Pubertal uterine bleeding

Pubertal uterine bleeding (PUB) is a pathological bleeding caused by abnormalities in the rejection of the endometrium in adolescent girls with disrupted cyclic production of sex steroid hormones from the moment of the first menstruation until the age of 18.

Epidemiology

The frequency of uterine bleeding during puberty in the structure of gynecological diseases in childhood and adolescence varies from 10 to 37.3%. Over 50% of all visits to a gynecologist by adolescent girls are associated with uterine bleeding during puberty. Almost 95% of all vaginal bleeding during puberty is due to MCPP. Uterine bleeding most often occurs in adolescent girls during the first 3 years after menarche.

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Causes Puberty-associated uterine bleeding.

The main cause of uterine bleeding in puberty is immaturity of the reproductive system at an age close to menarche (up to 3 years). Adolescent girls with uterine bleeding have a defect in the negative feedback of the ovaries and the hypothalamic-pituitary region of the central nervous system. The increase in estrogen levels characteristic of puberty does not lead to a decrease in FSH secretion, which in turn stimulates the growth and development of many follicles at once. Maintaining a higher than normal FSH secretion serves as a factor inhibiting the selection and development of a dominant follicle from many simultaneously maturing cystic follicles.

The absence of ovulation and subsequent production of progesterone by the corpus luteum leads to a constant effect of estrogens on target organs, including the endometrium. When the proliferating endometrium overflows the uterine cavity, trophic disorders occur in certain areas with subsequent local rejection and bleeding. Bleeding is maintained by increased formation of prostaglandins in the long-proliferating endometrium. Prolonged absence of ovulation and the influence of progesterone significantly increases the risk of uterine bleeding during puberty, while even one accidental ovulation is sufficient for temporary stabilization of the endometrium and its more complete rejection without bleeding.

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Symptoms Puberty-associated uterine bleeding.

The following criteria for uterine bleeding during puberty are distinguished.

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

Forms

There is no officially accepted international classification of uterine bleeding in the pubertal period. When 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 (hypermenorrhea) is uterine bleeding in patients with a preserved menstrual rhythm, in whom the duration of blood discharge exceeds 7 days, blood loss is more than 80 ml and there is a small number of blood clots in the abundant blood discharge, the appearance of hypovolemic disorders on menstrual days and the presence of moderate and severe iron deficiency anemia.
• Polymenorrhea is uterine bleeding that occurs against the background of a regular shortened menstrual cycle (less than 21 days).
• Metrorrhagia and menometrorrhagia are uterine bleeding that does not have a rhythm, often occurring after periods of oligomenorrhea and characterized by periodic increases in bleeding against the background of scanty or moderate blood discharge.

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Diagnostics Puberty-associated uterine bleeding.

The diagnosis of uterine bleeding during puberty is made after excluding the diseases listed below.

• Spontaneous termination of pregnancy (in sexually active girls).
• Diseases of the uterus (myoma, endometrial polyps, endometritis, arteriovenous anastomoses, endometriosis, presence of an intrauterine contraceptive device, very rarely adenocarcinoma and sarcoma of the uterus).
• Pathology of the vagina and cervix (trauma, foreign body, neoplastic processes, exophytic condylomas, polyps, vaginitis).
• Ovarian diseases (polycystic ovaries, premature failure, tumors and tumor-like formations).
• Blood diseases [von Willebrand disease and deficiency of other plasma hemostasis factors, Werlhof's disease (idiopathic thrombocytopenic purpura), Glanzmann-Nageli thrombasthenia, Bernard-Soulier, Gaucher, leukemia, aplastic anemia, iron deficiency anemia].
• Endocrine diseases (hypothyroidism, hyperthyroidism, Addison's or Cushing's disease, hyperprolactinemia, postpubertal form of congenital adrenal hyperplasia, adrenal tumors, empty sella syndrome, mosaic variant of Turner syndrome).
• Systemic diseases (liver disease, chronic renal failure, hypersplenism).
• Iatrogenic causes - application errors: failure to comply with the dosage and administration regimen, unjustified prescription of drugs containing female sex steroids, and long-term use of high doses of non-steroidal anti-inflammatory drugs (NSAIDs), antiplatelet agents and anticoagulants, psychotropic drugs, anticonvulsants and warfarin, chemotherapy.

