree of disorders of the upper urinary tract and bladder;
• general somatic status of the patient, presence and severity of concomitant diseases

When choosing a treatment method for a specific patient, it is necessary to evaluate a number of parameters. First of all, it is necessary to find out which manifestations of the disease dominate in the clinical picture of prostate adenoma: irritative symptoms or obstructive, whether the dynamic or mechanical components of obstruction predominate, and what is the degree of urodynamic disorders. The answer to these questions will allow us to predict the development of the disease with a high degree of reliability and choose the treatment method necessary for a given patient.

The next step in choosing a treatment method is determining the degree of treatment effectiveness with a sufficient level of safety required by a given patient. It is not always necessary to strive to achieve maximum urine flow rates in elderly patients if it is possible to provide satisfactory urination parameters with lesser means along with maintaining an acceptable quality of life. At an early stage of the disease, drug therapy and minimally invasive methods may well provide the necessary level of effectiveness with a minimal risk of complications. Alternative methods can be used both in patients with moderate manifestations of prostate adenoma and in somatically burdened patients, where it is unsafe to use surgical treatments.

Drug treatment of prostate adenoma

Medicines occupy an important place in the structure of prostate adenoma treatment. The principles of their use are based on modern concepts of the pathogenesis of the disease. The main directions of drug therapy used to treat prostate adenoma can be represented by the following classification.

• Alpha adrenergic blockers.
  • Non-selective.
  • Selective.
• 5-a-reductase inhibitors.
  • Synthetic.
  • Of plant origin.
• Phytotherapeutic agents.
• Combination drug therapy.

Alpha-adrenergic receptor blockers

In recent years, much attention has been paid to alpha-adrenergic receptor blockers, the use of which is considered a promising direction in the drug treatment of prostate adenoma. The basis for the use of alpha-adrenergic blockers in prostate adenoma is the accumulated data on the role of sympathetic regulation disorders in the pathogenesis of the disease. Studies have established that alpha-adrenergic receptors are localized mainly in the neck of the bladder, the prostatic part of the urethra, the capsule and stroma of the prostate. Stimulation of alpha-adrenergic receptors, which occurs as a result of the growth and progression of prostate adenoma, leads to an increase in the tone of the smooth muscle structures of the base of the bladder, the posterior part of the urethra and the prostate. This mechanism, according to most researchers, is responsible for the development of the dynamic component of obstruction in prostate adenoma.

The effect of alpha-adrenergic blockers depends on the selectivity of action on different receptor subtypes. Studies of adrenergic receptors of the prostate have established the predominant role of alpha-adrenergic receptors in the pathogenesis of prostate adenoma.

Further identification of alpha-adrenoreceptors localized in various tissues using pharmacological and molecular biological methods revealed three receptor subtypes. According to the new nomenclature adopted by the International Pharmacological Union, they are designated as alpha-A, alpha-B, and alpha-D in pharmacological studies. A series of studies have established that the alpha-A subtype, previously cloned as alpha-C, is present in the greatest quantity in the human prostate and accounts for up to 70% of all its alpha-adrenoreceptors. This subtype is primarily responsible for the contraction of the smooth muscle elements of the prostate and has the greatest impact on the development of dynamic obstruction in prostate adenoma.

The use of alpha-blockers reduces the tone of the smooth muscle structures of the bladder neck and prostate, which leads to a decrease in urethral resistance and, as a consequence, infravesical obstruction. Although it is currently unknown exactly which of the receptor subtypes is responsible for the regulation of blood pressure and the occurrence of adverse reactions when using alpha-blockers, it is assumed that it is the alpha-B subtype that is involved in the contraction of the smooth muscle elements of the walls of the main human arteries.

Since the first publication of materials on the effectiveness of alpha-blockers in the treatment of prostate adenoma in 1976, more than 20 studies of various drugs with similar effects have been conducted worldwide. The study of the results of using alpha-blockers in patients with prostate adenoma began with non-selective drugs, such as phentolamine. It has been established that long-term use of these drugs in stage I prostate adenoma allows achieving an effect in 70% of cases. However, today the use of non-selective alpha-blockers is limited due to the frequent occurrence of adverse reactions from the cardiovascular system, observed in 30% of patients.

