БИОГЕРОНТОЛОГИЯ

УДК 616.65-02

Age-related  androgen deficiency in Мen and cardiovascular diseases

Pozharskis A.¹, Ilnitski A.N.²

¹Stradynja University, Riga, Latvia, e-mail: pozharskis@mail.ru

²Belarusian Republican Association of Gerontology and Geriatrics, Vitebsk, Belarus,  e-mail: nimcgerontologija@mail.ru

In last year the very big interest to the problem of androgen deficiency take place (ADAM). The purpose of this study was to examine the VAD men in connection with the development of their cardiovascular disease and subsequent development of clinical and laboratory biochemical criteria to reduce gonadal function in this patient group. The study included 314 patients. The development of cardiovascular disease VAD is starting to influence the age of 40-50 years. Biochemical criteria for VAD in the presence of cardiovascular disease characterized by average levels of total testosterone level 2,28-2,29 ng / ml in serum free testosterone - 60,1-68,1 pg / ml. ADAM  in association with cardiovascular diseases, is  characterized by symptoms such as general weakness, difficulty in falling asleep and daytime sleepiness, irritability, panic attacks, the formation of  sense of" lifelessness’’, as well as  decreased libido, decrease in morning erections,decrease in   frequency of sexual activity.

Keywords: androgen deficiency, cardiovascular pathology.

ВОЗРАСТЗАВИСИМЫЙ АНДРОГЕННЫЙ ДЕФИЦИТ У МУЖЧИН И КАРДИОВАСКУЛЯРНЫЕ ЗАБОЛЕВАНИЯ

Пожарскис А. ¹, Ильницций А.Н ².

¹Университет Страдыня, Рига, Латвия, e-mail: pozharskis@mail.ru

²Белорусское республиканское геронтологическое общественное объединение, Витебск, Беларусь,                   e-mail: nimcgerontologija@mail.ru

В последние годы наблюдается повышенный интерес к проблеме возрастного андрогенного дефицита (ВАД). Цель данного исследования состояла в изучении ВАД у мужчин во взаимосвязи с развитием у них кардиоваскулярной патологии и последующей разработке клинических и лабораторно-биохимических критериев снижения гонадной функции у этой группы пациентов. В исследование было включено 314 пациентов. На развитие сердечно-сосудистой патологии ВАД начинает оказывать влияние в возрасте 40-50 лет. Биохимические критерии ВАД при наличии сердечно-сосудистой патологии характеризуются средними уровнями общего тестостерона на уровне 2,28-2,29 нг/мл в сыворотке крови, свободного тестостерона – 60,1-68,1 пг/мл. ВАД в ассоциации с кардиоваскулярной патологией характеризуется такими симптомами как общая слабость, утомляемость, сложностью в засыпании, дневной сонливостью, ощущением потери смысла жизни, вкупе со снижением либидо, уменьшением утренней эрекции, степени сексуальной активности.

Ключевые слова: андрогенный дефицит, кардиоваскулярная патология.

Introduction.

In recent years, much attention is paid to the reproductive health of men in all age groups. This is due to many factors of which increase in male infertility is an example, very much noticed in the general population especially in people with endocrine disorders, disorders that lead to a change in behaviour, and the development of associated somatic and neuro-psychiatric diseases [1, 3].

Another important aspect is the immense influence of somatic diseases on the male reproductive system. Not ruling out the high prevalence of harmful habits such as smoking, high alcohol consumption and Many forms of psychoactive substance addiction, which adversely affects the secretory function and homeostasis of the male sex hormones [2, 4, 5, 6].

The actual question of much relevance is the prevalence, early diagnosis and treatment of androgen deficiency in ageing men (ADAM) suffering from the most common group of diseases associated with the cardiovascular system.

The aim is the study of the prevalence of ADAM with concomitant cardiovascular disease and the development of clinical and laboratory-biochemical criteria for the diagnosis in the decrease of male gonadal function in this group of patients.

