Gonadal dysgenesis

Pathology caused by chromosomal defects, which is accompanied by abnormal gonadal development in the embryonic period, is called gonadal dysgenesis. The disorder is formed in the embryonic period and may be accompanied by certain somatic disorders.

Gonadal dysgenesis is a chromosomal disorder involving the loss of one X chromosome or a fragment thereof, which causes the development of problems with the sex glands. A typical disorder is the improper formation of testicles or ovaries. [1]

Epidemiology

The most frequent failure of ovarian capacity is gonadal dysgenesis, which can be observed in female patients with rudimentary ovaries, particularly in patients with Turner syndrome. This pathology is diagnosed in about 1-2 cases among three thousand born baby girls, which is associated with chromosome group 45X. The syndrome is often associated with mosaic types - for example, 45X/46XX, or 45X/46XY, as well as with karyotypes with an abnormal X chromosome (partial division of one arm of Xdel[Xp-], or Xdel[Xq-], or X chromosome).

Patients with a deletion of the short arm of the X chromosome have a phenotypic appearance similar to Turner syndrome, but are fertile. Deletion of the long arm of the X chromosome is accompanied by a normal physique against the background of ovarian dysfunction.

About 5% of patients diagnosed with Turner syndrome have monosomy X. The rest have mosaic forms. The presence of the SRY gene entails an increased risk of virilism and gonadal neoplasms. Patients with Turner syndrome often have dysgerminomas and gonadoblastomas.

In more than half of cases, the diagnosis of gonadal dysgenesis is made at age 12 or later, and in 20% of patients after age 16 years.

Gonadal dysgenesis is most often diagnosed in people from Eastern European and Western European countries. The incidence is much lower in Africa due to some racial, geographic and environmental determinism.

Causes of the gonadal dysgenesis

The reasons for the development of gonadal dysgenesis are not fully understood. This issue is still being studied by geneticists and gynecologists around the world. According to already known information, the disease can develop by such mechanisms:

• A spontaneous gene disorder that occurs under the influence of unfavorable external or internal factors.
• Genetic abnormality due to defective factors on the part of one of the parents.

Let's look at the above reasons in more detail.

The study of gene abnormalities was conducted using parental biomaterial, which yielded these results:

• Almost 5% of female individuals have mutations in their eggs. In such situations, fertilization results in a genetically determined abnormality in the development of the genitalia of the future baby, which occurs in 98% of cases.
• In 7-8% of males, there is a tendency to develop genetic defects. The risk is higher in men with asthenozoospermia or teratozoospermia: in 20% of these patients, there is a genetic defect in the gametes, while fertility is preserved.

Dysgenesis of the gonads, caused by genetic anomalies, can be accompanied by intellectual disability, and in a severe form.

As for accidental, or induced developmental defects, these occur most frequently and can be related to factors such as these:

• Abuse of smoking during childbearing (the main pathological role is played by carbon monoxide, nitric oxide and nitrosamines, which lead to the appearance of disorders in the future child in about 13-14% of cases);
• use of alcohol-containing drinks during pregnancy;
• unfavorable environmental conditions, exposure to high doses of ionizing rays, which leads to the formation of free radicals that damage chromosomal sites and disrupt the balance of genetic material (this occurs in 2-10% of cases);
• Consumption of foods with nitrates, both organic and inorganic (fruits and vegetables treated with nitrate fertilizers to increase yields);
• Prolonged and/or profound stress accompanied by excess corticosteroids and catecholamines in the bloodstream.

The specific mechanism of the negative impact of unfavorable factors on the development of gonadal dysgenesis and other embryonic pathologies is not fully understood.

Risk factors

Risk factors include factors such as:

• unsatisfactory obstetric history, prolonged toxicosis and other health problems of the expectant mother;
• viral, microbial, fungal infectious diseases during the gestation period;
• severe intoxication.

These factors are mainly important during the first trimester. During the formation of the future baby, the risk of dysgenesis is somewhat reduced, completely disappearing by about 4-5 months of pregnancy. Detect the influence of such factors - the task of the obstetrician-gynecologist. Prevention of unfavorable complications should be carried out in the planning period of conception, with the involvement of a geneticist.

