Delayed sexual development in women. Causes of delayed puberty

1. Etiology

A. Constitutional delay in sexual development is more common in boys than in girls. At the same time, the height is below the 3rd percentile of the age norm, the growth rate is normal, and the pubertal growth acceleration is delayed by several years.

b. Delayed sexual development occurs in diseases of the central nervous system (tumors of the pituitary gland and hypothalamus, congenital vascular anomalies, severe head injuries, asphyxia during childbirth), Kallmann and Lawrence-Moon-Biedl syndromes, as well as psychosocial deprivation.

V. The incidence of incomplete puberty and delayed puberty is increased in anorexia nervosa; severe diseases of the heart, lungs, kidneys or gastrointestinal tract; malabsorption syndrome; weight loss or obesity; sickle cell anemia, thalassemia, chronic infections, hypothyroidism, primary adrenal insufficiency.

G. Primary hypogonadism is observed in Turner, Noonan, Klinefelter, Reifenstein syndromes, seminiferous tubule dysplasia, testicular feminization, “pure” or mixed gonadal dysgenesis, cryptorchidism, anorchia, trauma, infection, irradiation of the pelvic area, as well as surgical castration.

2. Examination. Because the normal timing of pubertal development varies, delayed puberty should be suspected if a girl over 14 years of age or a boy over 15 years of age completely lacks secondary sexual characteristics or sexual development in adolescents is not completed within 5 years.

A. When collecting anamnesis, attention is paid to the details and chronology of sexual development, physical development, nutritional status, symptoms of central nervous system damage (for example, anosmia). Family history includes information about disorders of sexual development and sexual differentiation, amenorrhea, and infertility.

b. During a physical examination, anthropometric indicators are determined (height, weight, arm span, ratio of the length of the upper and lower half of the body), the stage of sexual development is assessed, the external genitalia are carefully examined to identify disorders of sexual differentiation, the groin area is palpated, a gynecological examination is performed, and a digital rectal examination is performed. , detect hereditary diseases. Virilization in girls or incomplete masculinization in boys indicates a disorder of sexual development and requires additional examination.

V. Analysis of physical development charts is required. Thus, a slight acceleration in growth may be the first sign of the onset of puberty, and a decrease in growth rate may be a symptom of delayed sexual development.

G.Laboratory and instrumental studies. A complete blood count, urinalysis, bone age assessment, CT or MRI of the head, and measurement of LH, FSH, estrogen and DHEA sulfate levels are required. Sometimes the karyotype is determined.

3. Diagnostics

A. The diagnosis of constitutional (hereditary) delayed sexual development in a healthy child is always presumptive, since it is confirmed only after the end of puberty.

b. In hypothalamic and pituitary insufficiency, LH and FSH levels are low (prepubertal). For differential diagnosis of hypothalamic and pituitary disorders, a stimulation test with gonadorelin is performed.

V. In primary hypogonadism, gonadotropin hormone levels usually increase by age 12–13.

4. Treatment. When starting treatment, it is necessary to take into account growth, the prognosis of final height, the psychological consequences of delayed sexual development, as well as the side effects of hormonal therapy.

A.Constitutional delay of sexual development. It is necessary to convince the child and his family members that there are no deviations from the norm and that normal puberty will soon begin. Constant monitoring and assessment of sexual development and moral support are recommended. In some cases, short-term hormonal therapy is prescribed to prevent psychological trauma.

b.Diseases of the central nervous system. In the case of secondary hypogonadism (reduced secretion of LH and FSH), hormonal therapy is indicated to stimulate sexual development. The emergence of GnRH analogues has revolutionized the treatment of such patients. With normal pituitary function, treatment with GnRH analogues allows completion of sexual development and fertility.

1) For girls replacement therapy includes conjugated estrogens for oral administration at a dose of 0.3 mg/day. Over the course of 9-12 months, the dose is gradually increased to 0.65-1.25 mg/day. Medroxyprogesterone is then added to induce menstruation, 10 mg/day from the 12th to the 25th day of each month.

2) In boys The most effective is hCG at a dose of 1000-2500 units intramuscularly every 5 days. The dose is adjusted depending on serum testosterone levels.

V.Systemic diseases. Treatment of systemic disease can help normalize sexual development. Sometimes hormone replacement therapy is required.

G.Primary (hypergonadotropic) hypogonadism

1) For girls Estrogens and progesterone are prescribed.

2) For boys with preserved testicular function, hCG is prescribed. If there is no reaction to hCG, then masculinization, normal libido and potency are ensured with the help of testosterone, 100-200 mg IM every 2-4 weeks. Fertility prognosis is determined.

J. Gref (ed.) "Pediatrics", Moscow, "Practice", 1997

Late menstruation: what threatens delayed sexual development in girls?

During puberty, parents should be especially attentive to their children, because sexual dysfunction in girls can often be corrected in the early stages of pathology development. If you do not pay attention to delayed sexual development in a girl in time, over time this can cause infertility in a woman at a more mature age.

You can worry about delayed sexual development if a girl’s menstruation does not begin until she is 15-16 years old. This pathology in medicine is called “primary amenorrhea.” The reasons for this phenomenon are different - from congenital absence of the uterus to pathology of the pituitary gland. Quite often, delayed sexual development in girls is caused by diet, stress, and excessive physical activity. Menstruation occurs later in girls who engage in very intense sports or heavy physical labor.

If your child aged 15-16 has never had menstruation, be sure to consult a teenage gynecologist to find out the state of the girl’s reproductive system.

Symptoms of late puberty in girls

In addition to the absence of menstruation, primary amenorrhea is usually accompanied by a delay in the development of secondary sexual characteristics: the mammary glands are practically undeveloped, there is scanty hair in the armpits and pubic area, and the genitals are also underdeveloped. A girl may exhibit signs of hyperandrogenemia—greasy skin, excess facial and chest hair, juvenile acne.

Symptoms of late puberty in girls also include:

• reduction in the amount of subcutaneous fat in female body types;
• moderate hypoplasia of the external and internal genitalia,
• weight loss;
• bradycardia - decreased heart rate;
• hypotension - low blood pressure;
• hypothermia - a decrease in core body temperature below 35 °C;
• irritability, aggressiveness;
• complete loss of appetite and aversion to food.

Delayed puberty in girls is a symptom of pathological processes

Amenorrhea is a symptom of the fact that pathological processes are occurring in a girl’s body associated with genetic predisposition or metabolic disorders. If cyclical changes do not occur in a girl’s body, then such amenorrhea is called true, but if cyclic changes occur, but menstrual blood is not released, then this form of amenorrhea is called false.

Reasons for the development of primary amenorrhea in girls

Her body weight plays a big role in a girl’s puberty. Typically, thin girls with a body weight of 45-47 kg begin puberty two to three years later than girls with normal weight, their mammary glands develop more slowly, and menstruation appears at about 16 years of age.

In some families, girls have a genetic predisposition to late puberty; amenorrhea in such families was once observed in the mother and other relatives, so girls usually mature later than their peers.

The causes of late puberty in girls also include:

• emotional and psychological shocks, such as shock, severe fear, stress;
• intensive sports - girls who professionally play sports and therefore experience intense physical activity are several years behind their peers in sexual development;
• diseases such as rheumatism, heart defects, liver diseases, tuberculosis, typhus, severe mercury and lead poisoning, alcoholism;
• hormonal pathologies - damage to the ovaries, adrenal glands, thyroid gland, pituitary gland, hypothalamus. The consequence of weak ovarian activity may be their disease or low activity of the pituitary gland and subcortical nerve nuclei, which stimulate ovarian function. The reasons are either their congenital underdevelopment, tumors, or the destruction of these structures by a pathological process. Low activity of subcortical structures is often a consequence of adverse effects on the fetus during pregnancy, birth trauma, diseases suffered by the girl in childhood and traumatic brain injuries;
• Turner syndrome is a chromosomal disease with anomalies of physical development, expressed by short stature and sexual infantilism at the age of puberty;
• severe chronic diseases such as diabetes;
• long-term use of hormonal, chemotherapy, psychotropic drugs;
• eating disorders, malnutrition, dieting, dystrophy or obesity, including complete refusal to eat (anorexia);
• change of time zone, permanent place of residence;
• polycystic ovary syndrome;
• increase in the level of pituitary hormones in the blood.

Causes of false delayed puberty in girls

False amenorrhea is caused by malformations of the uterus and vagina; they are very diverse, many appear only during the girl’s puberty. In these cases, surgical treatment is necessary, often followed by vaginal plastic surgery.

Hymenal atresia is the complete absence of an opening in the hymen. This pathology appears immediately shortly after the first menstruation. Blood accumulates in the vagina, the patient may complain of pain in the lower abdomen, painful urination, and a feeling of “fullness” in the pelvic area.

The causes of true delayed sexual development in girls can be mental or physical overload, a depressed mental state of a teenager, depression due to an unfavorable conflict situation in the family, school, or inability to find one’s place in the society of peers or adults.

Complete or partial absence of the vagina with a functioning uterus. At the same time, the size of the uterus increases monthly during menstruation, and the intensity of pain increases.

Underdevelopment of the uterus, which can be combined with underdevelopment of the vagina.

Features of diagnosis of late puberty

Diagnosis of primary amenorrhea is quite difficult. To do this, the girl will need to undergo an examination by an obstetrician-gynecologist, geneticist, neurologist, psychiatrist and endocrinologist. At the first appointment, the doctor will ask the mother about the specifics of pregnancy and childbirth, find out possible complications during childbirth, what diseases the girl had, whether she had any skull injuries or neurological diseases. 40% of mothers of girls with late puberty had complications during childbirth, and 30% of girls with delayed development of the reproductive system are seen by a neurologist.

To determine the cause of amenorrhea and develop a treatment plan, you will need to take:

• blood test for hormones;
• clinical and biochemical blood test;
• general urine analysis.

