Combined treatment of benign prostatic hyperplasia, lower urinary tract symptoms and erectile dysfunction as a factor in improving the quality of life of men in elderly

UN predicts that by 2025 the planet will be living 8,3-8,5 billion. It is important to note that in the second half of XX century. humanity is rapidly aging. In 1950 the number of older people (aged 65 and older) was about 128 million, by 2000. their number reached 419 million (6.8% of the total population).

According to UN projections for 2050, the number of older people will account for about 1.5 billion, which would correspond to 14.7% of the general population [1]. Species specialization is preserved thanks to permanent effects of hormones, carrying the expression of specific loci of the genome coding for the synthesis of specialized proteins, peptides and other compounds which are characteristic for this type of tissue. Consequently, the progressive decrease in the rate of hormone secretion observed with aging, will inevitably lead to specific cells of hormone-dependent tissues despetsializatsii with loss of their function and development of the syndrome of multiple morphofunctional insufficiency. At the cellular level, this syndrome is manifested by progressive reduction of the withering away and functionally active cells, the predominant development of dystrophic, and sclerotic malignant process [3]. Increased life expectancy and an aging population leads to an increase in the number of patients with symptomatic benign prostatic hyperplasia (BPH), lower urinary tract symptoms (LUTS) and erectile dysfunction (ED). These features of the patients, as older age, comorbid conditions, require an effective and safe treatment relieves symptoms of the disease and improves quality of life [2]. Modern man in any age seeking to preserve their sexual function satisfying the quality of life.

In large population studies and in the placebo group, double-blind randomized studies traced the natural history of BPH. One such study - Olmsted county study - a population study over 12 years have seen a 2115 men 40-79 years of age. [8] At baseline, 26% of men aged 40-49 years had moderate or severe LUTS. At the age of 70-79 years the prevalence of LUTS was 46%. During follow-up showed signs of disease progression: the severity of LUTS worsened, increased prostate volume, deterioration urodynamic parameters. The average annual increase of symptom severity on the international scale of IPSS (International Prostate Symptom Score) was 0.18 points / year, an annual prostate volume increased an average of 1.9%, peak urinary flow rate (Qmax) in average annual decreases of 2.1 %. The overall incidence of AUR in 4 years was 2.7%. Only 3% of men were operated on for BPH. [9] These studies have shown that BPH progresses in the absence of therapy, and identifying patients at high risk of disease progression is the foundation to optimize their treatment [8]. European Association of Urology Guidelines for the treatment of benign prostatic hyperplasia (2004) argues that the goal of treatment is to improve lower urinary tract symptoms (LUTS) and quality of life of patients, prevention of complications associated with an increase in RV and obstruction, such as urinary retention and expansion of the upper urinary tract [6].

Drug treatment in the last decade has become a standard in the management of patients with symptomatic BPH in the absence of absolute indications for surgical treatment. There is still leading in the treatment of BPH are two classes of drugs: α1-blockers and inhibitors of 5α-reductase (5 AR) [9,10].

The dynamic component of bladder outlet obstruction due to increased activity of α1-adrenergic receptors (α1-AR), prostate, bladder neck and prostatic urethra, which leads to the spasm of smooth muscles of the lower urinary tract. The use of α1-blockers pathogenetically substantiated by a large number of α1-adrenergic receptors in the prostate and bladder neck, increased activity of sympathetic innervation of the pelvic level, changing the spatial position of the prostate due to the lack of disclosure of the bladder neck and the onset of turbulent urine flow in the prostatic urethra. α1-blockers significantly reduce the severity of irritative symptoms of BPH, regardless of the size of the latter [8]. Affecting the dynamic component of bladder outlet obstruction, they facilitate the obstructive symptoms. Numerous studies have demonstrated that rapid relief SNMN achievable with drugs of the selective α1-blockers. [5] However, the results of MTOPS suggest that α1-blockers have no effect on prostate volume and do not reduce the risk of AUR and surgery for BPH [ 9].

At present, alpha 1-blockers were used most frequently for the treatment of LUTS. They significantly reduce the severity of BPH symptoms irritative regardless of volume. [8], affecting the dynamic component of bladder outlet obstruction, they facilitate the obstructive symptoms of the disease and improve urination disorders. Two major factors of nocturia - reservoir function of the bladder and obstructive micturition at night are associated with sympathetic nervous system activity. Dual inhibition of 5 AR achieves rapid and sustained suppression of dihydrotestosterone (DHT) for 4 years. [10] Time of onset of effect: 1 month - a decrease of prostate volume and improvement in urine flow. Efficiency continues to increase significantly during chronic administration: 6.5 AUA-SI score after 4 years (compared with baseline), a constant and significant decrease in prostate [9,10]

