The most effective medications for the treatment of prostate adenoma in men. The most effective medications for the treatment of prostate adenoma in men Creatine as a source of 5 alpha reductase

All processes occurring in the human body require the participation of biologically active substances.

The latter also include enzymes, for example, 5-alpha reductase. Many people are familiar with this name from advertising.

What is this enzyme and in what cases is it recommended by doctors? These are the questions most readers are interested in. And that’s right, before taking any medicine, you need to find out how it affects the body. You should also not forget about the consequences of therapy, side effects and contraindications.

First of all, we will find out what functions 5 alpha reductase performs and give a definition to this substance. This is a protein compound, its enzyme is involved in the processes of steroidogenesis.

Functions of 5 alpha reductase:

stimulation of the conversion of male sex hormones into more intense dihydrotestosterone;

participates in the formation of allopregnanolone and other neurosteroids.

5-alpha reductase is produced mainly in the organs of the reproductive system (seminal vesicles, prostate tissue). This enzyme is produced in small quantities by skin cells, hair follicles, and some parts of the nervous system.

What are inhibitors for?

Drugs of this group block the production of this enzyme. This affects the amount of male sex hormones.

5-alpha reductase inhibitors are widely used as drugs to treat:

• acne;
• alopecia (intense hair loss);

The positive results of therapy have been confirmed by scientific studies.

Herbal preparations

Many patients prefer. It’s easy to explain - they act gently on the human body and do not cause damage to it. Such medications are often used to treat the prostate gland.

Fruits of dwarf palm of different levels of maturity

Alopecia and acne are also often treated with herbal preparations. To combat hyperplastic phenomena in the prostate, the fruits of the dwarf palm are often used. They contain a large amount of phytosterols and fatty acids. Only ripe fruits are used for medicinal purposes.

Products made from the fruits of the dwarf palm are used as a diuretic, tonic for the treatment of:

• prostate gland;
• Bladder;

In nature, this plant is found on the southern coasts of America. Its second name is . The Indians used the fruits of the dwarf palm not only to treat the urethra, prostate, and bladder.

It was used for bronchitis and pulmonary tuberculosis. When a man was underweight and a woman had small breasts, healers offered them black sabal berries, and this made it possible to get rid of problems very quickly.

There is another group of substances that have antiandrogenic properties. They are called isoflavones. A high content of such substances was found in stinging nettle. The properties of this plant have been known since ancient times. Our ancestors washed and rinsed their hair with nettle decoctions.

In order for village healers to infuse nettles in water.

This medicine is effective, fast-acting and harmless. In order for nettles to bring maximum benefits, they need to be collected in May.

To prevent many diseases, salads and green soups are prepared from young nettles. Now shampoos and conditioners are produced based on this plant, since it has a beneficial effect on hair growth and appearance.

Synthetic origin

These drugs provide a pronounced effect in the fight against diseases, but they are dangerous due to side effects.

For the manufacture of 5-alpha reductase inhibitors, 2 main active ingredients are used:

• dutasteride (selective inhibitor), which is used to treat. The drug Avodart should be mentioned here;
• Finasteride is a synthetic substance that reduces the level of enzymes in the blood and in the prostate itself. The effect of taking it lasts almost 24 hours.

Finasteride is also used for treatment, but patients should not hope for its 100% effectiveness. It has not been confirmed by research. Much more drugs based on finasteride are known. These include Alfinal, Finast, Proscar, Zerlon, Penester, Urofin, etc.

Side effects

Synthetic 5-alpha reductase blockers should be taken with extreme caution. They have a direct effect on human hormonal levels.

Long-term use of the drug can negatively affect the patient’s sex life. Patients note a decrease and impaired potency.

During sexual intercourse, the following problems may arise: unstable erection, sexual intercourse of insufficient duration, small volume of ejaculate, and an increase in the size of the mammary glands.

The amount of neurosteroids also decreases, which can lead to prolonged depression. However, such a side effect is isolated cases. All of the above means that such therapy must be carried out under the supervision of a doctor.

The use of 5-alpha reductase of synthetic origin requires specialist supervision, this will make it possible to avoid unwanted side effects.

Side effects that can occur when using synthetic drugs frighten patients. Many of them choose herbal medicines. However, these drugs also have negative properties. The human body quickly gets used to them, as a result of which the effectiveness of the medicine gradually decreases.

Contraindications

This drug, which suppresses enzyme activity, cannot be used for treatment in all patients.

A contraindication is the presence of acute inflammatory processes in the body, which include and.

Before starting to take this medicine, the patient must undergo a detailed examination of the body. At the slightest suspicion of oncology, he is prescribed.

The postoperative period and renal failure are also contraindications for the use of this drug.