The attending physician may prescribe the following instrumental research methods:

• Ultrasound of the uterus, appendages, mammary glands, abdominal organs, kidneys and adrenal glands, thyroid and parathyroid glands;
• MRI of the brain, pelvic organs;
• hysterosalpingography;
• mammography.

Treatment of amenorrhea

Amenorrhea does not pose a threat to the patient’s life, but is often accompanied by infertility, and therefore girls with this disease often experience psycho-emotional disorders and a feeling of inferiority.

The choice of treatment for delayed puberty depends on its underlying cause. Often, a special diet to increase the volume of muscle and fat tissue, and hormone replacement therapy to stimulate the development of secondary sexual characteristics and the appearance of menstruation helps to cope with its consequences. If the cause of amenorrhea is anatomical, surgical intervention is necessary for treatment.

To ensure that your child does not experience delays in sexual development, you must take care of maintaining the girl’s health. She must eat right, exercise regularly and moderately, and alternate between work and rest. It is necessary to promptly and efficiently treat the girl’s endocrine and central nervous system diseases. If you suspect amenorrhea, do not delay visiting a specialist doctor.

In case of delay in sexual development associated with dysfunction of the pituitary gland and ovaries, with severe infantilism, hormonal therapy is necessary. It is carried out together with physiotherapy. The attending physician may prescribe mud therapy procedures, endonasal electrophoresis, abdominal-sacral diathermy, and galvanic collar. A psychoneurologist, if necessary, can prescribe the use of psychotropic drugs.

INTRODUCTION

Often parents (sometimes the children themselves) turn to doctors - pediatricians, therapists, urologists, endocrinologists - with complaints about a lag in the development of the genital organs relative to their peers. Some of these patients are referred for consultation by other specialists. In approximately 90% of cases, the examination reveals that there is no delay in sexual development in the child (teenager, young man). However, the vast majority of doctors, when addressing these issues, are guided only by the subjective perception of the patient’s somatic status and their practical experience. Meanwhile, objectification of the medical history, examination, and laboratory test results is necessary to obtain reliable results, regardless of the doctor’s personal experience and subjective opinion.

The timing of the onset of puberty in boys varies greatly depending on hereditary predisposition, nutritional patterns, previous diseases, etc. Consequently, when assessing the level of general and puberty, one can focus only on the average age of onset of signs of puberty in the majority of adolescents in the population and their significant delay should be considered as delayed sexual development.

The frequency of delayed puberty according to the literature ranges from 0.4% to 2.5%, which is due to the lack of clear criteria for the age limits of puberty and possible overdiagnosis.

One of the indirect signs (etiological factors) of a possible delay in sexual development in the pre-pubertal period can be considered testicular retention. Cryptorchidism leads to disruption of the development of testicular tissue and, as a consequence, disruption of the hormonal regulation of sexual development and maturation (especially with bilateral cryptorchidism). It is more difficult to determine uniform recommendations for the so-called sliding testicle or pseudoretention (false cryptorchidism). Most pediatricians and surgeons tend to consider this a normal option. However, even the periodic presence of the testicle in the inguinal canal changes the conditions of its existence and can lead to damage to the testicular tissue. L. M. Skorodok and O. N. Savchenko believe that we can talk about pathology if false cryptorchidism persists after the first pubertal enlargement of the testicles in the range from 11.5 to 12 years.

Even at pre-pubertal age, some boys prone to obesity experience feminization of the figure, false gynecomastia. This cannot be considered a pathology, but in the future it makes sense to more carefully monitor their puberty.

Hypogonadism, in contrast to delayed puberty, which can be considered a borderline condition, is a disease with a serious disorder in the functioning of the entire reproductive system, requiring long-term (sometimes permanent) hormonal therapy.

DEVELOPMENT NORMS FOR BOYS

Before talking about disorders of sexual development in boys, it is necessary to determine what is their statistical norm and determine the age dynamics of these indicators.

First, it is necessary to determine whether the boy’s general somatic development corresponds to the norm. To do this, we propose to use a summary standard centile table of the distribution of height, weight and chest circumference of boys by age (Table No. 13).

Next, it is necessary to determine how much the boy’s sexual development corresponds to the statistical norm. To assess the development of the genital organs, you can use the following table proposed by L. M. Skorodok and O. N. Savchenko (Table No. 13).

The appearance of secondary sexual characteristics lags behind the initial increase in the external genitalia by approximately 1 year. So, if the first significant enlargement of the testicles occurs at 11? years, then the diameter of the penis increases at 12 years, length - at 13 years, then its size increases gradually, mainly due to the diameter. Hair at the base of the penis or pubic area appears on average at 12.8 years of age (with an interval of 11 years to 14 years 11 months). Then other signs of puberty appear successively - a mutation of the voice, an increase in the cartilage of the larynx, acne, hair growth on the face, in the axillary cavities. By 15? By the time most teenagers reach puberty, pubic hair takes on a masculine appearance.

Adequate erections occur in boys on average at 13 years of age, and the first ejaculations occur at 14 years of age. However, since the second half of the twentieth century, every 10 years there has been a significantly earlier onset of puberty in adolescents.

Table No. 14 presents anthropometric indicators in healthy boys.

To divide puberty into stages, we propose to use the Tanner scale (1955) as modified by L. M. Skorodok and O. N. Savchenko (Table No. 15).

During puberty, a boy's hormonal levels change significantly. The content of sex hormones in blood serum and urine is presented in table. No. 16-19 in comparison with various options for delayed sexual development.

Based on the study of circadian (daily) rhythms of gonadotropic hormones and testosterone in healthy boys and with delayed puberty at the age of 11-13 years, we can recommend the time of collecting material for research when the discrepancy in levels is greatest. For LH it is 6.00 (difference 20 and 150 IU/l, respectively) or 14.00 (10 and 55), for FSH - 2.00 (15 and 4 IU/l, respectively) or 8.30 (14 and 7), for testosterone - from 0.00 to 6.00 (from 4 to 5 and from 1 to 3 nmol/l, respectively).

By the way, the length of the penis and the volume of the testicles do not depend on body length and muscle mass, but are inversely related to the amount of fat in the body (due to the good solubility of sex steroids in fats, they are partially utilized even during their normal production in the body) , which also needs to be taken into account when assessing the development of the genital organs of boys.

The causes of delayed sexual development can be very diverse. In families where parents and older relatives develop secondary sexual characteristics, ejaculation and menarche late, children tend to be delayed in sexual development. Excessive amounts of fatty tissue, infections, traumatic brain injuries and asphyxia in the intrapartum period, somatic diseases in childhood can also lead to a delay in both general and sexual development. There is also evidence of the influence of a number of factors in the prenatal period, which can also lead to this pathology.

Classification of delayed sexual development (L. M. Skorodok and O. N. Savchenko) includes the following options:

1. Constitutional somatogenic form (CSF);

2. False adiposogenital dystrophy (fAGD);

3. Microgenitalism (MG);

4. Irregular puberty syndrome (IPS)

CONSTITUTIONAL-SOMATOGENIC FORM

CONSTITUTIONAL-SOMATOGENOUS FORM of delayed sexual development is expressed in the absence of pubertal development of the testicles, penis, scrotum and a significant delay in the appearance of secondary sexual characteristics. As a rule, this is combined with a lag in physical development and ossification of the skeleton. Developmental delay in this form is closely related either to constitutional characteristics and family predisposition, or to somatic diseases.

Such boys, long before puberty, often have small external genitalia and have true or false cryptorchidism. Signs of delayed sexual development most fully manifest themselves at the age of 14 and are expressed, first of all, in the absence of age-related dynamics in the size of the external genitalia, secondary sexual characteristics are not expressed even at the age of 14-15, spontaneous erections of the penis are rare with a slight increase cavernous bodies, emissions are always absent. Growth rates are significantly slower, bone age lags behind the actual age, body weight is insufficient (mainly a deficiency of the muscle component), and dynamometry indicators are low.

The discrepancy between constitutional indicators and hormone levels in healthy boys and in the group with delayed sexual development of constitutional-somatogenic genesis is presented in Table. No. 16.

The basis for developmental delay is a decrease in the hormonal activity of the testicles and their production of predominantly inactive androgens. In addition, with delayed puberty, delayed maturation of testicular receptors probably occurs, leading to a decrease in hormone-receptor interaction in the LH system - Leydig cells. Dysfunction of the hypothalamic-pituitary system is either completely absent, or their role is limited to a latent insufficiency of the FSH system, revealed only by a functional test with spironolocatone.

FALSE ADIPOSOGENITAL DYSTROPHY

FALSE ADIPOSOGENITAL DYSTROPHY is characterized by underdevelopment of the external genitalia and the absence of secondary sexual characteristics against the background of severe obesity, which, as a rule, develops in prepubertal age and then progresses. False gynecomastia, feminization of the figure, and a gradual lag in the development of the external genitalia are formed. Secondary sexual characteristics are absent even at 14-15 years of age, although in some adolescents weak pubic hair can be detected - single straight hair at the base of the penis. There are also no other signs of puberty - juvenile acne, voice mutation, enlargement of the thyroid cartilage. Erections are very rare, and the penis enlarges slightly. No wet dreams. Obesity can be accompanied by diabetic-type carbohydrate metabolism disorders, increased levels of cholesterol and free fatty acids in the blood; various diencephalic signs can often be detected - stripes of stretched skin, predominantly pale pink in color, localized in the chest, abdomen, thighs, impaired thermoregulation, neurocirculatory dystonia of the hypertonic or hypotonic type, hyperostosis of the internal plate of the frontal bone. There is a pronounced family predisposition in some of these boys to obesity and delayed sexual development.

