Uterine bleeding of the puberty period

Uterine bleeding of the pubertal period (MKPP) is a pathological bleeding caused by abnormalities of endometrial rejection in adolescent girls with impaired cyclic production of sex steroid hormones from the moment of the first menstruation to 18 years.

Epidemiology

The frequency of uterine bleeding in the pubertal period in the structure of gynecological diseases of childhood and adolescence varies from 10 to 37.3%. Over 50% of all adolescent girls' visits to the gynecologist are associated with uterine bleeding in the puberty period. Almost 95% of all vaginal bleeding in the pubertal period is due to MTCT. Most uterine bleeding occurs in adolescent girls during the first 3 years after the menarche.

[1], [2], [3]

Causes of the uterine bleeding of the puberty period

The main cause of uterine bleeding in the pubertal period is the immaturity of the reproductive system at the age close to menarche (up to 3 years). In adolescent girls with uterine bleeding, there is a defect in the negative feedback of the ovaries and the hypothalamic-pituitary region of the central nervous system. Characteristic for the period of puberty, an increase in the level of estrogen does not lead to a decrease in FSH secretion, which in turn stimulates the growth and development of many follicles. The preservation of FSH secretion, which is higher than normal, serves as a factor inhibiting the choice and development of the dominant follicle from the set of simultaneously maturing follicular follicles.

The absence of ovulation and the subsequent development of progesterone by the yellow body leads to a constant effect of estrogens on the target organs, including the endometrium. When the proliferating endometrium overflows the uterine cavity, trophic disorders occur in some areas, followed by local rejection and bleeding. Bleeding is supported by increased production of prostaglandins in the long-proliferating endometrium. The prolonged absence of ovulation and the influence of progesterone significantly increases the risk of uterine bleeding in the pubertal period, whereas even one random ovulation is sufficient for temporary stabilization of the endometrium and more complete rejection without bleeding.

[4], [5], [6], [7]

Symptoms of the uterine bleeding of the puberty period

There are the following criteria for uterine bleeding in the pubertal period.

• The duration of blood vaginal discharge from the vagina is less than 2 or more than 7 days against a background of shortening (less than 21-24 days) or lengthening (more than 35 days) of the menstrual cycle.
• Blood loss of more than 80 ml or subjectively more pronounced compared with normal menstruation.
• The presence of intermenstrual or postcoital blood secretions.
• Absence of structural pathology of the endometrium.
• Confirmation of anovulatory menstrual cycle during the period of uterine bleeding (progesterone concentration in venous blood on the 21-25th day of the menstrual cycle is less than 9.5 nmol / l, monophasic basal temperature, absence of preovulatory follicle according to echography).

Forms

Officially accepted international classification of uterine bleeding puberty period is not developed. In determining the type of uterine bleeding in adolescent girls, as well as in women of reproductive age, the clinical features of uterine bleeding (polymenorrhea, metrorrhagia and menometrorrhagia) are taken into account.

• Menorrhagia (hypermenorrhoea) refers to uterine bleeding in patients with a preserved rhythm of menstruation, whose duration of blood discharges exceeds 7 days, blood loss is more than 80 ml, and a small number of blood clots in abundant blood, the appearance of hypovolemic disorders in menstrual days and the presence of iron deficiency anemia and severe.
• Polymenorrhea - uterine bleeding that occurs against the background of a regular shortened menstrual cycle (less than 21 days).
• Metrorrhagia and menometrorrhagia are uterine bleeding that do not have a rhythm, often occurring after intervals of oligomenorrhea and characterized by a periodic increase in bleeding against a background of meager or moderate bloody discharge.

[8]

Diagnostics of the uterine bleeding of the puberty period

The diagnosis of uterine bleeding in the pubertal period is made after the exclusion of the diseases listed below.

