Hyperandrogenia - Causes, symptoms and treatment. MF.

Hyperandrogenia is a condition associated with excessive androgen secretion and / or increased exposure to the body, which in women is most often manifested by virilization( appearance of male characteristics), in men with gynecomastia( enlargement of mammary glands) and impotence.

Androgens - the name of a group of steroid hormones produced mainly by testicles in men and ovaries in women, as well as by the adrenal cortex. Androgens include, for example: testosterone, 17-OH-progesterone( hydroxyprogesterone), DHEA-sulfate, etc.

Among all endocrine diseases in gynecological practice, most often there is a pathology of the thyroid gland and the hyperandrogenia we are considering. To understand this problem, it is necessary to describe a little the scheme of the synthesis of androgens, simplifying it as much as possible:

The whole process is controlled by hormones of the pituitary gland - ACTH( adenocorticotropic hormone) and LH( luteinizing hormone).

The synthesis of all steroid hormones begins with the conversion of cholesterol to pregnenolone. It is important to understand the following - this stage occurs in all steroid-producing tissues!

Other processes also occur to varying degrees in all organs related to steroidogenesis, but at the outlet in different organs both the same and different steroid hormones are produced. It can be depicted in this simplified scheme:

This scheme is simplified as much as possible. Here, most of the steroids produced by these organs are not represented. Only the most important and final products are marked.

In addition, it must be added that the production of steroid hormones can occur not only in these organs, but also at the periphery. In particular, for a woman, an important role in the production of steroids is played by subcutaneous fatty tissue.

Symptoms of hyperandrogenism

Among all the symptoms of hyperandrogenism, the following prevail:

• Hirsutism - excessive hair growth in women, the so-called hair follicle in the male type, is the most common sign of hyperandrogenism. You can talk about it when you have hair on your stomach along the median line, on the face, chest. However, on the head are possible bald patches.
  It is necessary to distinguish this symptom from hypertrichosis - excessive hair growth, not dependent on androgens, which can be both congenital and acquired( for various diseases, for example, in porphyria).We should also pay attention to the race belonging of the patient - the Eskimos and women from Central Asian countries have more hairiness than the women in Europe or North America.
• Acne, skin peeling is a cosmetic defect that is usually concomitant with other, more serious symptoms.
• Opiooligomenoreureas ( shortened and separated by a long period of time), amenorrhea( absence of menstruation) and infertility - most often this symptom occurs with polycystic ovaries accompanied by hyperandrogenism.
• Obesity - is typical for ovarian pathology, and for the pathology of the adrenal glands.
• Atrophy of the muscles of the of limbs, abdominal muscles, osteoporosis, skin atrophy - most characteristic of Cushing's syndrome( or Itenko-Cushing in the Russian-language literature).
• The high risk of infections is associated with a decreased immune response of the body, due to inadequate hormone production.
• Disorder of glucose tolerance - predominantly with adrenal damage, often also in the case of ovarian pathology.
• Formation of external genital organs of intermediate type ( hypertrophy of the clitoris, genito-urinary sinus, partial fusion of the labia majora) - is detected immediately after birth or in the early childhood;more often with congenital hyperplasia of the adrenal cortex.
• Arterial hypertension, myocardial hypertrophy, retinopathy ( non-infectious retinal damage).
• Depression, drowsiness, fatigue - is due in addition to the fact that the secretion of glucocorticoids of the adrenals is impaired.

Causes of hyperandrogenism

Conditions accompanied by hyperandrogenism:

Polycystic ovary syndrome ( Stein-Leventhal syndrome) is a combination of amenorrhea and bilateral multiple ovarian cysts. In this case, most often occurs: violation of the menstrual cycle, infertility, hirsutism and obesity. The diagnosis is based on the presence of hyperandrogenism and chronic anovulation. Increased risk of insulin resistance and hyperinsulinemia, diabetes mellitus is observed in 20% of patients.

Ultrasound with PCOS

Cushing's syndrome is a condition characterized by an excess of glucocorticoid production by the adrenal glands. In most patients, weight gain is noted with the deposition of fat on the face( moonlike face), neck, trunk. Characteristic: hirsutism;violation of menstrual function, infertility;muscle atrophy of limbs, osteoporosis;decreased immunoresistance;violation of glucose tolerance;depression and psychosis;in men, gynecomastia and impotence are possible.
There are the following syndrome variants:
A. ACTH( adenocorticotropic hormone produced by the pituitary gland) dependent syndrome:
Pituitary - most often tumor pituitary lesion
Ectopic - secretion of ACTH( or corticoliberin) by tumor, of any location
B. ACTH independent syndrome:
Adrenal -cancer, adenoma or hyperplasia of the adrenal cortex
Exogenous - self-medication with glucocorticoid medications or treatment of other pathology, with the forced intake of these drugs

Congenitaladrenal cortex hyperplasia - inherited genetic disorder. The following forms are important:

• Insufficiency of 21-hydroxylase( 90-95% of cases) - a frequent cause is aldosterone insufficiency. Characterized by: acidosis( shift of acid-base balance in the body towards increasing acidity);pathology of development of external genital organs.
• Insufficiency of 11β-hydroxylase - a violation of the formation of cortisol. Characterized: classical form - virilization, arterial hypertension, myocardial hypertrophy, retinopathy, pathology of external genital organs;nonclassical form - hirsutism, acne, disorder of the menstrual cycle.
• Insufficiency 3 β-hydroxysteroid dehydrogenase - it can be suspected when the levels of dehydroepiandrosterone and dehydroepiandrosterone sulfate increase at normal or slightly elevated levels of testosterone and androstenedione.

