Cardiovascular diseaseage-related androgen deficiency in male population

Summary

The aim of the study is to research the prevalence of androgen deficiency in ageing men (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. The Clinical diagnosis of ADAM is based on the “aging male questionnaire’’, or the AMS-questionnaire. ADAM, which often develops as a results of concomitant somatic and neuropsychiatric diseases. The article provides information that 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. 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:
Age-related – androgen deficiency – cardiovascular disease – male gonadal function – polymorbidity – testosterone

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, 2)}.

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 affect the secretory function and homeostasis of the male sex hormones⁽³⁾.

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⁽⁴⁾.

Objective. The aim of this research is to study the prevalence of ADAM with concomitant cardiovascular disease and the development of clinical and laboratory-biochemical criteria for the diagnosis, in terms of 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 a sexologist with sexual dysfunctions and these patients were also registered with cardiac dysfunctions which were graded as follows: 1–3 stage and 2–3 degrees risk of complications – 59 people, 1–2 degrees obesity – 41 patients, compensated diabetes mellitus – 32 patients, pro-atherogenic dyslipoproteinemia – 54, metabolic syndrome – 62 people; erectile dysfunction – 66 cases.

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 %), 56–60 years – 37 patients (11.8 %), 61–65 – 43 patients (13.7 %), 66–70 years – 47 persons (14.9 %) (Table 1).

It considered 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.

Interpretation of results by points: from 0 – complete absence of symptoms, up to 4 – highly symptomatic).

Laboratory diagnosis of ADAM was 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, bordeline decrease, decrease (Table 2).

For the statistical processes of the study results, the method of use was assessing the significance of differences between two sets by applying the criterion of t-Student. The difference in indicators is true when t³ 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 was carried out using the program «Stat graphics plus for Windows», the version 7.0.

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, „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 complaints by patients in the sexual sphere the normal values of fractional testosterone were observed in 18.2 % cases, bordeline values – 81.8 %. The content of total testosterone in the latter 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).

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.

ADAM is no exception, as it often develops as a result 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, characteristic 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 years 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 oestrogen i.e. testosterone because it is a major source of oestrogen. Oestrogens have direct protective effects on cardiomyocytes. Age associated reduction of the testosterone concentration in turn reduce oestrogen, which in turn leads to the overall reduction of the efficiency of cardio protection ^(5,6).

Androgens have a positive influence on the haemostatic 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-aggregation properties of prostaglandin

Testosterone, as shown in several studies, has antiatherogenic effects. Especially low levels of testosterone are associated with a high degree of occlusion of coronary artery. These are the pathogenetic relationships 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.

Ilnitski Andrei MD, PhD, DSc, Prof¹, Pozarskis Anatolijs²

¹Belarusian Association of Gerontology and Geriatrics, Vitebsk, Belarus; The Open Institute of Human and Nature, Vilnjus Lithuania

²Stradynja University, Riga, Latvia