Some application features

When visiting a doctor, the patient should be extremely frank, especially for young men.

The doctor should have no doubts when prescribing 5-alpha reductase.

If the patient plans to have a child in the near future, it is better to avoid taking this drug. Otherwise, the medicine may provoke the development of the fetus with pathologies.

Prospects for the use of 5-alpha reductase inhibitors in the prevention and treatment of prostate cancer

Prostate cancer (PCa) is one of the most common malignant tumors, ranking 2nd among the causes of male mortality from cancer in our country and 3rd among industrialized countries. Modern screening and diagnostic methods make it possible to detect prostate cancer at the stage of a localized process, which makes early radical treatment possible. However, at the same time, the number of patients for whom radical methods cannot be performed or are not indicated is still large: patients with a burdened somatic status, locally advanced and disseminated prostate cancer, as well as with relapse of the disease after radical prostatectomy, external beam radiation therapy or HIFU. therapy. That is why the issue of improving existing and developing new methods of conservative treatment of prostate cancer, as well as preventing the disease, remains extremely relevant.

Today, the first line of drug treatment for common forms of prostate cancer remains hormonal therapy. Recently, studies have been conducted to study its effectiveness as monotherapy for localized prostate cancer and relapses of the disease after radical treatment. The range of therapeutic approaches aimed at suppressing androgen stimulation of the tumor is quite wide and includes bilateral orchidectomy, which remains the “gold standard” when assessing the effectiveness of other castration methods, the use of gonadotropin-releasing hormone (GnRH) agonists and antagonists, antiandrogens (bicalutamide, cyproterone), synthetic estrogens (diethylstilbestrol), inhibitors of adrenal androgenesis (ketoconazole). The basis for various methods of hormonal therapy is the theory that has existed for 60 years that the growth of prostate cancer cells depends on androgenic effects. Primary hormonal therapy, the currently most widely used method of which is the administration of GnRH agonists, allows for rapid and effective relief of symptoms of metastatic prostate cancer. At the same time, various methods of hormonal therapy have disadvantages that make it impossible to use them in certain groups of patients: for example, the presence of the “flare” phenomenon in GnRH agonists does not allow their use in patients with symptomatic metastases of prostate cancer; estrogen drugs are characterized by a negative effect on cardiovascular -vascular system, the use of surgical castration is difficult due to psychological trauma. In addition, in most patients, after 18–24 months, hormonal therapy becomes ineffective, which indicates the development of castration resistance. The pronounced side effects of all methods of hormonal therapy do not allow the use of any of them for the prevention of prostate cancer, despite the fact that the role of androgens in the development of the disease has long been proven. In this regard, it is currently extremely important to further study the role of hormonal mechanisms in the etiology and pathogenesis of prostate cancer and the search for methods, means and new targets for conservative treatment and prevention of the disease.

Testosterone, which normally constitutes the main fraction (95%) of circulating androgens, is a steroid hormone synthesized in the testes by Leydig cells under the influence of luteinizing hormone of the pituitary gland. 4–5% of circulating androgens are dehydroepiandrosterone (DHEA) and androstenedione, produced by the stratum reticularis of the adrenal cortex. DHEA secretion is not suppressed when the gonadotropic function of the pituitary gland is turned off. Both testosterone itself and intermediate metabolites of androgenesis (progesterone, 17-hydroxyprogesterone, androsterone, androstenedione, DHEA) can act as ligands for androgen receptors (AR), but the affinity of testosterone for them is significantly higher than that of other sex steroids. In the nucleus, AR and these hormones interact with certain nucleotide sequences of target genes, which are known as androgen response sites (sites), which modulates the transcription mechanisms of genes responsible for the proliferation, growth and vital activity of cells and genes of secretory proteins, such as prostate-specific antigen (PSA) . This is what determines the value of PSA as one of the indicators of AR activity and allows us to indirectly assess the response to suppressive hormonal therapy.

In some target organs, which include the skin and its appendages, liver, prostate, testes, most of the testosterone under the influence of 5-alpha reductase isoforms is intracellularly converted into dihydrotestosterone (DHT), which has several times greater affinity for AR according to compared to testosterone. The higher affinity is due to the fact that, despite the same rate of binding of testosterone and DHT to AR, the dissociation of the latter with DHT occurs much more slowly compared to its predecessor, as a result of which DHT is a more powerful activator of AR. According to recent data, there are three isoforms of 5-alpha reductase, existing independently of each other at the genetic and enzymatic level. The first type of enzyme is encoded by a gene on chromosome 5 and is expressed mainly in skin and liver cells. The gene encoding the second isoform of 5-alpha reductase is located on chromosome 2, its expression occurs in the cells of the stroma and basal epithelium of the prostate gland. A third form of the enzyme, recently discovered, is expressed in all androgen-dependent and androgen-independent tissues and functions in the post-translational modification of certain membrane proteins. 5-alpha-reductase inhibitors were initially used in the treatment of benign prostatic hyperplasia (BPH) to reduce the volume of the latter and eliminate obstructive symptoms. The first drug in this group, finasteride, has inhibitory activity against the second form of 5-alphareductase, while the more modern dutasteride inhibits all isoforms of the enzyme. The mechanism of action of both drugs is based on the formation of a complex of 5-alpha reductase and nicotinamide adenine dinucleotide phosphate (NADPH) that is incapable of dissociation, which ensures irreversible suppression of the activity of the enzymatic complex and leads to a decrease in intracellular DHT production. The hormonally dependent nature of the growth of BPH determines the resulting decrease in the volume of hyperplastic tissue.