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History and physical examination

• Collection of anamnesis.
• Physical examination.
  • Comparison of the degree of physical development and sexual maturation according to Tanner with age standards.
  • Vaginoscopy and examination data allow to exclude the presence of a foreign body in the vagina, condylomas, lichen planus, neoplasms of the vagina and cervix. The condition of the vaginal mucosa and estrogen saturation are assessed.
    • Signs of hyperestrogenism: pronounced folding of the vaginal mucosa, juicy hymen, cylindrical shape of the cervix, positive "pupil" symptom, abundant streaks of mucus in bloody discharge.
    • Hypoestrogenemia is characterized by a pale pink vaginal mucosa; its folding is weakly expressed, the hymen is thin, the cervix is subconical or conical in shape, and bloody discharge is not mixed with mucus.
• Evaluation of the menstrual calendar (menocyclogram).
• Clarification of the patient's psychological characteristics.

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Laboratory research

• A general blood test to determine the concentration of hemoglobin and the number of platelets is performed on all patients with uterine bleeding during puberty.
• Biochemical blood test: study of the concentration of glucose, creatinine, bilirubin, urea, serum iron, trans-ferrin in the blood.
• Hemostasis (determination of activated partial thromboplastin time, prothrombin index, activated recalcification time) and assessment of bleeding time allow to exclude gross pathology of the blood coagulation system.
• Determination of the β-subunit of human chorionic gonadotropin in the blood of sexually active girls.
• Blood hormone concentration test: TSH and free T to clarify thyroid function; estradiol, testosterone, dehydroepiandrosterone sulfate, LH, FSH, insulin, C-peptide to rule out PCOS; 17-hydroxyprogesterone, testosterone, dehydroepiandrosterone sulfate, circadian rhythm of cortisol secretion to rule out congenital adrenal hyperplasia; prolactin (at least 3 times) to rule out hyperprolactinemia; serum progesterone on day 21 (with a 28-day menstrual cycle) or on day 25 (with a 32-day menstrual cycle) to confirm the anovulatory nature of uterine bleeding.
• Carbohydrate tolerance test for PCOS and overweight (body mass index equal to 25 kg/m2 ^and above).

Instrumental research

• Microscopy of a vaginal smear (Gram staining) and PCR of material obtained by scraping from the vaginal walls are performed to diagnose chlamydia, gonorrhea, and mycoplasmosis.
• Ultrasound of the pelvic organs allows to specify the size of the uterus and the condition of the endometrium to exclude pregnancy, uterine defects (bicornuate, saddle-shaped uterus), pathologies of the body of the uterus and endometrium (adenomyosis, uterine myoma, polyps or hyperplasia, adenomatosis and endometrial cancer, endometritis, receptor defects of the endometrium and intrauterine adhesions), to assess the size, structure and volume of the ovaries, to exclude functional cysts (follicular, corpus luteum cysts that provoke menstrual cycle disorders such as uterine bleeding both against the background of a shortened menstrual cycle and against the background of a preliminary delay in menstruation up to 2-4 weeks with corpus luteum cysts) and volumetric formations in the uterine appendages.
• Diagnostic hysteroscopy and curettage of the uterine cavity in adolescents are rarely used and are used to clarify the condition of the endometrium when ultrasound signs of endometrial polyps or cervical canal are detected.

Indications for consultation with other specialists

• Consultation with an endocrinologist is indicated if thyroid pathology is suspected (clinical symptoms of hypothyroidism or hyperthyroidism, diffuse enlargement or nodular formations of the thyroid gland upon palpation).
• A consultation with a hematologist is necessary at the onset of uterine bleeding in the pubertal period with menarche, indications of frequent nosebleeds, the occurrence of petechiae and hematomas, increased bleeding from cuts, wounds and surgical manipulations, and when an increase in bleeding time is detected.
• Consultation with a phthisiatrician is indicated in cases of uterine bleeding during puberty against the background of prolonged persistent subfebrile temperature, acyclic nature of bleeding, often accompanied by pain syndrome, in the absence of a pathogenic infectious agent in the discharge of the genitourinary tract, relative or absolute lymphocytosis in the general blood test, positive tuberculin tests.
• A consultation with a therapist should be carried out in case of uterine bleeding during puberty against the background of chronic systemic diseases, including diseases of the kidneys, liver, lungs, cardiovascular system, etc.

Differential diagnosis

The main goal of differential diagnostics of uterine bleeding in puberty is to clarify the main etiological factors that provoke the development of the disease. The diseases from which uterine bleeding in puberty should be differentiated are listed below.