Based on the study of the circadian (daily) rhythms of gonadotropic hormones and testosterone in healthy boys and with LAGD aged 11-13 years, we can recommend the time of sampling for research when the discrepancy in levels is greatest. For LH, the results do not differ significantly, but for a test with clomiphene citrate it is 2.00 (difference 14 and 110 IU/l, respectively) or 8.30 (13 and 125 IU/l), for FSH - from 20.00 to 8.30 (10-14 in healthy and 1-5 IU/l for LAGD, respectively), and when testing with clomiphene citrate 8-13 IU/l, for testosterone - from 0.00 to 8.00 (from 3.5 to 5 in healthy people and from 0.5 to 0.8 nmol/ l for LAHD, respectively).

The dynamics of developmental indicators in comparison in healthy boys and with LAGD are presented in Table. No. 17. The leading factor in delayed sexual development in this case is a decrease in the gonadotropic function of the pituitary gland at an age corresponding to the initial stage of puberty. Subsequently, pituitary activity is restored, which ultimately ensures puberty, but later than in the population. Apparently, both the decrease in the gonadotropic function of the pituitary gland and obesity in these boys are caused by primary, often functional changes in the hypothalamus. One should also take into account the pronounced family predisposition of some of these boys to obesity and delayed sexual development.

MICROPENIS or MICROGENITALISM

MICROPENIS or MICROGENITALISM is characterized by predominant underdevelopment of the penis with satisfactory testicle sizes and often timely appearance of secondary sexual characteristics. Strictly speaking, this form is not literally a delay in sexual development, since in most boys with a micropenis, puberty begins and passes at the usual time. This form can be considered as a unique type of delayed sexual development, limited only by insufficient growth of the corpora cavernosa. In a significant proportion of newborns and older children, the penis is not detectable at all during external examination - only the foreskin or the opening of the urethra is visible above the surface of the skin in the pubic area. However, with palpation it is possible in all cases to palpate the cavernous bodies and the head, hidden in the subcutaneous fatty tissue, and bring them out, pushing back the soft tissue with the second hand. Boys with a micropenis are often overweight.

It is necessary to take into account that micropenis is often one of the leading symptoms of some forms of hypogonadism, such as incomplete masculinization syndrome, testicular dysgenesis, Lawrence-Moon-Bardet-Biedl syndrome, Prader-Willi syndrome, etc. Micropenis can be a consequence of a congenital anomaly of the development of the cavernous bodies . Severe underdevelopment of the penis in some families is inherited as a dominant trait. It should be emphasized that in some adolescents with a micropenis, pubertal enlargement of the testicles and the appearance of secondary sexual characteristics are delayed.

The dynamics of development indicators in comparison in healthy boys and with microgenitalism are presented in Table. No. 18.

Underdevelopment of the penis, congenital and often familial, is unlikely to be associated with testicular failure. The pituitary-gonadal relationship in these boys is not disturbed, and testosterone production is even slightly increased. Apparently, the intrauterine formation of the reproductive tract in them occurs with sufficient production and secretion of testosterone, but low tissue sensitivity of the corpora cavernosa to androgens. A genetically determined defective hormone-receptor interaction at the level of the target tissue for testosterone leads to insufficient growth of the penis, which in some of these individuals is accompanied by an increase in testosterone production in accordance with the feedback principle.

ABNORMAL PUBERTY SYNDROME

ABNORMAL PUBERTY SYNDROME is characterized by the appearance of secondary hair growth without any pubertal changes in the external genitalia. Pubertal hair growth usually begins at an age corresponding to the initial stage of puberty (11-12 years). In 32% of those examined, false retention of the testicles was detected. Boys with this form of delayed puberty are usually of normal height and overweight, however, it is not uncommon to see boys who are not obese. Fatty tissue is deposited predominantly in the female type - on the hips, abdomen, and chest. M. b. false or true gynecomastia. Characteristic is the acceleration of skeletal differentiation (an average of 1 year ahead of the chronological age of the bones). The length of the arms, legs, and shoulder width are within the age norm, and the size of the pelvis is often larger than normal. In some people with SSP, dysfunctions of the diencephalic region are detected: polyphagia, arterial hypertension, pink stripes of skin stretching, etc.

It is necessary to distinguish between the syndrome of irregular puberty and the so-called premature adrenarche, when early puberty is combined with the timely development of other sexual characteristics of puberty.

After a test with spironolactone (veroshpiron) 150 mg/m2hd for 5 days. there is a sharp increase in LH at 16.00 - 00.00 to 75-120 IU/l (normal - 10).

Developmental indicators and laboratory test results in boys with SSP and healthy ones aged 11-13 years are presented in Table No. 8.

Excessive production of weak androgens by the adrenal cortex in the initial puberty and, probably, in the prepubertal period leads to complex changes in the hormonal regulation of the reproductive system with disturbances in the normal ratio and level of secretion of gonadotropic hormones, a decrease in the sensitivity of the gonads to LH and, as a consequence, a significant decrease in testosterone production in testicles. It is possible that the primary disorder is localized in the hypothalamus, a change in the function of which in the prepubertal period induces a discorrelation in the ACTH - adrenal cortex and gonadotropins - testes system.

Delayed puberty (DPS) is the absence of enlargement of the mammary glands in girls over 13 years of age, or development of secondary sexual characteristics at a time that exceeds the upper limit by 2.5 standard deviations age standard. In addition, the absence of menarche by the age of 15.5–16 years of a girl’s life or developmental cessation secondary sexual characteristics for more than 18 months or a delay in menarche of 5 years or more after a timely the beginning of mammary gland growth is also regarded as PVD. It should be noted that the appearance of sexual hair (pubic and axillary) should not be considered a marker of puberty.

SYNONYMS

Delayed sexual development of central origin, delayed sexual development of ovarian origin, gonadal dysgenesis, testicular feminization.

ICD-10 CODE
E30.0 Delayed puberty.
E.30.9 Puberty disorder, unspecified.
E45 Developmental delay caused by protein-energy deficiency.
E23.0 Hypopituitarism (hypogonadotropic hypogonadism, isolated gonadotropin deficiency, syndrome Kallmann, panhypopituitarism, pituitary cachexia, pituitary insufficiency NOS).
E23.1 Drug-induced hypopituitarism.
E.23.3 Hypothalamic dysfunction not elsewhere classified.
E89.3 Hypopituitarism occurring after medical procedures.
E.89.4 Ovarian hypofunction arising after medical procedures.
N91.0 Primary amenorrhea (impaired menstruation during puberty).
E28.3 Primary ovarian failure (low estrogen levels, persistent ovarian syndrome).
Q50.0 Congenital absence of ovaries (except Turner syndrome).
E34.5 Testicular feminization syndrome, androgen resistance syndrome.
Q56.0 Hermaphroditism, not elsewhere classified (gonad containing tissue components ovary and testicle).
Q87.1 Syndromes of congenital anomalies, manifested primarily by dwarfism (Russell–Silver syndrome).
Q96 Turner syndrome and its variants.
Q97 Other sex chromosome abnormalities, female phenotype, not elsewhere classified.
Q99.0 Mosaic [chimera] 46, XX/46, XY, true hermaphrodite.
Q99.1 46, XX true hermaphrodite.

EPIDEMIOLOGY

In the white population, about 2–3% of girls aged 12 years and 0.4% of girls aged 13 years do not have signs of puberty. In the structure of causes of PVD, the leading place is occupied by gonadal insufficiency (48.5%), then, in descending order of frequency, are hypothalamic insufficiency (29%), enzymatic defect synthesis of hormones (15%), isolated failure of the anterior pituitary gland (4%), pituitary tumors (0.5%), from of which 85% are prolactinomas. Prevalence of gonadal dysgenesis with karyotype 46,XY (Swyer syndrome) 1:100,000 newborn girls.

PREVENTION

Measures to prevent PVD in girls have not been developed. In central forms of the disease caused by deficiency nutrition or inadequate physical activity, advisable before the onset of puberty maintain a work-rest schedule with adequate nutrition. In families with constitutional forms of PVD observation by an endocrinologist and pediatric gynecologist is necessary from childhood. Prevention of gonadal dysgenesis and there are no testicles.

SCREENING

Screening with determination of sex chromatin in all newborns (laboratory confirmation of the child’s gender). Screening of growth dynamics is necessary in girls with stigmata of congenital syndromes for timely correction of growth rates puberty. Screening to determine annual growth dynamics, puberty, bone age, the content of gonadotropins (LH and FSH) and estradiol in the venous blood is necessary in girls during the treatment of PVD.

CLASSIFICATION

Currently, taking into account the level of damage to the reproductive system, three forms of PVD are distinguished.

• The constitutional form of PVD is a delay in the enlargement of the mammary glands and the absence of menarche in a somatically healthy woman. girls aged 13 years with equivalent physical (length and weight) and biological retardation (bone age) development.
• Hypogonadotropic hypogonadism - delayed sexual development caused by a pronounced deficiency of synthesis gonadotropic hormones due to aplasia or hypoplasia, damage, hereditary, sporadic or functional insufficiency of the hypothalamus and pituitary gland.
• Hypergonadotropic hypogonadism - PVD is caused by a congenital or acquired lack of hormone secretion gonads. Congenital forms are designated by dysgenesis or agenesis of the ovaries or testicles. Dysgenesis ovaries are divided into a typical form (Turner syndrome) and a pure form with a karyotype of 46, XX. Dysgenesis testicles are classified according to the following headings: typical (45, XO/46, XY), pure (Swyer syndrome) and mixed, or asymmetrical. In the typical form, patients experience multiple stigmata of embryogenesis, characteristic of Turner syndrome. The pure form is characterized by ribbon-shaped gonads in the absence of somatic abnormalities development. The mixed form is distinguished by asymmetrical variants of the development of the internal gonads (undifferentiated cord on one side and a testicle or tumor on the opposite side; absence of a gonad on one side side and tumor, cord or testicle on the opposite side). However, in recent years, in foreign literature, more and more often meet the division of XY dysgenesis (with the exception of Turner syndrome) into complete and incomplete forms (complete and partial gonadal dysgenesis), which expresses the opinion about gonadal dysgenesis as different parts of one pathogenetic mechanism of sexual differentiation disorders. Thus, this pathology is considered as one disease, as different spectrums of 46, XY gonadal dysgenesis.