Materials and methods. The study included 314 patients, 248 (79.0%) of them had no problems  of sexual nature and were patients of general practitioners who voluntarily completed the AMS-questionnaire, the remaining patients in this case, 66 men (21%) visited the sexologist with sexual dysfunctions and these Patients were also registered with cardiac dysfunction which included: 1 - 3 stage and 2 - 3 degrees risk of complications – 59 people, 1 - 2 degrees obesity – 41 patients compensated diabetes mellitus- 32 patient. Pro-atherogenic dyslipoproteinemia – 54, metabolic syndrome – 62 people; erectile dysfunction – 66 cases (table 1).

The patients aged from 40 to 70 years, the quantitative category of patients with different age groupings were as follows: 40 - 45 years - 28 patients (8.9%), 46 - 50 years -35 patients (11,2%), 51 – 55 years – 41 patients (13,1%), 56 - 60years – 37 patients (11,8%), 61 – 65 – 43 patients (13,7%), 66 - 70 years – 47 persons (14,9 %).

  Table 1

Age and  nosological  characteristics of patients used in this study

The Clinical diagnosis of  ADAM is  based on the "aging male questionnaire", or the AMS-questionnaire. It conceded  the following items: general patient  conditions; joint-muscle pain, sweating, insomnia,drowsiness, fatigue, irritability, restlessness, panic attacks, impatience; muscle weakness, depression,  the feeling of  "worthlessness", a feeling of emptiness, low growth of  facial hair, decreased libido, decrease in intensity and quality of erections ,decrease in performance and  number of sexual encounters.

Results interpretion   of points: from 0 - complete absence of symptoms  ,up to 4 -  were very symptomatic). Laboratory diagnosis of ADAM were performed  using the ELISA method  test systems ,with the help of a photometer «Multiskan Plus» at a wavelength of 450 nm.  The levels of total and free testosterone were determined, these were ranked  into three categories - normal, marginal  decrease,  decrease (table 2).

For  the statistical  processes of the study  results applied, the method of assessing the significance of  differences between  two sets by applying the criterion of t-Student. The difference in indicators is true when t ³  2, in this case, p <0.05. Student's  t criterion is used to identify  the main differences between the quantitative characteristics of the study process. During the statistical  calculations of the data, values were put into tables using <<Excel>>, mathematical and statistical processing were carried out using the program «Stat graphics plus for Windows»,  the version 7.0.

Table 2

Ranking  the total and free testosterone levels, depending on its degree of reduction in  the blood serum

Results.

According to the survey using a special scale, ADAM was detected in 80.7% of cases. The distribution of patients with ADAM  was of uniform nature up to 60 years:40 - 50 years - 42,0%, 51 - 60 years - 50,0%, 61 - 70 years - 8,0%.

Clinical symptoms of  ADAM  was of the following character: "decline in general state" 3,3+0,01 points,"increase  in exhaustion" - 2,8+0.01 points, "muscular weakness" - 2,9+0,02 points; "depression" - 2,8+0,02  points, the sense of "everything in life is behind" - 2,6+0,01 points, feeling "empty" - 2,8+0,01  points, the "reduce hair growth" -2,7+0,02  points, "reduction in  the frequency of sexual intercourse "- 2,9+0,02  points, a decrease of "morning erection" - 2,8 0.02 points, decrease in "libido " - 2,8+0,01points,p<0,05.

Testosterone levels in different clinical situations were as follows. It was noticed  that in the absence of  complains by patients in the sexual sphere  the normal values of fractional  testosterone were  observed in 18.2%  cases, marginal values - 81,8%. The content of total testosterone in the later case was 2,33+0,2 ng/ml , free testosterone ,4+5,0 pg/ml.

In the presence of  complaints of sexual nature normal testosterone was noted in 9.1%, marginal level values  - 18,2% , a decrease in testosterone serum content - 72,7%.

In the marginal hormonal levels the average values were as follows: total testosterone -  2,35+0,1  ng / ml, free testosterone 67,9+4,5 pg / ml, in decreased levels :total testosterone - 2,28+0,2 ng / ml, free testosterone -64,1+4,1  pg / ml (table 3).

Table 3

Testosterone levels in men with metabolic syndrome and sexual dysfunction

Discussion.