• Spontaneous abortion (in sexually active girls).
• Diseases of the uterus (myoma, endometrial polyps, endometritis, arterio-venous anastomoses, endometriosis, the presence of an intrauterine contraceptive, extremely rarely adenocarcinoma and uterine sarcoma).
• Pathology of the vagina and cervix (trauma, foreign body, neoplastic processes, exophytic condylomas, polyps, vaginitis).
• Diseases of the ovaries (polycystic ovaries, premature exhaustion, tumors and tumor-like formations).
• Diseases of blood [von Willebrand's disease and deficiency of other plasma factors of hemostasis, Verlhof disease (idiopathic thrombocytopenic purpura), Glanzmann-Negelia thrombastenia, Bernard-Soulier, Gaucher, leukemia, aplastic anemia, iron-deficiency anemia].
• Endocrine diseases (hypothyroidism, hyperthyroidism, Addison's or Cushing's disease, hyperprolactinaemia, post-puerperate form of congenital hyperplasia of the adrenal cortex, adrenal gland tumors, empty Turkish saddle syndrome, mosaic version of Turner's syndrome).
• Systemic diseases (liver disease, chronic renal failure, hypersplenism).
• Iatrogenic causes - mistakes in application: non-compliance with the dosing and receiving regimen, unreasonable prescription of drugs containing female sex steroids, and long-term use in high doses of nonsteroidal anti-inflammatory drugs (NSAIDs), disaggregants and anticoagulants, psychotropic drugs, anticonvulsants and warfarin, chemotherapy.

[9], [10]

Anamnesis and physical examination

• Anamnesis.
• Physical examination.
  • Comparison of the degree of physical development and puberty according to Tanner with age standards.
  • Vaginoscopy and examination data allow you to exclude the presence of a foreign body in the vagina, condyloma, red flat lichen, neoplasms of the vagina and cervix. Assess the condition of the vaginal mucosa, estrogen saturation.
    • Signs of hyperestrogenism: pronounced folding of the mucous membrane of the vagina, luscious hymen, cylindrical form of the cervix, a positive symptom of the "pupil", abundant veins of mucus in the blood secretions.
    • For hypoestrogenemia is characterized by a pale pink mucous membrane of the vagina; its folding is weakly expressed, the hymen is thin, the cervix of the uterus is subconical or conical, bloody discharge without mucus.
• Evaluation of the menstrual calendar (menocyclogram).
• Clarify the psychological characteristics of the patient.

[11],

Laboratory research

• A general blood test with determination of the concentration of hemoglobin, the number of platelets is performed by all patients with uterine bleeding of the pubertal period.
• Biochemical blood test: study of the concentration of glucose, creatinine, bilirubin, urea, serum iron, trans ferrin in the blood.
• Hemostasiogram (determination of activated partial thromboplastin time, prothrombin index, activated recalcification time) and evaluation of bleeding time make it possible to eliminate the gross pathology of the blood coagulation system.
• Determination of β-subunit of chorionic gonadotropin in the blood of sexually active girls.
• The study of the concentration of hormones in the blood: TTG and free T to clarify the function of the thyroid gland; estradiol, testosterone, dehydroepiandrosterone sulfate, LH, FSH, insulin, C-peptide to exclude PCOS; 17-hydroxyprogesterone, testosterone, dehydroepiandrosterone sulfate, daily rhythm of cortisol secretion to exclude congenital hyperplasia of the adrenal cortex; prolactin (at least 3 times) to exclude hyperprolactinemia; Progesterone in the serum on the 21st day (with a 28-day menstrual cycle) or on the 25th day (with a 32-day menstrual cycle) to confirm the anovulatory nature of uterine bleeding.
• A test for carbohydrate tolerance in PCOS and overweight (body mass index is 25 kg / m ² and above).

Instrumental research

• The microscopy of the vaginal smear (Gram stain) and the PCR of the material obtained by scraping from the vaginal walls are performed for the diagnosis of chlamydia, gonorrhea, mycoplasmosis.
• The ultrasound of the pelvic organs makes it possible to clarify the size of the uterus and the state of the endometrium for the elimination of pregnancy, uterine malformation (bicorneous, saddle-shaped uterus), pathologies of the uterus and endometrium (adenomyosis, uterine myoma, polyps or hyperplasia, adenomatosis and endometrial cancer, endometritis, endometrial receptor defects and intrauterine synechia), assess the size, structure and volume of the ovaries, exclude functional cysts (follicular, yellow body cysts, causing menstrual irregularities in the form of uterine bleeding as against the background of shortened Ia duration of the menstrual cycle, as well as on the background of the pre-delay menstruation to 2-4 weeks at a corpus luteum cyst) and space-occupying lesions in the uterine appendages.
• Diagnostic hysteroscopy and curettage of the uterine cavity in adolescents are rarely used and used to clarify the state of the endometrium when detecting ultrasound signs of the endometrial polyps or cervical canal.