Recent data on the mechanisms of development of castration-resistant prostate cancer open up new prospects for the use of 5-alpha reductase for the prevention and treatment of prostate cancer. Research shows that AR stimulation is necessary to maintain the vital activity of prostate cancer cells even in the stage of castration resistance. It was revealed that in the cells of castration-resistant prostate cancer the concentration of AR significantly exceeds the normal level, which is associated with an increase in the expression of their genes. Higher receptor density ensures maximum androgen effects even at low intracellular concentrations. In addition, AR mutations with changes in the conformation of the ligand binding site have been described. This allows the mutant receptors to interact with other steroids as strongly as they do with natural ligands.

AR in tumor cells use this substrate to maintain androgen stimulation, which is confirmed by data on the effectiveness of ketoconazole, which blocks adrenal androgenesis, in a number of patients with castration-resistant prostate cancer in the second line of hormonal therapy. The most important mechanism for tumor cell escape from hormone suppressive therapy is intratumoral androgen synthesis. Two independent studies showed that, despite a 95–97% decrease in circulating testosterone levels during medical castration, prostate tissue androgen concentrations decreased by only 50% and 61%, respectively. This may be due to the fact that castration-resistant PCa cells acquire the ability to synthesize testosterone and then DHT from DHEA, providing sufficient androgens to survive in situ under conditions of systemic androgen deprivation.

It is important that the conversion of testosterone to DHT by 5-alpha reductase is the final stage of all androgenesis pathways, providing cells with maximum androgenic stimulation. Various studies have shown that the expression of all isoforms of the enzyme is significantly increased in prostate cancer cells. In the cells of prostatic intraepithelial neoplasia and prostate cancer, an imbalance of the natural ratio of isoforms is also determined - the predominance of the first (neutral) form over the second (acidic, normally expressed in the prostate). The effect of 5-alpha reductase inhibitors on prostate cancer cells leads to androgen-dependent inhibition of cellular growth and proliferation mechanisms and increased apoptosis mechanisms, which is associated with the induction of the CASP7, CASP8, BNIP3, CDK8 and Skp2 genes; in one study, during dutasteride therapy, a decrease in the volume of foci of prostatic intraepithelial neoplasia was noted. Even at the stage of castration resistance, intracellular synthesis of androgens, the final stage of which is the conversion of testosterone to DHT, catalyzed by 5-alpha reductase, is necessary to maintain the vital activity of prostate cancer cells. That is why inhibition of 5-alpha reductase, which ensures deprivation of the most biologically active androgen, DHT, is a promising target for therapy and, possibly, prevention of prostate cancer.

The first large-scale study of the effect of finasteride on the development of prostate cancer was the PCPT (Prostate Cancer Prevention Trial) study. The study included more than 18 thousand men aged 55 years and older with a PSA level of less than 3 ng/ml and no pathological changes on rectal examination of the prostate. The patients were randomized into two groups; in the main group, they received treatment with finasteride at a dose of 5 mg daily; in the control group, men received placebo. During follow-up periods of up to 3 years, a decrease in the frequency of newly diagnosed prostate cancer was detected in the main group compared to the control group (18.4% and 24.4%, respectively). Although the difference appears small at first glance, the actual difference may be larger due to the fact that the likelihood of detecting prostate cancer on prostate biopsy and rectal examination is inversely correlated with prostate volume, which was significantly lower in patients treated with finasteride. In addition, an increase in the number of low-grade tumors was detected in patients of the main group: tumors with a Gleason score from 7 to 10 were found in 6.4% of patients receiving the drug and in 5.1% of patients in the placebo group. This fact has no precise explanation to date, although it does not contradict the hypothesis that the lower the degree of tumor differentiation, the less influence systemic androgen levels have on its growth. Despite the increased expression of all three isoforms of 5-alpha reductase by tumor cells, finasteride irreversibly blocked only one of them, which could open up bypass pathways for intratumoral DHT synthesis and reduce the effectiveness of therapy. The REDUCE (The Reduction by Dutasteride of Prostate Cancer Events) study examined the effects of dutasteride, which blocks all isoforms of 5-alpha reductase, on the development of prostate cancer in patients at high risk. The protocol included patients with a PSA level from 2.5 to 10 ng/ml and negative results of a biopsy performed no earlier than 6 months before the study. In randomized groups of patients, the effectiveness of therapy with dutasteride 0.5 mg daily was compared with placebo.

