This is the central genesis. Amenorrhea - central genesis, ovarian, uterine

Amenorrhea of ​​central origin is more often functional and, as a rule, occurs as a result of exposure to adverse environmental factors. The mechanisms of the disorder are realized through the neurosecretory structures of the brain that regulate the tonic and cyclic secretion of gonadotropins. Under the influence of stress, there is an excessive release of endogenous opioids that reduce the formation of dopamine, as well as a decrease in the formation and release of GnRH, which can lead to amenorrhea. With minor violations, the number of anovulatory cycles increases, and luteal phase insufficiency appears.

Symptoms of a fever of unknown origin

The main (sometimes the only) clinical symptom of a fever of unknown origin is a rise in body temperature. For a long time, fever can be asymptomatic or accompanied by chills, excessive sweating, heart pain, and suffocation.

Diagnosis of fever of unknown origin

The following criteria must be strictly observed in making a diagnosis of fever of unknown origin:

Fever patients are difficult to diagnose. Diagnosis of the causes of fever includes:

To identify the true causes of fever, along with generally accepted laboratory tests additional research is applied. For this purpose, the following are assigned:

• microbiological examination of urine, blood, swab from the nasopharynx (allows you to identify the causative agent of infection), a blood test for intrauterine infections;
• isolation of a viral culture from the secrets of the body, its DNA, viral antibody titers (allows you to diagnose cytomegalovirus, toxoplasmosis, herpes, Epstein-Barr virus);
• detection of antibodies to HIV (enzyme-linked immunosorbent complex method, Western blot test);
• examination under a microscope of a thick blood smear (to exclude malaria);
• blood test for antinuclear factor, LE cells (to exclude systemic lupus erythematosus);
• bone marrow puncture (to exclude leukemia, lymphoma);
• CT scan abdominal organs (exclusion of tumor processes in the kidneys and pelvis);
• skeletal scintigraphy (detection of metastases) and densitometry (determination of bone density) in osteomyelitis, malignant tumors;
• study of the gastrointestinal tract by the method of radiation diagnostics, endoscopy and biopsy (with inflammatory processes, tumors in the intestines);
• conducting serological reactions, including reactions of indirect hemagglutination with the intestinal group (with salmonellosis, brucellosis, Lyme disease, typhoid);
• collection of data on allergic reactions to drugs (if a drug disease is suspected);
• study of family history in terms of the presence of hereditary diseases (for example, familial Mediterranean fever).

To make a correct diagnosis of fever, an anamnesis can be repeated, laboratory tests, which at the first stage could be erroneous or incorrectly assessed.

Treatment of fever of unknown origin

In the event that the patient's condition with fever is stable, in most cases treatment should be withheld. Trial treatment for a febrile patient (tuberculostatic drugs for suspected tuberculosis, heparin for suspected deep vein thrombophlebitis, pulmonary embolism, bone-fixing antibiotics for suspected osteomyelitis) is sometimes discussed. The appointment of glucocorticoid hormones as a trial treatment is justified when the effect of their use can help in the diagnosis (if subacute thyroiditis is suspected, Still's disease, polymyalgia rheumatica).

It is extremely important in the treatment of patients with fever to have information about the possible previous use of drugs. The reaction to medication in 3-5% of cases may be manifested by an increase in body temperature, and be the only or main clinical symptom. hypersensitivity to medicines. Drug fever may not appear immediately, but after a certain period of time after taking the drug, and is no different from fevers of other origins. If drug fever is suspected, the drug should be discontinued and the patient monitored. If the fever disappears within a few days, the cause is considered to be clarified, and if the elevated body temperature persists (within 1 week after discontinuation of the medication), the medicinal nature of the fever is not confirmed.

There are different groups of drugs that can cause drug fever:

• antimicrobials (most antibiotics: penicillins, tetracyclines, cephalosporins, nitrofurans, etc., sulfonamides);
• anti-inflammatory drugs (ibuprofen, acetylsalicylic acid);
• medicines used in diseases of the gastrointestinal tract (cimetidine, metoclopramide, laxatives, which include phenolphthalein);
• cardiovascular drugs (heparin, alpha-methyldopa, hydralazine, quinidine, captopril, procainamide, hydrochlorothiazide);
• drugs acting on the central nervous system (phenobarbital, carbamazepine, haloperidol, chlorpromazine thioridazine);
• cytotoxic drugs (bleomycin, procarbazine, asparaginase);
• other drugs (antihistamines, iodine, allopurinol, levamisole, amphotericin B).

Fever of unknown origin - treatment in Moscow

Directory of Diseases

Respiratory diseases

Last news

• © 2018 "Beauty and Medicine"

is for informational purposes only

and is not a substitute for qualified medical care.

Antipyretic drugs in the practice of a pediatrician: tactics of choice and rational therapy of fever in children

About the article

Authors: Zaplatnikov (Russian Medical Academy of Continuing Professional Education, Ministry of Health of the Russian Federation, Moscow; Children’s City clinical Hospital them. PER. Bashlyaeva” DZ of Moscow), Zakharova I.N. (GBOU DPO "Russian Medical Academy of Postgraduate Education" of the Ministry of Health of the Russian Federation, Moscow), Ovsyannikova E.M.

For citation: Zaplatnikov, Zakharova I.N., Ovsyannikova E.M. Antipyretic drugs in the practice of a pediatrician: tactics of choice and rational therapy fevers in children // RMJ. 2000. No. 13. S. 576

Russian Medical Academy of Postgraduate Education of the Ministry of Health of the Russian Federation

Fever is an increase in body temperature as a result of a non-specific protective and adaptive reaction of the body, characterized by a restructuring of thermoregulation processes and occurring in response to exposure to pathogenic stimuli.

An increase in body temperature in children is one of the most common reasons for seeking medical care in pediatric practice. At the same time, fever can be a manifestation of not only infectious and (or) inflammatory processes, but also a consequence of violations of thermoregulation of a non-infectious nature. In the years on the pages of pediatric scientific and practical periodicals and monographic publications, a discussion was launched about the need to streamline the use of various terms that characterize the increase in body temperature. So, it was proposed to call fever only those cases of an increase in body temperature, which are based on infectious and inflammatory processes, and the rest of the cases should be considered hyperthermic reactions. However, these proposals have not received wide support, and it is now customary in practice to distinguish fever of infectious-inflammatory and non-infectious genesis.

Fever of infectious and inflammatory genesis

Fever of infectious-inflammatory genesis is most common and develops indirectly through interleukin-1 and prostaglandins E in response to exposure to microbial pyrogens (bacterial exo- and endotoxins, viruses, etc.) and non-infectious genesis (immune complexes, tissue decay products, etc.) .

Fundamental differences in the mechanisms of development of fever and normal thermogenesis were assumed for a long time, but became clear only after the fundamental scientific works of C. Liebermeister (1870), S.P. Botkin (1884), A.A. Likhachev and P.P. Avrorov (1902), who convincingly showed that fever is based on peculiar changes in the activity nerve centers regulation of heat transfer. These changes are aimed at switching temperature homeostasis to a higher level by simultaneously increasing heat production and limiting heat transfer. A detailed decoding of the pathogenesis of fever became possible only after a powerful breakthrough in immunology and biochemistry.

It has been established that phagocytic blood cells (neutrophils, monocytes) and tissue macrophages are an integral component of the pathogenesis of fever. A change in the homeostasis of the body during an infectious invasion or a non-infectious inflammatory process leads to the activation of phagocytosis and increased synthesis of a biologically active substance by phagocytes, leading to an increase in body temperature - leukocyte pyrogen. Leukocyte pyrogen is a group of proteins, among which 2 active polypeptides have been isolated. The latter, at the suggestion of J. Oppenheim (1979), are currently referred to as interleukin-1 (IL-1). IL-1 is considered one of the key mediators in the pathogenesis of fever and other processes of the acute phase of inflammation. IL-1 stimulates the secretion of prostaglandins, amyloids A and P, C-reactive protein, haptoglobin, a 1 -antitrypsin and ceruloplasmin. Under the action of IL-1, the production of interleukin-2 by T-lymphocytes is initiated and the expression of cell receptors increases. In addition, there is an increase in the proliferation of B-lymphocytes, stimulation of the secretion of antibodies and expression of the membrane Ig receptor. Under normal conditions, IL-1 does not cross the blood-brain barrier. However, when immune homeostasis is disturbed (infectious or non-infectious inflammation), IL-1 reaches the preoptic region of the anterior hypothalamus and interacts with neuronal receptors of the thermoregulation center. Through the activation of cyclooxygenase (COX), the synthesis of prostaglandins, an increase in the intracellular level of cyclic adenosine monophosphate (cAMP), the activity of heat production and heat transfer centers is restructured with an increase in the formation of thermal energy and a decrease in heat transfer. Increased heat production is achieved by enhancing metabolic processes and contractile thermogenesis. At the same time, vasoconstriction occurs subcutaneous tissue, the rate of peripheral vascular blood flow decreases, which leads to a decrease in heat transfer. A new, higher level of temperature homeostasis is established, which causes an increase in body temperature.

Non-inflammatory fever

Fever of non-inflammatory origin may be associated with neurohumoral disorders, reflex effects, vegetative and mediator imbalances. In this case, non-inflammatory fever is distinguished:

central genesis(defects in development and acquired lesions of the central nervous system);

psychogenic(neurosis, mental disorders, emotional stress, exposure to hypnosis, etc.);

reflex genesis(pain syndrome in urolithiasis, cholelithiasis, peritoneal irritation, etc.);

endocrine genesis(hyperthyroidism, pheochromocytoma);

medicinal genesis(enteral or parenteral administration of drugs such as caffeine, ephedrine, methylene blue, hyperosmolar solutions, antibiotics, diphenine, sulfonamides).

Each of these variants of fever has specific features of pathogenesis and clinical picture. Often, the main link in pathogenesis is a decrease in heat transfer without increasing heat production. As a rule, these patients have good tolerance to hyperthermia, the absence of significant differences between rectal and axillary temperatures. In addition, there is no proper increase in heart rate in parallel with the increase in temperature. It should be emphasized that central fever is not stopped by antipyretics. Antibacterial and anti-inflammatory therapy also do not work. The temperature reaction of the central genesis can spontaneously normalize as compensation for impaired functions of the central nervous system and the growth of the child. Vegetative disorders, accompanied by fever, are most common in children of preschool and school age, especially during puberty. In this case, the temperature often rises during the period of wakefulness, physical activity and emotional stress. Periods of temperature increase are seasonal (more often in autumn and winter) and can last from several weeks to several years. As a rule, after puberty, the temperature in most adolescents returns to normal. Antipyretics are not used for fever of vegetative origin. Sedative drugs are used good effect obtained from physiotherapy, massage, acupuncture, hypnotherapy, autogenic training.

With an increase in body temperature due to increased formation of hormones (thyroxine, catecholamines), an overdose of drugs, the appointment of antipyretics is also not required. The temperature usually normalizes against the background of treatment of the underlying disease.

The effect of fever on the body

Fever of infectious origin is most common and develops in response to exposure to pyrogens of a viral or bacterial nature. It is now generally accepted that fever in infectious diseases is an evolutionary defense response. An increase in body temperature activates metabolic processes, the functions of the nervous, endocrine, immune systems(the production of antibodies, interferon increases, the phagocytic activity of neutrophils is stimulated), the antitoxic function of the liver increases, and the renal blood flow increases. Most pathogenic viruses lose their virulent properties at 39°C. In this regard, initially healthy children with good reactivity and an adequate response to the infectious process when the temperature rises to 39 ° C do not require the appointment of antipyretics. However, fever, like any non-specific protective-adaptive reaction, with the depletion of compensatory mechanisms or with a hyperergic variant, can be the cause of the development of pathological conditions. At the same time, a burdened premorbid background is essential. So, in children with serious diseases of the circulatory and respiratory organs, fever can lead to decompensation of these diseases. In children with CNS pathology (perinatal encephalopathy with convulsive equivalents, hematoliquor disorders syndrome, epilepsy, etc.), fever can provoke the development of an attack of convulsions. Equally important in fever is the age of the child. How less age child, the more dangerous for him is a rapid and significant rise in temperature due to the high risk of progressive metabolic disorders, cerebral edema with transmineralization and impaired vital functions.