ETIOLOGY AND PATHOGENESIS

CONSTITUTIONAL FORM OF ZPS

Constitutional PVD is usually hereditary. Various etiological factors lead to formation of the syndrome of constitutional delay of puberty, influencing the key link of puberty-impulse secretion of hypothalamic LH releasing factor. Pathogenetic mechanisms of influence of polyetiological The factors leading to late activation of hypothalamic-pituitary function remain unclear. Numerous studies are devoted to the study of monoamine control of hypothalamic-pituitary function in children with delayed puberty. A general trend in changes in the concentration of catecholamines was revealed: a decrease in the levels of norepinephrine and adrenaline and increased serotonin concentrations. Another suspected reason for delayed puberty is functional hyperprolactinemia, which is associated with a decrease in dopaminergic tone, which leads to decrease in impulse secretion of both gonadotropic hormones and growth hormone.

PVD IN HYPOGONADOTROPIC HYPOGONADISM (CENTRAL GENESIS)

The basis of PVD in hypogonadotropic hypogonadism is a deficiency in the secretion of gonadotropic hormones as a result congenital or acquired disorders of the central nervous system. PVD was observed in patients with cysts and tumors of the central nervous system (pouch cysts Rathke, craniopharyngiomas, germinomas, gliomas of the optic nerve and hypothalamus, astrocytomas, pituitary tumors, including including prolactinomas, corticotropinomas, somatotropinomas, pituitary adenomas in patients with multiple endocrine neoplasia type 1).

PVD occurs in patients with developmental anomalies of cerebral vessels, hypoplasia of the septo-optic region and anterior lobes of the pituitary gland, post-infectious (tuberculosis, syphilis, sarcoidosis, etc.) and post-radiation (irradiation of the area tumor growth) lesions of the central nervous system, head injuries (during childbirth and neurosurgical operations). Among familial and sporadic congenital diseases accompanied by PVD, Prader–Willi syndromes are known and Lawrence-Moon-Bardet-Biedl, Russell-Silver, Hand-Schüller-Christian syndrome, or histiocytosis X (histiocytosis pituitary gland and hypothalamus with Langerhans cells and their precursors), and lymphocytic hypophysitis. Towards development hypogonadotropic hypogonadism results from a congenital absence or decreased ability of the hypothalamus secrete GnRH due to mutations in the KAL1 (Kalmann syndrome), FGFR1, GPR54, GnRH receptor gene, and leptin, and the pituitary gland - gonadotropins (deficiency of many tropic hormones due to mutations of the PROP1, HESX1 and PIT1, isolated FSH deficiency due to mutation of the FSH b subunit gene, prohormone convertase1).

PVD accompanies severe chronic systemic diseases. These include: uncompensated heart defects, bronchopulmonary, renal and liver failure, hemosiderosis in sickle cell anemia, thalassemia and Gaucher's disease, gastrointestinal diseases (celiac disease, pancreatitis, colitis with signs of malabsorption, Crohn's disease, cystic fibrosis), uncompensated endocrine diseases (hypothyroidism, diabetes mellitus, Itsenko– Cushing's, congenital leptin and somatotropic deficiency, hyperprolactinemia), chronic infections, including AIDS.

PVD can occur in girls due to malnutrition or eating disorders (forced or artificial starvation, nervous and psychogenic anorexia or bulimia, excess nutrition), increased physical loads that do not correspond to individual physiological capabilities (ballet, gymnastics, light and heavy athletics, figure skating, etc.), long-term use of glucocorticoids for medicinal purposes, abuse narcotic and psychotropic substances. It is possible that PVD may develop under the influence of negative environmental factors. factors, for example, an increase in lead levels in the blood serum above 3 μg/dl leads to delayed sexual intercourse development from 2 to 6 months.

PVD IN HYPERGONADOTROPIC HYPOGONADISM (GONADAL GENESIS)

Gonadal failure leads to a weakening of the blocking effect of ovarian steroids on the hypothalamic-pituitary region of the reproductive system and to a response increase in the secretion of gonadotropins.

The most common cause of the development of PVD in hypergonadotropic hypogonadism is agenesis or dysgenesis of the gonads or testicles during critical periods of human ontogenesis (primary hypergonadotropic hypogonadism). Most reasons hypergonadotropic hypogonadism - chromosomal and genetic abnormalities (Turner syndrome and its variants), familial and sporadic defects of ovarian embryogenesis (pure form of gonadal dysgenesis with karyotype 46, XX and 46, XY). The occurrence of 46, XY gonadal dysgenesis is caused by mutations of genes involved in differentiation body according to the male type. As a result of disruption of gonadogenesis in the embryonic period, the gonads are formed as connective tissue cords or undifferentiated gonads with the presence of male elements gonads (Sertoli cells, Leydig cells, tubular structures). In the absence of the influence of anti-Mullerian hormone (MIS substance) and androgens, the development of the internal and external genital organs occurs according to the female type.

Factors that disrupt normal embryogenesis may be inactivating mutations in the genes of the LH and FSH b subunits, mutations of LH and FSH receptors. Primary ovarian failure may result from autoimmune disorders, since in the blood serum of some patients with gonadal dysgenesis with a karyotype of 46, XX or 47, XXX, in addition loss of gonadal function, identified high titer of antibodies to the cytoplasmic component of the cells of the ovaries, thyroid and pancreas. Such patients show signs of hypothyroidism and diabetes mellitus. Gonadal insufficiency may occur with the development of resistance of normally developed ovaries to gonadotropic stimuli and premature ovarian failure. To rare autoimmune diseases accompanied by dysgenesis ovaries, include ataxia telangiectasia syndrome.

Metabolic disorders accompanied by primary ovarian failure include deficiency enzymes involved in the synthesis of ovarian hormones. Individuals with functional mutations in the gene responsible for formation of 20,22 desmolase, have a normal set of oocytes, but due to a defect in the biosynthesis of steroid hormones, their The ovaries are unable to secrete androgens and estrogens. Blockade of steroidogenesis at the stage of action of 17α-hydroxylase leads to the accumulation of progesterone and deoxycorticosterone. The mutation is transmitted vertically in the family and can affect both girls and boys. Gonadal dysgenesis is observed in some homozygous patients. Girls who lived to during puberty, have PVD, persistent arterial hypertension and high progesterone concentrations.

To a hereditarily determined enzymatic defect, accompanied by a delay in sexual and physical development are referred to as galactosemia. In this autosomal recessive disease, deficiency of galactose-1phosphate uridyl transferase, which is involved in the conversion of galactose to glucose, is observed.

PVD in girls may be caused by acquired ovarian failure (removal of the ovaries in early childhood, damage to the follicular apparatus during radiation or cytotoxic chemotherapy). There are messages about the development of hypergonadotropic hypogonadism after bilateral ovarian torsion, autoimmune oophoritis, infectious and purulent inflammatory processes. STF as a cause of PVD with primary amenorrhea is not recognized as true form of the RFQ, so it is presented in a separate chapter.

CLINICAL PICTURE

The main signs of PVD in girls against the background of hypofunction of the central parts of the regulation of the reproductive system (central form): absence or underdevelopment of secondary sexual characteristics at the age of 13–14 years, absence menstruation at the age of 15–16 years, hypoplasia of the external and internal genital organs in combination with growth retardation. A combination of the listed signs of hypoestrogenism with severe underweight or decreased vision, or disturbances in thermoregulation, or prolonged headaches, or other manifestations of neurological pathology may indicate a violation of central regulatory mechanisms.

The clinical picture of Turner syndrome (a typical form of gonadal dysgenesis) is characterized by a wide range chromosomal abnormalities. Patients have a stocky build and poor posture, disproportionately large shield-shaped chest with widely spaced nipples of undeveloped mammary glands, valgus deviation elbow and knee joints, aplasia of the phalanges, multiple birthmarks or vitiligo, hypoplasia of the IV and V phalanges and nails One often encounters a short “sphinx neck” with wing-shaped folds of skin (flipper neck) extending from ears to the shoulder process, and a low hairline on the neck. Patients are characterized by such bone changes facial skull, like a fish mouth, bird profile due to micro and retrognathia, deformation of teeth. Facial features changed due to strabismus, epicanthus, ptosis and deformation of the ears. Possible hearing impairment, congenital defects heart, aorta and urinary organs, meet hypothyroidism, autoimmune thyroiditis and diabetes mellitus. Underdevelopment of secondary sexual characteristics and genital infantilism are determined.

With erased forms, most congenital stigmas are not observed. However, even with normal growth of patients Irregularly shaped ears, high palates, low hair growth on the neck and hypoplasia IV and V may be found phalanges of the arms and legs. Secondary sexual characteristics do not appear in patients without taking estrogen drugs. At full In the absence of mammary glands, sparse hair growth in the pubis and armpits is possible. The structure of the external and internal genital organs is female, but the labia majora and minora, vagina and uterus underdeveloped. Cases of the so-called Turner syndrome with masculinization with karyotype 45, X/46, XY have been described, which characterized by clitoral hypertrophy and male pattern hair growth.

In patients with a pure form of gonadal dysgenesis, or Swyer's syndrome, with pronounced sexual infantilism there are no somatic developmental anomalies. The karyotype in patients is most often 46, XX, 46, XY. Observed family cases of pure form of gonadal dysgenesis necessitate a more thorough analysis of the family tree patients. The content of sex chromatin in most patients is reduced, but its amount is also normal (with karyotype 46, XX). Patients with a Y chromosome in the karyotype have a number of clinical and therapeutic diagnostic features. In addition to delayed sexual development, virilization of the external genitalia is possible with normal sexual hair growth in patients with a female type of structure of the internal genital organs and the location of dysgenetic gonads in the pelvic cavity.