The results were assessed after 2 and 4 years of follow-up. After the first two years, the frequency of detection of tumors with a Gleason score from 5 to 7 was significantly lower in the dutasteride group (12.9% versus 16.7%), while poorly differentiated tumors with a Gleason score from 8 to 10 were found in both groups. groups with the same frequency. However, when examining patients in the third and fourth years, a significant increase in the number of poorly differentiated forms of prostate cancer in the main group was noted (12 cases per 1 case in the control group). It remains unclear whether this dramatic difference was a result of treatment or due to the fact that many more patients in the placebo group were excluded from the study in the second year due to diagnosis verification, which could lead to overcompensation of the original data. Over the entire period of observation, a decrease in the frequency of moderately differentiated tumors (with Gleason score from 5 to 7) in the dutasteride group was shown to 19.9% ​​compared to 25.1% in the placebo group.

Both studies included patients who were at risk of developing prostate cancer, that is, they primarily investigated the role of 5-alpha reductase inhibitors as chemoprophylaxis for this disease. On average, both studies showed a 25% reduction in PCa incidence overall, accompanied by a significant increase in the incidence of low-grade tumors. The US Food and Drug Administration (FDA) reviewed the results of the REDUCE study by removing biopsy specimens and reviewing them by pathologists based on modified Gleason score criteria. The review found no change in the incidence of PCa with a Gleason score of 7 to 10, which was consistent with published study data. However, the absolute increase in the incidence of tumors with a score of 8 to 10 was 0.5% (risk ratio 2.06, 95% confidence interval) with dutasteride and 0.7% with long-term finasteride. It was suggested that the change in the incidence of high-grade tumors during treatment with finasteride could be associated not only with a decrease in prostate volume, but also with a decrease in serum PSA levels, which is known to increase the diagnostic sensitivity of this tumor marker. An increase in the incidence of low-grade tumors (Gleason score from 8 to 10) was noted not only during routine biopsies, justified by an increase in PSA, but also during “routine” biopsies in clinically and laboratory asymptomatic patients. About 56% of all PCa cases in the PCPT study and 90% of cases in the REDUCE study were diagnosed during these “routine” biopsies.

The hypothesis of an increase in the density of biopsy cores during manipulation in patients with a smaller volume of the gland in the main groups theoretically explains the increase in the likelihood of detecting tumors in patients receiving chemoprophylaxis. The use of various methods of regression analysis with extrapolation showed that, for the same prostate volumes, the relative risk of low-grade prostate cancer in the finasteride group was equal to 27% less than in the control group. However, the FDA's review of the data did not confirm that the resulting difference in the incidence of low-grade tumors could be quantitatively compared with the increase in the density of prostate tissue samples taken. Although many questions remain regarding the factors that may have confounded the incidence of prostate cancer in the groups, all subsequent exploratory analyzes have failed to demonstrate that the increased incidence of low-grade tumors in both groups may not be statistically significant. Study results show that the reduction in the risk of prostate cancer with the use of 5-alpha reductase inhibitors is limited only to tumors with a Gleason score of up to 6. Prospectively collected data from the REDUCE trial demonstrate that 80% of these tumors met Epstein's criteria for being extremely low-risk tumors, so the clinical significance of reducing their incidence is questionable. Analysis of the results of biopsies performed for biochemical (PSA increase) or clinical (rectal examination data) indications, which dominate modern clinical practice, found a reduction in the relative risk of PCa to a lesser extent compared with the protocols used in the PCPT and REDUCE studies (14% vs. 25%). Prescription of drugs leads to the emergence of one new case of low-grade cancer and the prevention of 3-4 cases of clinically insignificant well-differentiated tumors. Today there is a prospect of obtaining qualitatively new data on the role of 5-alpha reductase inhibitors in the prevention of prostate cancer. Relatively recently, 5-alpha reductase inhibitors began to be used to treat a “non-urological” disease – androgenetic alopecia. The majority of patients are young men (under 40 years of age). Finasteride is prescribed for this form of baldness in a dose of 1 mg (which is 5 times less than the standard dosage) with or without an elevated serum level of DHT. Determining the latter has become possible only in the last few years due to the advent of modern test systems capable of differentiating androgen fractions. Restoration of the natural life cycle of the follicular epithelium, cessation of hair loss and growth of new hair is achieved, probably, by reducing the production of DHT in the prostate and possibly hair follicles, which also leads to a decrease in serum concentrations of the hormone. In many cases, elevated DHT levels are asymptomatic, diagnosed only during evaluation for alopecia, and remain idiopathic, due to hereditary increased expression of 5-alpha reductase. It is noteworthy that, despite significant effectiveness in the treatment of alopecia in men, drugs of this group turned out to be practically ineffective in androgenic alopecia in women, which may indicate the importance of different fractions of androgens in the pathogenesis of the disease in patients of different sexes. Analysis of data on the effectiveness and safety of this therapy led the FDA to approve the use of finasteride at a dose of 1 mg (trade name Propecia) for the treatment of androgenetic hair loss in men. At the same time, there are no studies on the relationship between long-term increases in DHT levels and the risk of developing PCa, and this seems to be an extremely important issue, the solution of which may become possible after the introduction of DHT levels into routine practice and screening programs for PCa. A prospective urological study of patients receiving finasteride therapy for alopecia could provide new data on the effect of this drug on the risk of developing prostate cancer, especially if the control group were patients with elevated serum DHT levels who were not receiving treatment. The hypothetical cohorts of patients in this case would differ significantly from patients in the PCPT and REDUCE protocols both in age and in the presence of risk factors for the development of prostate cancer.

