Virilization is the appearance of secondary male sexual characteristics in women or girls. Occurs due to an excess of steroid hormones from the androgen group or with a violation of their metabolism. It manifests itself in the form of hirsutism, coarsening of the voice, menstrual cycle disorders. Baldness develops on the scalp, the mammary glands decrease in size, the clitoris increases. Diagnosis is based on clinical manifestations, hormonal background examination, ultrasound of the adrenal glands and MRI of the brain. Treatment is aimed at eliminating the root cause of endocrine disorders, carried out by conservative and surgical methods.
E25 Adrenogenital disorders
Virilization (masculinization, virilism) can develop in women of any age. The prevalence and severity of the pathological condition depends on its cause. Congenital forms occur in 1 case per 5 to 6,000 of all newborn girls. In the reproductive period, virilization associated with ovarian pathology occurs in 11% of patients. However, in women with endocrine infertility, virilization in combination with polycystic ovaries is detected in 70% of cases.
The production of male hormones, which leads to the appearance of hirsutism, may increase under the influence of constitutional and hereditary factors. Women of Eastern nationalities have increased hair growth on the face and external genitalia. But this is not considered a full-fledged virilization requiring treatment. The true reasons are:
- Adrenogenital syndrome. Congenital hyperplasia of the cortical zone of the adrenal glands is inherited in an autosomal recessive type. Signs of hyperandrogenism may appear already at birth, in girls, the external genitalia look like men’s. In adolescence, the formation of the skeleton occurs according to the masculine type, the menstrual cycle is disrupted.
- Tumors of the adrenal glands. Corticosteromas, androsteromas and corticoandrosteromas are more often diagnosed. They develop in the post-puberty period, accompanied by a change in the nature of hair loss, the appearance of acne, a violation of the distribution of fatty tissue. Women note a decrease in libido, become infertile.
- Itsenko-Cushing’s disease. It develops with a pituitary tumor producing an excess of adrenocorticotropic hormone. This leads to stimulation of all areas of the adrenal cortex, the development of hypercorticism. The disease is more often manifested in patients aged 20-40 years.
- Stein-Leventhal syndrome. Virilization in polycystic fibrosis is associated with excessive androgen synthesis in the ovaries. The disease develops in young women 20-30 years old, leads to hirusutism, the appearance of excess weight, menstrual disorders and infertility.
- Masculinizing ovarian tumors. Arise from the embryonic remains of the male gonads. In young patients, menstruation becomes rare, amenorrhea and infertility may develop. Mammary glands atrophy, uterine hypoplasia develops. At a late age, male pattern baldness occurs, coarsening of the voice and hypertrophy of the clitoris.
With adrenogenital syndrome, there is a defect of enzymes involved in the synthesis of adrenal hormones. This leads to insufficient cortisol production and excessive ACTH response production. The result is hyperplasia of the adrenal cortex, their cells actively produce progesterone, 17-hydroxyprogesterone and male hormones. Glucocorticoid deficiency leads to the development of hypoglycemia, which is hard to tolerate in children.
ACTH has an affinity for melanocyte-stimulating hormone receptors, enhances the synthesis of melanin in the skin, therefore, virilization is accompanied by hyperpigmentation. It manifests itself both in young children and in masculinization, which developed in adulthood. Increased pigmentation can be observed on any parts of the body, often on the face, genitals.
Hyperandrogenism during intrauterine development leads to the birth of girls with karyotype 46XX, but hypertrophied clitoris. In 1.5-2 years, pubic hair, armpits may appear. Growth accelerates, but there is a premature closure of growth zones at 9-10 years, so girls are lower than their peers. Menstruation may not begin or oligomenorrhea develops, but later menstruation stops.
In women with increased androgen production, which occurs more often with polycystic fibrosis, there is a deficiency of FSH, but the basal level of LH is increased. Stimulation of the ovaries by the pituitary gland does not lead to ovulation. The hyperproduction of androgens leads to follicle atresia, stroma hyperplasia and protein envelope. This closes a vicious circle, intensifies violations of the cycle. Excess testosterone leads to the manifestation of signs of virilization.
The pathological condition is classified according to the leading cause of the increase in androgen levels. Virilization is considered as a congenital or acquired condition. In this case, the adrenogenital syndrome belongs to the first group, and all other causes belong to the second. But more often a classification is used depending on the source of androgen synthesis:
- Adrenal virilization. It develops when the cortical substance is affected, it is characteristic of cortical hyperplasia. This group includes adrenocorticotropic syndrome, as well as pituitary tumors.
- Ovarian virilization. Occurs when androgens are hyperproducted by ovarian tissues. This group includes masculinizing tumors, PCOS.
The manifestations of virilization depend on the age at which endocrine changes occurred. The degree of severity depends on the level of increase in androgens in the blood. In newborns, virilization can lead to pseudohermaphroditism. A girl is born with external genitals that look like men’s: the clitoris is hypertrophied, the vagina is shortened and can open into the urethra.
With the progression of virilization during prepubertal, premature puberty is observed. The girl’s voice gets rougher, her height lags behind, her body type becomes stocky. Greasiness of the skin and hair increases, acne worries, hirsutism is noted. Hair grows in the armpits, in large quantities on the pubis, as well as on the arms and legs. Menstruation is irregular, amenorrhea often develops.