DIAGNOSTICS

ANAMNESIS

Determine the presence of stigmas of hereditary and congenital syndromes and characteristics of puberty of both parents and immediate relatives (I and II degree of relationship). Family history should be ascertained during a conversation only with relatives of the patient, preferably the mother. Assess the features of intrauterine development, the course of the period newborns, growth rates and psychosomatic development, find out the living conditions and nutritional characteristics of girls with moment of birth, data on physical, psychological and emotional stress, clarify the age and character operations, course and treatment of diseases suffered over the years of life, as well as family history. Late menarche mother and other close relatives, delayed and delayed sexual hair growth and development of the external genitalia organs from the father are noted in the majority of girls with the familial form of PVD. In patients with Kallmann syndrome, it is specified presence in the family of relatives with a reduced sense of smell or complete anosmia.

Mothers of girls with gonadal dysgenesis often indicate exposure to physical and chemical substances during pregnancy. hazards, high or frequent radiation exposure (X-ray, microwave, laser and ultrasound radiation), metabolic and hormonal disorders, intoxication due to taking embryotoxic drugs and narcotic substances, acute infectious diseases, especially viral ones. Before puberty The development of a child with XY gonadal dysgenesis does not differ from peers. At puberty, despite timely sexual hair growth, development of mammary glands is absent, menarche does not occur.

PHYSICAL INVESTIGATION

Conduct a general examination, measure height and body weight, record distribution features and degree of development subcutaneous tissue. Height and body weight are compared with regional age standards. Note the signs hereditary syndromes, scars after operations, including on the skull. Assessment of the stage of puberty Maturation of girls is carried out taking into account the degree of development of the mammary glands and genital (pubic) hair (criteria Tanner 1969 with modern amendments).

When examining the external genitalia, along with assessing the pubic hairline, the shape and size are assessed clitoris, labia majora and minora, features of the hymen and external urethral opening. Pay attention to the color of the skin of the labia, the color of the mucous membrane of the vaginal vestibule, the nature of discharge from the genital tract.

Examination of the walls of the vagina and cervix (colposcopy) should be carried out using special tubes or children's mirrors of different sizes with lighting. To reduce diagnostic errors, rectoabdominal examination It is advisable to carry out after a cleansing enema, which is prescribed to the patient on the eve of the examination.

LABORATORY RESEARCH

• Hormonal examination.

Determination of the content of FSH, LH, estradiol and DHEAS (according to testosterone, cortisol, 17-OP, pregnenolone, progesterone, growth hormone, prolactin, TSH, free T4, AT to thyroid peroxidase) allows you to clarify hormonal disorders underlying PVD. With constitutional PVD and hypogonadotropic hypogonadism, decrease in the concentration of LH and FSH. With primary damage to the gonads in girls aged 11–12 years, the level of gonadotropins hormone levels are many times higher than the upper limit of normal for women of reproductive age. Estradiol level corresponds to pre-pubertal values ​​(less than 60 pmol/l) in all patients with PVD. DHEAS content in girls with hypergonadotropic hypogonadism corresponds to age; with hypogonadotropic hypogonadism, including functional - below the age standard.

Carrying out a test with GnRH agonists (analogs) (the use of the test in patients with bone age less than 11 years is not informative!). The test is carried out in the morning after a full sleep. Since the secretion of gonadotropins has pulsed in nature, the initial values ​​of LH and FSH should be determined twice - 15 minutes before and immediately before the administration of GnRH. Basal concentration is calculated as the arithmetic mean of 2 measurements. A drug containing a GnRH analogue for daily use is administered rapidly as a single intravenous dose in a dose of 25– 50 µg/m2 (usually 100 µg) followed by venous blood sampling at baseline, 30, 45, 60 and 90 minutes. Compare baseline with any three highest stimulated values. Maximum increase in LH levels determined 30 minutes after drug administration, FSH - 60–90 minutes. Increased gonadotropin levels
(same for LH and FSH) to values ​​exceeding 5 IU/l, indicates sufficient reserve and functional capabilities of the pituitary gland in patients with functional immaturity and diseases of the hypothalamus. When leveling up FSH up to 10 IU/l or more and its predominance over the LH level can indicate early menarche (in the year of examination). On the contrary, the predominance of the stimulated level of LH over FSH is a frequent sign of partial enzymatic defects in the synthesis of sex steroids in patients with PVD. No dynamics or slight increase stimulated level of LH and FSH, which does not reach pubertal values ​​(below 5 IU/l), indicates reduced reserve capabilities of the pituitary gland in patients with hypopituitarism of congenital or organic nature. A negative test does not allow distinguishing between the pathology of the hypothalamus and pituitary gland. Hypergonadotropic reaction to administration of a GnRH agonist (increase in LH and FSH levels to 50 IU/l or more), including in patients with initial pre-pubertal levels of gonadotropins, characteristic of PVD due to congenital or acquired ovarian failure.

Determination of the level of estradiol in venous blood 5–7 days after administration of the GnRH agonist allows us to note its significant increase in girls with functional PVD and congenital defects of GnRH receptors.

Determination of LH levels every 20–30 minutes at night or the total daily excretion of LH in urine. Promotion nocturnal secretion of LH in patients with pre-pubertal values ​​of gonadotropin content allows diagnosing constitutional variant of PVD, and the absence of differences between night and daytime LH levels is hypogonadotropic hypogonadism.

• A cytogenetic study (karyotype determination) is carried out for the timely detection of the Y chromosome or its fragments in patients with hypergonadotropic PVD. In molecular genetic studies, in approximately 20% of patients detect mutations in the SRY gene.
• Determination of autoantibodies to ovarian Ag in case of suspected autoimmune nature of ovarian failure.

INSTRUMENTAL RESEARCH

• Echography of the pelvic organs allows one to assess the initial degree of development of the uterus and ovaries, including identifying an increase in the diameter of cavity follicles in response to a test with GnRH agonists in girls with functional PVD. At In the constitutional form of PVD, the uterus and gonads are well visualized, have pre-pubertal dimensions, and in most In patients, single follicles are identified in the ovaries. With hypogonadotropic hypogonadism, the uterus and ovaries are underdeveloped, and with hypergonadotropic hypogonadism, instead of ovaries or testicles, cords lacking follicular apparatus, the anteroposterior size of which does not exceed 1 cm (in the absence of a tumor in the gonad).
• Echography of the thyroid gland and internal organs (according to indications) in patients with chronic somatic and endocrine diseases.
• The echographic picture of the mammary glands corresponds to a period of relative rest, characteristic of girls pre-pubescent age.
• X-ray of the left hand and wrist to determine bone age and growth prognosis. Under constitutional ZPS bone age, height, puberty correspond to each other. With isolated gonadotropic or gonadal PVD bone age significantly lags behind the calendar age, not exceeding 11.5–12 years at the time physiological end of puberty.
• MRI of the brain makes it possible to clarify the state of the hypothalamic-pituitary region during hypogonadotropic ZPS form. Small-step scanning of the pituitary gland and hypothalamus, including supplemented with contrast vascular network, allows you to detect tumors with a diameter of more than 5 mm, congenital and acquired hypoplasia or aplasia of the pituitary gland and hypothalamus, abnormalities of cerebral vessels, ectopia of the neurohypophysis, absent or pronounced underdevelopment of the olfactory bulbs in patients with Kallmann syndrome.
• X-ray of the skull is a reliable informative method for diagnosing tumors of the hypothalamic-pituitary region, deforming the sella turcica (expansion of the entrance, destruction of the back, increase in size, thinning and deformation contour of the walls and bottom).
• Densitometry (X-ray absorptiometry) is indicated for all girls with PVD for the purpose of early diagnosis of deficiency BMD.
• Ophthalmoscopy has diagnostic value for diagnosing specific retinitis pigmentosa in patients with Lawrence–Moon–Bardet–Biedl syndrome, color vision defects and retinal coloboma in patients with the syndrome Kallmann, retinopathy in patients with PVD with diabetes mellitus, chronic liver and kidney failure, and determination of visual fields - the degree of damage to the optic chiasm by brain tumors.
• Hearing test for suspected isolated gonadotropin deficiency or Turner syndrome with minimal clinical manifestations.
• Testing the sense of smell for suspected Kallmann syndrome in patients with hypogonadotropic hypogonadism.

DIFFERENTIAL DIAGNOSTICS

Constitutional form of the ZPS

Parents (2 times more often mothers) of girls with PVD have similar rates of puberty and growth. In patients note a lag in growth and body weight from the 3rd to the 6th month of life, which leads to a moderate delay in physical development at the age of 2–3 years. At the time of examination, girls’ height usually corresponds to the 3rd–25th centile indicators of healthy peers. It is possible to reduce the ratio of the upper and lower body segments due to more prolonged growth of the lower extremities with delayed ossification of the epiphyses of tubular bones. Linear speed growth with this form of PVD is at least 3.7 cm per year. The pubertal growth spurt is less pronounced and occurs between the ages of 14 to 18 years old. The body weight of patients corresponds to age standards, but the figure remains infantile due to weak accumulation of subcutaneous fat on the thighs and buttocks. Biological age lags behind chronological age by 1.6–4 of the year. There are no somatic anomalies, the development of all organs and systems lags behind by an equal number of years (retardation). Characteristic features - correspondence of physical (height) and sexual (breast and pubic hair growth) maturation to the level of biological maturity (bone age) and the same lag of these parameters from calendar age. During a gynecological examination, insufficient development of the large and small genitalia is determined. lips, thin mucous membrane of the vulva, vagina and cervix, underdevelopment of the uterus.