Indications for consultation of other specialists

• Consultation of the endocrinologist is indicated for suspected thyroid pathology (clinical symptoms of hypothyroidism or hyperthyroidism, diffuse enlargement or nodular thyroid lesions upon palpation).
• Consultation of the hematologist is necessary at the onset of uterine bleeding from puberty with menarche, indications of frequent nasal bleeding, the emergence of petechiae and hematomas, increased bleeding in cuts, wounds and surgical manipulations, with an elongation of bleeding time.
• Consultation phthisiatrician is indicated in uterine bleeding puberty period against the background of long persistent subfebrile condition, acyclic nature of bleeding, often accompanied by pain syndrome, in the absence of a pathogenic infectious agent in the urogenital tract, relative or absolute lymphocytosis in a general blood test, positive tuberculin samples.
• Consultation of the therapist should be conducted with uterine bleeding of the puberty period against the background of chronic systemic diseases, including kidney, liver, lung, cardiovascular system, etc. 

Differential diagnosis

The main purpose of differential diagnosis of uterine bleeding puberty period is to clarify the main etiological factors provoking the development of the disease. The following diseases are listed, from which uterine bleeding of the pubertal period should be differentiated.

• Complications of pregnancy in sexually active adolescents. First of all, they clarify complaints and data of anamnesis that allow to exclude interrupted pregnancy or bleeding after abortion, including among girls denying sexual contacts. Bleeding occurs more often after a short delay in menstruation over 35 days, less with a shortening of the menstrual cycle less than 21 days or in terms close to the expected menstruation. In the anamnesis, as a rule, there are indications of sexual contacts in the previous menstrual cycle. Patients report complaints of breast engorgement, nausea. Bloody discharge, usually abundant, with clots, with pieces of tissue, often painful. Pregnancy tests are positive (determining the β-subunit of the chorionic gonadotropin in the patient's blood).
• Defects of the blood coagulation system. For the elimination of defects in the blood coagulation system, data on family history (predisposition to bleeding in parents) and a history of life (nasal bleeding, prolonged bleeding time during surgical manipulation, frequent and causeless occurrence of petechiae and hematomas) are elucidated. Uterine bleeding, as a rule, has the character of menorrhagia, beginning with menarche. The examination data (pallor of the skin, bruising, petechiae, icteric color of palms and upper palate, hirsutism, striae, acne, vitiligo, multiple birthmarks, etc.) and laboratory methods of investigation (coagulogram, general blood test, thromboelastogram, the main factors of blood coagulation) can confirm the pathology of the hemostasis system.
• Polyps of the cervix and the body of the uterus. Uterine bleeding, as a rule, acyclic, with short, light intervals; excretions are mild, often with strands of mucus. When ultrasound is often found, endometrial hyperplasia (thickness of the endometrium on the background of bleeding 10-15 mm) with hyperechoic formations of different sizes. The diagnosis is confirmed by the data of hysteroscopy and the subsequent histological examination of the remote endometrial formation.
• Adenomyosis. Uterine bleeding of the pubertal period against adenomyosis is characterized by pronounced dysmenorrhea, prolonged spotting bloody discharge with a characteristic brown tint before and after menstruation. The diagnosis is confirmed by the results of ultrasound in the 1st and 2nd phases of the menstrual cycle and hysteroscopy (in patients with severe pain syndrome and in the absence of the effect of drug therapy).
• Inflammatory diseases of the pelvic organs. As a rule, uterine bleeding is acyclic in nature, occurs after hypothermia, unprotected, especially accidental or promiscuity (promiscuity) of sexual contacts in sexually active adolescents, against the backdrop of exacerbation of chronic pelvic pain. Disturb pain in the lower abdomen, dysuria, hyperthermia, abundant abnormalities outside menstruation, gaining a sharp, unpleasant odor against bleeding. During recto-abdominal examination, a softened uterus enlarged in size, the pastosity of the tissues in the region of the uterine appendages; The study is usually painful. Bacteriological examination data (Gram stain smear microscopy, study of vaginal discharge for the presence of sexually transmitted infection, PCR, bacteriological study of the material from the posterior vaginal fornix) contribute to clarifying the diagnosis.
• Injury of external genital organs or foreign body in the vagina. For diagnosis, you need anamnesis and results of vulvovaginoscopy.
• Polycystic ovary syndrome. With uterine bleeding in the pubertal period, patients with developing PCOS, along with complaints of menstruation delay, excessive hair growth, acne on the face, chest, shoulders, back, buttocks and hips, indicate later menarche with progressive irregularities of the menstrual cycle as oligomenorrhoea.
• Hormone-producing ovarian formations. Uterine bleeding of the pubertal period may be the first symptom of estrogen-producing tumors or tumor-like ovarian formations. Clarification of the diagnosis is possible after ultrasound of the genitals with the definition of the volume and structure of the ovaries and the concentration of estrogens in the venous blood.
• Thyroid dysfunction. Uterine bleeding of the pubertal period occurs, as a rule, in patients with subclinical or clinical hypothyroidism. Patients complain of chilliness, swelling, weight gain, memory loss, drowsiness, depression. In hypothyroidism, palpation and ultrasound with the definition of the volume and structural features of the thyroid gland can reveal its increase, and the examination of patients - the presence of dry sub-bacterial skin, pastosity of the tissues, puffiness of the face, an increase in the tongue, bradycardia, an increase in the relaxation time of deep tendon reflexes. To clarify the functional state of the thyroid gland allows the determination of the content of TSH, free T 4 in the blood.
• Hyperprolactinemia. To exclude hyperprolactinemia as a cause of uterine bleeding in the pubertal period, examination and palpation of the mammary glands are shown with a refinement of the nature of the discharge from the nipples, determination of the prolactin content in the blood, radiography of the bones of the skull, aiming at studying the size and configuration of the Turkish saddle or MRI of the brain. Conducting trial treatment with dopaminomimetic drugs in patients with uterine bleeding puberty period, resulting from hyperprolactinaemia, helps restore the rhythm and character of menstruation for 4 months.