• Pregnancy complications in sexually active adolescents. First of all, the complaints and anamnesis data are clarified, allowing to exclude interrupted pregnancy or bleeding after an abortion, including in girls who deny sexual contacts. Bleeding occurs more often after a short delay of menstruation over 35 days, less often with a shortened menstrual cycle of less than 21 days or at times close to the expected menstruation. The anamnesis, as a rule, indicates sexual contacts in the previous menstrual cycle. Patients note complaints of engorgement of the mammary glands, nausea. Bloody discharge, usually profuse, with clots, with pieces of tissue, often painful. Pregnancy tests are positive (determination of the β-subunit of chorionic gonadotropin in the patient's blood).
• Blood coagulation system defects. To exclude blood coagulation system defects, family history data (parents' tendency to bleed) and life history data (nosebleeds, prolonged bleeding time during surgical procedures, frequent and unexplained occurrence of petechiae and hematomas) are obtained. Uterine bleeding, as a rule, has the character of menorrhagia, starting with menarche. Examination data (paleness of the skin, bruises, petechiae, yellowing of the palms and upper palate, hirsutism, striae, acne, vitiligo, multiple birthmarks, etc.) and laboratory research methods (coagulogram, general blood test, thromboelastogram, determination of the concentration of the main blood coagulation factors) allow confirming the pathology of the hemostasis system.
• Polyps of the cervix and body of the uterus. Uterine bleeding is usually acyclic, with short, light intervals; discharge is moderate, often with mucus strands. Ultrasound often reveals endometrial hyperplasia (endometrial thickness against the background of bleeding is 10-15 mm) with hyperechoic formations of varying sizes. The diagnosis is confirmed by hysteroscopy and subsequent histological examination of the removed endometrial formation.
• Adenomyosis. Uterine bleeding during puberty against the background of adenomyosis is characterized by severe dysmenorrhea, prolonged spotting of blood 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, occurs after hypothermia, unprotected, especially casual or promiscuous (promiscuity) sexual intercourse in sexually active adolescents, against the background of exacerbation of chronic pelvic pain. Pain in the lower abdomen, dysuria, hyperthermia, profuse pathological leucorrhoea outside of menstruation, acquiring a sharp, unpleasant odor against the background of bleeding, are of concern. Rectoabdominal examination reveals an enlarged softened uterus, pastosity of tissues in the area of the uterine appendages; the conducted examination is usually painful. Bacteriological examination data (microscopy of smears with Gram staining, examination of vaginal discharge for the presence of sexually transmitted infections using PCR, bacteriological examination of material from the posterior vaginal fornix) help to clarify the diagnosis.
• Trauma to the external genitalia or foreign body in the vagina. Anamnesis data and results of vulvo-vaginoscopy are required for diagnosis.
• Polycystic ovary syndrome. In patients with developing PCOS, uterine bleeding during puberty, along with complaints of delayed menstruation, excessive hair growth, acne on the face, chest, shoulders, back, buttocks and thighs, there are indications of late menarche with progressive menstrual cycle disorders such as oligomenorrhea.
• Hormone-producing ovarian formations. Uterine bleeding during puberty may be the first symptom of estrogen-producing tumors or tumor-like formations of the ovaries. A more precise diagnosis is possible after an ultrasound examination of the genitals with determination of the volume and structure of the ovaries and the concentration of estrogens in the venous blood.
• Thyroid dysfunction. Uterine bleeding during puberty usually occurs in patients with subclinical or clinical hypothyroidism. Patients complain of chills, swelling, weight gain, memory loss, drowsiness, and depression. In hypothyroidism, palpation and ultrasound with determination of the volume and structural features of the thyroid gland allow to detect its enlargement, and examination of patients - the presence of dry subicteric skin, pastosity of tissues, puffiness of the face, enlargement of the tongue, bradycardia, and increased relaxation time of deep tendon reflexes. Determination of the content of TSH and free T4 in the blood allows to clarify the functional state of the thyroid gland.
• Hyperprolactinemia. To exclude hyperprolactinemia as a cause of uterine bleeding in the pubertal period, examination and palpation of the mammary glands with clarification of the nature of discharge from the nipples, determination of the prolactin content in the blood, radiography of the skull bones with a targeted study of the size and configuration of the sella turcica or MRI of the brain are indicated. Conducting a trial treatment with dopaminomimetic drugs in patients with uterine bleeding in the pubertal period caused by hyperprolactinemia helps restore the rhythm and nature of menstruation within 4 months.

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Treatment Puberty-associated uterine bleeding.