Despite the mixed results of studies on the use of 5-alpha-reductase inhibitors as chemoprevention of PCa, work continues to study their potential as therapeutic agents for this disease. The REDEEM (Reduction with Dutasteride of Clinical Progression Events in Expectant Management) protocol examined the effect of dutasteride on the temporal characteristics of progression of histologically verified prostate cancer in low-risk patients. The study included 302 men with positive biopsy results who were monitored under an active surveillance program. Low-risk tumor criteria were defined as stage T1c–T2a, Gleason score no more than 6, and PSA level no more than 10 ng/ml. Patients were randomized into two groups: the main group was treated with dutasteride at a dose of 0.5 mg daily, patients in the control group received placebo. After 18 and 36 months, routine prostate biopsies were performed, as well as clinical examination, including PSA determination, transrectal ultrasound, and digital rectal examination. The primary endpoint of the study was the time until the onset of progression, that is, the appearance of clinical, laboratory and radiological symptoms of an aggressive tumor, which required termination of observation and transition to any therapeutic regimen, after which patients were excluded from the protocol. 23% of patients in the study group and 35% of patients in the placebo group had signs of progression at the end of the first observation period (18 months). Thus, the relative reduction in the risk of cancer progression during therapy was 38.9%. However, after three years, the proportion of patients with signs of progression in the dutasteride and placebo groups became almost the same (24% and 21%, respectively), which led many experts to interpret the study results as negative. According to the initial (before inclusion in the study) and final (after 3 years) biopsies, there was no increase in the proportion of poorly differentiated tumors in the dutasteride group compared to placebo - in both groups, approximately 15% showed progression of Gleason sum from< 6 до 7–8 баллов; ни у одного больного в конце исследования не было опухоли с суммой Глисона 9 или 10. Авторы исследования тем не менее признают, что количество больных в протоколе не позволяет достоверно судить о влиянии терапии на вероятность развития низкодифференцированных форм РПЖ. Кроме того, выявляемые при исходной биопсии низкодифференцированные опухоли делали невозможным включение больных в программу активного наблюдения и протокол. Примечательно, что у 23% (n = 31) больных контрольной группы и 36% (n = 50) пациентов группы дутастерида по данным конечной биопсии не было обнаружено злокачественной опухоли. Эти данные, с одной стороны, позволяют предположить, что терапия дутастеридом уменьшает количество опухолевых клеток в предстательной железе, с другой стороны, ставят под сомнение гипотезу о том, что уменьшение объема простаты на фоне приема препаратов увеличивает плотность биопсийного материала и способствует повышению частоты выявления РПЖ. В настоящее время проводятся исследования эффективности ингибиторов 5-альфа-редуктазы в качестве средств вспомогательной терапии при метастатическом и кастрационно-резистентном РПЖ в контексте влияния на кли- нические симптомы заболевания, онкоспецифическую и общую выживаемость. Данная группа препаратов продолжает исследоваться в комбинациях второй линии гормональной терапии РПЖ, то есть, фактически, речь идет о попытках преодоления кастрационной резистентности. В протоколе исследования TARP (Therapy Assessed by Rising PSA) в настоящее время сравнивается эффективность лечения дутастеридом в сочетании с бикалутамидом и монотерапии бикалутамидом у больных с кастрационно-резистентным РПЖ; критериями включения в исследование являются три последовательных повышения ПСА на фоне терапии агонистами ГнРГ, уровень сывороточного тестостерона менее 50 нг/дл, ПСА менее 20 нг/мл и отсутствие метастазов по данным инструментальных исследований.

