Hyperandrogenism is a pathological condition of the endocrine system of the female body, which develops as a result of excessive synthesis of male sex hormones such as the ovaries or the adrenal cortex. Syndrome giperandrogenii refers to the most common endocrine pathology, observed exclusively among female representatives in a different age period on a par with the incidence of thyroid pathology.
When determining the tactics of observation and treatment of patients who have signs of hyperandrogenism, it should be borne in mind that this pathology is not identified with an increase in the level of androgenous gomrons in the blood serum. Many women may have clinical criteria for hyperandrogenic syndrome and there are no laboratory signs of an increase in androgen content in the circulating blood.
Causes of hyperandrogenism
Pathogenetic mechanisms for the development of hyperandrogenism are either in the excess synthesis of male sex hormones by the adrenal and ovarian cortex, or in the increased formation of androgen hormones from precursors. In some situations, the development of clinical signs of hyperandrogenia, for example acne , occurs when the sensitivity of target tissues is increased to even the normal amount of androgenic hormones in the blood. At the same time, hirsutism , as a clinical symptom of hyperandrogenism, in almost 90% of cases is caused by an increase in the level of androgen hormones in the blood serum.
A rare etiopathogenetic mechanism of development of hyperandrogenism is a significantly reduced level of globulins responsible for binding of sex hormones. The action of this globulin is aimed at preventing the penetration of androgenic hormones into the cell, thereby disrupting the interaction of androgen hormones with specific receptors. The production of androgen hormones is mediated by the state of the hormone-synthesizing function of the thyroid gland, therefore various pathological changes in this endocrine organ inevitably provoke a hyperandrogenic syndrome.
There are a number of diseases accompanied by varying degrees of intensity of hyperandrogenism. For example, with Stein-Levental syndrome or polycystic ovaries , ovarian hyperandrogenism develops, manifestations of which most often become dysmenorrhea, obesity , increased hairiness, and the impossibility of conception and gestation. In the postmenopausal period, the cause of the development of the ovarian form of hyperandrogenism can become hypertecosis, in which patients are concerned about obesity, a tendency to arterial hypertension , and with instrumental examination, there are signs of adenocarcinoma of the uterus and a decrease in glucose tolerance.
Adrenal hyperandrogenism in the classical version develops with congenital hyperplasia of the adrenal cortex, which belongs to the category of hereditary genetic diseases. For this pathology, the inherent presence and subsequent progression of the following clinical signs is characteristic: arterial hypertension, virilization, myocardial hypertrophy , anomaly of the development of external genital organs and retinopathy. Fortunately, this pathology is rare, but there is another pathological syndrome that provokes hyperandrogenism called "Cushing's syndrome." The development of this syndrome, accompanied by the emergence of all clinical signs of hyperandrogenism, most often leads to adrenal tumor damage, but in some situations, Cushing's syndrome develops with exogenous effects of elevated doses of glucocorticosteroid drugs that are used in a wide range of pathological conditions of the human body.
A separate category of patients with signs of hyperandrogenism are patients with tumor lesions of the ovaries and adrenal glands, since recently there has been a significant increase in the incidence of androgen secretion forms of oncological pathologies.
Symptoms of hyperandrogenia
Hyperandrogenia in women in reproductive age is accompanied by a wide range of clinical manifestations, each symptom of which can be attributed to one of the three main syndromes: gynecological, dysmetabolic and cosmetic.
In the debut of this pathology, the woman has various forms of menstrual irregularity, manifested in its irregularity, up to the development of amenorrhea , which directly depends on the level of androgenic hormones in the circulating blood. A large number of women suffering from hyperandrogenism tend to develop anovulatory menstrual cycle, provoked by an insufficient content of progesterone in the blood and opposite to an increase in the level of estrogens. In addition to the violation of ovulation, this hormonal imbalance for a short period provokes the development of hyperplastic processes in the endometrium until the proliferation of neoplastic processes. In this regard, hyperandrogenism refers to provoking factors of secondary infertility.
In a situation where hyperandrogenism in girls is congenital, anomalies of the external genitalia are formed in the form of clitoris hypertrophy, partial coalescence of the labia majora, urogenital sinus.
Symptomocomplex of cosmetic defect includes hirsutism and various forms of skin lesions. Hirsutism or increased hairiness is the most common and pathognomonic clinical criterion of hyperandrogenism and consists in enhancing hair growth in the projection of the midline of the abdomen, face, side surfaces of the neck and chest with simultaneous hair loss on the head. Women suffering from hyperandrogenia are more likely than others to develop common skin rashes like acne and severe dry skin with areas of excessive peeling.