[12], [13], [14], [15]

Treatment of the uterine bleeding of the puberty period

Indications for hospitalization:

• Abundant (profuse) uterine bleeding that does not stop with drug therapy.
• A life-threatening decrease in the concentration of hemoglobin (below 70-80 g / l) and hematocrit (below 20%).
• The need for surgical treatment and blood transfusion.

Non-drug treatment of pubertal uterine bleeding

There are no data confirming the advisability of non-drug treatment of patients with uterine bleeding in the pubertal period, except for situations requiring surgical intervention.

Drug therapy for uterine bleeding in the pubertal period

The general goals of the medicinal treatment of pubertal uterine bleeding are:

• Stop bleeding in order to avoid acute hemorrhagic syndrome.
• Stabilization and correction of the menstrual cycle and the state of the endometrium.
• Anti-anemic therapy.

The following drugs are used:

At the first stage of treatment, it is advisable to use inhibitors of the transition of plasminogen to plasmin (tranexamic and aminocaproic acid). The intensity of bleeding is reduced due to a decrease in the fibrinolytic activity of the blood plasma. Tranexamic acid is prescribed internally at a dose of 5 g 3-4 times a day with profuse bleeding until the bleeding stops completely. It is possible to intravenously administer 4-5 g of the drug during the first hour, then drip the drug at a dose of 1 g / h for 8 hours. The total daily dose should not exceed 30 g. At high doses, the risk of developing the syndrome of intravascular coagulation increases, and with simultaneous the use of estrogens has a high probability of thromboembolic complications. It is possible to use the drug at a dose of 1 g 4 times a day from the 1st to the 4th day of menstruation, which reduces the blood loss by 50%.

A significant reduction in blood loss in patients with menorrhagia is observed with NSAIDs, monophasic COCs and danazol.