Dutasteride also reduces the risk of AUR (57%) and the need for surgery (48%) compared with placebo. [9]

As a rule, the development of benign prostatic hyperplasia (BPH) reverses the usual way of life of men. They have to avoid going to the theater, cinema, sports outdoors, places without toilets. In addition, male elderly are often detected late androgenodefitsit, which leads to a decrease in sexual activity. [2] Age-related decrease in levels of free androgen in the age groups 50-59, 60-69, 70-79 and 80-89 years have seen a ( according to a study conducted in the U.S.) in 9, 34, 68 and 91% respectively. [6] After 30-40 years the level of testosterone is reduced by about 1-2% per year. In men aged 80 testosterone levels averaged about 40% of testosterone in the 25-year-old man. The frequency of symptomatic androgen deficiency of the age in men older than 30 years, ranging from 7 to 30%. [1] When androgen deficiency occurs in adult men, the clinical picture may be very bright, and worn, which makes the diagnosis. The patient has decreased libido, erection fails, there is a weakness, fatigue, depression, vasomotor disturbances of the type of tide and cognitive impairment. Characterized by reduced body hair in the pubic area, armpits, growth of beard and mustache with a decrease in the frequency of shaving, decreased muscle mass and strength, reducing the size of the testicles and prostate, gynecomastia, osteoporosis and reduced hematocrit. In assessing the impact of age-related changes in pancreatic function was shown that insulin-independent diabetes mellitus occurs in 15-20% of men aged 65-75 years and 40% of men older than 80 years. [4] developed peripheral insulin resistance state due to the increase of fat deposits on the anterior abdominal wall, reduced muscle mass and physical activity. It should be noted that the low level of testosterone in men can lead to insulin resistance. Insulin sensitivity is increased again with the introduction of testosterone from the outside [4].

Process that occurs in men with age and leads to hypogonadism, now known as ADAM (androgen deficiency of aging male) or PADAM (partial androgen deficiency of aging male - a partial androgen deficiency of older men). [7] The combination of the symptoms of BPH and erectile dysfunction, contributing to display each other, often leads to depression in male elderly. Modern and effective treatments for BPH also reduce testosterone levels, which often affects potency. Laboratory signs of androgen is the level of total testosterone below 12 nmoll. [7]

Materials and Methods. The research, which included a group of 200 men aged 40 to 80 years with IPSS ≥ 12, ≥ 30 prostate volume cm3, total PSA (prostate-specific antigen) 1.5-10.0 ngml, Qmax> 5 and ≤ 15 MLS MLS and the residual urine volume ≥ 125 ml. Within this group were divided into 3 groups of patients (A, B, C), which prevailed on the severity of the symptoms of BPH and ED SMNP, respectively. Treatment of patients of these groups included the effect on BPH and ED SMMP.

We undertook a survey of 151 men aged 40 to 80 years old, who turned to various experts advice clinics for 2008. For this purpose, we used a questionnaire ADAM (Androgen Deficiency in Aging Males questionnaire), which includes 10 questions listed below [7].

1. Do you have a decreased sex drive?

2. Do you feel lack of energy?

3. Do you feel the reduction in strength and endurance?

4. Reduced if your growth?

5. Mark whether you drop "enjoying life"?

6. Are you susceptible to feelings of sadness and anger?

7. Have the your erections less strong?

8. Have you noticed the recent decline of abilities in sports?

9. Do you feel the need for after-dinner sleep?

10. Have you noticed the recent deterioration in performance?

A positive answer to the 1st or 7th or on the issue and any 3 other questions can be suspected testosterone deficiency. Also studied the content of total testosterone (nmoll) in blood plasma, a specific radioimmunoassay.

Also included in the study of the questionnaire Hospital Anxiety and Depression Score (HADS), productivity (modified Work Limitation Scale, mWLQ) [7]. The results of HADS> 8 indicated the possibility of anxiety and depression levels ≥ 11 indicated the presence of anxiety and depression. It is noted that in patients after 40 years is often pointed out the problems with erectile dysfunction, both in the presence or absence of BPH. Often this is due to the presence of the metabolic syndrome. Patients with metabolic syndrome are at high risk of coronary heart disease, peripheral vascular disease and type 2 diabetes.

