Treatment of prostate adenoma

Recently, treatment for prostate adenoma is rapidly developing. If 5 years ago there was practically no real alternative to surgical treatment of prostate adenoma (prostate gland), then today we offer a wide choice of various methods of treating this disease.

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

• Drug treatment of prostate adenoma (prostate gland).
• Operative treatment of prostate adenoma (prostate gland).
  • Open adenomectomy.
  • TOUR OF THE PROSTATE.
    • Transurethral electrosurgery 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 treatment of prostate adenoma (prostate gland).
    • Endoscopic thermal methods of prostate adenoma (prostate gland).
      • Interstitial laser coagulation.
      • Transurethral needle ablation.
    • Nonendoscopic thermal methods of prostate adenoma (prostate gland).
      • Transrectal microwave hyperthermia.
      • Transurethral microwave (radio frequency) thermotherapy.
      • Transurethral radiofrequency thermal destruction.
      • Transrectal focused ultrasound thermotherapy.
      • Extracorporeal pyrotherapy.
    • Balloon dilatation.
    • Prostatic stents.

The presence of a significant number of methods used to treat a single disease indicates that none of them is ideal and requires determining its place in the structure of treatment of prostate adenoma. In this case, the method of treatment of prostate adenoma in a specific clinical case is determined by the balance of the factors of effectiveness and safety, in aggregate ensuring the maintenance of the necessary quality of life of the patient.

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

• character (irritative / obstructive) and severity of symptoms (IPSS / QOL);
• the presence of complications of prostate adenoma;
• nature and extent of urodynamic disturbances according to the UFM data, determination of the amount of residual urine and complex UDI (cystomanometry, "pressure-flow");
• dimensions, ehostruktura and spatial geometry of the prostate;
• presence of concomitant (including relapsing) infection of the urogenital tract, primarily chronic prostatitis;
• condition and degree of disorders of the upper urinary tract and bladder;
• the overall status of the patient, the presence and severity of concomitant diseases

When choosing a method of treatment for a particular patient, it is necessary to evaluate a number of parameters. First of all, find out which manifestations of the disease dominate the clinical picture of prostate adenoma: irritative symptoms or obstructive, the dynamic or mechanical components of obstruction prevail and the degree of urodynamic disturbances. The answer to these questions will allow to forecast the development of the disease with a high degree of reliability and choose the method of treatment necessary for this patient.

The next step in choosing a method of treatment is determining the degree of treatment effectiveness with sufficient level of safety required for this patient. It is not always necessary to strive to achieve maximum urine flow rates in patients of senile age, if it is possible to provide with satisfactory means satisfactory parameters of urination while 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 efficacy with minimal risk of complications. Alternative methods can find application both in patients with moderate manifestations of prostate adenoma and in somatically burdened patients, where it is unsafe to use surgical treatments.

Medical treatment of prostate adenoma

Drugs take an important place in the structure of treatment for prostate adenoma. The principles of their application 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-adrenoblockers.
  • Non-selective.
  • Selective.
• Inhibitors of 5-a-reductase.
  • Synthetic.
  • Plant origin.
• Phytotherapeutic agents.
• Combined drug therapy.

Blockers of alpha-adrenergic receptors

In recent years, much attention has been paid to alpha-adrenoreceptor blockers, the use of which is considered as a promising direction of drug treatment for prostate adenoma. The basis for the use of alpha-adrenoblockers in prostate adenoma was the accumulated data on the role of sympathetic regulation disorders in the pathogenesis of the disease. Studies have shown that alpha-adrenergic receptors are located primarily in the neck of the bladder, the prostatic section of the urethra, the capsule and the stroma of the prostate. The stimulation of alpha-adrenergic receptors, resulting from 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 back 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-adrenoblockers depends on the selectivity of the action on various 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-adrenergic receptors localized in various tissues, using pharmacological and molecular biological methods, revealed three subtypes of receptors. According to the new nomenclature adopted by the International Pharmacological Union in pharmacological studies, they are designated as alpha-A, alpha-B and alpha-D. A series of studies found that the alpha-A subtype, previously cloned as alpha-C, is present in the largest amount in the human prostate and accounts for up to 70% of all its alpha-adrenergic receptors. This subtype is primarily responsible for the reduction of smooth muscle elements of the prostate and has the greatest effect on the development of dynamic obstruction in prostate adenoma.