Pathogenesis

The formation of the pathology of gonadal dysgenesis begins at the stage of embryogenesis, and the main sexual characteristics complete their formation by 5-6 weeks of gestation. Throughout the entire period of the first trimester, there are risks of phenotypic abnormalities in the future baby.

In order for the glands to form properly, 2 chromosomes are needed: XX or XY, according to the ovary or testicle. The appearance of dysgenesis is most often identified with an abnormality in the X chromosome. Glandular differentiation does not end; several variations of the disease can form.

In gonadal dysgenesis, the sex glands are fully developed, more often female, which serves as a difference from the true form of hermaphroditism. Full gonads are completely absent in about 20% of cases, which is associated with infertility.

About half of the patients have karyotype 45X, a quarter of the patients have mosaicism without structural changes (46XX/45X), and another quarter have structural changes on the X chromosome, both with and without mosaicism.

The 45X variation is due to loss of a chromosome during gametogenesis in the mother or father, or to erroneous mitosis during early division of a fertilized diploid cell.

Short stature and other somatic abnormalities are the result of loss of genetic material on the short arm of the X chromosome.

The formation of gonadal masses occurs when genetic material on the long or short arm of the X chromosome is lost. In patients with mosaicism or X-chromosome alterations, phenotypic abnormalities may vary in severity.

The pathogenesis of osteoporosis concomitant with gonadal dysgenesis is not fully understood. Presumably, the disorder is a direct consequence of missing genetic material on the X chromosome, resulting in the production of an irregular matrix by osteoblasts. A similar underlying cause is confirmed by mapping of the X chromosome. Additional factors become hormonal disorders. The level of estrogen necessary for puberty is not reached, the growth of the cortical bone layer is inhibited, the structure of the trabecular part is disturbed. In addition, the system of growth hormone - insulin-like growth factor at puberty is not activated in patients.

Symptoms of the gonadal dysgenesis

The symptomatology of the disease has its own differences, depending on the type of gonadal dysgenesis.

The typical form is characterized by features such as:

• small stature, in the vast majority of cases not exceeding 1.55 m;
• absence of a monthly cycle, absence of puberty as such, absence of reproductive capacity;
• The appearance of spontaneous monthly bleeding against the background of minimal ovarian reserve;
• understated ear placement;
• "Mongolian eyelids."
• color indistinguishability (color blindness);
• poor nail development;
• aortic changes, aortic narrowing.

In the pure variant of dysgenesis, no obvious pathologic changes are often found, but there is underdevelopment of the genital and glandular system. Patients have a high risk of developing neoplastic pathologies of the genital organs - in particular, dysgerminoma, gonadoblastoma, which are formed from residual cellular structures of the embryonic period. Neoplastic processes of this kind are particularly aggressive, difficult to treat, have radio resistance, so the chances of cure are slim. The first sign of complications is viril syndrome (male hair loss, voice coarsening, etc.).

The mixed form of gonadal dysgenesis is manifested by symptoms such as:

• stunting;
• infantile genitals;
• lack of a monthly cycle;
• disorders of the cardiovascular system (often - heart defects);
• chest configuration disorders (not in all patients).

The mixed variant is relatively rare, and the symptomatology is nonspecific. [2]

First signs

Common clinical signs of gonadal dysgenesis are considered to be:

• Lymphoedema of the feet, hands, upper body, neck area in newly born babies;
• lack of growth;
• stocky build;
• enlarged barrel-shaped breasts, wide-set mammary glands (often with retracted nipples);
• late formation of secondary sexual characteristics and the beginning of the menstrual cycle;
• hypoplasia of the external genitalia with normal clitoral size;
• marked uterine hypoplasia, vaginal elongation and narrowness;
• short-necked, low hair growth boundary;
• a characteristic facial type ("old age");
• mandibular maldevelopment, arched palate, dental deformity;
• hyperpigmentation of the eyelids;
• upper eyelid drooping, strabismus, epicanthus;
• pronounced transverse cervical folds;
• Musculoskeletal disorders (curvature of the spinal column, osteoporosis);
• cardiovascular, urogenital pathologies.