Indications for hospitalization:

• Heavy (profuse) uterine bleeding that is not relieved by drug therapy.
• Life-threatening decrease in hemoglobin concentration (below 70–80 g/l) and hematocrit (below 20%).
• The need for surgical treatment and blood transfusion.

Non-drug treatment of uterine bleeding during puberty

There are no data to support the use of non-drug therapy in patients with uterine bleeding during puberty, except in situations requiring surgical intervention.

Drug therapy for uterine bleeding during puberty

The general goals of drug treatment of uterine bleeding during puberty are:

• Stopping bleeding to avoid acute hemorrhagic syndrome.
• Stabilization and correction of the menstrual cycle and the condition of the endometrium.
• Antianemic therapy.

The following drugs are used:

At the first stage of treatment, it is advisable to use inhibitors of plasminogen to plasmin conversion (tranexamic and aminocaproic acids). The intensity of bleeding decreases due to a decrease in the fibrinolytic activity of blood plasma. Tranexamic acid is prescribed orally at a dose of 5 g 3-4 times a day for profuse bleeding until the bleeding stops completely. Intravenous administration of 4-5 g of the drug is possible during the first hour, then drip administration of drugs at a dose of 1 g / h for 8 hours. The total daily dose should not exceed 30 g. With large doses, the risk of developing intravascular coagulation syndrome increases, and with the simultaneous use of estrogens, the probability of thromboembolic complications is high. 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 volume of blood loss by 50%.

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

• Danazol is very rarely used in patients with uterine bleeding during puberty due to severe side effects (nausea, deepening of the voice, hair loss and increased oiliness, 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 volume of blood loss during menstruation by 30-38%. Ibuprofen is prescribed at a dose of 400 mg every 4-6 hours (daily dose 1200-3200 mg) on the days of menorrhagia. However, an increase in the daily dose can cause an undesirable increase in prothrombin time and the concentration of lithium ions in the blood. The effectiveness of NSAIDs is comparable to the effectiveness of aminocaproic acid and COCs. In order to increase the effectiveness of hemostatic therapy, the combined use of NSAIDs and hormonal therapy is justified. However, this type of combined therapy is contraindicated in patients with hyperprolactinemia, structural anomalies of the 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 COCs provides a hemostatic effect, and progestogens - stabilization of the stroma and basal layer of the endometrium. Only monophasic COCs are prescribed to stop bleeding.
  • There are many schemes for using COCs for hemostatic purposes in patients with uterine bleeding. The following scheme is often recommended: 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 of bleeding, COCs are prescribed for 3-6 cycles for regulating the menstrual cycle, 1 tablet per day (21 days of use, 7 days of rest). The duration of hormonal therapy depends on the severity of the initial iron deficiency anemia and the rate of restoration of hemoglobin content. The use of COCs in this regimen is associated with a number of serious side effects: increased blood pressure, thrombophlebitis, nausea and vomiting, allergies. In addition, there are difficulties in choosing the appropriate antianemic therapy.
  • An alternative is to use low-dose monophasic COCs at a dose of half a tablet every 4 hours until complete hemostasis, since the maximum concentration of the drug in the blood is achieved 3-4 hours after oral administration of the drug and decreases significantly in the next 2-3 hours. The total dose of EE in this case ranges 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 COCs is reduced - half a tablet per day. When reducing the daily dose to 1 tablet, it is advisable to continue taking the drug, taking into account the hemoglobin concentration. As a rule, the duration of the first cycle of COC intake should not be less than 21 days, counting from the 1st day from the onset of hormonal hemostasis. In the first 5-7 days of taking the drug, a temporary increase in the thickness of the endometrium is possible, which regresses without bleeding with continued treatment.
  • Subsequently, in order to regulate the menstrual rhythm and prevent recurrence of uterine bleeding, COCs are prescribed according to the standard scheme (21-day courses with 7-day breaks between them). All patients who took the drugs according to the described scheme noted cessation of bleeding within 12-18 hours from the start of administration and good tolerability in the absence of side effects. The use of COCs in short courses (10 days in the 2nd phase of the modulated cycle or in a 21-day regimen for up to 3 months) is not pathogenetically justified.
• If rapid stopping of life-threatening bleeding is required, the first-line drugs of choice are conjugated estrogens administered intravenously at a dose of 25 mg every 4–6 hours until bleeding stops completely, which occurs within the first 24 hours. It is possible to use the tablet form of conjugated estrogens at a dose of 0.625–3.75 mcg every 4–6 hours until bleeding stops completely, with a gradual reduction in the dose over the next 3 days to a dosage of 0.675 mg/day, or estradiol according to a similar scheme with an initial dose of 4 mg/day. After bleeding stops, progestogens are prescribed.
• Outside of bleeding, in order to regulate the menstrual cycle, conjugated estrogens are prescribed orally at a dose of 0.675 mg/day or estradiol at a dose of 2 mg/day for 21 days with the obligatory addition of progesterone for 12–14 days in the 2nd phase of the modulated cycle.
• In some cases, especially in patients with severe side effects, intolerance or contraindications to the use of estrogens, progesterone alone may be prescribed. Low efficacy of low doses of progesterone has been noted against the background of profuse uterine bleeding, primarily in the 2nd phase of the menstrual cycle with menorrhagia. Patients with profuse bleeding are prescribed 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), either every 2 hours in case of life-threatening bleeding, or 3-4 times a day in case of profuse but not life-threatening bleeding until bleeding stops. After bleeding stops, the drugs are prescribed 2 times a day, 2 tablets for no more than 10 days, since prolonged use may cause re-bleeding. The reaction of progestogen withdrawal usually manifests itself in profuse bleeding, which often requires the use of symptomatic hemostasis. In order to regulate the menstrual cycle in menorrhagia, medroxyprogesterone can be prescribed at a dose of 5-10-20 mg/day, dydrogesterone at a dose of 10-20 mg per day, or micronized progesterone at a dose of 300 mg per day in the second phase (in case of luteal phase deficiency), or at a dose of 20, 20 and 300 mg/day, respectively, from the 5th to the 25th day of the menstrual cycle (in case of ovulatory menorrhagia). In patients with anovulatory uterine bleeding, progestogens should be prescribed in the 2nd phase of the menstrual cycle against the background of constant use of estrogens. It is possible to use progesterone in micronized form at a daily dose of 200 mg for 12 days per month against the background of continuous estrogen therapy.