The appointment of alpha-adrenoblockers leads to a decrease in the tone of the smooth muscle structures of the neck of the bladder and prostate, which leads to a decrease in urethral resistance and, consequently, infravesical obstruction. Although at present it is not known exactly which of the receptor subtypes is responsible for the regulation of blood pressure and the occurrence of adverse reactions with the use of alpha-blockers. Suggest that it is the alpha-B subtype that is involved in contracting the smooth muscle elements of the walls of the main human arteries.

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

At present, selective alpha-blockers are successfully used in clinical practice. Such as prazosin, alfuzosin, doxazosin, and terazosin, as well as superseelective alpha-1 blocker tamsulosin. It should be noted that all of them (except tamsulosin) have a comparable clinical effect with an almost identical number of adverse reactions.

The data of controlled studies indicate that against the background of the use of alpha-adrenoblockers, the reduction of symptoms is about 50-60%. Reaching in some cases 60-75%. Selective alpha-blockers affect both obstructive and irritative symptoms of the disease. Studies with doxazosin and alfuzosin showed a 43% and 40% reduction in obstructive symptoms with a 35% and 29% regression of irritative symptoms, respectively. Alpha-adrenoblockers are especially effective in patients with severe day and night pollakiuria. Imperative urge to urinate with mild or moderate symptoms of dynamic obstruction.

Against the background of treatment with alpha-adrenoblockers, the improvement of urodynamic parameters is observed: an increase in Qmax on average by 1.5-3.5 ml / s or 30-47%. A decrease in the maximum detrusor pressure and opening pressure, and a decrease in the amount of residual urine by approximately 50%. The dynamics of these urodynamic indicators indicates an objective reduction in the infravesical obstruction in the treatment of alpha-adrenergic blockers. A significant change in the volume of the prostate during treatment with these drugs has not been recorded.

A series of studies with prazosin, alfuzosin, doxazosin, terazosin, and tamsulosin has shown the safety and efficacy of alpha-blockers with prolonged (more than 6 months) application. Currently, there are observations of the use of alpha-adrenoblockers for up to 5 years. Thus the expressed symptomatic improvement and dynamics of objective indicators usually are observed in the first 2-4 weeks of application and remain during the subsequent term of treatment. If the positive effect can not be achieved in 3-4 months. Then further use of these drugs is unpromising, it is necessary to decide on the choice of another type of treatment for adenoma.

It is important that alpha-adrenoblockers do not affect the metabolism and concentration of hormones and do not change the level of PSA. These drugs (doxazosin) can have a positive effect on the lipid profile of the blood, reducing the level of lipoproteins, cholesterol and triglycerols. In addition, alpha-adrenoblockers have a positive effect on the organism's tolerance to glucose, increasing its sensitivity to insulin.

According to statistics, adverse reactions against the background of the use of alpha-adrenoblockers are recorded in 10-16% of patients in the form of malaise, weakness, dizziness, headache, orthostatic hypotension (2-5%), tachycardia or tachyarrhythmia. In a number of cases (4%), cases of retrograde ejaculation have been reported. At the same time, 5-8% of patients refuse further treatment with alpha-adrenoblockers because of the development of adverse reactions. Thus, dizziness was observed in 9.1-11.7% of patients receiving terazozyme, 19-24% with doxazosin and 6.5% with alfuzosin. Headache was noted by 12-14% of patients at the time of taking terazosin and 1.6% of alfuzosin. Reduction of blood pressure was registered in 1.3-3.9% of patients with terazosin therapy. As well as 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 undesirable effects depends on the dose 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 amount, prazosin treatment. Alfuzosin. Doxazosin and terazosin should be started with the minimum starting dose, 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 mg / day (once).