Currently, selective alpha-adrenoblockers such as prazosin, alfuzosin, doxazosin and terazosin, as well as the superselective alpha1-adrenoblocker tamsulosin, are successfully used in clinical practice. It should be noted that all of them (except tamsulosin) have comparable clinical effects with virtually the same number of side effects.

Controlled studies show that with the use of alpha-blockers, the reduction in symptoms is about 50-60%. In some cases, it reaches 60-75%. Selective alpha-blockers affect both obstructive and irritative symptoms of the disease. Studies with doxazosin and alfuzosin have revealed a reduction in obstructive symptoms by 43 and 40% with a regression of irritative symptoms by 35 and 29%, respectively. Alpha-blockers are especially effective in patients with severe daytime and nighttime pollakiuria, imperative urge to urinate with minor or moderate symptoms of dynamic obstruction.

Against the background of treatment with alpha-adrenoblockers, an improvement in urodynamic parameters is observed: an increase in Qmax by an average of 1.5-3.5 ml/s or 30-47%. a decrease in maximum detrusor pressure and opening pressure, as well as a decrease in the amount of residual urine by about 50%. The dynamics of these urodynamic parameters indicate an objective decrease in infravesical obstruction during treatment with alpha-adrenoblockers. No reliable change in prostate volume was registered during treatment with these drugs.

A series of studies with prazosin, alfuzosin, doxazosin, terazosin and tamsulosin have proven the safety and effectiveness of alpha-blockers with long-term (more than 6 months) use. Currently, there are observations of taking alpha-blockers for up to 5 years. In this case, pronounced symptomatic improvement and dynamics of objective indicators are usually observed in the first 2-4 weeks of use and persist during the subsequent period of treatment. If a positive effect cannot be achieved after 3-4 months, then further use of these drugs is futile, it is necessary to decide on choosing another type of treatment for adenoma.

It is important that alpha-blockers do not affect metabolism and hormone concentrations and do not change the PSA level. The above-mentioned drugs (doxazosin) can have a positive effect on the blood lipid profile, reducing the level of lipoproteins, cholesterol and triglycerides. In addition, alpha-blockers have a positive effect on the body's tolerance to glucose, increasing its sensitivity to insulin.

According to statistics, adverse reactions against the background of the use of alpha-blockers are registered in 10-16% of patients in the form of malaise, weakness, dizziness, headache, orthostatic hypotension (2-5%), tachycardia or tachyarrhythmia. In some observations (4%), cases of retrograde ejaculation were noted. At the same time, 5-8% of patients refuse further treatment with alpha-blockers due to the development of adverse reactions. Thus, dizziness was observed in 9.1-11.7% of patients receiving terazozyme, in 19-24% while taking doxazosin and in 6.5% treated with alfuzosin. Headache was noted by 12-14% of patients during the use of terazosin and 1.6% of alfuzosin. A decrease in blood pressure was registered in 1.3-3.9% of patients during therapy with terazosin. and also in 8 and 0.8% of patients taking doxazosin and alfuzosin, respectively. Palpitations and tachycardia occurred in 0.9 and 2.4% of patients during treatment with terazosin and alfuzosin, respectively. It should be borne in mind that the frequency of adverse effects depends on the dose of the drug used and the duration of its administration. With an increase in the duration of treatment, the number of patients reporting adverse reactions decreases, and therefore, to reduce their number, treatment with prazosin. alfuzosin. doxazosin and terazosin should be started with minimal starting doses, followed by a transition to a therapeutic dosage. For prazosin, it is 4-5 mg / day (in 2 doses), for alfuzosin 5-7.5 mg / day (in 2 doses), for doxazosin 2-8 mg / day (single dose), for terazosin - 5-10 mg / day (single dose).

Clinical data on the use of tamsulosin indicate high efficacy of the drug, comparable to other alpha-blockers, with a minimum number of side effects. When treating with tamsulosin, side effects are observed in 2.9% of patients. At the same time, no effect of the drug on the dynamics of blood pressure was noted, and the incidence of other adverse reactions did not differ significantly from that in patients in the placebo group. Given the high efficacy and rapid onset of clinical effect, alpha-blockers are currently considered as first-line drug therapy.