Separately, hyperthermic syndrome is distinguished - a pathological variant of fever, in which there is a rapid and inadequate increase in body temperature, accompanied by impaired microcirculation, metabolic disorders and progressively increasing dysfunction of vital organs and systems. The development of fever against the background of acute microcirculatory and metabolic disorders underlying toxicosis (spasm followed by capillary dilatation, arteriovenous shunting, platelet and erythrocyte slugging, increasing metabolic acidosis, hypoxia and hypercapnia, transmineralization, etc.) leads to an aggravation of the pathological process . There is a decompensation of thermoregulation with a sharp increase in heat production, inadequately reduced heat transfer and lack of effect from antipyretic drugs.

Common therapeutic measures for febrile reactions in children include:

Bed rest in case of poor health of the child and fever above 38-38.5 ° C;

Plentiful drinking to ensure increased heat transfer due to profuse sweating (compote, sweetened tea, rosehip broth);

Feeding according to appetite (do not force the child to eat!). In this case, predominantly carbohydrate foods are recommended. Reception of fresh milk should be limited due to possible hypolactasia at the height of a feverish state;

Reception of ascorbic acid (the age norm can be increased by 1.5-2 times);

Control of regular bowel movements (cleansing enema with water at room temperature).

With a “pink type” of fever, to enhance the heat transfer of the child, it is necessary to undress and rub down with water at room temperature. It makes no sense to wipe the child with vodka or ice water, since a sharp decrease in body temperature leads to vasospasm and a decrease in heat transfer.

Fever within 38-38.5°C in the absence of toxicosis does not require drug antipyretic therapy. However, in children at risk, various complications are possible against the background of a less significant increase in temperature, which determines the need for the use of antipyretics in them. AT risk group for complications in febrile reactions, children should be included:

At the age of up to 2 months of life in the presence of body temperature above 38 ° C;

With a history of febrile convulsions;

With diseases of the central nervous system;

With chronic pathology of the circulatory system;

With hereditary metabolic diseases.

According to the recommendations of WHO experts, antipyretic therapy for initially healthy children should be carried out at a body temperature of at least 39-39.5 ° C. However, if a child has a fever, regardless of the severity of hyperthermia, there is a deterioration in the condition, chills, myalgia, impaired health, pallor of the skin and other manifestations of toxicosis (“pale version of fever”), antipyretic therapy should be prescribed immediately.

Children at risk for the development of complications due to fever require the appointment of antipyretics medicines even at subfebrile temperature (Table 1).

In cases where clinical and anamnestic data indicate the need for antipyretic therapy, it is advisable to follow the recommendations of WHO specialists when prescribing effective and safe drugs (drugs of choice). The drugs of choice for fever in children are paracetamol and ibuprofen. At the same time, it is believed that ibuprofen can be used as initial therapy in cases where the appointment of paracetamol is contraindicated or ineffective (FDA, 1992). However, domestic pediatricians still often use acetylsalicylic acid and analgin as initial antipyretic therapy, which, due to serious side effects in many countries, are either prohibited for use in children under the age of 12, or even excluded from national pharmacopoeias.

We noted a more pronounced and prolonged antipyretic effect of ibuprofen compared with comparable doses of paracetamol. A longer preservation of the antipyretic effect of ibuprofen is associated with its anti-inflammatory effect, which potentiates antipyretic activity. It is believed that this enhances and prolongs the antipyretic and analgesic effect of ibuprofen compared to paracetamol, which has less significant anti-inflammatory activity. It has been shown that with short-term use of ibuprofen, the risk of developing undesirable effects is as low as that of paracetamol, which is considered the least toxic among all antipyretic analgesics.

It should be especially noted that the course use of antipyretics without a serious search for the causes of fever is unacceptable. This increases the risk diagnostic errors(Omission of symptoms of serious infectious and inflammatory diseases, such as pneumonia, meningitis, pyelonephritis, appendicitis, etc.). In cases where the child receives antibiotic therapy, regular intake of antipyretics is also unacceptable, because. may contribute to unjustified delay in the decision on the need to replace the antibiotic. Since one of the earliest and objective criteria for the effectiveness of antimicrobial agents is a decrease in body temperature.

When "pale fever" is detected, it is advisable to combine the intake of antipyretic drugs with vasodilators (papaverine, dibazol, papazol). At the same time, single doses of antipyretic drugs are standard (ibuprofenamg/kg, paracetamolamg/kg). Of the vasodilators, papaverine is more often used in a single dose of 5-20 mg, depending on age. Only in cases where oral or rectal administration of first-line antipyretic drugs (paracetamol, ibuprofen) is not possible, parenteral administration of analgin (metamizole) is indicated.

With persistent fever, accompanied by a violation of the state and signs of toxicosis, as well as with hyperthermic syndrome, parenteral administration of a combination of antipyretics, vasodilators and antihistamines (or neuroleptics) drugs in age dosages is advisable. At intramuscular injection a combination of these drugs in one syringe is acceptable. Children with hyperthermic syndrome, as well as with intractable "pale fever" after emergency care must be hospitalized.

The introduction of a formulary system for the use of medicines into healthcare practice is aimed at standardizing and streamlining the choice and prescription pharmacological preparations. Strict and strict implementation of the recommendations proposed by the Federal Formulary for the Use of Medicines will allow not only avoiding medical errors, but also optimizing the pharmacotherapy of the most common pathological conditions, including fever. The main principles of rational therapeutic tactics for fever in children, based on WHO documents and the Ministry of Health of the Russian Federation, are summarized and presented below.

Thus, the appointment of antipyretic drugs is indicated only in those cases of infectious-inflammatory fever, when the hyperthermic reaction has an adverse effect on the child's condition or threatens the development serious complications. The use of antipyretic drugs in "non-inflammatory fevers" should be recognized as unreasonable and unacceptable.

References can be found at http://www.rmj.ru

1. Tsybulkin E.B. Fever// Threatening conditions in children. - St. Petersburg: Special Literature, 1994. - S..

2. Tatochenko V.K. Strategy for the use of antipyretic drugs in children / / Medical Market .. - No. 2 (29). - FROM..

3. Lourin M.I. Fever in children. - M.: Medicine..

4. Cheburkin A.V. Clinical significance of temperature response in children. - M., 1992. - 28 p.

5. Bryazgunov I.P., Sterligov L.A. Fever of unknown origin in children of early and older age // Pediatrics.-1981.-№8.-p.534

6. Korovina N.A., Zaplatnikov A.L., Zakharova I.N. Fever in children: rational choice of antipyretic drugs. - M., p.

7. Atkins E. Pathogenesis of fever // Physiol. Rev.. - 40. - R..

8. Oppenheim J., Stadler B., Sitaganian P. et al. Properties of interleukin-1// Fed. Proc.. - No. 2. - R..

9. Saper C.B., Breder C.D. Endogenous pyrogens in the CNS: role in the febrile responses// Prog. Brain Res.. - 93. - P..

10. Dinarello C.A. Interleukin-1// Rev. Infect. Dis.. - 6. - P..

11. Foreman J.C. Pyrogenesis // Nextbook of Immunopharmacology. - Blackwel Scientific Publications, 1989. - P..

12. Andrushchuk A.A. Feverish conditions, hyperthermic syndrome// Pathological syndromes in pediatrics. - K .: Health, 1977. - S ..

13. Papayan A.V., Tsybulkin E.K. Acute toxicosis in early childhood. - L .: Medicine, 1984. - 232.

14. Cheburkin A.V. Pathogenetic therapy and prevention of acute infectious toxicosis in children. - M., 1997. - 48 p.

15. Markova I.V., Kalinicheva V.I. Pediatric pharmacology: A guide for you. - L .: Medicine, 1987.p.

16. The management of fever in young children with acute respiratory infection in developing countries/ WHO/ ARI/ 93.90, WHO Geneva, 1993.

17. Federal guidelines for physicians on the use of medicines (formular system): Issue 1. GEOTAR MEDICINE, 2000.p.

Nurofen (trade name)

(Boots Healthcare International)

1. Only safe antipyretic drugs should be used in children.

2. The drugs of choice for fever in children are paracetamol and ibuprofen.

3. The appointment of analgin is possible only in case of intolerance to the drugs of choice or, if necessary, parenteral administration of an antipyretic drug.

4. The appointment of antipyretics for subfebrile fever is indicated only for children at risk.

5. The appointment of antipyretic drugs in healthy children with a favorable variant of the temperature reaction is indicated for fever > 39°C.

6. In case of “pale” fever, the appointment of a combination of an analgesic-antipyretic + a vasodilator drug (according to indications, antihistamines) is indicated.

7. The course use of antipyretic analgesics for antipyretic purposes is unacceptable.

8. The appointment of antipyretic drugs for "non-inflammatory fevers" (central, neurohumoral, reflex, metabolic, drug, etc.) is contraindicated.

Scientific and Clinical Department of Cystic Fibrosis, Moscow State Scientific Center of the Russian Academy of Medical Sciences

Introduction Cost of treatment cardiovascular disease in developed countries is 1.

© "RMJ (Russian Medical Journal)"

Register now and get access to useful services

• Medical calculators
• List of selected articles in your specialty
• Video conferencing and more

Register

Physiological amenorrhea is the absence of menstruation during puberty, during pregnancy, during breastfeeding (lactation) and in old age;

Pathological amenorrhea - occurs with various diseases of the female reproductive system: lesions of the central nervous system and hormonal disorders (hypothalamus, ovaries, pituitary and adrenal glands), acute and chronic infectious diseases (tuberculosis, adenovirus infection, septic conditions), severe intoxications (heavy metal poisoning, alcohol, household poisons), metabolic disorders (malnutrition, anemia, intense physical activity); in turn, pathological amenorrhea can be primary and secondary:

Primary pathological amenorrhea - the absence of menstruation in a woman who has reached the age of 16, or in a woman who has never had them;

Secondary pathological amenorrhea - the absence of menstruation for 3 or more terms of the normal menstrual cycle in a woman who used to menstruate;

FALSE - this is a condition in which cyclic processes in the reproductive system of a woman occur, however, there is no external bleeding due to psychogenic causes (false or imaginary pregnancy, emotional stress), mechanical obstacles (infection of the hymen, vagina; infection of the cervical canal (cervical canal); septa and adhesions in the uterine cavity); false amenorrhea occurs due to a violation of the development of the female genital organs and after reactive changes in the mucous membrane of the uterine cavity (endometritis, endocervicitis, frequent curettage of the walls of the uterine cavity, including during medical abortions).

I degree (mild) - the duration is not more than 1 year, there are no complaints, the uterus is slightly enlarged, according to the probe - from 5 to 7.5 cm;

II degree (moderate) - the duration of amenorrhea is from 1 to 3 years. Vegetovascular disorders appear (in 50% of women). The uterus is enlarged in size, the uterine cavity along the probe is from 3.5 to 5.5 cm;

III degree (severe) - duration more than 3 years, severe clinical manifestations, practically refractory to therapy;

By the time of occurrence: primary amenorrhea (menstruation has never been); secondary amenorrhea (develops after a period of normal menstruation (as a result of abortion, inflammatory, tumor processes, etc.);

Due to the occurrence: amenorrhea of ​​central origin (occurs due to changes in the cerebral cortex, hypothalamus, pituitary gland); amenorrhea of ​​peripheral genesis (due to changes in the adrenal glands, thyroid gland, ovaries, uterus);

Depending on the level of pathology: hypothalamic; pituitary; ovarian; uterine; adrenal; amenorrhea due to pathology thyroid gland.

Amenorrhea is a consequence of dysfunction of the cerebral cortex,

Amenorrhea due to damage to subcortical structures (hypothalamic-pituitary amenorrhea); disorders of the hypothalamic-pituitary system can be:

(1) - functional: chronic psychogenic stress, dietary disorders, chronic infections (frequent tonsillitis) and especially neuroinfections, endocrine diseases, taking drugs that deplete dopamine reserves in the central nervous system (reserpine, opioids, monoamine oxidase inhibitors) and affect the secretion and metabolism of dopamine ( haloperidol, metoclopramide);

(2) - organic (anatomical);

(3) - a consequence of congenital pathology.

Taking medications (psychotropic drugs, antihypertensives, hormonal drugs, sleeping pills);

Severe somatic or mental pathology;

Aplasia of the endometrium or uterine synechia (Asherman's syndrome);

organic neoplasms and pathological changes hypothalamic-pituitary region;

Endocrine-metabolic disorders, additionally confirmed by the results of hormonal studies.

