The appearance of a man, his libido, muscular strength and even metabolism depend on the balance in the body of sex hormones (androgens and estrogens). The level of these biologically active substances is influenced by many factors. Of great importance is heredity, age, physical exertion, the presence of bad habits, excess weight, etc. The concentration of androgens depends not only on the amount of their synthesis in the testicles and the reticular layer of the adrenal cortex. In many ways, the balance is also determined by the work of the enzyme systems of the body. The greatest role in this matter belongs to the aromatase enzyme.
What is this enzyme
Aromatase is an enzyme of the hemoprotein family. A large amount of aromatase is synthesized in fatty tissue, adrenal glands, liver, muscles, endothelium, prostate. The main function of the enzyme is the conversion of androgens into estrogens. Under the influence of aromatase, testosterone and androstenedione are modified to estradiol and estrone.
The enzyme is histospecific, that is, its structure in different tissues may differ. For example, aromatase in the liver has the ability to transform into estrogen not only androgens, but also other steroids.
The role of aromatase in men
The enzyme increases the level of female steroids in the body, while reducing the concentration of androgens. Aromatase is irreversible (the reaction proceeds only in one direction) turns testosterone and androstenedione into estrogens. In men, with the help of this enzyme, a large part of estrogen is produced (about 75%).
Figure 1 - The conversion of testosterone to estradiol by the action of the enzyme aromatase.
Normally, the level of estrone and estradiol should remain low enough so that feminization does not occur (a man acquiring the traits characteristic of women). At the same time, extremely low estrogen levels are also unfavorable.
Excess aromatase activity
Excessive aromatase synthesis occurs with genetic mutations, as well as secondarily. A severe enzyme excess occurs in a hepatocellular malignant liver tumor. In addition, the enzyme is activated by increasing the level of androgens in the blood.
The action of the enzyme increases under the influence of:
- tumor necrosis factor alpha;
- compounds affecting cAMP;
- prostaglandin E 2 .
Aromatase activity is associated with a number of chronic diseases. Long-term metabolic disorders in these conditions lead to oxidative stress, hypercorticism, autonomic dysfunction, etc. All these factors play a role in aromatase activation.
Most clearly increase the expression of aromatase:
- diabetes mellitus ;
- hypertension ;
- hepatitis and hepatosis;
- chronic inflammation;
- chronic nicotine intoxication;
- obesity in men , etc.
Enzyme activity increases in men with age. Also of great importance is lifestyle. Emotional stress, hypodynamia, overeating, lack of proper sleep and wakefulness may eventually cause an increase in aromatase production.
In addition, the use of testosterone preparations also affects the synthesis of the enzyme. Especially the effects of this process are noticeable with non-medical use of androgens.
Symptoms of an excess of estrogens in all these cases:
- gynecomastia ;
- decrease in muscle bulk;
- reduction of hair growth on the face and body of a male type;
- redistribution of adipose tissue;
- depression, etc.
Feminization in children and adolescents can also manifest itself as a change in the normal proportions of the body, a violation of skeletal maturation and sexual development.
Insufficient aromatase activity may be caused by heredity or other factors. With defects in the gene encoding the enzyme, the body loses the effects of estrogen. This is due to the fact that without aromatase, the transformation of androgens into female steroids is stopped.
In humans, it is especially sensitive to the deficiency of these biologically active substances: adenohypophysis, testicles, liver, kidneys, bone tissue, cartilage, central nervous system, thyroid, digestive tract, prostate, bladder, skin.
The lack of female steroids in men leads to:
- masculinization disorders during fetal development;
- short stature (no pubertal growth spurt);
- decreased libido and sexual activity;
- the development of severe osteoporosis;
Aromatase imbalance treatment
Clinically significant aromatase deficiency is quite rare. Men with such a diagnosis need to be treated with estrogen drugs. The earlier the diagnosis is established, the better the prognosis for life and disability. The time-initiated therapy with hormones helps to avoid infertility, hepatosis, dyspedemia and atherosclerosis, osteoporosis.
More often in medical practice, there is an excess aromatase activity in men with overt or covert symptoms of hypoandrogenism. Such patients may be assigned a modification of lifestyle, more often - in conjunction with drug therapy.
Men are advised:
- moderate balanced nutrition with the restriction of animal fats and simple carbohydrates;
- physical activity (strength training, aerobic exercise);
- weight loss;
- rejection of bad habits;
- normalization of work and rest.
Drug treatment includes two groups of drugs:
- aromatase inhibitors.
Natural Aromatase Inhibitors
Some medicinal plants and food products contain enzyme blockers.
Natural aromatase inhibitors include:
Fig. 2 - Resveratrol is found in the skin of grapes, as well as in natural wine.
Official medications have a stronger blocking effect. But these drugs have higher probable side effects.
Aromatase inhibitors include:
- 4-hydroxyandrostenedione (first generation steroid);
- pomestan (second generation steroid);
- exemestane (second generation steroid);
- aminoglutethimide (first generation nonsteroid);
- rogletimid (second generation nonsteroid);
- fadrozol (second generation nonsteroid);
- Vorosol (third generation nonsteroid);
- letrozole (third generation nonsteroid);
- anastrozole (third generation nonsteroid).
The first preparations of enzyme blockers appeared in the 70-80s of the last century. Drugs of the first generation, especially steroids, were distinguished by a large number of side effects. Thus, iatrogenic adrenal insufficiency was often observed in patients.
Modern drugs are much safer. Thus, anastrozole (third-generation nonsteroid) does not suppress the synthesis of cortisol and aldosterone. The effectiveness of the tool is extremely high (during the day the concentration of estrogen is reduced by 80-90%). The drug has a long half-life, which means its action profile is safe and stable.
Letrozole is even more effective against blockade of cytochrome aromatase. This drug also does not affect the work of the adrenal glands. Similar properties are demonstrated by the new drug - Vorosol (not widely used).
Fig. 3 - Letrozole is a third-generation non-steroid aromatase inhibitor.
From modern steroid bolkatorov aromatase used exemestane. This remedy is practically safe for the adrenal glands. However, in case of overdose, cases of hypocorticism are possible.
Endocrinologist Tsvetkova I.G.