Stages

Sexual differentiation is a definite order of stages and processes. The chromosomal sex, which is formed at fertilization, determines the gonadal sex, which determines the development of phenotypic sex, according to which the male or female urogenital system is formed. Failures at any of the stages of embryogenesis entail a disorder of sexual differentiation.

In the first stage, the formation of chromosomal sex occurs. Then, until approximately 40 days of gestation, the embryos develop according to the same scenario with the formation of undifferentiated gonads.

In the second stage, undifferentiated gonads transform into ovaries or testes. Further phenotypic sex development leads to the formation of male and female urogenital system. Formation of the internal genitalia occurs from the Müllerian and Wolff ducts, which are located close together early in embryonic development. The external genitalia and urethra in different sexes are formed from a common element, the urogenital sinus, the genital tubercle, folds and swellings.

The formation of the male phenotype occurs under the influence of hormones: substances that inhibit the Müllerian ducts and testosterone, a product of embryonic testicular secretion. In the absence of testicles, the phenotypic sex develops along female lines.

Forms

Four types of gonadal dysgenesis are known:

• Typical dysgenesis (Shereshevsky-Turner syndrome) is a clear defect, total sexual underdevelopment. The uterine organ and fallopian tubes are underdeveloped. The gonads have the appearance of thin connecting strands, indicating a karyotype of 45X. The height of the patients does not exceed 1.5 meters, there are defects in the formation of the dentition, strabismus, "Mongolian fold". The physique is stocky, with a shortened neck covered with skin folds. Underweight, edema of the limbs, cranial and elbow deformity, violations of the configuration of the ears and chest, asymmetry and depression of the nipples are characteristic. Hyperpigmentation on the body, protruding shoulder blades can be observed. Often patients have disorders of the cardiovascular, musculoskeletal, urinary apparatus. Secondary sexual characteristics are absent. A decrease or absence of sex chromatin is detected. For infants, the "old man's face" is considered a characteristic sign.
• Mild dysgenesis is caused by the 45X/46XX genetic mosaicism. The magnitude of the chromosomal defect determines the intensity of the symptomatology and its proximity to the manifestations of Shereshevsky-Turner syndrome. The predominance of the correct chromosomal set facilitates the clinical picture. Patients more often have normal growth, the development of sexual characteristics is possible against the background of a normal monthly cycle. However, the development of genitalia is incomplete.
• Pure gonadal dysgenesis is caused by karyotype 46XX or 46XY (complete dysgenesis, Swyer syndrome) and is characterized by predominance of female features with eunuchoid physique (broad breasts on the background of narrowed pelvis). Growth is average or even high, sex differences are not detected, but there is sexual infantility without marked violations of the anatomy of the organs. Reproductive glands appear as fibrous tracts, with the presence of adequate germ cells. The syndrome is often combined with an increased risk of tumor formation in the gonads, as a result of which the glands are removed. The pathology becomes known not earlier than puberty: the mammary glands are small, or have the appearance of small seals. It is noted sexual hypoplasia, low hair loss. There may be scanty discharge like menstruation.
• Mixed dysgenesis is a typical manifestation of hermaphroditism. There is a karyotype 45X/46XY, which is represented by both male and female phenotype. There is a defective alteration of gonosomes with multiscale formation of a genetic sex-cell phenotype. In the complete absence or inactivity of Y, X-chromosomes, the formation of undifferentiated tissue of gonadal thrusts is observed. Pathologic symptomatology is detected immediately after the child's birth. External genitalia are mixed: against the background of hypertrophied clitoris there are enlarged labia of the scrotal type, and in the course of puberty prevail male signs (verilny syndrome), such as facial hair, coarsening of the voice. Breast glands are underdeveloped, there is hypoplasia of the uterus and fallopian tubes. The pathology may resemble typical dysgenesis, but defects in internal organs are rarely observed.

