Age-related androgen deficiency (VAD, male menopause, age-related hypogonadism, PADAM syndrome, ADAM) is a syndrome caused by an age-related decrease in blood testosterone levels.
There are the following forms of VAD:
- Relative VAD - androgen level is within the normal range (more than 12 nmol / l). VAD is caused by a decrease in the level of androgens relative to previous years.
- Absolute VAD - the level of sex hormones is less than normal and is less than 12 nmol / l.
Frequency of pathology
According to some authors, the frequency of pronounced androgen deficiency in men older than 30 years varies from 7% to 30%. The percentage of patients with VAD is highly dependent on the age group to which the man belongs. For example, men aged 40-49 years, suffer from VAD twice as often as men of the age group 30-39 years.
Fig.1 - Age dynamics of testosterone secretion in men.
The timing of the offensive WAD
In the male climax, in contrast to the female, there is no pronounced decrease in the production of androgens, and therefore the age of diagnosis of VAD can vary from 35 to 70 years. Why is there so much variation? Primary is associated with the initial level of the hormone at the age of its peak production (20-25 years), with the so-called sexual constitution of a man (Fig. 2).
Fig.2 - Individual dates of onset of age-related androgen deficiency depending on the sexual constitution (testosterone level at 20) 1 - a man with a weak sexual constitution, 2 - a man with an average sexual constitution, 3 - a man with a strong sexual constitution.
Men, whose hormone levels during the peak period of their secretion are closer to the upper level (33 nmol / l), have a stronger sexual constitution, and with a decrease in testosterone production (1% per year after 30 years), they later note symptoms of VAD, and in consequence, they can only have a relative form of androgen deficiency.
Men who have a low sexual constitution, more quickly notice the effects of a natural decrease in androgens. Moreover, in such men, the absolute form of age-related hypogonadism is more often diagnosed earlier.
Thus, men have a strong individual indicator of the onset of androgen deficiency, due to its sexual constitution.
In addition to the sexual constitution of a man, the following chronic diseases can lead to early androgenic deficiency:
In men with these chronic diseases, there is a decrease in testosterone levels by 10–15% compared with healthy men of the same age, which approximates the time taken to reduce the secretion of sex hormones by an average of 5–7 years (Fig. 3). But at the same time, the decrease in the level of androgens occurs at the same rate as in healthy men.
Fig. 3 - The effect of chronic diseases on the onset of VAD.
Pathogenesis and clinical manifestation of VAD
The reasons for the age-related decline in androgens are:
- a decrease in the number of Leydig cells located in the testicles responsible for the synthesis of sex hormones;
- a decrease in the density of receptors for luteinizing hormone (LH);
- reduction of enzymes of the metabolic pathway of testosterone synthesis;
- dysregulation in the hypothalamus-pituitary system;
- genetic predisposition associated with the amount of GAG-repeat in the androgen receptor gene.
Table 1 - Clinical manifestation of VAD
|ORGANS AND SYSTEMS||CLINICAL SIGNS|
|The cardiovascular system|
|Genitourinary system and sexual function|
Diagnosis of VAD
- Collecting history. The presence of characteristic complaints for several years, filling in the self-help questionnaire;
- Physical examination. Diagnosing symptoms of androgen deficiency, such as sagging of the skin, loss of its elasticity, an increase in adipose tissue mainly in the upper torso, a decrease in muscle mass and muscle flabbiness, gynecomastia, and reduction of hair on the body and limbs (see table 1);
- Laboratory diagnosis. The level of total testosterone is less than 12 nmol / l, and the indicators of SHBG are increased.
- Instrumental examination. Diagnosing osteopenia and osteoporosis is a decrease in bone density.
The first attempts to treat androgen deficiency in older men were made as early as 1940. However, they were not widely used among doctors, for some reason: first, the drugs of that time did not have all the effects of natural testosterone, and, moreover, had pronounced side effects and toxic effects on the body; secondly, the prevailing opinion of doctors about the physiology of the processes taking place during aging was another reason to refuse substitution therapy.
The emergence of new, more advanced testosterone drugs, as well as new data on the positive effect of androgens and the significant role of androgen deficiency in the aging process of the male body, prompted the interest of doctors and patients in hormone therapy for men with age-related hypogonadism.
However, in spite of the acknowledged fact of the need for hormone replacement therapy in VAD, there are still no clear indications for its use.
Approaches to hormone therapy for VAD
The treatment of age-related hypogonadism is aimed at normalizing the level of androgens in the serum of a man. There are two approaches in the treatment:
- hormone replacement therapy;
- stimulating therapy of chorionic gonadotropin (CG).
Table 2 - Types of hormone therapy for men
|Substitution Therapy||STIMULATING THERAPY|
|Application||It can be used in all forms of androgen deficiency ( primary or secondary hypogonadism )||It is used only in the treatment of secondary forms of hypogonadism , when testicular function is preserved.|
|Effect on the synthesis of sex hormones||Exogenous androgen administration can inhibit the production of your own sex hormones.||Stimulation of androgen synthesis|
|Effect on spermatogenesis||Reversible inhibition of spermatogenesis during therapy||Does not inhibit spermatogenesis|
|Effect on testicle size||Reversible decrease in testicles during therapy with injectable form of the drug||It does not cause a decrease in the testicles when used, moreover, it can lead to the normalization of the initial size of the reduced testicles, after applying the injection forms of the drug|
Choosing a hormone therapy method
As can be seen from the table. 2 replacement and stimulating therapies have their advantages and disadvantages.
Therapy with HCG is a new form of hormone therapy, and has a significant advantage: stimulation of the production of its own sex hormones and spermatogenesis. To identify the possibility of using CG in the treatment, CG test is made: after a three-day injection of the drug at a dose of 1500 IU, the patient should have a testosterone increase of at least 50% the next day. The drug has only an injection form. The frequency of injections is 2-3 times a week, starting with 1500 IU and is conducted in courses of one month, followed by a month break.
Replacement therapy is a proven and popular method for the treatment of androgen deficiency. The main advantages of replacement therapy consist, firstly, in a variety of forms of drug administration (see hormonal drugs for men ), secondly, in the convenience of therapy (thanks to the injection drug Nebido, which has a therapeutic effect for 10-14 weeks), third, substitution therapy will be effective regardless of the reasons for the low level of androgens.
Do I need to resort to hormone therapy in old age?
Modern medicine has the latest drugs that meet stringent conditions, as well as extensive experience in their use. Despite this, questions remain about the effect of substitution therapy on some systems of the male body. The use of androgens in prostate cancer is the most controversial. Although there is not a single study proving a clear relationship between the pathological effects of androgens on the prostate, today prostate cancer is an absolute contraindication to the use of androgens and stimulating therapy.
On the other hand, there are accurate data on the positive effect of androgens on:
- bone mineralization;
- muscle mass and strength;
- adipose tissue;
- sexual function.
As a result, using the androgen therapy, older men can avoid the diseases characteristic of this period and significantly improve the quality of life.
Today, older men have the opportunity to extend the days of their youth and avoid the many ills of old age. Our fathers or grandfathers did not have such an opportunity, but they lived in more “health-friendly” conditions. But whatever optimistic predictions of hormone therapy, the patient always has a choice.
Dedov I.I. "Age androgen deficiency in men."