Hormonally active pituitary tumors: prolactinoma, mixed prolactin- and ACTH-secreting pituitary adenomas;

Damage to the hypothalamus and pituitary stalk as a result of: tumors (eg, craniopharyngioma), trauma (trauma to the base of the skull, hemorrhage), basal meningitis, granuloma, reticulosis, surgery, exposure to radiation, infectious-allergic and neuro-reflex lesions of the hypothalamic region in chronic tonsillitis ;

Necrosis of pituitary tissue due to thrombosis of the pituitary vessels or massive postpartum or post-abortion bleeding.

The central genesis is

L.A. Ulitsky, M.L. Chukhlovina, E.P. Shuvalova, T.V. Belyaeva, St. Petersburg 2001

The so-called habitual or constitutional fever deserves special attention. It really exists, especially in young people (more often in young women) with a labile autonomic nervous system and an asthenic constitution in situations of high physical or emotional stress. Currently, such temperature disorders are considered as manifestations of cerebral autonomic disorders and are included in the picture of the syndrome of autonomic dystonia (dysfunction). The latter is interpreted as a psychovegetative syndrome. It should be emphasized that autonomic dysfunction syndrome can develop against the background of clinical signs hypothalamic dysfunction or without it. In the first case, monotonous low-grade fever is more common in combination with endocrine and autonomic disorders of permanent or paroxysmal. In the second case, thermoregulation disorders occur without signs of damage to the hypothalamus, hyperthermia is characterized by febrile numbers. is persistent in nature. However, to establish that hyperthermia is due to cerebral autonomic disorders. it is possible only after a detailed and persistent examination, excluding other causes of a prolonged increase in body temperature.

Currently, subfebrile condition is called an increase in body temperature not higher than 37.9 C, lasting more than 3 weeks.

It is completely unacceptable after the first unsuccessful attempts to discover the cause of subfebrile condition to suspect a simulation of the disease. Unfortunately, such unfounded suspicions sometimes arise. Meanwhile, even our teachers argued: the simulation cannot be assumed. it must be proven. Currently, subfebrile condition of infectious and non-infectious etiology is still distinguished. The cause of the latter may be tumors of various localization, lesions of the diencephalic region of the brain. systemic blood diseases, diffuse connective tissue diseases. With the infectious nature of subfebrile condition, one should, first of all, exclude certain infectious nosological forms, identify or exclude pulmonary and extrapulmonary tuberculosis, and then direct one's efforts to search for focal infection.

And, nevertheless, many therapists, as experience shows, in the absence of obvious pathology from the lungs, lymphatic glands and with a normal blood picture, make hasty conclusions about that. that the patient has subfebrile condition "on a nervous basis" and patients are often assured of this. As a result, a patient with persistent low-grade fever in some cases becomes a permanent patient of a neurologist or psychotherapist.

What diseases of the nervous system can cause perennial subfebrile conditions? First of all, these are diseases associated with damage to the hypothalamus, due to its most important role in thermoregulation. It is known that damage to the hypothalamus is polyetiological. So, in case of trauma in case of a fracture of the base of the skull, there may be direct damage to the pituitary stalk, in case of traumatic extra-, subdural or intracerebral hematoma, ventral displacement of the hypothalamus leads to local circulatory disorders. The latter may affect the supraoptic nuclei. In this case, transient diabetes insipidus occurs, combined with central fever.

Among tumors affecting the hypothalamus and optic chiasm by compression, suprasellar meningiomas are the most common. craniopharyngiomas and pituitary tumors. These tumors can also cause diabetes insipidus, mental and emotional disorders. and in some cases - central fever.

With a large aneurysm of the vessels of the circle of Willis, it, like a tumor formation, can compress the hypothalamus. In cases of granulomatous basal meningitis (eg tuberculosis or syphilis), the blood vessels can be constricted due to vasculitis, which leads to the formation of areas with insufficient blood supply in the hypothalamus.

From the above data it follows that there are many reasons for the development of central fever, hyperthermia, low-grade fever, and yet this is rare. However, the neurologist must use all modern methods studies (including CT, MRI, ultrasound) to exclude damage to the hypothalamic region. If all this is done and during dynamic observation it is not possible to identify the symptoms of a primary CNS disease, the neurologist has the right to give an opinion that explains the presence of persistent subfebrile condition neurological disease currently not possible.

In order to assess how completely a patient with subfebrile condition is somatically examined, a neurologist must know other, non-neurological causes of persistent subfebrile conditions.

Diagnostic search should begin with an analysis of infectious causes: conduct a survey aimed at identifying infectious nosological forms, pulmonary and extrapulmonary tuberculosis and the so-called focal infection with and without generalization.

As for infectious nosological forms. then, first of all, brucellosis should be excluded (reactions of Wright and Heddelson, immunological methods, intradermal poba Byurne).

In the presence of persistent subfebrile condition, it is recommended to show the patient to an ophthalmologist, as it is necessary to make sure that there is no chorioretinitis, especially when photopsy and metamorphopsia appear in the patient. These symptoms, combined with subfebrile condition, make one think of chronic toxoplasmosis. The disease is not as rare as it is commonly thought.

A neurologist should remember that in the case of a manifest form of toxoplasmosis, patients complain of an asthenoneurotic nature (general weakness, fatigue, irritability, headaches, memory loss, sleep disturbance, muscle and joint pain). Women often have a history of recurrent miscarriages. lead serological studies and intradermal test with toxoplasmin. This disease affects people at any age, but more often young cat lovers.

The neurologist must be aware of the possibility of HIV infection, especially if he works in prehospital care.

It should also be noted that due perseverance in the diagnosis of tuberculosis in febrile patients on the part of outpatient doctors and therapeutic hospitals is not shown. At the same time, the possibility of tuberculosis of the mesenteric nodes and serous membranes must be considered in all cases of prolonged subfebrile condition. It is precisely in these localizations of the tuberculous process that the fever is distinguished by particular persistence and "dumbness".

It is also known that one of the causes of prolonged subfebrile condition can be helminthiases (ascariasis, trichocephalosis, diphyllobothriasis), according to the latter, St. Petersburg and the region are endemic. In some cases, persistent low-grade fever is caused by infection of the intra- and extrahepatic biliary tract, as well as pathology of the urinary structures.

special attention deserves focal infection. Suffice it to say that granulomas of the tips of the roots of the teeth are one of the most common causes of prolonged low-grade fever. Such patients, as a rule, are referred to the dentist, and they return to the attending physician with the conclusion: "the oral cavity is sanitized." Meanwhile, granulomas and apical abscesses can also affect apparently healthy, sealed teeth. In order not to miss the source of infection, an x-ray examination of this area is required, and in the absence of soreness of the teeth during percussion, it is often not performed.

Sometimes chronic purulent sinusitis and frontal sinusitis can proceed for a long time without pronounced clinical symptoms, but in some cases they end in a brain abscess. Apparently, a thorough, sometimes repeated x-ray examination is required, so as not to miss the cause of subfebrile condition and prevent formidable complications.

Taking into account the history, one should keep in mind the possibility of subphrenic, subhepatic, perirenal abscesses, which are not easy to recognize. One of the common causes of persistent subfebrile conditions is the pathology of the female genital organs and, in particular, the uterine appendages. Experience shows that in some cases in women, prolonged subfebrile condition may be the result of various kinds of hormonal disorders. In this regard, it is recommended to refer such patients for a consultation with a gynecologist-endocrinologist.

It should be emphasized that in whatever direction the research into the causes of persistent subfebrile condition is conducted, they should not be superficial and fragmented.

Post comments:

Post comments:

Where should I go with my illness?

precocious puberty

Precocious puberty (PPS) is understood as the appearance of secondary sexual characteristics (SPD) up to 7 years and menstruation up to 10 years. There are isosexual (WFPs correspond to the sex of the child) and heterosexual (WFPs are opposite to the sex of the child) forms of PPS. Regardless of the genesis of the disease, there are still complete and incomplete forms of PPS. Complete is manifested by the development of the runway and menstruation, incomplete - the presence of at least one of the runways in the absence of menstruation.

premature puberty according to the female type (isosexual type of sexual development). The goal of treatment is to eliminate cerebral disorders that have arisen as a result of pathological processes of a predominantly organic or functional nature with simultaneous inhibition of PPS. The principles of management and therapeutic measures for disorders of sexual development depend on the form of the disease and the level of hormonal regulation at which this or that lesion is realized.

Central genesis of the disease

Of great importance in the prevention of PPS of this type is the fight against intranatal and antenatal pathology (fetal hypoxia, birth asphyxia, birth trauma). It has a direct damaging effect and creates a favorable background for the effects of toxic, infectious factors in the neonatal period and in early childhood. All activities should be aimed at the treatment of diencephalic pathology: dehydration therapy, vitamins, AFT. If a hamartoma is detected (computed tomography), a conservative hormonal treatment. With isolated transient thelarche (enlargement of the mammary glands) at the age of 2 to 4 years, the use of any type of therapy in this contingent of girls is impractical. Dispensary observation of a pediatric gynecologist before the onset of puberty is shown (up to 4 years 1 time in six months, after 4 years - 1 time per year), prevention viral diseases, respiratory diseases, abstinence from vaccinations (except for polio) until the complete disappearance of the manifestations of PPS.

Patients with isolated early thelarche should be under the supervision of a pediatric gynecologist (once every six months) until the end of puberty. With true PPS, patients have no disorders menstrual function, comes in early age fertility, the timing of menopause correspond to physiological parameters (i.e., the generative period increases). Upon reaching reproductive age, these patients suffer from short stature (height 130–150 cm).

Pharmacotherapy

Hormone therapy is aimed at inhibiting PPS, improving the prognosis of the final growth of patients, improving the social adaptation of patients among peers and adults. The main indication for hormonal therapy is the full form of PPS with the manifestation of PPP and menstruation at the age of up to 3 years. This is the most severe contingent of patients with PPS: the appearance of runway and menstruation at an early age, the rapid closure of growth zones, the appearance of feminine features in the figure of a little girl make it impossible for her to stay in the children's team.

For hormonal therapy, progesterone preparations are used (medroxylrogesterone capronate, chlomadinone acetate, 17-OPK); synthetic progestins ("Diane-35", androkur), sigetin; synthetic analogues of luliberin. Medroxyprogesterone capronate is prescribed at a dose of 100-200 mg / day. every 10-14 days within 2-6 months, sometimes the dose is increased to 200-300 mg / day. (suppresses thelarche, menstruation, but does not inhibit the process of bone maturation). The drugs of choice are antiandrogens - cyproterone acetate (Androkur), Diane-35. Androkur is prescribed orally, the dose is selected individually, it ranges from 25 to 100 mg / day. At doses of 50-75 mg / day. in girls, a regression of the PRP occurs, the rate of differentiation of the bone skeleton stabilizes, short stature is prevented.

Cancellation of the drug should be carried out gradually, as well as cortisol drugs. Sigetin is prescribed in age dosages for 2-3 months. The gonadotropin-releasing hormone (GT-RH) agonist buserelin is administered daily at 400–600 mg intranasally for “pituitary desensitization” and suppression of pubertal levels of gonadotropins and sex steroids. Combination therapy with a GT-RH agonist and androcur is acceptable in the initial stages of treatment. The GT-RH agonist has a stimulating effect at the beginning of therapy, which is leveled by androcur. Subsequently, Androkur is canceled.

Monitoring of patients receiving hormones should be carried out in highly specialized institutions at least once every six months until the end of puberty and the establishment of a regular menstrual cycle after discontinuation of therapy, which should last at least 8 years. Girls with a complete form of PPS and the onset of clinical symptoms at a time close to the physiological period of puberty (6-8 years), given the favorable results of long-term follow-up, hormone therapy is not indicated. The child is observed once a year by a pediatric gynecologist, a neuropathologist until the end of puberty. Symptomatic therapy is prescribed according to indications.