Such a wide variety of forms of dysgenesis is due to the negative impact of certain factors during the formation of genetic phenotypic structures that determine the sexual identity or development of the glandular group of the sexual system. Defective gonadal tissues die and transform into connective tissue elements unable to produce male germ cells and develop. [3]

Complications and consequences

Skeletal growth disorders are observed in more than 95% of cases of gonadal dysgenesis. Growth retardation begins in the intrauterine period, but becomes most noticeable after 10-12 years of age.

The absence of pubertal development is characteristic, although partial puberty is sometimes noted in cases of mosaic karyotype variation, and in isolated situations there is a possibility of independent pregnancy.

Lymphoedema of the extremities, which occurs directly in newborn babies, disappears within a few days or months. But even at an older age, swelling can reappear with certain loads (running, hypothermia). This is due to the improper development of the lymphatic system. In severe cases, the help of a surgeon may be required: patients undergo angioplasty.

In 30% of patients with gonadal dysgenesis, heart defects (more often left-sided) are diagnosed due to improper formation of the lymphatic system. The most common pathologies are aortic coarctation, bicuspid aortic valve, root dilatation. With timely diagnosis, surgery is often prescribed to prevent formidable complications. In relatively mild cases, cardiac dysfunction is noted: increased blood pressure, mitral valve prolapse.

Hearing loss is often observed in the auditory organs. Neurosensory or conductive hearing loss develops, often in childhood and in adults over 35 years of age. Hearing problems in childhood often lead to poor psychomotor development: speech skills and intelligence are impaired.

Renal damage is noted in about half of patients with gonadal dysgenesis. Irregular shape of organs, their fusion, hypoplasia, atypical localization - all these defects over time can lead to high blood pressure, contribute to infectious urinary diseases.

Another important consequence of gonadal dysgenesis is psychological and behavioral disorders provoked by external and other features of patients. Often a sick person is isolated from peers even at a young age, due to which he/she experiences difficulties with socialization. [4]

Implications for patients with XX-dysgenesis of the gonads:

• due to impaired estrogen production, the breast glands do not develop, the uterus does not function, and the monthly cycle is absent prior to estrogen treatment;
• progesterone is not produced, the monthly cycle is unstable until progestin treatment is given;
• against the background of the inability of the gonads to produce eggs, a woman can not get pregnant on her own.

Diagnostics of the gonadal dysgenesis

Diagnostic measures are carried out by a gynecologist in cooperation with a medical geneticist: the diagnostic process is usually not very difficult. Specialists visually assess the development of the musculoskeletal system, external genitalia, glandular system, and additionally conduct genetic tests. Perform ultrasound examination of the pelvic organs and kidneys, assess the work of the heart with electrocardiography. Laparoscopic examination of the gonads, biopsy, measurement of chromatin level and quality of hormonal background.

In early childhood, gonadal dysgenesis is recognized by the presence of lymphoedema of the hands and feet, cervical folds, low hairline, excessive occipital skin folds, thyroid breasts with widely separated nipples, and underweight at birth. In addition, patients have a typically shaped face with a reduced jaw, epicanthus, undersized or irregularly shaped ears, drooping eyelids and the so-called "fish mouth". One in two patients has shortening of the IV metacarpals and one in 4-5 patients has aortic coarctation.

Associated disorders include renal malformations, hyperpigmentation, nail hypoplasia, hearing impairment, autoimmune pathologies, and hypothyroidism.

Until a few years ago, sex chromatin tests were performed to assess X-chromosome disruption. These are specific Bara cells, which are the product of inactivation of one of the X chromosomes. Patients with chromosome set 45X were referred to the chromatin-negative series. But only half of patients with gonadal dysgenesis (individuals with karyotype 45X, marked mosaicism and structural disorders) can be referred to the same series. Therefore, for diagnostic accuracy, such an analysis must necessarily be supplemented by karyotype examination.