Hypogonadotropic hypogonadism

In the clinical picture, signs of significant PVD are combined with symptoms of chromosomal diseases, neurological symptoms (with volumetric, post-traumatic and post-inflammatory diseases of the central nervous system), characteristic changes in mental status (anorexia nervosa and bulimia), specific signs of endocrine and severe chronic somatic diseases.

In girls with Kallmann syndrome, physical development does not differ from regional age standards. ZPS has a pronounced character. The most common symptom of the syndrome is anosmia or hyposmia. Possible hearing loss cerebral ataxia, nystagmus, epilepsy, as well as malformations (cleft lip or hard palate, unpaired incisor
upper jaw, aplasia or hypoplasia of the kidney or optic bulb, shortening of the metacarpal bones). In patients with Prader-Willi syndrome, muscle hypotonia of newborns and seizures are detected from early childhood. lethargy, hyperphagia, dwarfism, reduction in the size of the arms and legs and shortening of the fingers, bulimia and pathological obesity, moderate mental retardation, severe stubbornness and tediousness. Girls have characteristics faces (almond-shaped, close-set eyes, narrow face, triangular mouth).

In Lawrence-Moon-Bardet-Biedl syndrome, the most significant, in addition to dwarfism and early obesity, is pigmentation. retinitis and coloboma of the retina. Other signs of the disease include spastic paraplegia newborns, polydactyly, cystic kidney dysplasia, mental retardation, diabetes mellitus.

Girls with Russell–Silver syndrome have a marked delay in physical development since childhood (dwarfism) and lack of puberty, asymmetry of skeletal development, including facial bones of the skull, characteristic triangular face due to underdevelopment of the lower jaw (hypognathia) and pigment spots on the skin of the body coffee color.

Hand–Schueller–Christian syndrome, caused by multiple ectopia and proliferation of histiocytes in the brain, including including in the hypothalamus, stalk and posterior lobe of the pituitary gland, skin, internal organs and bones, manifested by growth retardation and PVD, diabetes insipidus and symptoms of damage to relevant organs and tissues. During orbital infiltration observed exophthalmos, jaw bones - loss of teeth, temporal and mastoid bones - chronic otitis media and hearing loss, eosinophilic granulomas and fractures in the bones of the limbs and ribs, symptoms in the internal organs multiple tumor growth.

A congenital mutation of the GnRH receptor gene can be suspected in girls who do not have any other causes of PVD. upon examination, pronounced manifestations of estrogen deficiency are determined, normal or moderately reduced (usually below 5 IU/l) concentrations of LH and FSH, normal levels of other pituitary hormones, absence of developmental anomalies. Unlike constitutional PVD, signs of hypogonadotropic hypogonadism are not disappear with age.

Hypergonadotropic hypogonadism

With Turner syndrome and its variants, patients with the so-called a typical form of gonadal dysgenesis with structural abnormalities of the only X chromosome (Chmonosomy), especially its short shoulder. These babies are born with low birth weight and lymphedema of the arms and legs (Bonnevie syndrome). Ullrich). Growth rates up to 3 years are relatively stable and differ slightly from standards, but bone age in patients aged 3 years it lags by 1 year. Subsequently, the slowdown in growth rates progresses and bone age lags behind. stronger. The pubertal growth spurt, not exceeding 3 cm, is shifted to 15–16 years.

Typical external manifestations of Turner syndrome: a disproportionately large shield-shaped chest with a wide splayed nipples of undeveloped mammary glands, valgus deviation of the elbow and knee joints, multiple birthmarks or vitiligo, hypoplasia of the terminal phalanges of the IV and V fingers and nails, short neck sphinx" with wing-shaped folds of skin (fin-shaped neck) running from the ears to the shoulder process, deformation ears and low hairline on the neck. Facial features are changed due to strabismus, Mongoloid eye shape
(epicanthus), drooping of the upper eyelid (ptosis), tooth deformation, underdevelopment of the lower jaw (micro and retrognathia), there is a Gothic palate.

In patients with Turner syndrome, otitis media and hearing loss, color blindness, congenital heart defects, and aortic diseases are common. (coarctation and stenosis of the orifice) and urinary organs (horseshoe kidney, retrocaval location ureters, their duplication, unilateral renal aplasia), meet hypothyroidism, autoimmune thyroiditis and diabetes mellitus diabetes. With erased forms, most stigmas do not appear. However, careful examination of even patients normal height allows you to detect irregularly shaped ears, gothic or high palate, short stature hair on the neck and hypoplasia of the terminal phalanges of the fourth and fifth fingers and toes. The structure of the external and internal genital organs female, but the labia majora and minora, vagina and uterus are sharply underdeveloped.

About 25% of girls with Turner syndrome experience spontaneous puberty and menarche, which is due to maintaining a sufficient number of oocytes at the time of birth. During puberty for menstruating women patients are characterized by uterine bleeding.

The pure form of gonadal dysgenesis is manifested by pronounced sexual infantilism in the absence of anomalies development of muscle, bone and other systems. Typically, patients have normal height and a female phenotype, as in karyotype 46,XX. The bone age of such patients lags behind the calendar age, but this lag is less pronounced than in Turner syndrome.

With 46.XY gonadal dysgenesis, differential diagnosis is carried out with the central forms of PVD, the pure form gonadal dysgenesis with a female set of sex chromosomes, with other forms of XY sex reversion. From central forms PVD patients with XY gonadal dysgenesis are distinguished by high levels of gonadotropic hormones in the blood and smaller sizes gonads (according to echographic examination) and the absence of the follicular apparatus in them, greater (by 3 and more than years) lag of biological age from calendar age, absence of pathology from the central nervous system. From pure form of gonadal dysgenesis, not accompanied by sex reversal, patients with XY gonadal dysgenesis are characterized by negative sex chromatin and the presence of the Y chromosome in the karyotype, possible virilization of the external genitalia. From patients with false male hermaphroditism (who have both gonadal and hormonal sexes male) patients with XY gonadal dysgenesis are distinguished by the presence of derivatives of the Müllerian ducts, the location of dysgenetic reproductive organs glands in the abdominal cavity, hypergonadotropinemia against the background of low levels of estradiol and testosterone.

INDICATIONS FOR CONSULTATION WITH OTHER SPECIALISTS

Consultation with a geneticist for the hypergonadotropic form of PVD for genealogical and cytogenetic testing examinations. Consultation with an endocrinologist to clarify the diagnosis, features of the course and treatment of diabetes diabetes, hypercortisolism syndrome, thyroid pathology, obesity, as well as to clarify the causes short stature and addressing the issue of the possibility of therapy with recombinant growth hormone in patients with PVD.

Consultation with a neurosurgeon to resolve the issue of surgical treatment when identifying space-occupying lesions in brain in patients with hypogonadotropic hypogonadism. Consultations with specialized pediatricians, taking into account systemic diseases that caused PVD. Consultation with a psychotherapist for the treatment of anorexia nervosa and psychogenic bulimia. Consultation with a psychologist to improve the psychosocial adaptation of girls with PVD.

EXAMPLE OF FORMULATION OF DIAGNOSIS

ZPS. Hypopituitarism (hypogonadotropic hypogonadism or isolated gonadotropin deficiency or syndrome Kallmann or panhypopituitarism or pituitary cachexia or pituitary insufficiency NOS).
ZPS. Drug-induced hypopituitarism.
ZPS. Ovarian failure resulting from medical procedures.
ZPS. Hypopituitarism occurring after medical procedures.
ZPS. Hypothalamic dysfunction not elsewhere classified.
ZPS. Primary ovarian failure (low estrogen levels, persistent ovarian syndrome) or congenital absence of ovaries.
ZPS. Testicular feminization syndrome, androgen resistance syndrome.
ZPS. Hermaphroditism, not elsewhere classified [gonad containing tissue components ovary and testis (ovotestis)].
ZPS. Russell-Silver syndrome.
ZPS. Turner syndrome.
ZPS. Primary amenorrhea (impaired menstruation during puberty).
ZPS. A woman with a karyotype of 46,XY.
ZPS. Mosaic (chimera) 46,XX/46,XY, true hermaphrodite.
ZPS. 46,XX True hermaphrodite [with streaked gonads or 46,XY with streaked gonads or pure gonadal dysgenesis (Swyer's syndrome)].
PVD caused by protein-energy deficiency.

TREATMENT

TREATMENT GOALS

• Prevention of malignancy of dysgenetic gonads located in the abdominal cavity.
• Stimulation of the pubertal growth spurt in patients with growth retardation.
• Replenishment of the deficiency of female sex hormones.
• Stimulation and maintenance of the development of secondary sexual characteristics for the formation of a female figure.
• Activation of osteosynthesis processes.
• Prevention of possible acute and chronic psychological, personal and social problems.
• Prevention of infertility and preparation for childbearing through IVF of a donor egg and ET.

INDICATIONS FOR HOSPITALIZATION

Carrying out therapeutic and diagnostic measures (test with hormone releasing hormone analogues, studying the circadian rhythm and night secretion of gonadotropins and growth hormone, testing with insulin and clonidine to clarify reserves somatotropic secretion). Determination of the Y chromosome in the karyotype of a patient with a female phenotype is absolute indication for bilateral removal of the gonads in order to prevent tumor degeneration of the genitals iron

NON-DRUG TREATMENT

Compliance with the work and rest regime, correction of physical activity, maintaining adequate nutrition and compensation main somatic disease in girls with central and constitutional forms of PVD.

DRUG TREATMENT

There is no evidence on the effectiveness of the use of vitamin-mineral complexes and adaptogens in girls with constitutional PVD. Activation of puberty was observed in such children after a test with GnRH. Girls with constitutional PVD may undergo 3–4 month courses of sex steroid therapy.