The primary endpoint of the study is the time until biochemical or radiological evidence of tumor progression appears. A phase II study examined the effectiveness of adding dutasteride 0.5 mg daily and hydrocortisone (40 mg/day) to ketoconazole therapy in the development of castration-resistant PCa. According to the study design, 56 patients were treated with a combination of the three agents mentioned above while castration therapy was continued. A decrease in PSA of more than 50% was recorded in 56% of patients, the median duration of response was 20 months, and the median time to progression was 14.5 months. Grade III toxicity was observed in 32% of patients, grade IV toxicity was observed in only one observation. Serum levels of DHEA decreased by 89%, androstenedione by 56%, and testosterone by 66%. The level of DHT in the serum ceased to be determined after treatment, while before inclusion in the study, minimal concentrations of the hormone were determined in patients, despite the castration level of testosterone. However, the decrease in hormone concentrations did not differ significantly between patients with signs of response to therapy (decrease in PSA) and those without, and there was no increase in hormone levels from the nadir reached (lowest level) with the development of biochemical relapse. A retrospective analysis showed that the proportion of patients who responded to combination therapy in the protocol did not differ from that with ketoconazole monotherapy according to previous studies.

At the same time, a significant increase in the median time to progression was shown. The study authors concluded that further research is required to determine the appropriateness of prescribing 5-alpha-reductase inhibitors to patients who have ceased to respond to standard hormonal therapy, the effectiveness of inhibition of intratumoral androgenesis, and the long-term consequences of these changes. Thus, despite the received clinical evidence of the effectiveness of 5-alpha-reductase inhibitors in reducing the incidence of prostate cancer, the increase in the proportion of patients with poorly differentiated tumors does not allow us to recommend 5-alpha-reductase inhibitors for the prevention and treatment of prostate cancer today. In December 2010, the FDA published a final analysis of the clinical trials that dutasteride and finasteride did not have a favorable benefit/risk profile for chemoprophylaxis of PCa. Further studies may shed light on the mechanism of the increase in the proportion of poorly differentiated PCa during therapy with 5-alpha-reductase inhibitors and, possibly, ways to correct this side effect. The results of protocols that study the use of 5-alpha-reductase inhibitors in the conservative treatment of PCa can also provide urological oncologists with new clinically important data on the possibilities and prospects for the use of this group of drugs in a disease whose hormonally mediated mechanisms still remain a “black box.” It is hoped that constantly updated information about the pathogenesis of the disease, innovative screening programs, new effective methods of treatment and diagnosis will significantly reduce mortality caused by prostate cancer, thus solving this important medical and social problem.

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Andriole G.L., Bostwick D.G., Brawley O.W. et al. Effect of dutasteride on the risk of prostate cancer // N. Engl. J. Med. 2010. Vol. 362. No. 13. P. 1192–1202.

FDA Briefing Document: meeting of the Oncologic Drugs Advisory Committee. 2010. 1 December NDA 20180/S034 // www.fda.gov/ downloads/AdvisoryCommittees/CommitteesMeetingMaterials/ Drugs/OncologicDrugsAdvisoryCommittee/UCM234934.pdf

Rossi A., Cantisani C., Scarno` M. et al. Finasteride, 1 mg daily administration on male androgenetic alopecia in different age groups: 10-year follow-up // Dermatol. Ther. 2011. Vol. 24. No. 4. P. 455–461.

Fleshner N., Gomella L.G., Cookson M.S. et al. Delay in the progression of low-risk prostate cancer: rationale and design of the Reduction by Dutasteride of Clinical Progression Events in Expectant Management (REDEEM) trial // Contemp. Clin. Trials. 2007. Vol. 28. No. 6. P. 763–769.

Sartor O., Gomella L.G., Gagnier P. et al. Dutasteride and bicalutamide in patients with hormone-refractory prostate cancer: the Therapy Assessed by Rising PSA (TARP) study rationale and design // Can. J. Urol. 2009. Vol. 16. No. 5. P. 4806–4812.

Taplin M.E., Regan M.M., Ko Y.J. et al. Phase II study of androgen synthesis inhibition with ketoconazole, hydrocortisone, and dutasteride in asymptomatic castration-resistant prostate cancer // Clin. Cancer Res. 2009. Vol. 15. No. 22. P. 7099–7105.

Use of 5-alpha reductase inhibitors for the treatment of prostate adenoma

Example

Active substance	Drug name
dutasteride
finasteride

Operating principle

5-alpha reductase inhibitors reduce the effect of certain male hormones (androgens) on the prostate. Which slows down the growth of the prostate and can even lead to its shrinkage, which in turn can alleviate the symptoms of prostate adenoma.