Ovarian origin of PPS

In the presence of a hormonally active ovarian tumor, surgical treatment is indicated. The volume of the operation depends on the morphogenesis of the tumor, taking into account the young age of the patient. Usually after removal of the tumor after 2 weeks. signs of PPP disappear. To prevent recurrence of the tumor in the remaining ovary, the girl must be under constant control. When a follicular ovarian cyst is detected, the gynecologist's tactics should be expectant due to the functional nature of the disorders, the short duration of the existence of the cyst. The exception is patients with a long-term increase in the size of the ovaries when it is impossible to exclude a hormonally active tumor. Surgical intervention is indicated no later than 2 months later. careful observation of the patient.

Non-drug treatment

Phytotherapy is most often used to curb the development of CAP - freshly prepared potato juice orally (2 tablespoons per day) for 2–3 months.

Premature puberty according to the male type (heterosexual type of sexual development). It is characterized by premature adrenarche (appearance of pubic hair growth in girls under the age of 8–9 years), often resulting from congenital adrenal dysfunction (CHD) or adrenogenital syndrome (AGS).

Pharmacotherapy

Cortisol replacement therapy is the treatment of choice. At the same time, adrenal insufficiency is compensated and excessive secretion of androgens is suppressed. Treatment is carried out continuously, for life. At the beginning of treatment, a dexamethasone test (large doses of the drug) is necessary, followed by individual selection of the therapeutic dose of dexamethasone or prednisolone. The level of urine 17-KS, the bone age of the child, the degree of virilization at the beginning of treatment are taken into account. The dose is considered adequate when the level of 17-KS in the daily urine remains within the normal range. The dose is increased with age and with concomitant infectious diseases. Long-term use of prednisolone inhibits virilization, suspends fast growth and development, feminization occurs in girls. In the salt-losing form of VDKN, prednisolone therapy is supplemented with the introduction of sodium chloride and DOKS inside.

Surgery

It is carried out simultaneously with glucocorticoid therapy in the form of plasty of the external genitalia (amputation of the hypertrophied clitoris - up to 3-5 years; dissection of the urogenital sinus - at 10-12 years).

I. Primary amenorrhea (absence of menstruation in girls aged 15-16 years and older, menstruation has never been).

1) May occur with organic lesions of the central nervous system: brain tumors, chronic meningoencephalitis, arachnoiditis, chronic serous meningitis, epidemic encephalitis;

2) Psychogenic amenorrhea - associated with negative emotions, mental and physical overstrain;

3) Pathology of the hypothalamic-pituitary region:

Adiposogenital dystrophy is a disease associated with intrauterine infection, toxoplasmosis, with infection in childhood and adolescence. Manifested by obesity with a pronounced deposition of fat in the pelvis and hips. Defects in the development of the skeleton, hypoplasia of the genital organs and amenorrhea;

Laurence-Moon-Beadle syndrome is a hereditary family disease caused by gene defects. It is characterized, in addition to the signs characteristic of adiposogenital dystrophy, by a sharp mental retardation and numerous malformations;

Hand-Schuller-Christian disease is a hereditary disease characterized by dwarf growth, sexual infantilism, xanthomatosis, osteoporosis, diabetes insipidus, endophthalmos;

Pituitary cachexia (panhypopituitrism) is a disease that occurs with hypofunction of the entire pituitary gland and is characterized by dwarfism (dwarfism) with sexual infantilism and amenorrhea.

II. Secondary amenorrhea (cessation of menses after they have been at least once):

1. Psychogenic amenorrhea - occurs as a result of acute or chronic emotional and mental trauma.

Under the influence of stress, there is an increase in the release of beta-endorphins, neurotransmitters of the class of endogenous peptides. This leads to a decrease in the formation of dopamine and a decrease in the formation and release of gonadoliberins, which in turn causes a decrease in the release of gonadotropins.

In psychogenic amenorrhea, along with secondary amenorrhea, psychopathic disorders are noted, often leading to the development of asthenoneurotic, asthenodepressive, or asthenohypochondriac syndrome.

Hormonal studies reveal the monotonous nature of the blood levels of luteinizing and follicle-stimulating gonadotropins, the number of which fluctuates within the lower limit of the basal level. The content of estradiol in the blood is reduced, the karyopyknotic index ranges from 25-30% and also has a monotonous character.

With prolonged psychogenic amenorrhea, the size of the uterus may decrease somewhat.

The diagnosis of psychogenic amenorrhea is established on the basis of a typical history and clinical picture. Involvement of hypothalamic structures is confirmed by a positive test with GnRH.

Treatment is carried out in conjunction with a psychoneurologist. Mandatory: normalization of living conditions, elimination of stress. Antidepressants and antipsychotics are used (it must be remembered that these drugs increase the inhibition of the gonadotropic function of the pituitary gland, which leads to a slowdown in the recovery of the menstrual cycle). Normalization of menstrual function and restoration of ovulatory cycles occur after the improvement of the mental state of patients. Therapy with vitamins of groups A, E and B is also shown.

2. Hypothalamic form of secondary amenorrhea (amenorrhea against the background of weight loss) - develops in girls and young women who use a diet poor in proteins for cosmetic purposes.

The cause of amenorrhea in this case is the insufficiency of the pituitary zone of the hypothalamus due to infectious-toxic effects in childhood and puberty. Psycho-emotional stress can be a resolving factor. A certain role is played by the volume of adipose tissue - the place of extragonadal estrogen synthesis.

The clinical picture of this form of amenorrhea is characterized primarily by a decrease in body weight by 15-25% of the age norm, moderate hypoplasia of the mammary glands, external and internal genital organs. A sharp decrease, and sometimes lack of appetite, high performance and social activity.

The diagnosis is simple due to the typical history and clinical presentation. Hormonal studies reveal a decrease in the level of gonadotropic hormones to the lower limit of the basal level, the karyopyknotic index is reduced to 20-25%. ultrasound examination shows a decrease in the size of the uterus with normal sizes of the ovaries.

Treatment includes complete fractional nutrition, the appointment of enzyme preparations, vitamins (B1, B6, C and E), glutamic acid, valerian infusion or decoction. Psychotherapy is very effective.

As a rule, the menstrual cycle is restored upon reaching the body weight corresponding to age standards, however, the menstrual cycle can be unstable.

35.1. Endocrine infertility- infertility due to ovulation disorders:

1. Anovulation.

Chronic anovulation may be the result of dysfunction of the hypothalamic-pituitary system (impaired rhythm and amount of release of GnRH and gonadotropic hormones of the pituitary gland). Developed as a result of neuroinfection, intoxication, psycho-emotional stress, cerebral injury, etc. Anovulation is also a symptom of endocrine diseases, namely polycystic ovaries, dysfunction of the adrenal cortex, hyperprolactinemia. Postpartum obesity, hypo- and hyperthyroidism. Itsenko-Cushing's disease, nervous and mental diseases.

Manifestations of chronic anovulation, in addition to infertility, may be menstrual disorders - dysfunctional uterine bleeding, amenorrhea, oligomenorrhea.

The diagnosis of anovulation is based on the data of functional diagnostic tests: monophasic basal temperature, monotonous karyopyknotic index (as a rule, fluctuating within the limits characteristic of the beginning of the first phase of the cycle), absence of the “pupil” symptom, cervical mucus tension 2-6 cm, laparoscopy is used for diagnostic purposes , at which they evaluate appearance ovaries, the absence of ovulatory stigma and corpus luteum, reveal non-endocrine causes of infertility - adhesions, the presence of endometrioid ectopia in the pelvis. Additional chromopertubation - the introduction of a dye (indigo carmine, methylene blue) through the external uterine os - allows you to establish obstruction of the fallopian tubes or the localization of their obstruction.

2. Luteinization of the unovulated follicle.

It is believed that stress plays a role in the occurrence of this pathology. Hyperprolactinemia and inflammation of the ovaries.

The diagnosis is very difficult, because. tests of functional diagnostics and the content of hormones in the blood and urine do not differ from those during the ovulatory cycle. Ultrasound examination and measurement of the diameters of the follicles note a slow gradual decrease in the size of the preovulatory follicle (whereas the disappearance of the dominant follicle is characteristic of ovulation). Laparoscopy performed on the 13-15th day of the cycle reveals a hemorrhagic corpus luteum without ovulatory stigma.

3. Insufficiency of the luteal phase of the cycle (hypofunction of the corpus luteum) - accompanied by a decrease in the synthesis of progesterone.

The cause of infertility in case of insufficiency of the luteal phase of the cycle can be: defective secretory transformations of the endometrium, which prevent the implantation of a fertilized egg; decrease in peristaltic activity of the fallopian tubes due to progesterone deficiency.

Insufficiency of the luteal phase of the cycle can be observed as a physiological phenomenon after menarche, childbirth, abortion during several menstrual cycles. The causes of insufficiency of the luteal phase of the cycle may be hyperandrogenism of adrenal origin, hyperprolactinemia, inflammatory diseases uterus and appendages, hypothyroidism. In addition to infertility, with insufficiency of the luteal phase of the cycle, scanty spotting is noted on the 4-7th day before the next menstruation.

The diagnosis of insufficiency of the luteal phase of the cycle is established on the basis of a shortening of the hyperthermic phase of the basal temperature to 4-8 days with a temperature difference in the first and second phases of the cycle of less than 0.4 ° C; a decrease in the content of pregnandiol in the urine below 3 mg / day, progesterone in the blood below 15 nmol / l on the 4th day of an increase in basal temperature; defective phase of secretion in the endometrium 2-3 days before menstruation.

All numerous variants of endocrine disorders leading to ovulation disorders can be conditionally combined into separate clinical groups, which are characterized by the corresponding symptom complex:

Group I - hypothalamic-pituitary insufficiency (pathological conditions defined as genital underdevelopment);

Group II - hypothalamic-pituitary dysfunction (patients with menstrual disorders);

III group- ovarian failure;

Group IV - congenital or acquired disorders of the reproductive system;

Group V - hyperprolactinemia in the presence of a tumor in the hypothalamic-pituitary region;

Group VI - hyperprolactinemia without lesions in the hypothalamic-pituitary region;

Group VII - amenorrhea against the background of a tumor in the hypothalamic-pituitary region.

Treatment of endocrine infertility is carried out for women under 35 years of age in the absence of somatic diseases which are a contraindication to pregnancy and childbirth.

In the presence of endocrine diseases, therapy of this etiology is necessary.

A common method of anovulation is to stimulate ovulation. The following schemes for the administration of drugs are used:

1) Clomiphene (clomiphenititrate, clostilbegid) - 50-150 mg from the 5th to the 9th day from the onset of menstruation or from the onset of a menstrual reaction induced by drugs. For this purpose, oral contraceptives such as non-ovalon, bisekurina, etc. are used, 1 tablet per day for 7-10 days;

2) Clomiphene at the same dose and at the same time in combination with chorionic gonadotropin, which is administered after the dominant follicle reaches preovulatory dimensions (at least 18 mm in diameter) at a dose of 4500-3000 IU;

3) You can use tamoxifen (zitozonium), which has antiestrogenic activity. The drug is prescribed from the 5th to the 9th day of the cycle at a dose of 10-20 mg per day;

4) Pergonal (human menopausal gonadotropin) from the 5th day of the induced menstrual reaction at a dose of 150 IU daily under the control of ultrasound measurement of the diameter of the follicles.

You can use synthetic analogues of gonadotropic releasing hormones of the hypothalamus, which stimulates the release of luteinizing gonadotropin by the pituitary gland and indirectly ovulation in the ovary. The drug is administered intravenously at hourly intervals in the so-called pulsating mode, which simulates the release of GnRH by the hypothalamus.

In case of infertility caused by insufficiency of the luteal phase of the cycle, pathogenetic treatment diseases that caused this dysfunction of the ovaries. Spend also hormone therapy replacement nature with corpus luteum preparations or norsteroids with a progestogenic effect. Progesterone is used in 1 ml of 1% solution in / m from the 18-20th day of the cycle for 6-8 days; 17-hydroxyprogesterone capronate, 1 ml of a 12.5% ​​solution on the 17th or 20th day of the cycle; norkolut, which is prescribed from the 16th to the 26th day of the cycle at a dose of 5 mg per day. The use of chorionic gonadotropin, which stimulates the hormonal secretion of the corpus luteum, is recommended (1000-1500 IU IM on the 2nd, 4th, 6th day of increasing basal temperature). The duration of therapy is 3-4 menstrual cycles.

In case of infertility due to luteinization of the unovulated follicle, ovulation stimulation is recommended.

It must be remembered that with the wrong dose of drugs that stimulate ovulation, a complication may occur - ovarian hyperstimulation syndrome.