• Danazol in patients with uterine bleeding puberty is used very rarely due to severe adverse reactions (nausea, coarsening of the voice, loss and increase of greasiness of the hair, the appearance of acne and hirsutism).
• NSAIDs (ibuprofen, diclofenac, indomethacin, nimesulide, etc.) affect the metabolism of arachidonic acid, reduce the production of prostaglandins and thromboxanes in the endometrium, reducing the blood loss during menstruation by 30-38%. Ibuprofen is prescribed in a dose of 400 mg every 4-6 hours (daily dose of 1200-3200 mg) on days of menorrhagia. However, an increase in the daily dose may cause an undesirable increase in prothrombin time and a concentration of lithium ions in the blood. The effectiveness of NSAIDs is comparable to that of aminocaproic acid and COC. In order to improve the effectiveness of hemostatic therapy, the combined use of NSAIDs and hormone therapy is justified. However, this type of combined therapy is contraindicated in patients with hyperprolactinaemia, structural abnormalities of genital organs and thyroid pathology.
• Oral low-dose contraceptives with modern progestogens (desogestrel at a dose of 150 mcg, gestodene at a dose of 75 mcg, dienogest at a dose of 2 mg) are more often used in patients with profuse and acyclic uterine bleeding. Ethinyl estradiol in the COC provides a haemostatic effect, and progestogens - stabilization of the stroma and basal layer of the endometrium. To stop bleeding appoint only monophasic COCs.
  • There are many schemes of using COC for haemostatic purposes in patients with uterine bleeding. Often recommend the following scheme: 1 tablet 4 times a day for 4 days, then 1 tablet 3 times a day for 3 days, then 1 tablet 2 times a day, then 1 tablet a day until the end of the 2nd package of the drug. Outside the bleeding for the purpose of regulating the menstrual cycle, COCs are prescribed for 3-6 cycles of 1 tablet per day (21 days of intake, 7 days off). The duration of hormonal therapy depends on the severity of the initial iron deficiency anemia and the recovery rate of the hemoglobin content. The use of COC in this mode is associated with a number of serious side effects: increased blood pressure, thrombophlebitis, nausea and vomiting, allergies. In addition, there are difficulties in the selection of suitable anti-anemic therapy.
  • An alternative can be considered the use of low-dose monophasic COC in a dose of half a tablet every 4 hours before the onset of complete hemostasis, since the maximum concentration of the drug in the blood is reached 3-4 hours after oral administration of the drug and significantly reduced in the next 2-3 hours. This varies from 60 to 90 mcg, which is more than 3 times less than with the traditionally used treatment regimen. In the following days, the daily dose of COC is reduced - by half a tablet a day. With a decrease in the daily dose to 1 tablet, it is advisable to continue taking the drug taking into account the concentration of hemoglobin. As a rule, the duration of the first cycle of COC intake should not be less than 21 days, counting from the first day of the onset of hormonal hemostasis. In the first 5-7 days of taking the medication, a temporary increase in the thickness of the endometrium is possible, which regresses without bleeding while continuing treatment.
  • In future, in order to regulate the rhythm of menstruation and prevent relapse of uterine bleeding, COCs are prescribed according to the standard scheme (21-day courses with 7-day intervals between them). All patients taking the drugs according to the described scheme, noted the stop of bleeding within 12-18 hours from the beginning of the reception and good tolerability in the absence of side effects. Pathogenetically, the use of COCs in short courses (10 days in the 2nd phase of the modulated cycle or in the 21-day regime up to 3 months) is not justified.
• If an accelerated stop of life-threatening hemorrhage is necessary, the preparations of the first choice line are conjugated estrogens, administered iv in a dose of 25 mg every 4-6 h until the bleeding stops completely, which occurs during the first day. It is possible to use the tablet form of conjugated estrogens at a dose of 0.625-3.75 μg every 4-6 hours until the bleeding stops completely, gradually reducing the dose for the next 3 days to a dosage of 0.675 mg / day or estradiol in a similar scheme with an initial dose of 4 mg / day . After stopping bleeding appoint progestogens.
• Outside the bleeding, in order to regulate the menstrual cycle, conjugated estrogens are administered at a dose of 0.675 mg / day or estradiol at a dose of 2 mg / day for 21 days with the mandatory addition of progesterone for 12-14 days in the 2nd phase of the modulated cycle.
• In a number of cases, especially in patients with severe side effects, intolerance or contraindications to the use of estrogens, it is possible to prescribe only progesterone. Low effectiveness of small doses of progesterone against the background of profuse uterine bleeding was noted, primarily in the 2nd phase of the menstrual cycle with menorrhagia. Patients with heavy bleeding show high doses of progesterone (medroxyprogesterone acetate at a dose of 5-10 mg, micronized progesterone at a dose of 100 mg or dydrogesterone at a dose of 10 mg), or every 2 hours for life-threatening bleeding, or 3-4 times a day with copious , but not life-threatening bleeding until the bleeding ceases. After stopping bleeding drugs are prescribed 2 times a day for 2 tablets not more than 10 days, as prolonging the intake can cause a second bleeding. The reaction of progestogen cancellation, as a rule, is manifested by abundant bloody discharge, which often requires the use of symptomatic hemostasis. In order to regulate the menstrual cycle with menorrhagia, medroxyprogesterone can be prescribed in a dose of 5-10-20 mg / day, dydrogesterone - in a dose of 10-20 mg per day, or micronized progesterone - at a dose of 300 mg per day in the second phase (with luteal insufficiency phase), or at a dose of 20, 20 and 300 mg / day, respectively, the form of the drug from the 5th to the 25th day of the menstrual cycle (with ovulatory menorrhagia). In patients with anovulatory uterine bleeding, it is advisable to administer progestogens in the 2nd phase of the menstrual cycle against the background of the constant use of estrogens. It is possible to use progesterone in micronized form at a daily dose of 200 mg for 12 days a month on the background of continuous estrogen therapy.