Clinical data of tamsulosin application indicate a high, comparable with other alpha-adrenoblockers, efficacy of the drug with minimal amount of adverse reactions. In the treatment 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 undesirable reactions did not differ significantly from that in patients in the placebo group. Given the high efficiency and rapid onset of the clinical effect, alpha-adrenergic blockade is currently being considered as a first-line drug therapy.

[1], [2], [3], [4], [5]

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

The most common methods of treating prostate adenoma include 5-a-reductase inhibitors (finasteride, dutasteride). At present, the greatest experimental and clinical experience is associated with the use of finasteride. Finasteride. Related to 4-azasteroid, is a potent competitive inhibitor of the enzyme 5-a-reductase. Predominantly 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 drugs.

Toxicological studies in humans have demonstrated good tolerability of finasteride. In healthy male volunteers, the drug was first used in 1986. Currently, there is an experience of its use for 5 years or more without any significant adverse reactions.

As a result of the research, the optimal dose of finasteride was determined: 5 mg / day. In patients who received finasteride at a dose of 5 mg / day. After 6 months, a decrease in the level of dihydrotestosterone by 70-80% is noted. The decrease in prostate size after 3 months was 18%. Reaching 27% in 6 months. Qmax after 6 months increased by 3.7 ml / s. In addition, after 3 months of admission finasterida noted a decrease in PSA by about 50%. In the future, the concentration of PSA remains low, correlating with the activity of prostate cells. Reduction of the PSA content on the background of therapy with finasteride may complicate the timely diagnosis of prostate cancer. When evaluating the results of the PSA study in patients taking Finasteride for a long time, it should be taken into account that the PSA values in this group are 2 times lower in comparison with the corresponding age norm.

Studies have shown that the use of finasteride leads to a significant reduction in the risk of acute urinary retention by 57% and a reduction 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)

In 1992, there were first reports about the advisability of using alpha-adrenoblockers 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 carried out to date do not provide sufficient evidence to confirm the clinical advantages of combined therapy with alpha-adrenoblockers (terazosin) and finasteride compared with monotherapy with alpha-adrenoblockers.

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

Data from large-scale MTOPS studies in which a combination of finasteride and doxazosin and COMBAT evaluating a combination of dutasteride and tamsulosin suggests a significant benefit of combination therapy as compared to monotherapy for each of the drugs for improving symptoms, urinary frequency, patient's quality of life, and slowing progression disease.

The modern 5-a-reductase inhibitor-dutasteride (Avodart) suppresses the activity of the I and II type 5-a-reductase isoenzymes, which are responsible for converting testosterone to dihydrotestoeron, 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, the median values of dihydrotestosterone concentrations in serum are reduced by 85 and 90%.

Data from a 4-year, large-scale, multicenter, randomized clinical trial demonstrate the efficacy and safety of an avtard.

Dutasteride provides a steady decrease in symptoms and slows the progression of the disease in patients with prostate volume of more than 30 ml. Qmax and prostate volume change during the first month of therapy, which is probably due to inhibition of both types of 5-a-reductase, in contrast to the first drug from this group, finasteride, which blocks only 5-a-reductase II type.

Prolonged treatment with prostate adenoma led to an ongoing improvement in the total score of AUA-SI (-6.5 points) and Qmax (2.7 ml / s).

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

Studies have also shown a reduction in the risk of acute urinary retention by 57% and the need for surgical intervention by 48% when treated with avatart compared to placebo.

At present, the 2-year period of the international COMBAT study has been completed, which for the first time showed a significant advantage in improving symptoms when using combination therapy compared to monotherapy with each drug during the first 12 months of treatment.

The occurrence of undesirable phenomena associated with the drug in patients receiving dutasteride is more common at the beginning of treatment for prostate adenoma and decreases over time.

There may be impotence, decreased libido, impaired ejaculation, gynecomastia (includes soreness and enlargement of breast glands). Very rarely: allergic reactions.

[6], [7], [8], [9], [10]