The prognosis for the restoration of reproductive function with the correct determination of the cause of endocrine infertility and the timely conduct of adequate therapy is favorable. If a woman has diseases or dysfunctions of the endocrine glands, treatment should begin with the treatment of these endocrine diseases. Usually, the normalization of the function of the endocrine glands leads to the restoration of the ovulatory menstrual cycle. Only with ongoing anovulation or insufficiency of the luteal phase of the cycle, ovulation stimulation and therapy, as mentioned above, is recommended.

In cases where infertility is associated with dysfunction of the hypothalamic-pituitary system, therapy is ineffective.

When pregnancy occurs after treatment, it is necessary to monitor women from an early date, since these pregnant women are at high risk for miscarriage in the first trimester of pregnancy.

37.1 Modern means of contraception:

1. Intrauterine contraception:

1) neutral intrauterine devices (IUDs) - the most widely used are the Lips loop (a polyethylene device in the form of a double Latin letter), the IUD in the form of the letter T and the number 7.

The mechanism of action of neutral IUDs is that they disrupt the implantation of a fertilized egg, which is associated with accelerated peristalsis of the fallopian tubes and the resulting inferiority of the egg.

Pearl index when using neutral naval forces - 4.

2) medical IUDs - contain copper, gestagens. The mechanism of action of medical IUDs:

Copper has a bactericidal and spermicidal effect;

Gestagens change the property of cervical mucus, which leads to difficulty in the penetration of spermatozoa into the uterine cavity, and also causes the inability of the endometrium to implant an egg.

The Pearl Index when using medical IUDs is 1-2.

Contraindications to the use of IUDs:

Acute and subacute inflammatory diseases of the genital organs;

Chronic inflammatory processes with frequent exacerbations;

Infectious-septic diseases and fever of any etiology;

Isthmic-cervical insufficiency;

Benign and malignant tumors of the genital organs;

Polyps of the cervical canal;

Erythroplakia and leioplakia of the endometrium;

Polyposis and endometrial hyperplasia;

Tuberculosis of the genital organs;

Malformations of the uterus;

Intrauterine synechia;

Violations of the menstrual cycle by the type of meno- or metrorrhagia;

Violations of the blood coagulation system, accompanied by increased bleeding.

The IUD is inserted by a doctor in compliance with the rules of asepsis on the 5-7th day of the menstrual cycle, after an artificial abortion - immediately (or after the next menstruation), after childbirth - after 3 months. The necessary conditions are: a normal blood picture, 1-2 degree of frequency of the vagina.

After the introduction of the IUD, the doctor should examine the woman in a week, after the first menstruation, then after 3 months, subsequent examinations are carried out 1 time in 6 months. The duration of the IUD in the uterine cavity is 3-5 years.

Complications of intrauterine contraception:

Lower abdominal pain;

Uterine bleeding;

Ectopic pregnancy;

Uterine pregnancy, often ending in spontaneous abortion;

Perforation of the uterus (partial - with the introduction of the IUD into the muscle of the uterus in the area of ​​the bottom or side walls; complete - with the movement of part or all of the IUD into the abdominal cavity).

2. Hormonal contraception.

Classification of hormonal contraceptives:

1) according to the method of application:

Tablets (oral);

Injected intramuscularly (medroxyprogesterone);

Implanted under the skin (levonoreggrel);

2) by composition:

a) combined estrogen-gestagen hormonal contraceptives:

Single-phase - tablets with a constant content of estrogens and gestogens (non-ovlon, bisekurin, ovulen, rigevidon). Pearl index when using single-phase hormonal oral contraceptives - less than 1.

Biphasic - include tablets of 2 types, designed respectively to be taken in the first and second phase of the menstrual cycle. The content of estrogen in them is the same, but the tablets taken in the second phase of the menstrual cycle contain more gestogens;

Three-phase - contain gestagens and estrogens in various combinations (trisyston, tirquilar). In tablets of the first type, the content of estrogens in gestagens is the lowest (ratio 1: 1.2), in tablets of the second type, the dose of estrogens and especially gestagens increases (ratio 1: 1.5), in tablets of the third type, the content of estrogens decreases to the initial level, and the dose of gestagens increases (ratio 1:4). The three-phase administration of sex steroids allows for the same change in the content of estrogens and progestogens in the blood, as in a normal menstrual cycle. The Pearl index when using three-phase combined oral contraceptives is less than 1.

The contraceptive effect of combined estrogen-gestagenic oral contraceptives is to inhibit ovulation due to suppression of the ovulatory release of gonadotropins of the anterior pituitary gland, implantation disorders as a result of inhibition of secretory changes in the endometrium and impaired spermatozoa movement due to thickening of mucus in the cervical canal;

b) gestagen-containing hormonal contraceptives:

Mini-drank (continuin, fermulen) - contain 500-300 mcg per tablet. The contraceptive action is based on inhibition of the contractile activity of the fallopian tubes, an increase in the viscosity of mucus in the cervical canal, a violation of cyclic processes in the endometrium, the Pearl Index is 1.5-2.

Postcoital oral contraceptives (postinor) - for women with irregular sex life. The contraceptive action is based on preventing the implantation of a fertilized egg due to changes in the endometrium and its rejection in response to a decline in hormone levels after taking the drug;

Long-acting agents (medroxy-progesterone acetate - injected intramuscularly, norplant - implanted subcutaneously in a capsule). The contraceptive effect of these drugs is associated with a decrease in the permeability (increase in viscosity) of cervical mucus for spermatozoa, suppression of the ovulatory release of gonadotropins, and atrophic changes in the endometrium. Pearl index - 1.

Also, among hormonal contraceptives, funds are allocated:

The closest to cyclic changes in the body of a woman (three-phase oral contraceptives);

Least close to cyclic changes in the body of a woman (single-phase oral contraceptives);

With a minimum content of hormones (used for hypoestrogenemia, hypogonadotropinemia);

High in hormones

With a therapeutic effect (single-phase oral contraceptives - contribute to the regulation of the menstrual cycle, reduce blood loss during menstruation, disappearance of pain and other painful symptoms during menstruation, have a pronounced therapeutic effect in endometriosis of any localization, fibrocystic mastopathy, hyperplasia of endometrial polyposis, follicular ovarian cysts ; three-phase oral contraceptives - reduce the content of low-density lipoprotein in the blood, have healing effect with various progesterone deficiency conditions, namely: mastopathy, some forms of premenstrual syndrome, anovular menstrual cycles).

14.1 Endoscopy– inspection internal organs using special optical instruments and devices. Using these methods, targeted biopsy can be performed.

In gynecological practice, the following main endoscopic methods are used:

1) Colposcopy - examination of the vagina and the vaginal part of the cervix using a binocular or monocular loupe equipped with a lighting device (an increase in the area under study by 30 times or more);

2) Microscopic colposcopy (colpomicroscopy) - colposcopy under high magnification (80-90 times) using a contact lens and with preliminary staining of the study area;

3) Cervicoscopy - examination of the mucous membrane of the cervix using a cervicoscope;

4) Hysteroscopy - examination of the inner surface of the uterus in order to identify pathological changes in the endometrium;

5) Peritoneoscopy (laparoscopy) is a research method by which the organs of the small pelvis and abdominal cavity are examined with an optical instrument inserted into the abdominal cavity through an opening in the anterior abdominal wall.

With the help of laparoscopy, a number of gynecological surgical interventions can be performed - sterilization (coagulation of the fallopian tubes, application of a tantalum bracket or suture), dissection and coagulation of adhesions in the small pelvis, coagulation of endometrioid nodes, puncture of ovarian retention formations, coagulation of ovarian tissue in patients with ovarian apoplexy;

37.3 CHORIONEPITHELIOMA.

II. Chorionepithelioma is a malignant tumor originating from epithelial cells chorionic villi.

Classification of chorionepithelioma:

1. Non-metastatic - the process is limited to the uterus.

2. Metastatic - the process extends beyond the uterus (into the gastrointestinal tract, genitourinary system, liver, lungs, brain):

With a favorable prognosis (low risk) - with a short duration of the disease (less than 4 months), the titer of chorionic gonadotropin before treatment is less than 40,000 mIU / ml, there is no need for chemotherapy;

With an unfavorable prognosis (high risk) - with a disease duration of more than 4 months, a chorionic gonadotropin titer before treatment of more than 40,000 mIU / ml, metastases to the liver and brain, no effect from previous chemotherapy, the onset of the disease after full-term pregnancy.

The clinical picture of chorionepithelioma is manifested primarily blood secretions caused by tumor destruction of blood vessels. Initially, the discharge is moderate, in-law intensifies. When the tumor is located in the thickness of the uterine wall and the serous cover of the organ is destroyed, profuse intraorgan bleeding occurs. Bleeding can occur in the abdominal cavity and from metastatic nodes in the liver and intestines. External bleeding may have its source in metastases of chorionepithelioma in the vagina.

The second important symptom is anemia, which progresses rapidly. It is the result of both uterine bleeding and intoxication due to the absorption of tumor decay products.

Due to necrosis and infection of the chorionepithelioma nodes, a feverish state may develop.

With the defeat of metastases of chorionepithelioma of the lungs, a cough with sputum, pain in the chest appears. Metastases in the brain cause pain and the appearance of other neurological symptoms associated with the localization of metastatic nodes. Metastases in the digestive organs cause bleeding, pain, and dyspepsia.

The walls of the vagina and the cervix are cyanotic, the uterus is enlarged, thecalutein cells appear in the ovaries. The mammary glands may be enlarged, colostrum is secreted from them, the areolas are pigmented.

Chorionepithelioma cells have a pronounced ability to produce chorionic gonadotropin, which circulates in the blood and is excreted in the urine, and trophoblastic beta-globulin, which is secreted into the blood.

Diagnostics:

Anamnesis - an indication of the appearance of bleeding from the genital organs after a former pregnancy and especially after a hydatidiform mole;

Inspection in the mirrors - tumor metastases in the form of dark red elevations and nodules;

Positive immunological test for trophoblastic beta-globulin;

Histological examination of a scraping from the uterus reveals elements of the tumor;

Pelvic angiography - abundant vascularization and the formation of lacunar accumulations of a contrast agent in the affected area;

Hysterography - detection of chorionepithelioma nodes with their submucosal location;

Ultrasound examination - detection of chorionepithelioma nodes.

1. The use of antitumor drugs: antimetabolites (methotrexate, 6-mercaptopurine), antibiotics (rubomycin, lactinomycin), drugs plant origin(vinblastine, vincristine) and others:

Treatment with one antitumor drug is carried out with the localization of the tumor only within the uterus, with the duration of the disease less than six months, the small size of the uterus (not exceeding those during pregnancy 8 weeks);

Various combinations of drugs are used for the duration of the symptoms of the disease for more than six months, the occurrence of chorionepithelioma after childbirth, the ineffectiveness of treatment with one drug, in the presence of metastases.

2. Surgical treatment (extirpation of the uterus with or without appendages) - with uterine bleeding that is life-threatening for the patient, the threat of destruction of the uterine wall by a tumor, the ineffectiveness of drug antitumor therapy;

3. Radiation therapy - additional method treatment for metastases in parametric tissue (remote gamma therapy) and in the vagina (intracavitary irradiation).

The criteria for cure are the restoration of menstrual function, a decrease in the size of the uterus to normal, the normalization of the content of chorionic gonadotropin and trophoblastic beta-globulin in the blood serum.

After treatment, the woman is regularly monitored for 2 years with a general examination, gynecological examination, x-ray of the lungs, a blood test with the determination of chorionic gonadotropin.

Prevention of chorionepithelioma consists in the rational treatment of hydatidiform drift using according to indications.

5.1 Uterine amenorrhea:

1. Primary form - due to changes in the endometrium, the degree of which can be expressed differently: from a decrease in the sensitivity of its receptors to the effects of sex hormones to the complete destruction of the entire endometrium (most often due to the tuberculosis process).

2. Secondary form:

1) Intrauterine synechia (Asherman's syndrome) - Intrauterine synechia - are formed after traumatic curettage for abortion, uterine bleeding, rough separation of the placenta. Synechiae are avascular strands in the uterine cavity, running between its walls, more often in the fundus, and deforming the uterine cavity. The clinical manifestation of this pathology, called Asherman's syndrome, is amenorrhea or hypomenorrhea in combination with ovulatory infertility.