Androgen secretant tumors of ovaries and adrenals - most often this pathology is typical for people with severe virilization or with its sharp appearance and rapid progression. In this case, increasing testosterone levels is more typical for ovarian tumors, and an increase in the level of dehydroepiandrosterone sulfate - for adrenal tumors. Most common in:

Granular cell tumors of the ovaries,
Tecome aspen,
Androblastome ovary,
Steroid ovary tumors( luteem of beremennosti, leidigoma),
Adeoma adrenal glands - 90% of all ovarian tumors that are characterized by the production of androgens alone.

Stromal ovarian hyperplasia and hypertecosis - is observed most often after 60-80 years. The ratio of the levels of estradiol and estrone is increased.
Characterized by: hyperandrogenism, obesity, arterial hypertension, impaired tolerance to glucose and uterine body cancer.

The above pathologies are most often accompanied by hyperandrogenia, but this list can be significantly supplemented. In view of the inability to describe everything in one article, we found it prudent to present only the main pathology.

Diagnosis of hyperandrogenism

The first and main method in the diagnosis of hyperandrogenic conditions is a laboratory study of blood to maintain the level of steroid hormones. Retreating not for a long time to the side, we give the rates for steroid hormones in the blood:

Standards for women:

Testosterone 0.2-1.0 ng / ml or 0.45-3.75 nmol / l
Estradiol 0.17 ± 0.1 nmol / l folliculin phase, 1.2 ± 0.13 nmol / L-ovulation, 0.57 ± 0.01 nmol / l - luteal phase. Progesterone - 1.59 ± 0.3 nmol / l - folliculin phase, 4.77 ± 0.8 nmol / l-ovulation, 29.6 ± 5.8 nmol / l - luteal phase
Cortisol - 190-750 nmol / l
Aldosterone 4-15 ng /ml

In addition, you need to know the norms of hormones that affect the production of steroids:
LH - folliculin phase - 1,1 - 11,6 mIU / l, ovulation 17 - 77 mIU / l, luteal phase 0 -14.7 mIU / l
ACTH - 0 - 46 pg / ml
FSH - folliculin phase-2,8-11,3 mIU / l, ovulation - 5,8 - 21 mIU / l, luteal phase - 1,2 - 9,0 mIU / l

A variety of diseases that are accompanied by hyperandrogenic conditionsand predisposes consideration diagonstiki methods( as well as treat) separately for each disease. Consider the methods for diagnosing the abnormalities described above:

Polycystic ovary syndrome( PCOS):

History and examination data( see above)
Blood test for hormones - an alignment of testosterone and LH is usually observed;FSH level change is possible;in 25% of cases, hyperprolactinemia;increase in glucose level
Ultrasound - ovarian enlargement and bilateral multiple cysts
Laparoscopy - is rarely used, as a rule, with pain syndrome of unknown origin, when for any reason it is impossible to perform ultrasound

Cushing's syndrome:

In general blood analysis - leukocytosis;lymphopenia and eosinopenia.
Blood test for hormones concurrent excess of sex hormones synthesized by the adrenal glands.
Ultrasound examination - possibly for the diagnosis of the ectopic form( detection of tumors localized outside the adrenal glands) and adrenal( for the diagnosis of large adrenal tumors).
MRI( magnetic resonance imaging) - if there is a suspicion of oncology, if the ultrasound is uninformative.
Craniography - X-ray study of the skull in 2 projections for the diagnosis of pituitary pathologies( deformation of the Turkish saddle - location of the pituitary gland in the sphenoid bone of the skull).

Congenital adrenal hyperplasia:

Elevation of 17-hydroxyprogesterone in serum with 21-hydroxylase deficiency( above 800 ng%);it is possible to sample with ACTH.It is important to note that this condition can be detected in the fetuses even before birth and begin treatment in the womb of the mother. Diagnosis with a high risk of this pathology consists in examining the amniotic fluid to the level of progesterone and androstenedione.
Samples with ACTH are also performed for the diagnosis of deficiency of 11β-hydroxylase and 3 β-hydroxysteroid dehydrogenase.

Androgen secretion tumors:

Blood test for hormones - increasing the level of androgens - testosterone for ovarian tumors;dehydroepiandrosterone - for adrenal tumors
Ultrasonography of the small pelvis - for ovarian tumors.
CT( computed tomography) and MRI - mainly for adrenal tumors.
Catheterization of the adrenal vein with testosterone levels is a controversial method, due to a large number of complications.
Scintigraphy of the abdominal cavity and small pelvis with I-cholesterol.