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Treatment of prostate adenoma (prostate gland): 5-a-reductase inhibitors

The most common methods of treating prostate adenoma include 5-a-reductase inhibitors (finasteride, dutasteride). Currently, the greatest experimental and clinical experience is associated with the use of finasteride. Finasteride, which belongs to 4-azasteroids, is a powerful competitive inhibitor of the enzyme 5-a-reductase. mainly type II, blocks the conversion of testosterone to dihydrotestosterone at the prostate level. The drug does not bind to androgen receptors and does not have the side effects characteristic of hormonal agents.

Toxicology studies in humans have demonstrated good tolerability of finasteride. The drug was first used in healthy male volunteers in 1986. There is currently experience of its use for 5 years or more without any significant adverse reactions.

As a result of the studies, the optimal dose of finasteride was determined: 5 mg/day. In patients receiving finasteride at a dose of 5 mg/day, a decrease in the level of dihydrotestosterone by 70-80% was noted after 6 months. At the same time, the decrease in the size of the prostate after 3 months was 18%, reaching 27% after 6 months. Qmax after 6 months increased by 3.7 ml/s. In addition, after 3 months of taking finasteride, a decrease in PSA by about 50% was noted. Subsequently, the PSA concentration remains low, correlating with the activity of prostate cells. A decrease in PSA content during finasteride therapy can complicate the timely diagnosis of prostate cancer. When assessing the results of a study of PSA content in patients taking finasteride for a long time, it should be taken into account that PSA levels in this group are 2 times lower compared to the corresponding age norm.

Studies have shown that the use of finasteride leads to a reliable reduction in the risk of developing acute urinary retention by 57% and a decrease in the likelihood of surgical treatment of prostate adenoma by 34%. The use of finasteride reduces the risk of prostate cancer by 25%.

Combined treatment of prostate adenoma (prostate gland)

In 1992, the first reports appeared on the advisability of using alpha-blockers in combination with 5-a-reductase inhibitors in patients with prostate adenoma to ensure rapid improvement in urination with subsequent reduction in prostate volume. However, despite the fact that this approach is pathogenetically justified, the studies conducted to date do not provide sufficient grounds to confirm the clinical advantages of combined therapy with alpha-blockers (terazosin) and finasteride compared to alpha-blocker monotherapy.

The distinct and complementary mechanisms of action of 5-a-reductase inhibitors and alpha-blockers provide a powerful, rational rationale for combination therapy.

Data from the large-scale MTOPS trial, which investigated the combination of finasteride and doxazosin, and the COMBAT trial, which evaluated the combination of dutasteride and tamsulosin, indicate a significant advantage of combination therapy compared with monotherapy with each drug in terms of improvement in symptoms, urinary flow rate, patient quality of life, and slowing of disease progression.

The modern 5-a-reductase inhibitor dutasteride (Avodart) inhibits the activity of 5-a-reductase isoenzymes type I and II, which are responsible for the conversion of testosterone to dihydrotestosterone, which is the main androgen responsible for the development of benign prostatic hyperplasia.

After 1 and 2 weeks of taking dutasteride at a dose of 0.5 mg per day, median values of serum dihydrotestosterone concentrations decrease by 85 and 90%.

Data from 4-year, large-scale, multicenter randomized clinical trials demonstrate the efficacy and safety of avodart.

Dutasteride provides sustained symptom reduction and slows disease progression in patients with prostate volumes greater than 30 ml. Qmax and prostate volume change already within the first month of therapy, which is likely due to inhibition of both types of 5-a-reductase, unlike the first drug in this group, finasteride, which blocks only type II 5-a-reductase.

Long-term treatment of prostate adenoma with avodart resulted in continued improvement in the total AUA-SI score (-6.5 points) and Qmax (2.7 ml/s).

Avodart produces a significant reduction in both total prostate volume and prostate transition zone volume (by 27%) in men with benign prostatic hyperplasia compared with placebo.

Studies also demonstrated a 57% reduction in the risk of acute urinary retention and a 48% reduction in the need for surgery with Avodart compared to placebo.

The international COMBAT study has now completed its 2-year period, showing for the first time a significant benefit in symptom improvement with combination therapy compared to monotherapy with each drug during the first 12 months of treatment.

The occurrence of drug-related adverse events in patients receiving dutasteride is more common early in the treatment of prostate adenoma and decreases over time.

Impotence, decreased libido, ejaculation disorders, gynecomastia (includes tenderness and enlargement of the mammary glands) may occur. Very rare: allergic reactions.

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