Based on the hysteroscopic picture, the following forms of intrauterine synechia are distinguished:

Mild form - synechia thin, filamentous, occupy less than a quarter of the uterine cavity, tubal angles are free or obliterated;

The form moderate- synechiae occupy more than a quarter of the uterine cavity, the bottom of the uterus is partially obliterated, the tubal angles are obliterated;

Severe form - synechia occupy more than a quarter of the uterine cavity, the fundus of the uterus is obliterated, tubal angles are obliterated.

The cause of intrauterine synechia can also be a tuberculous lesion of the endometrium.

Diagnosis is based on a typical history; hysteroscopy is crucial in the diagnosis, in which the degree of prevalence of the process is determined.

Treatment: sharp separation of adhesions under the control of hysteroscopy and the introduction of a special protector, which is a polyethylene frame with a catheter. A mixture containing 64 units of lidase, a 0.1% solution of estradiol dipropionate and 125 mg of hydrocortisone acetate suspension is injected through the catheter for a week. The frame is removed on the 7th-8th day and a Lips loop is inserted into the uterine cavity for a period of 2 years. Within 6 months after separation of adhesions, cyclic hormone therapy is recommended.

The prognosis for the restoration of menstrual function is favorable, for reproductive function - less encouraging. The onset of pregnancy is often complicated by miscarriage, and childbirth by dense attachment of the placenta.

2) Specific (tuberculous) endometritis - Pr

Tuberculous endometritis most often does not have characteristic symptoms. The main complaint is infertility, often primary, rarely secondary. Pain in the lower abdomen and lower back is not associated with the menstrual cycle, is permanent and is due to adhesive changes in the pelvis. There are symptoms of tuberculous intoxication, menstrual disorders (hypomenorrhea, primary and secondary amenorrhea, algomenorrhea, oligomenorrhea).

Tuberculosis of the genital organs is often combined with other gynecological diseases, which can prevail in the clinical picture and determine the further treatment tactics of the doctor.

The most common are small and latent forms of the disease with minor anatomical and functional changes that are difficult to recognize. Bimanual examination data are not informative: either there are no abnormalities, or there are small adhesive changes in the area of ​​non-enlarged uterine appendages. In this form, the only complaint is infertility. Rarely, tuberculous intoxication, bacilli excretion occur, and menstrual irregularities are more often noted.

In the form with pronounced anatomical and functional changes, pain syndrome, bacilli excretion, tuberculous intoxication, and menstrual irregularities are more often observed. The uterine appendages are tubo-ovarian inflammatory formations. Very often, the peritoneum is involved in the process.

Tuberculomas in the area of ​​the uterine appendages (determined by X-ray) require prompt removal, since they are a depot of Mycobacterium tuberculosis and pose a constant threat of exacerbation of the process. The clinical picture of the disease depends on the severity of the inflammatory reaction around the caseous focus.

8.1. Artificial abortion (from obstetrics) is a deliberate interruption pregnancy produced in medical institutions.

There are induced abortions:

Early dates (up to 12 weeks)

Late dates(from 13 to 27 weeks)

The operation of artificial termination of pregnancy is allowed only in medical institutions. Artificial abortion in early pregnancy (up to 12 weeks) is performed:

Terminate the pregnancy at the request of the woman

For medical reasons:

Neoplasms

Diseases endocrine system, blood, hematopoietic organs

Mental disorders

Diseases of the nervous system and sensory organs

Diseases of the circulatory system, respiration, digestion, genitourinary system.

Complications of pregnancy, childbirth and the postpartum period

Diseases of the skin and subcutaneous tissue

Diseases of the musculoskeletal system and connective tissue

congenital anomalies

hereditary diseases

Early abortion methods:

1. mini-abortion - the method can be used when menstruation is delayed from 2-3 days to 25 days. Before performing a mini-abortion, it is necessary to accurately determine the presence and duration of pregnancy, for which it is recommended to use a vaginal examination, measurement of basal temperature, immunological reactions for pregnancy, ultrasound.

A mini-abortion is performed using a vacuum apparatus and flexible polyvinyl chloride plastic cannulas with a diameter of 4.5-6 mm with two holes at the end. Cannulas are introduced into the uterine cavity without preliminary expansion of the cervical canal after probing the uterine cavity. A negative pressure of 0.6-.0.8 atmospheres is created and the contents of the uterine cavity are aspirated. The manipulation is considered complete if the contents do not enter the tank. Anesthesia is not required. A mini-abortion can be performed both in a hospital and on an outpatient basis.

2. Artificial abortion by curettage of the uterus - one-stage surgical removal of the fetal egg by curettage with mandatory anesthesia. The operation of curettage of the uterus is reduced to the expansion of the cervical canal with a Hegar dilator (up to No. 12-14, depending on the gestational age), the removal of large parts of the fetus with a blunt curette or aborts, scraping the remains of the fetal egg and the decidua of the uterus with a sharp curette.

Complications:

Immediate (occur at the time of surgery or shortly after it)

Perforation of the uterus

Bleeding

Leaving parts of the ovum

Acute hematometra

Remote:

Inflammatory processes inside the genitals

Ovarian dysfunction with menstrual irregularities

Infertility

Ectopic pregnancy

Isthmic-cervical insufficiency (ICI)

Anomaly of labor activity during subsequent births.

Bleeding in the afterbirth or early postpartum period

For a more gentle expansion of the cervix (prevention of CCI), you can insert a suppository with prostaglandin F2 and E2 into the cervical canal the night before the operation.

3. Artificial abortion by vacuum aspiration - simultaneous surgical removal of the fetal egg by vacuum aspiration with mandatory anesthesia. The main parts of the vacuum aspirator:

 set of tips

 electric suction

 tubes connecting the electric aspirator with the handpiece.

After anesthesia, the cervical canal is expanded using a Hegar dilator or a vibrodilator.

After expanding the cervical canal to the required diameter, the tip of the vacuum aspirator is inserted into the uterine cavity and the electric suction device is turned on, negative pressure is created. During aspiration, in the side opening of the tip, turn to the wall of the uterus and make a movement (non-scraping) from the bottom to the internal pharynx and in a circle of 360 degrees. The tip should be periodically withdrawn from the uterine cavity so that the air sucked in this way contributes to the movement of parts of the fetal egg through the hose. The operation is considered completed if the contents from the uterine cavity no longer enter the reservoir, and the operating hand feels the walls of the contracted uterus through the tip. After the artificial termination of the first pregnancy, women with Rh-negative blood are immunized with human Rh (D) anti-Rh (D) immunoglobulin.

Amenorrhea of ​​central origin includes dysfunctions of both the cerebral cortex and subcortical structures (hypothalamic-pituitary amenorrhea). Violations of the hypothalamic-pituitary system can be functional, organic and the result of congenital pathology.

Amenorrhea of ​​central origin is more often functional and, as a rule, occurs as a result of exposure to adverse environmental factors. The mechanisms of the disorder are realized through the neurosecretory structures of the brain that regulate the tonic and cyclic secretion of gonadotropins. Under the influence of stress, there is an excessive release of endogenous opioids that reduce the formation of dopamine, as well as a decrease in the formation and release of GnRH, which can lead to amenorrhea. With minor violations, the number of anovulatory cycles increases, and luteal phase insufficiency appears.

Most often, the emergence of central forms of amenorrhea is preceded by mental trauma, neuroinfection, intoxication, stress, complicated pregnancy and childbirth. Amenorrhea is observed in every 3rd patient with schizophrenia and manic-depressive psychosis, especially during an exacerbation. Psychological stress and infectious diseases transferred in childhood are important. Physical overload associated with significant emotional and volitional stress can cause amenorrhea with mental, asthenoneurotic, asthenodepressive or asthenohypochondriac disorders. Menstruation stops suddenly. Along with amenorrhea, irritability, tearfulness, headache, memory impairment, working capacity, and sleep disturbance are observed. During the war, as a result of forced starvation, women dramatically lost weight, which led to a violation in the hypothalamic-pituitary region and to the so-called wartime amenorrhea. Psycho-emotional stress also contributed to this.

Functional disorders of the hypothalamic-pituitary system lead to the development anorexia nervosa, Itsenko-Cushing's disease, gigantism, functional hyperprolactinemia. Causes of functional disorders of the hypothalamic-pituitary system:

Chronic psychogenic stress;

Chronic infections (frequent tonsillitis) and especially neuroinfections;

endocrine diseases;

Taking drugs that deplete dopamine stores in the central nervous system (reserpine, opioids, monoamine oxidase inhibitors) and affect the secretion and metabolism of dopamine (haloperidol, metoclopramide).

Anatomical disorders of the hypothalamic-pituitary structures, leading to Sheehan's syndrome and hyperprolactinemia, are as follows:

Hormonally active pituitary tumors: prolactinoma, mixed prolactin- and ACTH-secreting pituitary adenomas;

Damage to the pituitary stalk as a result of trauma or surgery, exposure to radiation;

Necrosis of the pituitary gland tissue, thrombosis of the pituitary vessels.

Congenital pathology of the hypothalamic-pituitary system can lead to adiposogenital dystrophy.

Regardless of the causes of damage to the hypothalamic-pituitary region, there is a violation of the production of hypothalamic GnRH, which leads to a change in the secretion of FSH, LH, ACTH, STH, TSH and prolactin. In this case, the cyclicity of their secretion may be disturbed. When the hormone-forming function of the pituitary gland changes, various syndromes arise. A decrease in the secretion of FSH and LH leads to a violation of the development of follicles and, consequently, insufficient production of estrogens by the ovaries. Secondary hypoestrogenism, as a rule, is accompanied by hyperandrogenism, which, in turn, contributes to the emergence of a viril syndrome, moderately pronounced in hypothalamic-pituitary disorders.

Since the pituitary gland is also responsible for metabolic processes, when the hypothalamic-pituitary region is affected, patients are distinguished by a characteristic appearance: obesity, moon-shaped face, fatty apron, stretch marks on the abdomen and thighs, however, excessive thinness with mild secondary sexual characteristics is also possible. Obesity and severe weight loss as a result of disorders of the hypothalamic-pituitary region exacerbate the manifestations of hormonal dysfunction.

to amenorrhea anorexia nervosa leads to a sharp decrease in the secretion of gonadotropins. This is often observed with an insistent desire to lose weight and a rapid decrease in body weight by 15% or more. This pathology is common among teenage girls who exhaust themselves with diet and physical activity, and can be the beginning of a mental illness. The absence of menstruation is one of the first signs of the onset of the disease, which leads girls to a gynecologist. On examination, there is a sharp decrease in subcutaneous adipose tissue with female type physique. Secondary sexual characteristics are developed normally. Gynecological examination reveals moderate hypoplasia of the external and internal genital organs. Continued weight loss can lead to bradycardia, hypotension, and hypothermia. In the future, irritability, aggressiveness, cachexia with total loss appetite and aversion to food. The hypoestrogenic state, along with a lack of nutrition, predisposes patients to osteoporosis.

Syndrome (disease) Itsenko-Cushing characterized by increased production of corticoliberin by the hypothalamus. This causes activation of the adrenocorticotropic function of the anterior pituitary due to hyperplasia of basophilic cells and, as a result, hypertrophy and hyperfunction of the adrenal glands, excessive production of glucocorticosteroids and androgens. The consequence of such hormonal disorders is hypercortisolism, which leads to hypokalemic acidosis, increased gluconeogenesis processes, an increase in blood sugar and, as a result, to steroid diabetes. The disease is observed at any age. In children, Itsenko-Cushing's disease is accompanied by virilization of varying severity, in adults, amenorrhea is observed at the onset of the disease, later signs of virilization appear. Characterized by disproportionate obesity with the deposition of subcutaneous fatty tissue on the face, neck, upper body. In patients, the face is round, cyanotic red.

The skin is dry, atrophic, with a marble pattern and areas of pigmentation and acne. Crimson-red stripes of stretching on the chest, abdomen, thighs.

Gigantism also becomes a consequence of hyperplasia of eosinophilic cells of the pituitary gland with increased production of somatotropic and lactogenic hormones. With hyperproduction of growth hormone, growth is excessively high, relatively proportional or disproportionate. An excessive increase in height is usually noticed in the prepubertal and pubertal periods, over a number of years. Over time, acromegaloid enlargement of facial features may develop. From the very beginning of the disease, hypogonadism, primary amenorrhea, or early cessation of menstruation are noted.