Signs of dysmetobolic disorders that occur in any form of hyperandrogenism are the appearance of excess weight, atrophy of muscle fibers and the formation of impaired glucose tolerance, which is a provoker of the development of diabetes mellitus , dysmetabolic cardiomyopathy and obesity.
Quite a specific manifestation of hyperandrogenism is barium, which implies a coarsening of the voice, which has nothing in common with the organic pathology of the vocal cords. In a situation where signs of hyperandrogenism develop at a young age, there is an increased development of the muscular massif of the trunk with a maximum redistribution in the upper half of the chest, the shoulder girdle.
Hyperandrogenia in pregnancy
Among all the possible causes of spontaneous abortion in a pregnant woman in the first trimester, hyperandrogenism takes a leading position. Unfortunately, during the detection of signs of hyperandrogenism in a woman during an already existing pregnancy, it is extremely difficult to determine whether this pathology is innate or acquired. In this period, the definition of the genesis of the disease is not so important, as it is necessary to implement all measures for the preservation of pregnancy.
Phenotypic signs of hyperandrogenia in a pregnant woman do not differ from any manifestations of this pathological condition in any other female representative, the only difference being that in some situations, hyperandrogenia manifests itself in the form of abortion at an early age, which is not always regarded as a miscarriage by a woman. The development of spontaneous miscarriage at an early stage is due to inadequate attachment of the fetal egg to the uterine wall and rejection of it even with the slightest traumatic effect. A vivid clinical manifestation of this condition is the detection of vaginal bleeding, which, incidentally, may not be as intense, pulling pain in the suprapubic region and leveling signs of early toxicosis.
After 14 weeks of pregnancy, physiological conditions are created to prevent the fact of termination of pregnancy, as in this period there is an increase in the activity of female sex hormones secreted by the placenta in large numbers.
Another critical period of the threat of termination of pregnancy in a woman suffering from hyperandrogenism is the 20th week of pregnancy , when there is an active release of dehydroepiandrosterone by the adrenal glands of the fetus, which inevitably provokes an increase in the androgenation of the pregnant woman. Complication of these pathological changes is the development of signs of ischemic-cervical insufficiency, which can provoke the onset of premature delivery. In the third trimester of pregnancy, hyperandrogenia is a provoker of early discharge of amniotic fluid, as a result of which a woman can give birth before the due date.
To determine hyperandrogenism in a pregnant woman, it is advisable to use only laboratory diagnostic methods that are fundamentally different from the examination of the remaining category of patients. In order to determine the concentration of male sex hormones, it is necessary to examine the urine of a pregnant woman with the definition of "the sum of 17-ketosteroids".
It should be taken into account that not all cases of detection of signs of hyperandrogenism in a pregnant woman should be subjected to drug correction, even if the diagnosis is confirmed by laboratory methods. Medical methods of therapy are used only in the case of an existing threat of fetal bearing. The drug of choice for the treatment of hyperandrogenism in pregnancy is Dexamethasone, the initial daily dose of which is ¼ tablets, whose action is aimed at inhibiting the function of the pituitary gland, which has an indirect effect on the production of male sex hormones. The use of this drug is justified by the complete absence of a negative effect on the development of the fetus with a simultaneous positive effect with respect to leveling the signs of hyperandrogenism.
In the postpartum period , women suffering from hyperandrogenism must necessarily be monitored not only by the gynecologist, but also by the endocrinologist, since this pathological condition tends to progress and provoke serious complications.
Diagnosis of hyperandrogenia
The basic link among all possible diagnostic manipulations for hyperandrogenism is a laboratory assessment of the level of steroid hormones. In addition to determining steroid hormones, it is advisable to control the content of hormones involved in the regulation of steroid production.
Due to the fact that hyperandrogenism is a consequence of a number of diseases characterized by developmental mechanisms and clinical manifestations, the diagnostic criteria for each of these pathologies will differ.
Thus, in the polycystic ovary syndrome, the luteinizing hormone and testosterone levels are balanced, the follicle-stimulating hormone decreases, and in some cases the prolactin level in the blood increases. Nonspecific laboratory signs of hyperandrogenism in polycystic ovaries are an elevated concentration of glucose in the blood. Ultrasound scanning by the method of transvaginal access allows almost 100% of cases to visualize a cystic change in the structure of the ovary parenchyma, accompanied by an increase in the overall parameters of the ovaries.