To identify links with the metabolic syndrome and erectile dysfunction in men with hypogonadism have been allocated a group of 30 patients with metabolic syndrome. Metabolic syndrome was exposed on the basis of the criteria American Heart Association (AHA) [7]. Also among the studied patients allocated to group B of 60 people aged 40-75 years with erectile dysfunction and LUTS and International Prostatic Symptom Score (IPSS)> 8. These patients were selected for the study of a combination of a combination of alpha blockers and inhibitors of 5-phosphodiesterase. The survey was conducted before treatment and after 12 weeks of therapy. Patients were treated with sildenafil (In-Car) 50 mg (20) or tamsulosin (Omnic Okas) 4 mg (20 persons) or a combination of these drugs (20). Omnic-Okas was selected us as the base of the drug due to the fact that the slow, constant and independent of food intake and absorption of the release of his (lack of peak concentration) reduces the risk of adverse events and expressed allows for better control and blood pressure and symptoms of BPH. A group of patients C (30) with severe manifestations of benign prostatic hyperplasia (prostate volume ≥ 45 cm 3, Qmax ≤ 12 MLS, residual urine volume ≥ 125 mL), extracted from the total number of patients who received dutasteride (Avodart) in standard dosages 0.5 mgsut.

All participants answered questions on erectile function according to the International Index of Erectile Function (IIEF-EF) [1] and the IPSS. Significant differences between the maximum (Qmax) and mean flow velocity (Qave). The study included laboratory tests (Uroflowmetry) and answers patients' questions. Statistical analysis was performed using one-way ANOVA: Differences between groups were a confidence level p4. All the patients before the first treatment was determined by total and free PSA, all of the ratio of free and total PSA greater than 0.21.

Results and discussion. When completing the questionnaire, HADS (151chelovek) more than 65% of surveyed men suffering from BPH and ED SMNP, noted the level of HADS ≥ 8 on anxiety and depression, and more than 40% indicated the level of ≥ 11 on anxiety and depression.

Table 1. Effect of BPH-LUTS in combination with the ED and on anxiety, depression, and productivity

p <0.0001dlya all indicators

The use of dutasteride in the group reduced the volume of BPH and improve urine flow after 3 months, which improved the quality of life after 3-4 weeks of admission.

Table 2. Patients treated with dutasteride (n = 30) F = 4,3

Investigation of total testosterone (group B) in the age group 40-50 years (12) found levels of 17.5 2.3 nmoll, androgenodefitsit detected in every four men. At the age of 51 to 60 years (14) androgenodefitsit found one in three men, the average content of total testosterone 15,11,4 nmoll. At the age of 61-70 years (14), the average content of total testosterone 13,31,5 nmoll, androgenodefitsit set at 9. In the age group 71-80 years (10), the average content of total testosterone 12,31,1 nmoll, androgenodefitsit installed in 8 patients (80%). When you receive a 5AR blocker testosterone levels in each age group was reduced by another 4-12%, which exacerbates the symptoms of erectile dysfunction, although the manifestation of improved LUTS. It is noteworthy that the issues of potency more troubled urban residents aged 40 50 years (41%) and rural residents aged 50 60y.o. (38%). After 60 years in 64% of the respondents quality of life was associated more with the severity of the manifestations of SMNP. However, 21% of men after the age of 70 and 14% of men after 80 years of age, sexual function is marked as a major factor in quality of life. And 66% of them - men who live in rural areas, and men without higher education and engaged in physical labor.

In studying the relation of the metabolic syndrome (group A) with ED, the following data: the average age of men was 65 years (41-80), 41% of patients had metabolic syndrome according to the criteria AHA (≥ 3 of 5: waist circumference, elevated triglycerides, cholesterol , hypertension, and low tolerance to carbohydrates) (Table 3).

Table 3. American Heart Association criteria for identifying metabolic syndrome in the study group patients.

Low testosterone was detected in 26% of patients with ED and was observed in patients who had and did not have metabolic syndrome. 48% of patients were smokers or former smokers. Angina or liver disease, indicated 15% and 9% respectively. Testicular volume less than <15 cm was detected in 13% bilaterally and in 6% of patients with one of the parties.

We have identified a control group of patients (group D), in which the prostate volume was low, the severity of LUTS secondary or small, and the problem of ED pronounced. The study included a group of 30 men aged 60-70 years, the volume of the prostate which was, on average, 31 cm 3 (20-53 cm), the results of IPSS - 10.0 points (0-30), serum total PSA 1.4ngml (0, 2-7,2), testosterone, on average, 9.4 nmoll (5-12). The study took 12 months. After using the substitution testosteronterapii AndroGel prostate volume increased, on average, by 5.5 cm (20-58), the level of IPSS decreased from 2 to 8 (1-28), PSA decreased an average of 2.1ngml (0.3-13.8) and the level testosterone rose an average of 21.1nmoll (13-36.8). After 12 months of research prostate volume, as measured by TRUS, increased by 3cm (21-90), IPSS by 8.3 (0-19) and PSA of 2.3 ngml (0.4 -7.5).