To Sheehan's syndrome lead to structural changes in the pituitary gland due to massive postpartum or post-abortion bleeding. At the same time, necrotic changes and intravascular thrombosis in the pituitary gland are detected. Pituitary ischemia also contributes to the physiological decrease in ACTH release in the postpartum period. Intravascular thrombosis also leads to changes in the liver, kidneys, and brain structures. The severity of the clinical manifestations of Sheehan's syndrome depends on the size and localization of the pituitary lesion and, accordingly, the insufficiency of its gonadotropic, thyrotropic, adrenocorticotropic functions. The disease is often accompanied clinical picture hypofunction of the thyroid gland or vegetovascular dystonia of the hypotonic type (headache, fatigue, chilliness). A decrease in the hormonal function of the ovaries is manifested by oligomenorrhea, anovulatory infertility. The symptomatology of the total hypofunction of the pituitary gland is due to a pronounced insufficiency of gonadotropic, thyrotropic and adrenocorticotropic functions: persistent amenorrhea, hypotrophy of the genital organs and mammary glands, baldness, memory loss, weakness, adynamia, weight loss.

When collecting an anamnesis, the connection between the onset of the disease and complicated childbirth or abortion is clarified. You can clarify the diagnosis by lowering the blood levels of gonadotropins, TSH, ACTH, as well as estradiol, cortisol, T 3 and T 4.

Hyperprolactinemia. The occurrence of amenorrhea of ​​the hypothalamic-pituitary genesis is often accompanied by excessive secretion of prolactin - hyperprolactinemia. Prolactin is the only anterior pituitary hormone whose secretion is constantly suppressed by the hypothalamus and increases sharply after the release of the pituitary gland from hypothalamic control. Physiological hyperprolactinemia is observed during pregnancy and lactation, in practically healthy women during sleep, after physical activity as well as under stress. Hyperprolactinemia is possible due to damage to intrauterine receptors with frequent curettage of the mucous membrane of the uterine body, manual examination of the walls of the uterus after childbirth.

Etiology and pathogenesis. The cause of hyperprolactinemia can be both anatomical and functional disorders in the hypothalamus-pituitary system. In addition, the production of prolactin is affected by:

Estrogens, estrogen-containing oral contraceptives;

Drugs that affect the secretion and metabolism of dopamine (haloperidol, metoclopramide, sulpiride);

Drugs that deplete dopamine stores in the central nervous system (reserpine, opioids, monoamine oxidase inhibitors);

Stimulants of the serotonergic system (hallucinogens, amphetamines);

Hypothyroidism.

The pathogenesis of hyperprolactinemia is a violation of the tonic dopaminergic inhibitory control of prolactin secretion caused by dysfunction of the hypothalamus. Of the endogenous prolactin-inhibiting substances, dopamine is the most important. A decrease in its content in the hypothalamus leads to a decrease in the level of prolactin inhibitory factor and an increase in the amount of circulating prolactin. Continuous stimulation of prolactin secretion leads to hyperplasia of prolactotrophs, and then micro- and macroadenoma of the pituitary gland can form.

In 30-40% of women with hyperprolactinemia, the level of adrenal androgens, DHEA and DHEA-S, is elevated. Hyperandrogenism in hyperprolactinemia is explained by the common hypothalamic regulation of prolactin and ACTH secreting functions of the pituitary gland. In addition, prolactin receptors have been found in the reticular zone of the adrenal cortex.

The mechanism of reproductive dysfunction against the background of hyperprolactinemia is as follows. In the hypothalamus, under the influence of prolactin, the synthesis and release of GnRH and, accordingly, LH and FSH decrease. In the ovaries, prolactin inhibits gonadotropin-dependent steroid synthesis, reduces the sensitivity of the ovaries to exogenous gonadotropins.

Clinical symptoms. Hyperprolactinemia is manifested by menstrual disorders such as hypo-, oligo-, opso- and amenorrhea, as well as infertility.

In women with hyperprolactinemia, galactorrhea is often observed, and it does not always correlate with the level of prolactin. So, galactorrhea is possible even at its normal level, which is associated with hypersensitivity of prolactin receptors in the mammary gland.

The so-called asymptomatic hyperprolactinemia is distinguished, in which the level of biologically active prolactin is increased. About 50% of women with hyperprolactinemia report headache and dizziness, a transient increase in blood pressure.

Diagnostics hyperprolactinemia includes the study of the general and gynecological history, a detailed general therapeutic examination. Particular attention deserves the state of the endocrine system, mainly the thyroid gland and the adrenal cortex.

An increase in the level of prolactin in the peripheral blood plasma is one of the confirmations of hyperprolactinemia. The ratio of the content of gonadotropic and sex hormones is also important. For the differential diagnosis of hyperprolactinemia, and in particular its transient form, it is necessary to repeatedly determine prolactin over time. Most informative functional tests with dopamine agonist - bromocriptine (Parlodel ♠) and dopamine antagonist - metoclopramide (Cerukal ♠). Functional hyperprolactinemia is not accompanied by

changes in the Turkish saddle on the radiograph, with CT and MRI in the case of an increase in the level of prolactin to 2000 mIU / l.

To exclude anatomical changes in the pituitary gland, an X-ray examination of the skull is performed in order to identify changes in the area of ​​the Turkish saddle. With pituitary macroadenoma, the size of the Turkish saddle is increased, its bottom is 2-3-contour, there are signs of sclerosis of the Turkish saddle. The level of prolactin in macroadenoma exceeds 5000 mIU / l. With pituitary macroadenoma, amenorrhea and galactorrhea are noted. Diagnosis of pituitary microadenoma is possible using CT or MRI. The level of prolactin in microadenoma ranges from 2500 to 10,000 mIU / l.

Treatment hyperprolactinemia is carried out taking into account its form. Dopamine agonists are widely used to treat functional hyperprolactinemia. Treatment begins with the appointment of 1 / 2 tablets of bromocriptine per day with meals, then the dose is increased every two days by 1 / 2 tablets, bringing up to 3-4 tablets per day under the control of blood prolactin levels and basal temperature. When restoring ovulatory menstrual cycles, the dose is reduced to 1 tablet per day; such treatment is carried out for 6-8 months. Fertility is restored in 75-90% of cases. In case of insufficiency of the 2nd phase of the cycle, you can additionally prescribe clomiphene from the 5th to the 9th day of the menstrual cycle, which stimulates ovulation. To drugs latest generation in the treatment of hyperprolactinemia are quinagolide (norprolac ♠) and cabergoline (dostinex ♠) (1 mg per week for 3-4 weeks). These are long-acting drugs with minimal side effects.

With pituitary microadenoma, therapy is also carried out with bromocriptine or its analogues. At long-term treatment develop dystrophic changes in a tumor decreases until it disappears completely. Pregnancy during treatment in patients with pituitary microadenoma proceeds safely. During pregnancy, the supervision of a neurologist and an ophthalmologist is mandatory.

Pituitary macroadenoma is an indication for surgical treatment performed by a neurosurgeon, or for radiation therapy.

Adiposogenital dystrophy is a consequence of congenital pathology of the hypothalamic-pituitary region. The disease is accompanied by progressive obesity as a result of a violation of the central regulation of satiety due to damage to the paraventricular nuclei of the hypothalamus. A decrease in the gonadotropic function of the pituitary gland causes the underdevelopment of the reproductive system (hypogonadism). Infectious processes in the pituitary region and pituitary adenoma with hyperplasia of eosinophilic pituitary cells can lead to hyperproduction of growth hormone and excessively high growth (relatively proportional or disproportionate gigantism).

Ovarian amenorrhea

Ovarian forms of amenorrhea are caused by functional, organic changes and congenital pathology ovaries. The most common cause of functional and morphological disorders on

ovarian level of regulation of the menstrual cycle is polycystic ovary syndrome(PCOS). A decrease or depletion of the hormonal function of the ovaries is noted with resistant ovary syndrome(SRY) and ovarian failure syndrome(SIA). Organic changes in the ovaries, accompanied by menstrual dysfunction, are due to hormonally active ovarian tumors(See "Tumours of the ovaries").

PCOS - pathology of the structure and function of the ovaries with a very diverse clinical picture, the most constant component of which is anovulation. PCOS consists of significant morphological changes in the ovaries. This is a smooth and dense albuginea, proliferation of connective tissue, an increase in the number of cystic-modified follicles in the absence of a dominant follicle. Polycystic ovaries are enlarged (>9 cm 3 ) as a result of proliferation of connective tissue, the albuginea is pearly white. When cut, the cortical layer resembles a honeycomb, since the follicles are of different diameters.

PCOS is accompanied by chronic anovulation, infertility, often metabolic disorders, decreased glucose tolerance, as well as hyperandrogenism and, consequently, virilization. Excessively high production of androgens contributes to the growth of interstitial tissue

with PCOS.

According to the results of numerous hormonal and clinical research distinguish between primary (Stein-Leventhal syndrome, described in 1935) and secondary polycystic ovaries, the latter developing with adrenal hyperandrogenism, hyperprolactinemia, neuroexchange-endocrine syndromes.

The most convenient for use in clinical practice is the one proposed by M.L. Crimean classification, including three forms:

A typical form, accompanied predominantly by ovarian hyperandrogenism, is primary polycystic ovaries;

Combined or mixed form with both ovarian and suprarenal hyperandrogenism;

The central form with hyperandrogenism and severe dysfunction of the central parts of the reproductive system with a predominance of secondary polycystic ovaries.

Etiology and pathogenesis. The etiology and pathogenesis depend on the form of PCOS. In the 1960s, pathogenesis typical shape PCOS (Stein-Leventhal syndrome) has been associated with a genetically determined deficiency of ovarian enzymes that blocks the conversion of androgens to estrogens. However, later it was shown that the activity of granulosa cells depends on FSH. Violation of the process of aromatization of androgens into estrogens leads to the accumulation of testosterone (active androgen) and a decrease in the level of estrogen in the ovaries. As a result, the cyclic secretion of gonadotropins is disrupted by the feedback mechanism, which, in turn, leads to hyperplasia of the stroma and theca cells of the ovaries, excessive or increased production of androgens. Androgens are partially converted to estrone, and some of the estrone is converted to estradiol. However, this is not enough for

occurrence of preovulatory and luteal peaks. The menstrual cycle becomes monophasic.

In pathogenesis mixed (form PCOS can be triggered by primary dysfunction of the adrenal cortex or a transient excess of adrenal androgens during the adrenarche period. In peripheral tissues, androgens are partially converted into estrogens. Upon reaching the critical body weight, the peripheral conversion of androgens in adipose tissue increases. This is accompanied by an increase in the synthesis of LH in the pituitary gland and a violation of the ratio of LH / FSH, which leads to hyperplasia of the theca cells and ovarian stroma. These structures synthesize androgens in excess. Hyperandrogenism inhibits follicular maturation, leads to anovulation, and further suppresses FSH secretion. Thus the vicious circle closes.

Participation of brain structures in development central form PCOS is confirmed by a chronological relationship between the onset of the disease and a stressful state (the onset of sexual activity, mental trauma, childbirth, abortion). CNS dysfunction may result from acute or chronic infection or intoxication. At the same time, the synthesis and release of endogenous opioids increase, which disrupts the dopaminergic regulation of GnRH secretion, leads to an increase in the basal level of LH secretion, a relative decrease in FSH production, and impaired folliculogenesis. An increase in LH release in PCOS is due to both a primary violation of GnRH synthesis and chronic anovulation; these effects are mutually potentiated.

The current understanding of the pathogenesis of PCOS, in addition to disorders of the hypothalamic-pituitary complex, ovaries and adrenal glands, includes metabolic disorders and autoparacrine factors regulating steroidogenesis in the ovaries. Metabolic disorders are associated with the insulin-glucose system, since insulin is involved in the production of ovarian androgens. Obesity does not play a decisive role in the pathogenesis of PCOS, however, as a result of hyperinsulinemia and insulin resistance, existing endocrine disorders are exacerbated. In patients with obesity and insulin resistance, chronic hyperinsulinemia stimulates the formation of insulin-like growth factor-1 (IGF-1). The latter, through specific receptors, increases the formation of androgens in the cells and interstitial tissue of the ovaries. In addition, insulin is able to inhibit the formation of sex hormone-binding globulins in the liver, as a result of which the free biologically active fraction of testosterone increases in the blood.