At the reproductive age, virilization develops gradually, not all symptoms are present. The skin becomes rough, thickened, greasy, acne-type rashes appear. Due to the thickening of the ligaments, the voice becomes coarsened. Hirsutism is sometimes the only sign of virilization, which makes it difficult to diagnose and leads to a late visit to the doctor.
A persistent decrease in sexual desire disrupts relationships in the family, increases the state of stress. Menstruation becomes irregular, the duration of bleeding shortens, and the cycle lengthens until amenorrhea occurs. Endocrine infertility develops, which cannot be cured without eliminating hyperandrogenism and its causes.
Virilism is accompanied by a change in the distribution of fiber under the skin, in patients, fat deposits accumulate in the upper part of the trunk, so the limbs look disproportionately thin. Carbohydrate and lipid metabolism is disrupted, so pathology is often combined with diabetes mellitus.
The consequences of hyperplasia of the adrenal cortex is a violation of calcium metabolism and the development of osteoporosis. Women feel pain in the tubular bones, pathological fractures may occur, which are difficult to recover. Often, against the background of virilization, secondary immunodeficiency is formed, therefore, chronic vaginal candidiasis occurs, and with obesity, the infection affects the skin folds, the area under the breast.
Possible lesions of the cardiovascular system, which are the result of violations of carbohydrate and fat metabolism, electrolyte balance. In patients with virilization, based on the causes of this condition, arterial hypertension, hypertrophy of the left ventricle are detected. In childhood, severe electrolyte disorders can lead to death.
When complaining of menstrual irregularities, infertility, hirsutism, a woman should contact an obstetrician-gynecologist. Additionally, an endocrinologist’s consultation will be required, and if a pituitary pathology is suspected, a neurologist’s examination will be required. Diagnostics is aimed at establishing the cause of the development of the virilization, because it determines the approaches to treatment. The following methods are used:
- Gynecological examination. Hyperpigmentation of the labia majora, increased pubic hair, enlarged clitoris is determined. The uterus can be hypoplasized palpationally. Mammary glands with long-term virilization syndrome are reduced in size.
- Laboratory diagnostics. The concentration of steroid hormones is being investigated. There is a decrease in corizole, an increase in testosterone. In polycystic ovary syndrome, FSH is reduced and LH is increased. For the differential diagnosis of adrenogenital syndrome, a test with ACTH is performed.
- Gynecological ultrasound. Examination of the pelvic organs shows a decrease in the size of the uterus and the thickness of the endometrium. There are multiple follicles on the ovaries, but there is no dominant one, there are no signs of ovulation.
- MRI of the pituitary gland. With adenoma, a tumor-like formation is detected. The technique makes it possible to detect neoplasms of 1-3 mm in size, contrasting increases the effectiveness of the study.
- Densitometry. In women with virilization, bone mineral density is reduced, osteoporosis is diagnosed. Children are measured bone age to determine the possible development potential.
Therapy should be started as early as possible to prevent the effects of hyperandrogenism. Hospitalization in the department of gynecology may be required for laparoscopic resection of polycystic ovaries. Medical treatment is carried out on an outpatient basis with periodic observation by a gynecologist or an endocrinologist in a polyclinic.
Treatment of virilization is selected individually, based on the causes of pathology. The goal of therapy in children is adequate development of the child, inhibition of premature puberty. For women, it is necessary to preserve or restore fertility. The following groups of drugs are used:
- Glucocorticoids. They are prescribed in the treatment of adrenogenital syndrome to compensate for the violation of the synthesis of their own hormones, according to the feedback principle, the production of ACTH decreases and the level of androgens normalizes. In combination with electrolyte disorders, mineralocorticoid preparations are used.
- Antiestrogens. Women with polycystic fibrosis who are planning pregnancy are prescribed drugs to stimulate ovulation. Antiestrogens are prescribed in combination with gonadotropins to cause the maturation of the dominant follicle and the release of the egg. Hormones are administered according to a special scheme, strictly adhering to the days of the cycle.
- Biguanids. They are prescribed to women who have developed diabetes mellitus at the same time with virilization. Drugs of this group reduce insulin resistance of tissues, help to improve carbohydrate metabolism. The duration of therapy is 3-6 months, can be carried out against the background of ovulation stimulation.
With congenital adrenal hyperplasia, surgical treatment is not used. It is indicated for masculinizing ovarian tumors, adrenal neoplasms. To remove pituitary adenoma, hospitalization in the neurosurgical department is necessary. After surgery, a course of radiation therapy with gamma rays or protons may be required.
Surgical correction of the virilization is effective in polycystic. By laparoscopic access, wedge-shaped resection or cauterization of the ovaries is performed by thermal or laser method. Ovarian demodulation is also used. After the intervention, pregnancy occurs within 6-12 months, but later the probability of conception decreases rapidly.
Prognosis and prevention
In the congenital form of virilization, the prognosis is not always favorable due to a combination with electrolyte disorders. In other cases, timely treatment can compensate for hormonal abnormalities, normalize the level of androgens. Life-long treatment is often necessary to preserve the female phenotype and fertility.
Specific prevention of virile changes is aimed at early diagnosis of adrenogenital syndrome. All children are given a blood test on the 3rd day to identify genetic abnormalities and prescribe treatment on time. For women of fertile age, prevention consists in a healthy lifestyle, reducing the risk of sexual infections, which can indirectly cause inflammation of the ovaries and increase the likelihood of polycystic fibrosis.