In recent years, considerable attention was  paid to polymorbidity  and common aggravation of diseases. It is from these positions that we consider the question of progression, diagnosis and treatment of diseases in persons aged 50 years and over. There is no exception  to ADAM, which often develops as a results of concomitant  somatic and neuropsychiatric diseases.

The effects of somatic  and  psycho-neurological  pathology  in  ADAM  can  significantly  reduce both the quality of diagnosis of disease and the effectiveness of prevention likewise the treatment programs. It should be noted that, in general, ADAM  occurs in persons aged over 50 years, and at this age there is an accumulation  of a number of age-related and pathological changes that contribute to the alteration  of the disease progress.  These features include:

1. There is an overall increase in pathological conditions, when there is a corresponding increasing number of nosological forms, dominated by chronic diseases, characteric of polymorbidity.     

2. Peculiar etiological features in diseases of the elderly: is affected by the internal environmental factors (age-related changes in organ systems, metabolism, and regulation) increases the aggressiveness of pathogens and reduces the resistance of older people.

3. Peculiarity of the pathological Pathogenesis in the middle and old age, quite often changes the specific pathogenic mechanisms of disease.

4. Clinical features of disease in  the elderly: the diseases are usually atypical – less symptomatic, latent, diseases masks itself as other diseases and are often very severe, more often disabling, more likely to relapse, and often the transition of acute forms to chronic, shorten latent period of the disease; leading to frequent complications, reduced time  for the development of complications, by increasing the functional decompensation of the affected system, thus the reduction of life expectancy of the patient.

Thus, patients above 50 year of age with cardiovascular disease are prone to the development of ADAM. On the other hand, testosterone deficiency can also causes development of a vicious circle within the cardio-vascular diseases cycle. Therefore the influence of androgens on the cardiovascular system is very significant.

It has been proven that there is a direct effect of androgens on the vascular wall, this entails in the modulation  of activity in the  potassium channels and stimulating the  secretion of nitric oxide. This causes  vasodilating  effect in the vessels.  The Positive effect of testosterone  mainly undertaken by estrogen i.e.  testosterone because it is a major source of estrogen. Estrogens have direct protective effects on cardiomyocytes ,Age associated reduction of the testosterone concentration in turn  reduce estrogen, which in turn leads to the the overall  reduction of the  efficiency of cardio protection.

Androgens  have a positive influence on the hemostatic system. This is reflected in  its ability to reduce the level of fibrinogen, proconvertin clotting factor VII. at the same time a number of studies have shown that testosterone seems to have pro-aggregation properties due to its ability to decrease the activities of cyclooxygenase and to  reduce anti aggregatory properties of prostaglandin 

Testosterone, as shown in several studies, has  antiatherogenic  effects.  particulaly, low level of testosterone is associated with a high degree of  occlusion of  coronary artery. These are the pathogenetic relationship between cardiovascular disease and ADAM `.These were   confirmed in  our studies and put  into practice by the development   of diagnostic algorithms ADAM   for  the most common disease of the heart and blood vessels.

Conclusion. 

In the study of cardiovascular disease ADAM occurs from the age of 40 – 50 years. ADAM  in association with cardiovascular diseases, is  characterized by symptoms such as general weakness, difficulty in falling asleep and daytime sleepiness, irritability, panic attacks, the formation of  sense of "lifelessness", as well as  decreased libido, decrease in morning erections,decrease in  frequency of sexual activity.  Biochemical characteristics of ADAM  in the presence of cardiovascular disease is the average level of total testosterone within the range 2.28 - 2.29 ng / ml, free testosterone - 60,1 - 68,1 pg / ml.

Список литературы.