Stromal ovarian hyperplasia and hypertecosis:

Blood test for hormones - levels of ovarian androgens are usually equal to the male norm.
The level of gonadotropic hormones is usually normal - differential diagnosis from PCOS

Treatment of hyperandrogenism

PCOS:

Medication
A. Medroxyprogesterone - effective in hirsutism.20-40 mg / day vnut or 150 mg intramuscularly once every 6-12 weeks.
B. Combined oral contraceptives - reduce the secretion of steroid hormones, reduce hair flow in 70% of patients with hirsutism, treat acne, fix dysfunctional uterine bleeding. Preferred PC with a weak androgenic effect: desogestrel, gestodene and norgestimate.
B. Glucocorticoids - dexamethosone - 0.25 mg / day( not more than 0.5 mg / day).
G. Ketoconazole - 200 mg / day - suppresses steroidogenesis.
D. Spironalactone 200 mg / day for 6 months.- improvement in 70-80% of patients - with hirsutism;Possible disruption of the menstrual cycle

Surgical treatment - with ineffective medical treatment:
A. Viseous resection is once popular, now this method is not so often used in hospitals
B. Laparoscopic electrocoagulation of the ovaries - coagulate( cauterize) the ovary at 4-8 points with the

electrode

Cushing's syndrome:

ACTH dependent
A. Drug treatment - unfortunately, in many cases the diagnosis is made rather late. Drug treatment is often seen as preparation for surgery, rather than as an independent method of treatment. Steroidogenesis inhibitors are used, most often ketoconazole - 600-800 mg / day
B. Surgical treatment - produce adenomectomy, which, with microadenomas( less than 1 cm tumor size), positive results are noted in 80% of patients;with macroadenomas - in 50%.
B. Radiation therapy - usually with pathology of the pituitary gland. Positive results in adults in 15-25% of cases.

ACTH independent - most often the only radicular method of treatment for adrenal tumors - surgery followed by the appointment of glucocorticoids in the postoperative period and mitotane, to prevent relapses.

Congenital adrenal hyperplasia:

Dexamethosone - to suppress ACTH secretion, at a dose of 0.25-0.5 mg / day inwards. Carry out treatment under the control of cortisol( if its level is not less than 2 μg%, then the treatment is effective without subsequent complications from the hypothalamic-pituitary system).
It was mentioned above that the detection of pathology and its treatment is possible in the womb( for deficiency of 21-hydroxylase).Dexamethosone is used at a dose of 20 mcg / kg / day in 3 divided doses. At a high risk of pathology in a child, treatment begins with the moment of pregnancy detection. In case the fetus is male, the treatment is terminated, if the fetus is continued. If treatment is started before 9 weeks of pregnancy and before childbirth - the risk of pathology of genital organs formation is much less. This scheme of treatment is a matter of dispute among specialists, indicating that there may be a large number of complications for the mother, with the rather low effectiveness of the treatment itself.

Androgen secretant tumors of ovaries and adrenals

Treatment only in an oncological hospital, most often an operation in combination with chemotherapy, radiotherapy or hormone therapy. Prognosis treatment depends on the time of diagnosis and the nature of the tumor itself.

Stromal ovarian hyperplasia and hypertecosis:

With a mild form, wedge resection of the ovaries is effective. It is possible to use analogues of gonadoliberin. In severe pathology, bilateral ovarian amputation is possible to normalize blood pressure and correct glucose tolerance disorders.

With the advent of symptoms of hyperandrogenism, it is necessary to consult a doctor. Most often - an endocrinologist or gynecologist, often a therapist. Be sure to thoroughly understand the causes of hirsutism and other symptoms, and if necessary, send to a specialized hospital.

Any self-treatment is completely and categorically contraindicated! Only hair removal by cosmetic means is allowed.

Prevention of hyperandrogenism

Hyperandrogenism does not have specific preventive measures. The main ones are observance of the diet and lifestyle. Each woman needs to remember that excessive weight loss contributes to hormonal disorders and can lead to both the described condition and to many others. In addition, one should not get involved in sports, which too( especially when taking steroid drugs) can lead to hyperandrogenism.

Rehabilitation is required by patients with hyperandrogenia of tumor origin, who underwent operative and chemotherapeutic treatment. In addition, it is necessary to consult with a psychologist, especially for young girls with pronounced hirsutism and gynecological problems.

Complications of hyperandrogenism

The spectrum of possible complications with all the diseases described above is extremely high. It is possible to note only some, the most important:

• With congenital pathology developmental anomalies are possible, the most common of them are abnormalities of genital organs development.
• Metastasis of malignant tumors is a complication more characteristic of adrenal tumors.
• Complications from other organ systems that are adversely affected by hormonal changes in the pathology of the adrenal, pituitary and ovarian: chronic renal failure, thyroid pathology, etc.

This simple listing list is far from over, which speaks in favor of a timely call to the doctor, in order to anticipate their offensive. Only timely diagnosis and qualified treatment contribute to the achievement of positive results.

Doctor gynecologist-endocrinologist Kupatadze D.D.