But since the size of the prostate is not always related to the degree of symptoms, these drugs are not effective in all cases.

As soon as you stop taking the drug, symptoms usually return.

In what cases are these drugs used?

How well do the drugs help?

In most cases of use of 5-alpha-reductase inhibitors, there is a reduction of 3 points in the American Urological Association (AUA) symptom index. This reduction gives a feeling of significant relief from symptoms. 5-alpha reductase inhibitors also reduce the risk of complications such as inability to urinate (urinary recession) and reduce the likelihood of needing surgery.

Significant improvement in symptoms is observed after 6-12 months.

Past studies have found that dutasteride is as effective as finasteride in reducing BPH symptoms. But comparative studies of the effectiveness of dutasteride and finasteride have not been conducted.

Using a combination of alpha blockers with 5-alpha reductase inhibitors is more effective than using them alone.

Side effects

Decreased sexual desire.

Ejaculatory dysfunction (such as ejaculating less sperm).

Difficulty with erection.

Swelling or enlargement of the mammary glands.

One large study found that after 1 year of treatment with finasteride, the rate of side effects such as decreased libido and erection problems was similar to that due to treatment with finasteride. The same study found that the risk of ejaculatory dysfunction was higher with finasteride. .

For a complete list of side effects, see the Medications link.

Things to think about

5-alpha reductase inhibitors reduce prostate size, but since prostate size is not always related to the severity of symptoms, these drugs are not effective in all cases. As soon as you stop taking the drug, symptoms usually return.

5-alpha reductase inhibitors reduce prostate-specific antigen (PSA) levels. Because PSA levels are used to detect early stage prostate cancer, patients taking 5-alpha reductase inhibitors should consider the following:

In the future, if after 6 months of use the PSA level has not decreased by approximately 50%, you need to continue screening for prostate cancer.

A PSA level of more than 2 ng/mL (nanograms per milliliter) while taking 5-alpha reductase inhibitors may indicate the need for further testing for prostate cancer.

5-alpha reductase inhibitors may be less effective in reducing symptoms than alpha blockers.

The drug should not be taken by a man who is planning to have a child, due to the small likelihood of fetal malformations. Pregnant women or women preparing to become pregnant should avoid contact with broken or crushed tablets containing finasteride or dutasteride.

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Therapist, Endocrinologist

Hello, this hormone is usually often ignored when examining for hyperadrogenism, because the norms that are indicated in laboratory forms are precisely for this purpose, the tests are very arbitrary and it is still unclear what the norms should be for this hormone. So if you have no complaints... then just forget about it, if you have complaints about hyperadrogenism (increased hair growth in the backend area, midline of the abdomen in intimate areas, or vice versa, hair loss on the head), then write about your complaints and write the results of all your examinations for hormones (with the standards of your laboratories) .... if the clinical picture is pronounced and the levels of hormones are very high, then you can look for a tumor.... but as a rule, the whole reason is PCOS or its combination with a disruption of the functioning of adrenal enzymes - there are tests for these disorders, but to know which enzyme to check you need to see the hormones

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Rustem, Hello. Thank you for your reply. There are just complaints - thinning and thinning of hair on the head and increased growth on the body. Using computed tomography, no tumors were found either in the pituitary gland or in the adrenal glands. There is no tumor and no ovaries - multifollicularity and absence of ovulation are established. At the time of visiting the local endocrinologist, the hormones tested were LH, FSH, Estradiol, Testosterone, Prolactin, 17-OH-Progesterone, DHEA-SO4, Cortisol, Progesterone, thyroid hormones - TSH and free T4, Androstenedione, as well as the insulin resistance index. The excess was in Prolactin 557, the upper limit is 714, my result is insignificant, in Testosterone it is insignificant - the norm is 0.52-1.72, I have 1.73 nmol/l, in DHT the norm is 24-450, I have 878. The endocrinologist prescribed Diane- 35, but my hair was still falling out, I took DHT again, and even when taking Diane-35 it was also increased by 2 times. That is, such therapy with COCs does not even completely mask the disorders. Now I’m still on COCs, because without them the external changes are even worse and I have terrible pain during my not particularly regular periods. Tell me in what direction to be examined further, so that I can then contact you with the results and draw some conclusions?