The level of follicle-stimulating hormone in serum, which is elevated in early childhood, then decreases to normal values, and after 9 years of age increases to values characteristic of castrates. At the same time, serum luteinizing hormone levels also increase and estradiol levels decrease. In about 2% of patients with 45X variation and 12% of patients with mosaicism, the ovaries have enough follicles to produce periodic menstrual bleeding. And with minimal lesions, patients sometimes become pregnant, although their reproductive period is usually short.

Instrumental diagnostics is most often represented by radiography, ultrasound, electrocardiography.

Changes in the side of the spinal column can be monitored radiographically:

• an undersized first cervical vertebra;
• vertebral body abnormalities;
• scoliosis.

Some patients with gonadal dysgenesis also have congenital hip dysplasia. In some cases, there are dental growth abnormalities that require the help of an orthodontist.

There is quite a lot of information about the formation of osteopenia or osteoporosis in people with gonadal dysgenesis. Patients have an increased incidence of bone fractures, especially in the wrist, vertebral column, and femoral neck. Changes in the bone apparatus occur in early childhood: mostly the cortical layer is affected, which occurs against the background of slow intraosseous metabolic processes. In adulthood, intraosseous metabolism increases significantly.

Differential diagnosis

Typical gonadal dysgenesis must be distinguished:

• from a mixed variant of pathology, when on one side there is a testicle and on the other side there is a gonadal mass;
• from the pure variant of dysgenesis, when gonadal tracts on both sides are found against the background of normal karyotype, adequate growth and primary amenorrhea;
• from Noonan syndrome, an autosomal dominant pathology with skin folding in the neck, short stature, congenital heart defects, valgus curvature of the forearms and other congenital anomalies against the background of normal gonads and karyotype.

Diagnosis is carried out immediately after birth, or in puberty, when amenorrhea is detected against the background of congenital developmental defects.

Noonan syndrome is a pathology with phenotypic characteristics of gonadal dysgenesis and normal chromosomal typing. The syndrome is inherited in an autosomal dominant pattern or occurs due to the expression of an abnormal gene located on the long arm of the twelfth chromosome.

The features of differentiation and diagnosis of pure gonadal dysgenesis and Noonan syndrome are summarized in the following table:

Symptom	Gonadal dysgenesis	Noonan syndrome
Appearance	Typical of gonadal dysgenesis.	Reminiscent of the appearance in gonadal dysgenesis
Heart defects	Predominantly left-sided heart defects, aortic stenosis	Right-sided heart defects, pulmonary artery stenosis
Intellectual development	More often normal	Disturbed in almost one in two patients
Birth height	Below normal	Norma
Final growth	Below normal	Below normal in one in two patients
Gonads	Gonadal dysgenesis	Norma
Gender	Female	Male and female
Karyotype	There's been a change	Norma

Treatment of the gonadal dysgenesis

In the expected period of puberty begin substitution estrogen therapy, which is necessary to stimulate the development of mammary glands, external and internal genitalia. During the first year of estradiol administration, the development of the musculoskeletal system is approximately doubled, but growth in most cases does not reach the absolute norm.

Gonadal neoplasms are infrequent in patients with 45X variation, in contrast to patients with Y-chromosome mosaicism. Given this, removal of gonadal masses is recommended in all cases of virile syndrome.

Main Treatment Objectives:

• increase in growth performance;
• installation of regular menstruation, the formation of secondary sexual characteristics;
• therapy of concomitant pathologies, correction of developmental defects;
• prevention of disorders of the bone system (in particular, osteoporosis).

Currently, recombinant growth hormone obtained by rDNA technology is used to normalize growth. In our country, such drugs as Norditropin, Genotropin, Humatrop, Saizen, Rastan are often used. The modern scheme of therapy for growth correction is as follows: every day in the evening subcutaneously inject the drug at a dosage of 0.05 mg per kilogram per day. Treatment is completed when the patient's bone age is equal to 15 years, against the background of a drop in growth of up to 2 cm per year. Prolonged growth-stimulating treatment during puberty leads to improved final growth. The therapy is monitored by a pediatric endocrinologist, with repeated monitoring every six months.