Cushing's syndrome is accompanied not only by a change in the hormonal status, but also by non-specific laboratory signs in the form of leukocytosis , lymphopenia and eosinopenia. The imbalance of the hormonal status consists in the detection of the excess content of hormones produced by the adrenal glands in the blood serum. Radial imaging methods in this situation are used as a diagnosis of the primary tumor process located in the adrenal glands, however, the most informative in terms of detection of tumors of small dimensions is magnetic resonance imaging. In connection with the fact that Cushing's syndrome with accompanying hyperandrogenism can develop as a consequence of pathological changes in the pituitary gland, craniography with X-ray metrology of the Turkish saddle is necessarily included in the complex of screening of patients of this category.
Diagnosis of congenital hyperplasia of the adrenal cortex should be carried out even in the prenatal period of fetal life by the method of amniotic fluid research for the indicator of the level of androstenedione and progesterone. The pathognomonic sign of this pathology is an increase in serum 17-hydroxyprogesterone by more than 800%.
If there is a suspicion that the patient has an adrenosecretory tumor of the ovaries or adrenal glands, special attention should be paid to the evaluation of testosterone and dehydroepiandrosterone, the level of which is significantly increased for these pathologies. As additional diagnostic measures, which are necessary to evaluate the possible surgical treatment of the tumor process, radial imaging methods, as well as magnetic resonance imaging, are used.
Treatment of hyperandrogenism
The choice of treatment of hyperandrogenism largely depends on the background disease that caused the development of this pathological condition, as well as the severity of the disease and the severity of laboratory signs of hyperandrogenism. In this regard, the management of patients and the definition of treatment tactics should be predominantly individual, taking into account all the characteristics of each particular patient. In many situations, the treatment of hyperandrogenia implies the implementation of a whole range of therapeutic measures, both conservative and operational.
Polycystic ovary syndrome, which is the most common cause of ovarian hyperandrogenism, in many cases is well suited to conservative treatment using a whole spectrum of hormonal drugs. The patient's signs of hirsutism are the basis for the use of Medroxyprogesterone at a dose of 150 mg parenterally every three months prior to leveling the clinical defect or long-term administration of Spironolactone at a daily dose of 200 mg, which also has a beneficial effect on the normalization of the menstrual cycle. With the aim of eliminating uterine bleeding and preventing, treating acne and reducing the manifestations of hirsutism, oral contraceptives of combined action are used (Norgestimate in an average daily dose of 250 mg orally). However, it should be borne in mind that all representatives of this group of drugs are not devoid of side effects, therefore, there are a number of conditions that are an absolute contraindication to their use ( thrombosis of any site, severe liver parenchyma damage, tumor process of any site, presence of endometriotic foci). To suppress steroidogenesis, it is recommended to use ketonazole in a daily dose of 200 mg. Operative treatment for polycystic ovaries, as a rule, is used only if there is no effect on the medication, and when diffuse widespread cystic changes in the ovarian parenchyma occur. At present, the most rational and sparing surgical benefit for polycystic ovaries is the electrocoagulation of the ovaries by laparoscopic access.
With Cushing's syndrome with signs of hyperandrogenism in patients suffering from oncological pathologies of the adrenal glands, the only effective method of treatment is surgical. The preparatory stage before the operative treatment is the use of drugs, whose action is aimed at suppressing steroidogenesis (ketoconazole in a daily dose of 600 mg). The effectiveness of surgical treatment directly depends on the size of the tumor, so at a size not exceeding 10 mm a positive result is achieved in 80% of cases. In the postoperative period, it is advisable to use preventative treatment with Methanol in a daily dosage of 10 g to prevent the recurrence of growth of the tumor substrate.
Treatment of congenital adrenal hyperplasia should begin as early as the intrauterine development of the child, since this pathology leads to the development of severe hyperandrogenism. To this end, a pregnant woman is assigned Dexamethasone at a calculated daily dose of 20 mcg / kg until the sex of the unborn child is determined. In a situation where a woman is carrying a boy, treatment should be stopped. The greatest impact on the effectiveness of treatment of congenital adrenal hyperplasia is due to early diagnosis and timely administration of hormonal treatment.
In a situation where the hyperandrogenia in a patient is a symptom of an androgen-secreting ovarian tumor, the only effective treatment option is a combination of operative, radiation and chemoprophylactic therapy.
Treatment of women suffering from hyperandrogenism in the postmenopausal period consists in the appointment of Klimen according to the generally accepted scheme, which has a pronounced antiandrogenic effect.
Cosmetic manipulations to eliminate cosmetic defects that affect the majority of women with hyperandrogenia should be of secondary importance, and their implementation is recommended only when combined with the main methods of drug treatment.