Avodart (dutasteride) is the first dual acting 5 alpha-reductase inhibitor. It means that it reduces the size of the prostate, improves urination, and reduces the risk of acute urinary retention and the need for surgical treatment
Dosage and administration
Take one capsule of dutasteride (0.5 mg) daily orally. The capsules should be taken as a whole. Avodart can be taken with or without food. The effect is quite fast, but treatment should be continued for at least 6 months in order to objectively evaluate the effect of the drug.
BPH is a progressive disease. There are a number of scientific observations that are exactly determined that the progression of BPH. If so, then the treatment of BPH should be prolonged.
Therefore the need for long-term course Avodart is not a manifestation of the “weakness” of dutasteride against adenoma, but rather due to the need to nosology. Meanwhile Avodart begins to act quickly – within the first month of patients reported improvement in urination. And only 6 months of treatment will be sufficient for an objective evaluation of the effect of pathogenetic therapy.
As for prostate cancer, it is now time for the disease develops a special situation: the early diagnosis of cancer, it can be effectively treated successfully. Unfortunately, the identification of the disease in most cases is not timely, since many patients seek medical attention very late.
With the aging of all organs and tissues of different processes occur in varying degrees, affect their function and morphological structure. In some cases, reduced function of organs and systems, in others – are developing the disease, not peculiar to the young age.
In women, age-related changes of the genital organs leads to menopause with various hormonal disorders, involutional changes in the uterus and other reproductive organs are accompanied by significant changes in the psycho-emotional sphere. Indicative time-point of these changes is the disappearance of menstruation.
The men are also seen various age-related changes of the sexual sphere, but they are not so clearly defined the nature of time and the local manifestations. Thus, reduction in gonadal function and, accordingly, decreased testosterone levels in the peripheral blood are not always accompanied by a decrease or disappearance of sexual function (one of the manifestations of normal hormonal males). It is not always observed changes in other organs and systems associated with a decrease in the level of sex hormones. And since there is no clearly defined time period or the beginning of any clinical manifestations of the decline of gonadal function, many of the emerging clinical symptoms associated with the aging of the male body.
With age, there is a benign growth of the prostate. The basis for this process lies tissue hyperplasia paraurethral glands and stromal elements of the central zone of the prostate gland. By itself, this process is not life threatening, but complications of the adjacent organs significantly alter the quality of life of elderly people, which requires long-term medication, and sometimes surgery.
Frequency of benign prostatic hyperplasia (BPH) is dependent on the age male. In various studies, the frequency of BPH vary at different ages, as in some cases, these data are based on clinical studies, in others – the results of postmortem studies of prostate glands of the dead men. In five of generalized pathology studies of various age groups of the male population were no signs of hyperplasia none of the men under the age of 30 years. At the same time, half of men 50-60 years old and 90% of men older than 80 years was revealed BPH. No obvious adverse epidemiologically countries regarding the incidence of benign prostatic hyperplasia (according to various reviews) no.
The first histological signs of the disease are found in the microscopic study of prostate glands have been thirty-men. However, clinically significant disease, which is defined by standard methods (digital rectal examination, ultrasound, MRI), appears later in life. By age 50, 50% of men have BPH determined that requires on the part of the treatment they need.
The nature of treatment strategy in patients with BPH is determined by many factors. By the time of diagnosis, all patients can be divided into the following groups:
1st: Patients who do not require special treatment.
2nd: Patients who need medication.
3rd: Patients who need surgical treatment.
4th: Patients who need to be seen in the dynamics of the use of special methods of examination.
Patients with BPH have the first group, which was confirmed at least by ultrasound, but it does not appear clinically (strangury, nocturia, and the like). They have a normal level of PSA (prostate-specific antigen), Creatinine and urea, no residual urine, expanding the upper urinary tract. They should be observed at the urologist once a year, but there is no need for special treatment. It’s an absolute majority of patients with newly diagnosed BPH, is 65-75%.
In the second group of patients diagnosed BPH against clinical disease observed (nocturia, urinary stream attenuation, urgency of urination, etc.) can be determined by residual urine to 150 ml. They revealed normal PSA values, urea and creatinine, there is no extension of upper urinary tract. Usually they come to see a urologist, noting the significant deterioration in the quality of life, and sometimes even impossible to perform his duties because of urinary disorders. This contingent of medical therapy, the frequency and volume of follow up is determined by the nature of the treatment, its efficacy, tolerability, etc. According to various authors, such patients account for 20-25% of all newly diagnosed BPH.
The third group – are patients with BPH who have a diagnosis in the primary is already indicated for surgical treatment. The examination revealed they residual urine 150 ml secondary bladder stones, extending the upper urinary tract, with or without renal failure.
The fourth (the most little-studied) group consists of patients with newly diagnosed BPH, against which at the same time revealed an elevated PSA level (greater than 4 ng / ml). Such patients require more in-depth study of prostate (transrectal ultrasound (TRUS) biopsy multifocal), more frequent observation of monitoring PSA to exclude or confirm the diagnosis of prostate cancer. This leaves open the question of the possibility of appointing these patients current medications – inhibitors of 5-alpha-reductase inhibitors (I5AR) that long-term use can reduce PSA levels.