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

All patients with uterine bleeding during puberty are prescribed iron preparations to prevent the development of iron deficiency anemia. High efficiency of using iron sulfate in combination with ascorbic acid at a dose of 100 mg of divalent iron per day has been proven. The daily dose of iron 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 a reticulocyte crisis (an increase of 3 times or more in the number of reticulocytes 7-10 days after the start of administration). Antianemic therapy is carried out for at least 1-3 months. Iron salts should be used with caution in patients with concomitant gastrointestinal pathology.

Sodium etamsylate in recommended doses has low effectiveness in stopping profuse uterine bleeding.

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Surgical treatment

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

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

If it is necessary to remove an ovarian cyst (endometrioid, dermoid follicular or corpus luteum cyst that has persisted for more than 3 months) or to clarify the diagnosis in patients with a volumetric formation in the area of the uterine appendages, therapeutic and diagnostic laparoscopy is indicated.

Patient education

• The patient should be provided with rest, and in case of heavy bleeding - bed rest. It is necessary to explain to the teenage girl the need for a mandatory examination by an obstetrician-gynecologist, and in case of heavy bleeding - hospitalization in the gynecological department 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 inattentive attitude to the disease.
• It is advisable to conduct conversations during which the causes of bleeding are explained, and an attempt is made to relieve the feeling of fear and uncertainty about the outcome of the disease. The girl, taking into account her age, needs to be explained the essence of the disease and taught how to correctly follow medical instructions.

Further management of the patient

Patients with uterine bleeding during puberty require constant dynamic monitoring once a month until the menstrual cycle is normalized, after which the frequency of examination can be limited to once every 3–6 months. Ultrasound of the pelvic organs should be performed at least once every 6–12 months. All patients should be trained in the rules of maintaining a menstrual calendar and assessing the intensity of bleeding, which allows assessing the effectiveness of the therapy.

Patients should be informed about the advisability of correcting and maintaining optimal body weight (both in case of deficiency and excess), and normalizing work and rest regimes.

Forecast

Most adolescent girls respond to drug therapy and develop full ovulatory menstrual cycles and normal menstruation within the first year.

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

The most severe complications of uterine bleeding in puberty are acute blood loss syndrome, which, however, rarely leads to a fatal outcome in somatically healthy girls, and anemic syndrome, the severity of which depends on its duration and the intensity of uterine bleeding in puberty. Mortality in adolescent girls with uterine bleeding in puberty 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, and the development of irreversible systemic disorders against the background of chronic iron deficiency anemia in girls with prolonged and recurrent uterine bleeding.

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