According to the existing hypothesis, the stimulating effect of insulin on the synthesis of androgens in the ovary is due to a genetic predisposition.

PCOS develops in women with normal body weight. In their blood, the level of growth hormone is increased, which causes the formation of IPFR-1 in granulosa cells and enhances the formation of ovarian androgens. The study of hormone biosynthesis in granulosa cells of polycystic ovaries showed

It was shown that luteinized cells lose their ability to synthesize progesterone. This is one of the possible mechanisms of anovulation in patients.

Clinical symptoms. The clinical manifestations of PCOS are very different, but the main ones in all forms of PCOS are hypo-, opso-, oligo- and amenorrhea. Violations of folliculogenesis lead to the development of anovulatory primary and secondary infertility.

In the typical form of PCOS, menstrual irregularities begin with menarche. In the mixed form of PCOS, late menarche is combined with a violation of the menstrual cycle in the future by the type of secondary amenorrhea. In the reproductive age, chronic anovulation and infertility, more often primary, are observed. In the central form of PCOS, menarche is normal, but the menstrual cycle is unstable. Subsequently, this leads to hypo-, opso-, oligo- or amenorrhea. Violations of the reproductive function are in miscarriage at short terms and secondary infertility. In addition to menstrual dysfunction, dysfunction of the hypothalamic-pituitary system is noted. The onset of the disease may be associated with stress, adenovirus infection, brain injury.

main reason When patients of young age go to the doctor, excessive hair growth becomes, the frequency of which in PCOS is, according to different authors, from 50 to 100%. Hirsutism in typical PCOS develops gradually from the menarche period. There is excessive hair growth on the upper lip, chin, along the white line of the abdomen. Pronounced hirsutism and hypertrichosis are not typical for this form of PCOS, but with a mixed form, hirsutism is observed in all patients. Areas of excessive hair growth - inner and outer thighs, white line of the abdomen, upper lip, shins. Hair growth starts at or before menarche. In the central form of PCOS, hirsutism is detected in 90% of patients, occurs 3-5 years after menstrual dysfunction, already against the background of obesity, and is more pronounced in reproductive age. In these patients, dystrophic changes can be noticed: stretch marks on the chest, abdomen, thighs, brittle nails and hair.

The clinical picture of PCOS is largely determined by general metabolic disorders - such as dyslipidemia, carbohydrate metabolism disorders, and an increased risk of developing genital hyperplastic processes. These disorders can cause early development of atherosclerotic vascular changes, hypertension, coronary disease hearts. In 50% of patients with typical PCOS with adolescence there is an increased body weight with a uniform distribution of subcutaneous adipose tissue. Obesity is rare in mixed PCOS. In the central form, the leading complaint is overweight. Obesity reaches II-III degree; adipose tissue is localized mainly on the shoulder girdle, lower abdomen and thighs.

Diagnostics PCOS should begin with a thorough history and physical examination. The formation of PCOS begins with puberty

period and is accompanied by a violation of the formation of menstrual function. Primary polycystic ovaries cause irregular menstruation from puberty, which distinguishes them from secondary polycystic ovaries.

The clinical criterion for the diagnosis of PCOS is hirsutism (in 69% of patients), which appears simultaneously with the onset of puberty. The severity of other clinical manifestations of hyperandrogenism is different. With the progression of symptoms of virilization (hypertrophy of the clitoris, defeminization of the figure, lowering the timbre of the voice), it is necessary to exclude hormonally active tumors of the ovaries and adrenal glands; this is usually atypical for PCOS.

The main methods for diagnosing PCOS include echography of the pelvic organs, the study of blood plasma hormones, laparoscopy with biopsy and histological examination ovarian tissue.

Bilateral enlargement of the ovaries is pathognomonic for PCOS, often with a hypoplastic uterus, which is clearly defined by echography. The echoscopic picture of the ovaries with transvaginal ultrasound (Fig. 9.1) shows an increase in the volume of the ovaries by more than 9 cm 3 (on average 16-20 cm 3), hyperplastic stroma, more than 10 atretic follicles located along the periphery under a thickened capsule.

The hormonal criteria for the diagnosis of PCOS include an LH/FSH ratio of more than 2.5-3. However, in recent years it has been shown that a normal level of gonadotropic hormones does not exclude the diagnosis of PCOS. So, the level of DHEA and DHEA-S is normal in the typical form and elevated in the presence of the adrenal component (mixed form of PCOS). In the central form of PCOS, the LH/FSH ratio is the same as in typical PCOS, but the history and clinical symptoms allow verification of the diagnosis.

Rice. 9.1. Polycystic ovary syndrome. ultrasound

An obligatory stage in the examination of patients with PCOS is the diagnosis of metabolic disorders: hyperinsulinemia and insulin resistance. BMI over 25 kg/m 2 and dyslipidemia indicate hyperinsulinemia and insulin resistance.

A typical laparoscopic picture of the ovaries in PCOS: increased size (up to 5-6 cm in length and 4 cm in width), smoothed, thickened, pearly whitish capsule. The absence of translucent small follicular cysts and ovulation stigmas indicates a pronounced thickness of the ovarian capsule, which sometimes makes biopsy difficult (Fig. 9.2).

Treatment. The sequence of therapeutic measures in patients with PCOS depends on the complaints, clinical manifestations and age of the patient. Since the main reason for seeking medical attention in patients of reproductive age is infertility, the goal of treatment is the restoration of menstrual and reproductive functions at the same time, the prevention of hyperplastic processes in target organs and the correction of the prevailing symptom complex. For this purpose, conservative and surgical methods of treatment are used.

With obesity, the first stage of treatment (regardless of the form of the disease) is the normalization of body weight. However, curative fasting is contraindicated; The greatest therapeutic effect is given by a combination of diet therapy with physiotherapeutic measures - massage, physiotherapy exercises, acupuncture. Weight loss leads to the normalization of the endocrine blood profile, a decrease in the level of insulin and androgens, and the restoration of regular menstruation. In PCOS of central origin, the use of drugs that correct neurotransmitter metabolism (phenytoin - diphenin *), beclamid - chloracone *) is pathogenetically justified. It is possible to prescribe orlistat, which selectively inhibits lipid metabolism, or subitramine, which blocks the saturation center.

The next stage of treatment is the stimulation of ovulation. Stimulation begins with the use of clomiphene, which has an antiestrogenic effect by blocking estradiol receptors. After discontinuation of the drug, the gonadotropic function returns to normal. Clomiphene does not directly stimulate

Rice. 9.2. Biopsy of the ovary. Laparoscopy

ovaries, but causes ovulation due to short-term normalization of the hypothalamic-pituitary-ovarian system. The drug is prescribed 100 mg from the 5th to the 10th day of the menstrual cycle. Treatment with clomiphene restores ovulation in 48-80% of patients, pregnancy occurs in 20-46%. With resistance to clomiphene, ovulation stimulation can be carried out with gonadotropic drugs (pergonal ♠, humegon ♠) according to individual schemes. However, stimulation of ovulation, especially when elevated level insulin and obesity, increases the risk of hyperstimulation syndrome or may lead to ovarian unresponsiveness.

Treatment of women who do not plan pregnancy is aimed at restoring the menstrual cycle, treating hirsutism, and preventing long-term effects of PCOS that worsen the quality of life. For this purpose, combined oral contraceptives (COCs) are used, which reduce the level of androgens, normalize the menstrual cycle and help prevent endometrial hyperplastic processes. In patients with PCOS and impaired fat metabolism, COCs should be combined with drug therapy insulin resistance. The combination of COCs with antiandrogens potentiates a decrease in androgen secretion. Antiandrogens block androgen receptors in the target tissue and suppress gonadotropic secretion. The use of drugs with antiandrogenic properties (Diana-35 *) has significantly expanded the therapeutic options for PCOS. The antiandrogenic effect of Diane-35 ♠ can be enhanced by the additional administration of cyproterone (Androkur ♠) at 25-50 mg from the 5th to the 15th day of the menstrual cycle. Duration of treatment - from 6 months to 2 years or more.

Spironolactone (veroshpiron ♠) has an antiandrogenic effect, blocking peripheral receptors and androgen synthesis in the adrenal glands and ovaries. Its long-term use at a dose of 100 mg / day reduces hirsutism. However drug treatment hirsutism is not always effective.

Surgical treatments for PCOS are often performed using endoscopic access. Surgical treatment normalizes gonadotropic secretion by reducing the volume of androgen-secreting tissues of polycystic ovaries. As a result, the level of extragonadal estrogens decreases, which increases the sensitivity of the pituitary gland to GnRH. To surgical methods PCOS correction includes wedge resection, thermocauterization (Fig. 9.3), thermovaporization and decapsulation of polycystic ovaries. Surgical treatment is most effective in the typical form of PCOS.

The ineffectiveness of wedge-shaped resection of the ovaries in some patients indicates combined adrenal-ovarian hyperandrogenism.

The incidence of endometrial hyperplastic processes and the risk of endometrial cancer in patients with PCOS, especially in typical and central forms, determine the active management tactics (hysteroscopy with separate diagnostic curettage) even in the absence of complaints. Timely diagnosis and treatment of such patients are measures to prevent endometrial cancer.

Rice. 9.3. Ovary after cauterization. Laparoscopy

Resistant ovary syndrome. Rarely, ovarian failure may be due to resistant ovarian syndrome (ROS; Savage's syndrome). In women younger than 35 years, amenorrhea, infertility, micro- and macroscopically unchanged ovaries are noted with a high level of gonadotropins. Secondary sexual characteristics are developed normally. The causes of SOS have not been studied; the autoimmune nature of this pathology is assumed. It is known that hypergonadotropic amenorrhea can be combined with autoimmune diseases: Hashimoto's disease, myasthenia gravis, alopecia, thrombocytopenic purpura, autoimmune hemolytic anemia. Ovarian resistance to high levels of gonadotropins may be due to an abnormal FSH molecule or lack of biological activity of the hormone. A large role is given to intraovarian factors involved in the regulation of ovarian function. There is evidence of the influence of iatrogenic factors - radiotherapy, cytotoxic drugs, immunosuppressants, ovarian surgery. The development of resistant ovaries can be facilitated by damage to the ovarian tissue in tuberculosis, mumps, and sarcoidosis.

Clinical symptoms and diagnosis. Most patients associate the onset of the disease with stress, severe viral infections. The first menstruation, as a rule, occurs in a timely manner, and after 5-10 years amenorrhea develops, but 84% of patients subsequently have episodic menstruation. Pregnancy and childbirth are observed in 5% of patients. Patients with EDS have a correct physique, satisfactory nutrition, and well-developed secondary sexual characteristics. Periodically, they feel flushes of heat to the head. When examined according to tests of functional diagnostics, they reveal signs of ovarian hypofunction: thinning of the mucous membranes of the vulva and vagina, a weakly positive "pupil" phenomenon, low rates KPI (from 0 to 25%).

During gynecological examination, echography, laparoscopy, the uterus and ovaries are somewhat reduced. Most authors believe that the diagnosis of EOC can only be made after laparoscopy and ovarian biopsy, followed by a histological examination, in which

primordial and preantral follicles are formed. With laparoscopy, translucent follicles are visible in the ovaries.

Hormonal studies indicate a high level of FSH and LH in the blood plasma. The level of prolactin is normal.

Hormonal tests are of great diagnostic value. A decrease in the level of FSH with the introduction of estrogens and an increase in the level of FSH and LH in response to the administration of luliberin indicate the preservation of the feedback mechanism between the hypothalamic-pituitary system and sex steroids.

Treatment. The treatment of SOC presents great challenges. In the treatment of gonadotropins received conflicting data. Some authors noted an increase in follicles and menstrual-like discharge against the background of the introduction of FSH and LH, others - only the growth of follicles (empty follicles) without an increase in blood estrogen levels.

The appointment of estrogens is based on the blockade of endogenous gonadotropins and the subsequent rebound effect (reflection effect). In addition, estrogens increase the number of gonadotropic receptors in the ovaries and, possibly, thus increase the response of follicles to endogenous gonadotropins. Restoration of the generative function is possible only with the help of assisted reproductive technologies (IVF of a donor egg).