After bilateral gonadectomy and tubectomy, daily therapy is prescribed for the initial estrogenization of the body estrogens in the gel (divigel©, estrogel ©, etc.) or in tablet form, or in the form of a patch (klimar©, etc.), or conjugated estrogens tablets daily, or ethinyl estradiol tablets daily.

When natural menstrual-like reactions appear, the complex of therapy includes gestagens in a cyclic regimen (dydrogesterone 10–20 mg/day or progesterone 10–20 mg/day or norethisterone 5–10 mg/day from the 12th to the 21st day taking estradiol). Or estradiol is prescribed in sequential combination with progestogens for 21 days regimen with 7-day breaks (medroxyprogesterone + estradiol or estradiol + levonorgestrel or estradiol + cyproterone), and continuously without interruptions (estradiol + dydrogesterone). In patients over 16 years of age for the rapid appearance of secondary sexual characteristics and enlargement of the uterus, it is advisable to use medroxyprogesterone + estradiol. It is also possible to use COCs to accelerate the formation of mammary glands. After achieving the desired results in both cases, a transition to drugs used in sequential mode.

In addition to HRT, if a decrease in BMD is detected, osteogenon© is prescribed, 1 tablet 3 times a day for 4–6 months. annually under the control of bone age until the closure of growth plates and under the control of densitometry. It is advisable to carry out 6-month courses of therapy with calcium preparations.
In short patients with growth indices below the 5th percentile of the normal growth curve with hypo and hypergonadotropic gonadism, somatropin (recombinant growth hormone) is used. The drug is administered daily once subcutaneously at night. The daily dose is 0.07–0.1 IU/kg, or 2–3 IU/m2, which corresponds to a weekly dose 0.5–0.7 IU/kg, or 14–20 IU/m2. As the girl grows, it is necessary to regularly change the dose taking into account the mass or area body surface. Therapy is carried out under growth control every 3–6 months until the period corresponds to the indicators
bone age 14 years, or when the growth rate decreases to 2 cm or less per year. Girls with Turner syndrome require a larger initial dose of the drug. The most effective dose is 0.375 IU/(kg per day), but it can be increase. In order to improve the growth prognosis in short girls with Turner syndrome during the use of growth hormone can be prescribed for 3–6 months oxandrolone (non-aromatizing anabolic steroid) at a dose of 0.05 mg/(kg per day).

Sex steroid therapy aimed at replenishing estrogen deficiency begins at the age of 14–15 years (bone age of at least 12 years) according to an increasing pattern. Currently, it is common to use drugs similar to natural estrogens.

The initial dose of estrogen should be 1/4–1/8 of the dose used to treat adult women - estradiol in in the form of a patch 0.975 mg/week or gel 0.25 mg/day, or conjugated estrogens 0.3 mg/day, prescribed for 3–6 months. At absence of reactive bleeding according to the type of menstruation during the first 6 months of taking estrogen, initial dose The drug is doubled and progesterone is additionally prescribed for 10–12 days. When a response appears bleeding should proceed to modeling the menstrual cycle - estradiol in the form of a patch 0.1 mg/week or gel 0.5 mg/day, or conjugated estrogens 0.625 mg/day with the addition of drugs containing progesterone (dydrogesterone 10–20 mg/day or micronized progesterone 200–300 mg/day), according to the following regimen: estrogens take 21 days with a 7-day break, and progesterone - from the 12th to the 21st day of taking estrogen. More comfortable continuous use of estrogens with additional progesterone every 2 weeks. Within 2–3 years hormonal treatment, the dose of estrogen should be gradually increased, taking into account growth dynamics, bone age, size of the uterus and mammary glands. Standard dose of estrogen to compensate for the deficiency of estrogenic effects, not having negative effects is 1.25 mg/day for conjugated estrogens, 1 mg/day for estradiol-containing gel and 3.9 mg/week for the estrogen patch. Drugs have undoubted convenience, containing estradiol and progesterone (medroxyprogesterone, dydrogesterone) in a fixed sequence. Therapy with higher doses of estrogen leads to accelerated closure of epiphyseal growth zones and development mastopathy, increases the risk of developing endometrial and mammary gland cancer.

The main criteria for the effectiveness of the therapy: the appearance of growth and development of the mammary glands, the appearance sexual hair growth, increased linear growth and progressive skeletal differentiation (approximation biological age to passport age).

SURGERY

Surgical intervention is performed in patients with growing cysts and tumors of the pituitary gland, hypothalamic region and the third ventricle of the brain. Due to the increased risk of neoplastic transformation of dysgenetic gonads, located in the abdominal cavity, as well as a high frequency of detection of pathology of the fallopian tubes and mesosalpinxes in patients with XY gonadal dysgenesis, all patients undergo bilateral removal immediately after diagnosis uterine appendages (together with fallopian tubes) mainly by laparoscopic access.

APPROXIMATE DURATION OF DISABILITY

From 10 to 30 days when undergoing examination and conducting diagnostic tests in a hospital setting. Within 7– 10 days during surgical treatment.

FOLLOW-UP

All girls with constitutional PVD should be included in the risk group for developing BMD deficiency and need dynamic observation until the end of puberty.

Patients with hypo and hypergonadotropic hypogonadism require lifelong HRT with sex steroids (until the period natural menopause) and in constant dynamic monitoring. To avoid overdose and unwanted side effects during the first 2 years of treatment, it is advisable to conduct a control examination every 3 months. This tactic allows you to establish psychological contact with patients and promptly adjust the prescribed treatment. In subsequent years, it is sufficient to carry out control examinations every 6–12 months. Control
It is advisable to carry out examinations during long-term hormonal treatment once a year. Minimum the examination complex should include ultrasound of the genital organs, mammary and thyroid glands, colposcopy and determination of the content of FSH, estradiol in the blood plasma in the second phase of the simulated menstrual cycle, progesterone, according to indications - TSH and T4. An estradiol concentration of 50–60 pmol/l is considered the minimum to ensure response from target organs. Normal estradiol content necessary for the functioning of major organs reproductive system and metabolic needs of the body, is in the range of 60–180 pmol/l. Dynamics of bone age, if it lags behind the calendar, it should be monitored at least once every 2 years; if possible, use densitometry.

INFORMATION FOR THE PATIENT

It is advisable to train patients in the use of drugs (transdermal dosage forms, injections growth hormone) and an explanation of the need for strict control of drug intake due to the danger of acyclic uterine bleeding in case of violation of the treatment regimen. If growth hormone therapy is necessary, patients and their parents must be trained in the technique of administering the drug by experienced medical personnel.

Patients should be informed about the need for long-term (up to the age of 45–55 years) HRT in order to compensate deficiency of the influence of estrogenic hormones, affecting not only the uterus and mammary glands, but also the head brain, blood vessels, heart, skin, bone tissue, etc. Against the background of HRT, annual monitoring of hormonal status is necessary. dependent organs. It is advisable to keep a self-control diary indicating the timing of the onset, duration and intensity of a natural menstrual-like reaction. Despite the impossibility of independent pregnancy, with regular use of female sex steroid hormones, the size of the uterus reaches the size allowing the transfer of a donor egg fertilized artificially. Breaks in the conduct Therapy in patients with hypogonadotropic and hypergonadotropic hypogonadism is unacceptable!

FORECAST

The prognosis for fertility in patients with the constitutional form of PVD is favorable. With hypogonadotropic In hypogonadism, fertility can be temporarily restored by exogenous administration of LH and FSH analogues (if secondary hypogonadism), analogues of GNRH in the circhoral mode (tertiary hypogonadism). With hypergonadotropic hypogonadism, only patients taking adequate HRT can become pregnant through donor ET into the uterine cavity and full compensation of the deficiency of corpus luteum hormones. Interruption of therapy usually leads to spontaneous termination of pregnancy. In 2–5% of women with Turner syndrome who have had spontaneous sexual intercourse maturation and menstruation, pregnancies are possible, but their course is often accompanied by the threat of interruption different stages of gestation. Favorable course of pregnancy and childbirth in patients with Turner syndrome is rare phenomenon, it is more often observed at the birth of boys.

In patients with congenital hereditary syndromes accompanied by hypogonadotropic hypogonadism, the prognosis depends on the timeliness and effectiveness of correction of concomitant diseases of organs and systems. At With timely and adequate treatment, in patients with hypergonadotropic hypogonadism, reproductive function can be realized through IVF donor egg and PE. In patients who did not receive during the reproductive period HRT significantly more often than in the population develops arterial hypertension, dyslipidemia, obesity, osteoporosis, psychosocial problems arise, especially with Turner syndrome.

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Puberty is a transitional period of life when a girl develops secondary characteristics characteristic of the female phenotype. Regulation of maturation occurs due to the functioning of the nervous system and the secretion of hormones. But sometimes, under the influence of various external or internal factors, delayed sexual development syndrome develops. It is necessary to look for the reasons for the appearance of this pathology, and begin correction as early as possible so that the body has time to reach its passport age.

Normal Developmental Stages

Puberty begins imperceptibly at the hormonal level with an increase in male sex hormones in a girl’s body. Most often this occurs at the age of 10 years, but the norm is considered to be the appearance of the first signs of maturation as early as 9 years. The maximum age at which the process can begin is 14 years. The following factors may influence it:

• genetic characteristics;
• nature of nutrition;
• health status;
• physical exercise.

An inadequate diet leads to a lack of essential nutrients and malnutrition, which can result in developmental delays. Severe pathologies also negatively affect the functioning of the nervous and endocrine systems.

The appearance of secondary sexual characteristics must also occur in a certain sequence and within time intervals. Pubic hair appears first, but in some girls this stage is preceded by primary changes in the mammary glands. A year after the start of breast cancer, the first menstrual bleeding occurs. It takes about 1-1.5 years to establish a regular cycle, but the final formation of the ovulatory monthly cycle occurs only by the age of 18-20.