Estrogen replacement treatment is prescribed to mimic adequate sexual development as much as possible. Normally, the development of the mammary glands starts at about 10 years of age, after which the first monthly response begins. Before prescribing estrogen therapy, gonadotropic hormones are evaluated to ensure that spontaneous puberty is not possible. If gonadotropins are elevated, estrogen therapy is started.

With normal values of LH and FSH perform ultrasound of the uterus and appendages. Treatment is carried out taking into account the dose-dependent effect of estrogen on skeletal maturation: low doses stimulate skeletal growth, and high doses inhibit it. It has been found out that substitutive use of estradiol from the age of 12 years has no adverse effect on the final growth of patients on the background of growth hormone treatment. It is allowed to use oral preparations, transdermal means (patches, gels, etc.). The initial dosage can be a tenth or an eighth of the adult amount of estradiol, with a further increase over 24 months.

After two years switch to dosages equivalent for girls: 2 mg/day estradiol, 0.1 mg in transdermal version, 2.5 mg/month estradiol dipropionate in the form of v/m injections. Progesterone is connected after 2 years from the start of estrogen intake, before the onset of menstruation.

The use of synthetic contraceptives is undesirable.

In adulthood, imitation of adequate ovarian function is performed by prescribing substitute estrogenic and progesterone preparations. The use of conjugated or natural estrogens is recommended:

• Premarin at a dosage of 0.625-1.25 mg per day;
• Estrophene at a dosage of 2 mg per day.

Progesterone-containing drugs are used as an adjunct, from day 15 to 25 of cyclic treatment:

• Medroxyprogesterone acetate 5 to 10 mg per day;
• Norethindrone 1-2 mg per day.

It is allowed to prescribe combined means, which contain natural estrogens and gestagens (Divina, Cycloprogynova), according to the cyclic scheme.

The use of synthetic estrogen-containing drugs or contraceptives containing ethinylestradiol is discouraged. End estrogens and progestins at the age of the expected norm of menopause (from 50 years), or continue taking only estrogens in order to prevent osteoporosis. Calcium (1000-1200 mg per day) is taken prophylactically for the same purpose.

Hormone replacement therapy for gonadal dysgenesis is often accompanied by undesirable side effects, such as:

• pain in the breast area;
• nausea, increased appetite, abdominal pain;
• changes in the amount of cervical mucus;
• a feeling of fatigue, general weakness;
• muscle spasms in the extremities;
• weight gain, edema;
• increased risk of thrombosis.

However, despite the possible side effects, the use of replacement drugs for gonadal dysgenesis is a therapeutic necessity endorsed by international medical experts. [5]

Physiotherapy treatment

Physical therapy is not the definitive treatment for gonadal dysgenesis. However, this adjunctive treatment helps to improve the well-being of patients and enhances the effectiveness of other treatments.

• Acupuncture points nei-guan, da-ling, tung-li, meng-men, sony-yiqiao.
• Aerotherapy - taking air baths with air temperature of at least 18°C.
• Hydrotherapy (dousing, rubdowns, rain showers, coniferous, contrast, sage baths).
• Balneotherapy (carbon dioxide, pearl, oxygen, radon, iodobromic baths).
• Endonasal electrophoresis of magnesium, lithium, bromine.

Magnetotherapy on the collar zone is prescribed to accelerate blood circulation, normalize pressure in the vessels, improve the work of the pituitary-hypothalamic system. The procedures are repeated daily for 12-15 days.

In addition, physical therapy and massage are prescribed to improve trophics and nerve conduction, strengthening the musculoskeletal system. General massage, kneading of extremities and growth zones, massage of the collar zone and spinal muscles are practiced.

Herbal treatment

Phytoestrogens are natural substances contained in various herbs that have estrogenic properties. The main sources of such natural estrogens are soy and soy-based products. Phytoestrogens have structural similarity to estradiol and bind to estrogen receptors.