The boundaries of modern drug therapy of BPH were significantly wider than 15-20 years ago. This is due to the development of the pharmaceutical industry and in-depth understanding of the pathogenesis of the disease. Research and development causes BPH indicates that most likely enlargement of the prostate is the result of increasing the activity of the enzyme 5-alpha-reductase (5AR). Determined that with age increases its activity in the transition zone of prostate. Using this enzyme in cells of the prostate gland is of dihydrotestosterone (DHT), which are much more active circulating testosterone. In this case, there are two types of the enzyme carrying out this process. DHT stimulates the production of growth factors, cell proliferation providing stromal elements of the prostate gland, which lies at the basis of benign hyperplasia. During the formation of prostatic DHT and provides the final differentiation of epithelial cells. After the formation of glandular tissue formed from slices of prostate ducts with their epithelial cover. Thus, the development of prostate cancer, all of its elements are under the supervision and with the direct participation of DHT, and in the elderly and old age and the same applies to the processes of hyperplasia, and perhaps even cancer.
Currently able to reduce the activity of 5AR two synthetic drugs – finasteride and dutasteride. Finasteride long been known as a drug for the treatment of BPH, but it pharmacokinetic study shows its effect on a second type of 5AR, accompanied by a decrease in blood levels of circulating DHT about 70%. In view of the results it is logical to assume that the rest of the formation of DHT 5AR likely catalyzed by the first type. Dutasteride – the first selective inhibitor of both types of 5AR. Therefore dutasteride 0.5 mg / day in the first week of coupon reduces DHT levels by 85% and after 2 weeks – 90%.
Clinical efficacy of dutasteride evaluated in three large-scale, placebo-controlled randomized studies. Two of them (ARIA3001, ARIA3002) conducted in the United States, and the third (ARIA3003) – in 19 countries. In total study involved 400 medical centers.
The study included men aged 50 years and older with a clinical diagnosis of BPH and prostate size 30 cm 3 or more. Size of the prostate were determined by TRUS. The degree of urinary disorders was evaluated on a scale of the American Urological Association (AUA-SI). With a score of more than 12 patients included in the study. The criterion for inclusion in the study was also a top speed of urination (Qmax) of 15 ml / s or less. Not participate in the study, patients with residual urine of more than 250 ml and after surgery, with acute urinary retention, if not the last three months with permission, patients with prostate cancer, previously taken 5AR inhibitors, as well as with a PSA more than 10 and less 1.5 ng / ml. Thus, in the study included 4325 patients. Of these 2167 dutasteride prepared at 0.5 mg / day, 2158 – placebo. The study lasted 24 months. Then, in the open phase of the study included 2,340 patients who were administered at a dose of dutasteride 0.5 mg / day, 2 more years. Those who took part in the second part of the study in 1188 patients have received the drug for two years, 1152 – placebo.
As early as the first month of dutasteride in patients noted reduction in the size of the prostate gland, which by the end of the reception at 24 months was reflected in statistically significant reduction of total prostate volume by 25.7%, while the volume of the transition zone – 20.4% . At the same time reduced the degree of urinary disorders that manifest decrease in total AUA-SI score of 4.5 points. In the placebo group the decrease was 2.3 points.
After receiving dutasteride top speed of urination increased by 2.2 ml / s. In the comparison group – only 0.6 ml / sec.
Over the two-year period of observation acute urinary retention occurred in 39 men taking dutasteride, which amounted to 1.8%. In the placebo group – in 90 persons (4.2%). Thus, the relative risk of acute urinary retention for dutasteride relative to placebo was 0.43 with a confidence interval of 95%. Consequently, the risk of acute urinary retention in patients with BPH dutasteride within two years is reduced by 57% (p <0.001).
The effect of the drug had an impact on the number of surgeries performed. During the observation period, 47 patients were operated during treatment with dutasteride (2.2%) and 89 (4.1%) receiving placebo. In the group of men treated with dutasteride, the risk of surgery for BPH decreased by 48%.
Analysis of 4-year results of applying dutasteride testified that the level of DHT as dosing continued to decline. By the end of the 4-year period, a decrease of 95.3%. This process is accompanied by a reduction in prostate volume, expressed in more than 2 years, although a statistically significant difference in the average volume of the prostate 2 and 4, the treatment is not observed.
The increase in the average rate of urination was also more pronounced in 4-year-old taking the drug than with 2-year-old, but statistically significant differences were observed. However, a reduction of the total score on a scale of AUA-SI was statistically significantly greater after 4 years of the drug (down 6.5 points) than in 2 (a decrease of 4.4 points).
The tolerability of dutasteride. With increasing duration of dosing frequency of complications such as erectile dysfunction, gynecomastia, decreased libido decreased. While taking the drug for 4 years, their number was reduced in comparison with the 2-year therapy.
Thus, treatment of dutasteride, which has an inhibitory effect on both types of 5AR, accompanied by the rapid (within two weeks) decrease DHT levels by the absolute majority of patients with BPH. This helped to reduce the size of BPH, reduced the risk of acute urinary retention and frequency of surgical procedures for BPH compared with patients receiving placebo. Based on the results of two-year studies noted that PSA levels decreased in the three months to 40%, and six – 50%. This should be considered when evaluating PSA levels in patients during treatment with dutasteride. Further research in this direction will help determine the value of dutasteride in the prevention of prostate cancer.