In combination therapies of alpha blockers and inhibitors of 5-phosphodiesterase (5FDE) in Group B - IIEF-EF tended to improve only when receiving tamsulosin (Omnic-Okas) + 15.8%, only sildenafil (In car) + 37.6%. The best results were given a combination of both drugs (Omnic-Okas + In-car) + 39.5%. Qmax improvement was noted in both groups, but patients receiving combination therapy reported an improvement of 30% when treated only as tamsulosin - 22%, while receiving only sildenafil - 10%. IPSS improved significantly while taking tamsulosin at 27.2%, and in combination therapy - at 41.6%. IPSS improvement in the treatment of sildenafil noted 9.6%, but it was not statistically significant. Monitoring of blood pressure showed no statistically significant change.

Findings

1. Использование дутастерида (аводарта) позволяет уменьшить объем ДГПЖ и улучшить качество жизни уже после 3-4 недель приема, а также улучшить поток мочи уже через 3 месяца , однако может снижать потенцию, особенно на фоне позднего гипогонадизма.

2. С помощью вазоактивных свойств альфа-1-адреноблокаторов достигается восстановление резервуарной функции мочевого пузыря т.к. циркуляторная гипоксия рассматривается в качестве ведущего звена патогенеза никтурии.

3. Пероральная система ОCAS╝ является более селективным препаратом по отношению к α1А-адренорецепторам и α1D-адренорецепторам, расположенным в нижних мочевых путях, чем к α1B- адренорецепторам, что объясняет более высокое соотношение ее эффективности/безопасности по сравнению с другими антагонистами α1-АР

4. Мужчинам старше 40 лет необходимо проводить гормональный скрининг для выявления возрастного андрогенного дефицита, т.к. ранняя диагностика и лечение предотвращают развитие достаточно серьезных осложнений, в т.ч. сердечно-сосудистых заболеваний и остеопороза, а также развитие метаболического синдрома в целом.

5. Цель заместительной терапии в лечении возрастного андрогенного дефицита состоит в нормализации концентрации сывороточного тестостерона до физиологического уровня и в минимизации проявлений гипогонадизма.

6. У мужчин с поздним андрогенодефицитом после заместительной андрогенотерапии Анрогелем╝ в течение 1 года отмечена тенденция к увеличению размеров простаты без негативного влияния на симптомы нижних мочевых путей.

7. Терапия тестостероном не должна назначаться отдельными курсами, прерываться (если не возникли абсолютные противопоказания), не следует переходить на пониженные (╚поддерживающие╩) дозы тестостерона, так как это приводит к возобновлению симптомов андрогенного дефицита.

8. Комбинация препаратов тамсулазин (Омник-окас) и силденафил (В-кар) показала достоверное улучшение показателей урофлоуметрии, IPSS и IIEF-EF у пациентов, страдающих СМНП и ЭД. Все пациенты также отметили улучшение качества жизни.

9. Силденафил (В-кар) может уменьшить выраженность симптомов нижних мочевых путей (СНМП) у больных с ДГПЖ за счет прямой релаксации детрузора. Этот эффект не зависит от ингибирования 5ФДЭ.

10. У больных старческого и пожилого возраста, страдающих ДГПЖ с проявлениями СНМП и ЭД, в комплексной терапии может использоваться комбинация ингибиторов 5ФДЭ, антагонистов α1-АР, блокаторов 5АР и препаратов тестостерона в различных сочетаниях соответственно показаниям.

11. Использование комплексной терапии позволяет улучшить качество жизни мужчин, независимо от их возраста, без негативных последствий для здоровья в целом.

References:

1. Аляев Ю.Г., Григорян В.А., Чалый М.Е. нарушение половой и репродуктивной функции у мужчин.-М.:Литература,2006.

2. Дедов И.И., Калиниченко С. Ю. Возрастной андрогенный дефицит у мужчин.≈ М.: Практическая медицина, 2006.

3. Козлов С.А. Состояние половой функции у больных аденомой предстательной железы. Дис.канд.мед.наук,М.,2005

4. Мазо Е.Б.и соавт. Эректильная дисфункция у больных сахарным диабетом: современные методы лечения. Фарматека, -2004.-№5.-С.42-44.

5. Пушкарь Д. Ю., Сегал А.С. // Фарматека.≈ 2006.≈ № 15.≈C.62≈65.

6. EAU BPH guidelines. Madersbacher S et al. Eur Urol 2004; 46: 547√554.

7. 10th World Congress of the International Sosiety for Sexual and Impotence Research Venue √Monreal, Canada Date-September 22-26, 2002

8. Chatelain (ed) In: BPH International Consultation. Health Publication, 2001.

9. Debruyne F et al. Eur Urol 2004; 46: 488√495.

10. GlaxoSmithKline, Avodart SPC, September 2005.