Another group of substances useful in gonadal dysgenesis are phytohormones. These are components of medicinal plants that do not have estrogenic ability, but show a favorable effect on the quality of the monthly cycle. Phytohormones are present in such herbs as cimicifuga, malbrosia, raconticin and so on. There are a number of pharmacy preparations, the composition of which is represented exclusively by plant components:

• Climadinon (contains 20 mg of cimicifuga extract, taken 1 tablet twice a day);
• Remens (represented by five plant components, taken 30 drops twice a day);
• Mastodinon (represented by extracts of tsimitsifuga, stemleaf basilistnikovidnyi, alpine violet, groudannik bitter, casatnik variegated, tiger lily and is taken 30 drops twice a day).

Among folk remedies, the following are particularly popular:

• Infusion of white mistletoe is prepared from 2 tsp. Crushed raw material and 250 ml of boiling water. Insist under a lid for twenty-four hours. Take the obtained remedy during the day, divided into three portions, after meals.
• Tincture of shepherd's purse is prepared from the proportion of 1 part of the plant to 10 parts of vodka. The remedy is insisted for 14 days, take 35 drops three times a day.
• Infusion of Aralia Manchurian is prepared from 1 tsp. Crushed raw material of the plant and 1 liter of boiling water. Infusion is infused for ten minutes, take 1 tbsp. L. Up to five times a day daily.

Surgical treatment

Laparoscopy is performed to visualize the gonads and decide whether gonadectomy is necessary.

Gonadectomy is performed if immature tissue is found in the gonads. If there is mature ovarian tissue in the lobular ovotesticular gonad, separation with preservation of the ovarian component is performed. The technical side of the surgical intervention is determined by the structure of the gonad. If necessary, feminizing plasty is performed.

However, surgeons do not always have to choose partial resection of the ovotestis on the basis of intraoperative histologic diagnosis, preservation of the sex-specific glands, and removal of undifferentiated areas of the gonads. Gonadectomy is much more commonly resorted to due to the increased risk of ovotesticular gonad malignancy. According to statistics, malignant processes in the form of dysgerminomas, seminomas, gonadoblastomas are diagnosed in almost 3% of patients.

Prevention

Since the underlying causes of gonadal dysgenesis have not been fully elucidated, experts have not yet developed a clear scheme for the prevention of the disease. Specific prevention to date does not exist. Doctors advise to observe the following general rules:

• Future parents should refrain from drinking alcohol, from smoking and, even more so, from using drugs.
• An expectant mother should pay attention to nutrition. It is necessary to give preference to natural, fresh, nutritious food, without chemical additives. Optimally, if the menu will be adjusted by a specialist nutritionist.
• It is necessary to devote enough time to physical activity (1-2 hours a day, involving all muscle groups).
• During pregnancy, it is important for women to avoid contact with chemicals and radiation. If the professional activity is associated with risk factors, it is necessary to change the job even before planning pregnancy.
• A pregnant woman should avoid viral, microbial and fungal infections.
• Stressful and psycho-emotional situations should be avoided if possible.
• Even at the planning stage of pregnancy, you should visit a geneticist to assess the likelihood of fetal abnormalities.

Forecast

Timely diagnosis, a full course of research with subsequent medical supervision, comprehensive treatment with all available and recommended medications allows patients with gonadal dysgenesis to live an almost full and active life, without any domestic, psychological and social problems.

The overall prognosis for life is considered satisfactory if the patient does not have gross cardiovascular malformations.

The growth of patients, even with growth hormone treatment, is often shorter than the population average. Life expectancy may also be shorter, but with regular medical supervision and preventive measures, life expectancy is significantly increased.

The quality of the forecast is directly influenced by:

• timing of treatment initiation;
• Adequacy of doses of hormone replacement therapy;
• the proper selection of medications;
• Patients' compliance with doctors' recommendations.

With early rehabilitation, a patient with gonadal dysgenesis can have a normally formed uterus, breast glands, and menstruation. Natural independent pregnancy is rare: assisted reproductive technologies are recommended.

Literature used

Reproductive endocrinolgy. A guide for physicians. A.V. Dreval, 2014

Baseline and Clinical Endocrinology. Book 2 - David Gardner, Dolores Schobeck