Continuation of bleeding against the background of hormonal hemostasis serves as an indication for hysteroscopy to clarify the state of the endometrium.

All patients with uterine bleeding puberty period are shown iron preparations to prevent the development of iron deficiency anemia. The high efficiency of iron sulfate in combination with ascorbic acid in a dose of 100 mg of ferrous iron per day is proved. The daily dose of ferric sulfate is selected taking into account the concentration of hemoglobin in the blood. The criterion for the correct selection of iron preparations for iron deficiency anemia is the development of the reticulocytic crisis (an increase of 3 times or more of the number of reticulocytes in 7-10 days after the beginning of admission). Anti-anemic therapy is carried out for at least 1 to 3 months. Iron salts should be used with caution in patients with concomitant gastrointestinal pathology.

Sodium etamzilate in recommended doses has a low efficiency for stopping profuse uterine bleeding.

[16], [17], [18], [19]

Surgery

Scraping the body and cervix (separate) necessarily under the control of a hysteroscope in girls are very rare. Indications for surgical treatment are:

• acute profuse uterine bleeding, which does not stop with drug therapy;
• presence of clinical and ultrasound signs of endometrial polyps and / or cervical canal.

If necessary, removal of the ovarian cyst (endometrioid, dermoid follicular or cyst of the yellow body persisting for more than 3 months) or clarifying the diagnosis in patients with volumetric education in the area of the uterine appendages treatment and diagnostic laparoscopy is shown.

Training patient

• It is necessary to provide the patient with peace, with heavy bleeding - bed rest. It is necessary to explain to the teenage girl the necessity of obligatory examination by the obstetrician-gynecologist, and with heavy bleeding - hospitalization in the gynecological ward of the hospital in the first days of bleeding.
• It is recommended to inform the patient and her immediate family about possible complications and consequences of inattention to the disease.
• It is advisable to conduct conversations, during which explain the causes of bleeding, seek to stop feeling of fear and uncertainty in the outcome of the disease. The girl, given her age, needs to clarify the essence of the disease and teach her how to properly perform medical appointments.

Further management of the patient

Patients with uterine bleeding pubertal period need constant dynamic observation 1 time per month before the normalization of the menstrual cycle, after which you can limit the frequency of examination to 1 time in 3-6 months. Ultrasound of pelvic organs should be performed at least once every 6-12 months. All patients should be trained in the rules for managing the menstrual calendar and assessing the intensity of bleeding, which makes it possible to evaluate the effectiveness of the therapy.

Patients should be informed of the advisability of correcting and maintaining optimal body weight (both with its deficiency and in excess), normalizing the working and rest regime.

Forecast

In most adolescent girls, drug therapy is effective, and during the first year they develop full-fledged ovulatory menstrual cycles and normal menstruation.

In patients with uterine bleeding puberty period against the background of therapy aimed at inhibition of PCOS formation during the first 3-5 years after menarche, recurrences of uterine bleeding are extremely rare. The prognosis for uterine bleeding of the pubertal period, associated with the pathology of the hemostasis system or systemic chronic diseases, depends on the degree of compensation for existing disorders. Girls who are overweight and who have recurrent uterine bleeding at the age of 15-19 should be included in the risk group for developing endometrial cancer.

The most severe complications of uterine bleeding in the pubertal period are acute blood loss syndrome, which, however, rarely leads to death in somatically healthy girls, and anemic syndrome, the severity of which depends on the duration and intensity of pubertal uterine bleeding. Mortality in adolescent girls with uterine bleeding in the pubertal period is more often due to acute multiple organ dysfunction as a result of severe anemia and hypovolemia, complications of transfusion of whole blood and its components, development of irreversible systemic disorders against chronic iron deficiency anemia in girls with prolonged and recurrent uterine bleeding.

[20], [21], [22], [23]