1. Cas L.D. Prevention and management of chronic heart failure in patients at risk / L.D. Cas, M. Metra, S. Nodari [et al.] // American Journal of Cardiology. – 2003. - Vol. 91, № 9A. – Р. 10F-17F.
2. Clopper P.R. Psychosexual behavior in hypopituitary men: a controlled camparison of gonadotropin and testosterone replacement / P.R. Clopper, M.L. Voorhess, M.H. MacGillivray // Psychoneuroendocrinology. – 1993. - №. 18. – Р. 149–161.
3. Collin R. Blood pressure, antihypertensive drug treatment and the risk of stroke and of coronary heart disease / R. Collin, S. MacMahon // Br. Med. Bull. – 1994. - Vol. 50, № 3. – Р. 272–298.
4. Mauras N.Testosterone deficiency in young men: marked alterations in whole body protein kinetics, strength, and adiposity / N. Mauras, V. Hayes, S. Welch // J Clin. Endocrinol. Metab. – 1998. - №. 83. – Р. 1886 – 1892.
5. Stuckey B.G. Sildenafil citrate for treatment of erectile dysfunction in men with type 1 diabetes: results of a randomized controlled trial / B.G. Stuckey, M.N. Jadzinsky, L.J. Murphy // Diabetes Care. – 2003. - Vol. 26, № 2. – Р. 279 – 284.
6. Yassin A.A.Treatment of sexual dysfunction of hypogonadal patients with long-action testosterone undecanoate (nebido) / A.A. Yassin, F. Saad // World J. Urol. – 2006. - Vol. 24, № 6. – Р. 639 – 644.

References.

1. Cas L.D., Metra M., Nodari S. et al. American Journal of Cardiology. 2003, Vol. 91, no. 9A, pp. 10F-17F.
2. Clopper P.R., Voorhess M.L., MacGillivray M.H. Psychoneuroendocrinology. 1993, Vol. 18, pp. 149–161.
3. Collin R., MacMahon S. Br. Med. Bull. 1994, Vol. 50, no. 3, pp. 272–298.
4. Mauras N., Hayes V., Welch S. J. Clin. Endocrinol. Metab. 1998, Vol. 83, pp. 1886 – 1892.
5. Stuckey B.G., Jadzinsky M.N., Murphy L.J. Diabetes Care. 2003,Vol. 26, no. 2, pp. 279 – 284.
6. Yassin A.A., Saad F. World J. Urol. 2006, Vol. 24, no. 6, pp. 639 – 644.

1.	Cas L.D. Prevention and management of chronic heart failure in patients at risk / L.D. Cas, M. Metra, S. Nodari [et al.] // American Journal of Cardiology. – 2003. - Vol. 91, № 9A. – Р. 10F-17F.
2.	Clopper P.R. Psychosexual behavior in hypopituitary men: a controlled camparison of gonadotropin and testosterone replacement / P.R. Clopper, M.L. Voorhess, M.H. MacGillivray // Psychoneuroendocrinology. – 1993. - №. 18. – Р. 149–161.
3.	Collin R. Blood pressure, antihypertensive drug treatment and the risk of stroke and of coronary heart disease / R. Collin, S. MacMahon // Br. Med. Bull. – 1994. - Vol. 50, № 3. – Р. 272–298.
4.	Mauras N.Testosterone deficiency in young men: marked alterations in whole body protein kinetics, strength, and adiposity / N. Mauras, V. Hayes, S. Welch // J Clin. Endocrinol. Metab. – 1998. - №. 83. – Р. 1886 – 1892. 
5.	Stuckey B.G. Sildenafil citrate for treatment of erectile dysfunction in men with type 1 diabetes: results of a randomized controlled trial / B.G. Stuckey, M.N. Jadzinsky, L.J. Murphy // Diabetes Care. – 2003. - Vol. 26, № 2. – Р. 279 – 284. 
6.	Yassin A.A.Treatment of sexual dysfunction of hypogonadal patients with long-action testosterone undecanoate (nebido) / A.A. Yassin, F. Saad // World J. Urol. – 2006. - Vol. 24, № 6. – Р. 639 – 644.

Пожарскис А., Ильницкий А. Н. ВОЗРАСТЗАВИСИМЫЙ АНДРОГЕННЫЙ ДЕФИЦИТ У МУЖЧИН И КАРДИОВАСКУЛЯРНЫЕ ЗАБОЛЕВАНИЯ // ГЕРОНТОЛОГИЯ. – 2013. – № 3;
URL: gerontology.esrae.ru/ru/3-25 (дата обращения: 23.12.2024).

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