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Rustem, problems with the cycle since the age of 12. But then the doctor said that “there is a teenage “settling down” of hormones, take your vitamins, come back later if you have problems.” There were problems - periods were 3-10 days behind, painful to the point of nausea. Janine was appointed. My weight is 51 kg with a height of 170, it has not grown or decreased as with oncology. Weight has been stable since the age of 12 +- 1-2 kg. But my hair thins starting at age 20. About two or three years ago, the apotheosis of the loss came. All this time, Diana-35 was already prescribed. The cycle is now smooth, but the DHT is still high and the hair is growing and thinning. And the most important thing is that the diagnosis has not yet been established. As I understand it, you need to interrupt the COC for a month and take hormones to understand what you have come to. LH, FSH, Prolactin, Free testosterone, DHT, 17-OH progesterone, DHEA-s and ultrasound - maybe something extra or, on the contrary, is something else needed to clarify the diagnosis, if after the test I contact you for a fee?

The human enzyme involved in the formation of steroids from cholesterol is 5-alpha reductase. The main function of the enzyme is to convert the male sex hormone testosterone into, which is the strongest androgen; participation in the formation of allopregnanolone (progesterone metabolite) and tetrahydrodeoxycorticosterone.

Since 5-alpha reductase is an enzyme that is located in the nucleus of the stromal cells of the male prostate, it is a catalyst in the conversion of testosterone to dihydrotestosterone (DHT). It is dihydrotestosterone, through communication with the nuclear androgen receptor, which is located in the stromal cells of the prostate, that causes cell growth and distribution.

The human body contains two types of 5-alpha reductases:

• Contained in hair follicles, as well as in the dermis - cutaneous. This type regulates the development of acne and causes hair loss.
• Genital, which collects in the male prostate gland and acts as a regulator of sexual functions.

Modern means of self-defense are an impressive list of items that differ in their operating principles. The most popular are those that do not require a license or permission to purchase and use. In the online store Tesakov.com, you can buy self-defense products without a license.

In medicine, inhibitors are very often used to combat. It is thanks to blockers that a kind of barrier is created that restrains dihydrotestosterone and allows hair to grow. This is due to a decrease in the sensitivity of the androgen receptor in the hair follicle to DHT.

However, the most common area of ​​application is considered. Thanks to their ability to reduce, inhibitors slow down its growth, and with timely treatment they can reduce it in size, which leads to a significant relief of symptoms.

The effectiveness of the drug was not noted in all cases (only with an increase in the size of the prostate), and upon withdrawal, all symptoms return. When using inhibitors, there is a decrease in the AAU index (American Urological Association Symptom Questionnaire) by three points. In addition, they help reduce the development of complications, such as urinary recession, and also reduce the need for surgery.

A positive result in patients is observed after 6-12 months of taking the inhibitory drug.

It is very important to know that the use of inhibitors reduces the concentration of PSA, which has a decisive role in detecting prostate cancer in the early stages of the disease. This is why it is important to understand that it is best to perform a PSA test before starting medication; if after six months of treatment with blockers there is no decrease in PSA by at least 50%, it is necessary to resume; a PSA concentration of more than 2ng/ml may be a sign of the development of cancer.

Drugs

There are currently two 5-alpha reductase inhibitors - dutasteride and finasteride.

Dutasteride is a selective inhibitor used in the treatment of benign prostatic hyperplasia. Use in combination with CYP3A4 inhibitors is not recommended, because they increase the level of the blocker in human blood.

Women and children should be especially careful when handling damaged capsules, because the drug can be absorbed through the dermis.

Finasteride is a drug that helps reduce 5-alpha-dihydrotestosterone not only in the blood, but also in the tissues of the prostate gland 24 hours after administration. Helps inhibit testosterone stimulation, which can cause tumor development.

It is experimentally used to treat prostate cancer and is statistically 25% more effective than placebo.

Drugs that are used to treat benign prostatic hyperplasia:

Containing the active substance dutasteride:

• Avodart.

Features of therapy with 5-alpha-reductase inhibitors for prostate adenoma

With the help of blockers, it is possible to reduce the size of a sufficiently large adenoma by 20%. With long-term use of drugs, a pronounced remission can occur, as well as the process of urination can be completely restored.

But, despite the fact that the drugs are considered quite effective, it is best to use complex treatment, which not only contributes to the development of stable remission, but also restores the man’s health and confidence. The use of the drug is strictly prohibited for men who are planning to have a child, because it can provoke the development of fetal defects.

Side effects

In most cases, 5-alpha reductase inhibitors are well absorbed by the body and rarely cause side effects. The main impact occurs in the first year of use, when the body is not yet familiar with the drug.

The most common side effect is considered to be a violation of potency, as well as a decrease in libido and the onset of depression.

Hypersensitivity and angioedema may also develop, which is considered a sign of a response from the body's immune system. Palpitations may occur, and the level of liver transaminase activity may increase. The skin may develop a small rash, hives, or itchy skin.

The reproductive system most often suffers, because side effects include: the appearance of pain in the mammary glands, pain in the testicles, the onset of male infertility or a decrease in sperm quality.

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