Adulthood is also determined by bone age measurements. The growth spurt occurs on average at 12 years of age. Regarding the time of menarche - 1.3 years after the first menstruation. From the moment of menarche, a girl’s height increases by an average of 8-10 cm, and the later the first menstrual bleeding appears, the lower the growth potential.

Bone age is determined using x-rays of the hands. When it begins to correspond to 15 years, 99% of the girl's growth has stopped.

How is the menstrual cycle established in teenage girls? What is considered normal and what is a violation? About this in ours.

Concept of pathology

Delayed puberty (DPH) involves a delay in the appearance of secondary sexual characteristics. It is characterized by:

• a 14-year-old girl has no signs of maturation or has a significant deviation from the norm accepted for a given region;
• the development of secondary phenotypic characteristics began, but suddenly stopped for a period of 18 months or more;
• 5 years or more have passed since the start of breast growth, but menarche has not occurred.

Only the appearance of hair on the pubis or in the armpits is not considered a sign of the onset of maturation.

The prevalence of pathology among children is not high. According to statistics, only 2% of girls under 12 years of age and 0.4% under 13 years of age do not show signs of puberty.

It is important to identify violations in time and begin to treat them. This allows you to correct hormonal insufficiency and bring the rate closer to normal and corresponding to the passport age.

Laboratory determination of sex chromatin in all newborns is used as screening. Pediatricians and parents themselves should monitor growth dynamics, this is especially important for children with stigmata of dysembryogenesis. Girls receiving treatment for PVD should be monitored annually for growth dynamics, bone age, and estradiol and gonadotropin levels.

Causes and symptoms

Damage to the reproductive system can occur at three levels, and therefore there are three forms:

1. Constitutional - with it there is a delay in bone growth and the appearance of secondary symptoms in somatically healthy girls.
2. Hypogonadotropic hypogonadism is a deficiency in the synthesis of gonadotropic hormones.
3. Hypogonadotropic hypergonadism is the absence of secretion of gonadal hormones.

The severity of each pathology may differ, and treatment depends on the exact cause of the appearance.

Constitutional form

The pathology is often congenital and inherited. Constitutional delay in sexual development acts through congenital or acquired disorders of the secretion of the hypothalamic LH releasing factor. The pathogenesis of the disease is not fully known. But the action of various pathological factors that lead to late activation of the hypothalamic-pituitary-ovarian system cannot be ruled out.

Functional is also possible, which leads to disruption of dopamine synthesis, as well as to a decrease in the impulse release of gonadotropic hormones and somatotropin. Changes in the secretion of catecholamines are also noted: a decrease in the secretion of adrenaline and norepinephrine, and an increase in serotonin.

Features of constitutional developmental retardation are proportional stunting, but the appearance of secondary sexual characteristics occurs according to bone age, which may be ahead of passport data.

For girls with this pathology, growing up is not easy. It takes the body much longer to reach its genetically determined age. Growth may be delayed until age 19 or longer.

Seeing a doctor often occurs after a subjective assessment of your data. The girl’s parents or she herself note the absence of a growth spurt characteristic of this condition and the absence of phenotypic measurements.

Similar growth disorders are often possible in close relatives. But after the onset of puberty, gradually the difference between sex characteristics and bone age becomes unnoticeable.

Hypogonadotronic hypogonadism

Delayed sexual development of central origin may be associated with minimal changes in brain centers, as well as in tumor and non-tumor formations. But the basis of the pathology is the insufficiency of secretion of gonadotropic hormones due to congenital or acquired function of the central nervous system. The condition may occur in the following cases:

• abnormalities of cerebral vessels;
• hypoplasia of the anterior pituitary gland;
• consequences of tuberculosis, sarcoidosis;
• post-radiation changes as a result of exposure;
• condition after head injury.

Hypogonadotropic hypogonadism can also be a consequence of severe systemic chronic pathologies:

• severe heart defects;
• renal, liver failure;
• sickle cell anemia;
• thalassemia;
• Gaucher disease;
• Crohn's disease;
• cystic fibrosis (and other variants of digestive tract pathologies).

Chronic infections, as well as HIV, can cause damage to the hypothalamus. Increased physical activity, poor nutrition, eating disorders (anorexia or bulimia), long-term treatment with psychotropic drugs, glucocorticoids can negatively affect the condition of the pituitary-ovarian axis. Ecology also affects the pace of development. It has been established that an increase in blood lead to 3 μg/dL leads to developmental delays of 3-6 months.

Hypergonadotropic hypogonadism

ZPR of ovarian origin is often associated with dysgenesis or agenesis of the gonads. Also, the reasons may be chromosomal or genetic abnormalities:

• Turner syndrome;
• gonadal dysgenesis with karyotype 46 x.

Impaired maturation can occur against the background of metabolic disorders leading to disruption of hormone synthesis.

In some cases, PVD is a consequence of an autoimmune disease, and the following symptoms are observed:

• diabetes mellitus;
• thyroiditis;
• ataxia telangiectasia syndrome.

With this pathology, there may be a deficiency of enzymes involved in the formation of ovarian hormones. In girls, against the background of hypergonadotropic hypogonadism, persistent arterial hypertension can develop, and an increased concentration of progesterone is noted in the blood.

Rarely, the pathology is caused by ovarian failure, which develops as a result of the removal of part or all of the organ, the use of certain medications, or ionizing radiation.

Diagnostic rules

To establish the causes of a girl’s pathology, her family history must be clarified in a conversation with her parents, preferably with her mother. Also assessed:

• the course of pregnancy;
• the presence of its complications;
• during the neonatal period;
• stages of growing up and their compliance with norms;
• transferred pathologies.

It should be remembered that diagnosis begins only with the approach of puberty, when we can speak with confidence about the degree of maturity and the appearance of the necessary signs.

Inspection

In terms of diagnosis, a thorough general examination is required, during which height, weight, distribution and severity of fiber are recorded. It is necessary to pay attention to traces of possible operations, scars that could be the result of injuries.

The vaginal examination is carried out in the presence of the mother or the child's legal representative. Special children's mirrors are used for it. In some cases, a vaginal examination is replaced by a rectal examination, which should be performed after a cleansing enema.

Laboratory research

Blood is donated for hormones on an empty stomach and in full. It is necessary to determine both estradiol and DHEAS. According to indications, the concentration of progesterone, prolactin, cortisol, growth hormone, TSH, antibodies to T4-a, and to thyroid peroxidase are examined.

In girls with a bone age of more than 11 years, a test with gonadotropin agonists is performed. At a younger age, the study is not informative. 5-7 days after the sample is taken, an analysis for estradiol is carried out. With functional mental retardation and defects in the receptors for the hormone, its increase in the blood occurs.

Determination of LH secretion at night and total secretion in urine is also used every 20-30 minutes. If there is an increase in it at night, this speaks in favor of constitutional ZPR. The lack of difference between concentrations at night and during the day speaks in favor of hypogonadotropic hypogonadism.

The detection of autoantibodies to the ovaries indicates the autoimmune nature of the pathology.

Instrumental diagnostic methods

They include performing an ultrasound of the pelvic organs to determine the degree of development of the genital organs. An ultrasound is also necessary at the time of performing a functional test to find out how the ovaries responded to hormone stimulation.

If the developmental delay is of a constitutional nature, then on ultrasound the uterus and ovaries remain in pre-pubertal size, and there may be single follicles. In other variants of ZPR, the uterus and appendages have a low degree of development, sometimes even represented by strands of tissue.

They are performed in a state of rest, characteristic of pre-pubertal age.

Volumetric formations of the brain are determined using MRI. The tumor must be larger than 5 mm in size to be visible during the examination. Changes in the structure of blood vessels, nutrition of areas of the neurohypophysis and other areas of the brain may also be observed.

The following diagnostic methods are also used:

• densitometry;
• ophthalmoscopy;
• X-ray of the skull;
• hearing test;
• Olfactory diagnostics.

These techniques are important in the diagnosis of certain genetic syndromes that may not always be suspected.

Treatment approaches

Treatment for delayed puberty is complex. In case of malnutrition or violation of its rationality, it is necessary to correct the diet in accordance with age and medical standards. Girls with anorexia and bulimia need help from a psychologist or psychiatrist, depending on the severity of disturbances in the perception of their body.

It is also necessary to adjust the level of physical activity, the amount of stressful situations, social and living conditions and all environmental factors that can negatively affect the child’s growing up period.

Drug treatment can be started as early as in a 12-year-old girl if there are reliable signs of growth and development retardation. For constitutional mental retardation, treatment includes sex steroids in short courses of 3-4 months.

If the cause of the disease is removal of the ovaries, treatment includes, as well as in the second phase of the cycle -. Medicines are taken or administered intramuscularly daily. Sex steroids from age 12 are prescribed in increasing doses to mimic the natural increase that occurs during normal maturation.

Girls with short stature need to be prescribed somatotropin to stimulate indicators of increasing the length of tubular bones and maximally approaching their peers in height.

The criteria for the effectiveness of therapy are the growth of the mammary glands, an increase in total body length, the appearance of menstruation and its regular rhythm, as well as bone age equal to the passport age.

Sometimes surgical treatment is performed when pituitary tumors do not allow the body to develop normally. This approach is also necessary in the presence of cerebral ventricular cysts.

Patients with hypogonadotropic hypogonadism require lifelong administration of steroid hormones until physiological symptoms occur. To prevent the development of complications, medication violations or overdose, dynamic monitoring by a doctor is necessary. Control examination includes ultrasound of the chest and pelvis at least once a year, blood tests for hormones, and periodic examination of the thyroid gland.

Reproductive function in girls with delayed sexual development can be realized in the constitutional form with timely treatment. With hypogonadotropic hypogonadism, this is possible through the use of a donor egg.