Neuroendocrinal syndromes in gynecology (Shikhane syndrome, hyperandrogeny, hyperprolactinemia). 1.Relevance Sheehan's syndrome, also known as postpartum pituitary gland necrosis, is hypopituitarism (decreased functioning of the pituitary gland), caused by ischemic necrosis due to blood loss and hypovolemic shock during and after childbirth In a study of 1,034 symptomatic adults, Sheehan’s syndrome was found to be the sixth-most frequent etiology of growth hormone deficiency, being responsible for 3.1% of cases (versus 53.9% due to a pituitary tumor). Hyperandrogenemia (HA) describes the condition of a patient with increased production of a group of steroid hormones known as androgens, from the Greek prefix “andro” meaning “man.” While these hormones play a central role in male physiology, they are also present to a lesser degree in females, with the most predominant androgens including testosterone, dihydrotestosterone (DHT), androstenedione, dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate (DHEA-S). The overall incidence of HA in women is approximately 5%–10%, with polycystic ovarian syndrome (PCOS) accounting for approximately 80% of cases. In general, HA may be caused by exogenous medications, endogenous neoplasms, or via the nonneoplastic overproduction of androgens. Clinical signs of HA include acne, abnormal hair growth (hirsutism), and male pattern baldness (alopecia). Other signs of HA may also be present, including irregular menstrual cycles, virilization (deepening voice, enlarging clitoris, ), or insulin resistance. Excessive upper lip hair in a third of women ages 14-45 Hyperprolactinemia may result in hypogonadism, infertility, and , or it may remain asymptomatic Testing for hyperprolactinemia is straightforward, owing to the ease of ordering a serum prolactin measurement. Accordingly, an evidence-based, cost-effective approach to management of this relatively common endocrine disorder is required. Prolactin acts to induce and maintain lactation of the primed breast. Nonpuerperal hyperprolactinemia is caused by lactotroph adenomas (prolactinomas), which account for approximately 40% of all pituitary tumors.. Bone loss occurs secondary to hyperprolactinemia-mediated sex steroid attenuation. Spinal bone density is decreased by approximately 25% in women with hyperprolactinemia and is not necessarily restored with normalization of prolactin levels. Modern knowledge about neuroendocrinological syndroms of the female reproductive system function, role of hormones and biological active substances are at the heart of gynecology. 2. Objectives (are described in the terminology of professional activity, taking into account the system of classification of the objectives of the respective levels of cognitive, emotional and psychomotor spheres): -To analyze the results of main methods of functional diagnostics in gynecology -To explain The levels of regulation of woman`s genital functions -To suggest tactics of management of patients with neuroendocrinological syndroms. -To classify mestrual disordes (irregularities) -To interpret the results of laboratory and instrumental examinations of the cervix, endometrium, ovaries, depending with fazes of MC, the clinical and biochemical, hormonal studies of blood, results of colpocytologycal examination -To draw a diagram scheme of menstrual cycle --To make the analysis of the methods of functional diagnosis in gynecology -To make up the models of clinical cases with various hormanal pathology in women of reproductive and premenopausal age.

3. The basic level of expertise, skills, abilities, required for learning the topic

(interdisciplinary integration ) The name of the previous Acquired skills disciplines Normal Anatomy Structure of female genital organs. Topography of abdominal organs and pelvic organs. Histology Histological structure of the cervix, vulva and endometrium in normal and in pathological conditions. Notmal Physiology Physiological changes occurring in the hypothalamic- pituitary-ovarian system of women and target organs of the sex hormones action at different ages. Pathological Physiology Hormonal changes in the body during the menstrual cycle and disorders of the microbiota of the female reproductive system. Pharmacology Groups of medications that affect the function of the hypothalamus, pituitary gland, ovaries, adrenal glands; mechanism of pharmacological action of hormonal, hemostatic, anti-inflammatory, antiviral drugs.

4. Tasks for independent work in preparation for the lesson and in class.

4.1. The list of the major terms, parameters, characteristics to be acquired by a student to be prepared for the lesson The term Definition Adrenogenital syndrome (AGS) is congenital adrenal hyperplasia, female hermaphroditism, or advanced sexual development of the heterosexual type develops as a result of necrotic changes in the hypophysis, which appeared Sheehan’s syndrome against the background of a spasm or intravascular blood coagulation in the vessels of the adenohypophysis after hemorrhages and septic shock during delivery or abortion Hyperprolactinemia . distinct clinical entity and resulted in distinguishing prolactin-secreting tumors from nonfunctioning adenomas Female Sex steroid hormones luteonizing hormone (LH) prolactin follicle-stimulating hormone (FSH) estrogens progesterone Replacement hormonal therapy (RHT) is aimed at the prevention and recovery of metabolic disorders of the climacteric period. Hirsutism Increased Terminal Hair male- patterned growth in women

Alopecia Female-Patterned Hair Loss (central hair thinning)

Acne Vulgaris is a long-term skin disease that occurs when dead skin cells and oil from the skin clog hair follicles.Typical features of the condition include blackheads or whiteheads, pimples, oily skin, and possible scarring

4.2 Theoretical questions for the lesson: 1. Regulations mechanisms of menstruation at different levels. 2. Biologic action of sex hormones, hypophysis hormones and releasing hormones. 3. Basic levels of menstruation regulation and physical stages of their establishment. 4. Pathogenesis of menstrual disorders. 5. Pathogenesis of adrenogenital syndrome 6. Clinic of adrenogenital syndrome 7. Management of adrenogenital syndrome 8. Pathogenesis of Sheehan`s syndrome 9. Clinic of Sheehan`s syndrome 10. Management of Sheehan`s syndrome 11. Pathogenesis of hyperprolactinemia 12. Clinic of hyperprolactinemia 13. Management of hyperprolactinemia

4.3 Practical activities (tasks) to be performed on the lesson:  To Describe the proposed changes in organs of women during menstrual cycle.  To Evaluate proposed by instructor menstrual cycle, amount of blood loss during normal and pathologic menstrual cycle (anovulatory cycle, luteine phase insuffi-ciency).  To analyze the results of main methods of functional diagnostics in gynecology  To suggest tactics of management of patients with hormonal imbalance of female reproductive system.  To classify mestrual disordes (irregularities)  To interpret the results of laboratory and instrumental examinations of the cervix, endometrium, ovaries, depending with fazes of MC, the clinical and biochemical, hormonal studies of blood, results of colpocytologycal examination  To draw a diagram scheme of menstrual cycle and chart of basal temperature  To make up the models of clinical cases with various hormanal pathology in women of reproductive and premenopausal age.

Adrenogenital Syndrome

Adrenogenital syndrome (AGS) is congenital adrenal hyperplasia, female hermaphroditism, or advanced sexual development of the heterosexual type. It should be noted that the adrenal glands synthesize 3 main groups of steroids of different biological action: 1) mineralocorticoids; 2) glucocorticoids; 3) reticular zone hormones – androgens (strong – testosterone, weak – дегідроепіандростерон, dehydroepiandrosterone sulfate, androstenedione), and estradiol with estrone, a small quantity of which is also formed here. Etiology and pathogenesis. AGS is a consequence of congenital genetically conditioned deficiency of enzyme systems, which take part in the synthesis of adrenal steroid hormones. At that, by the feedback principle there increases ACTH formation in the adenohypophysis and the synthesis of cortisol precursors, which form androgens due to enzyme deficit.

Symptoms and Signs

A. General appearance 1. Muscular male body habitus (e.g. Shoulder girdle) 2. Android Obesity B. Miscellaneous Changes 1. Deepening of voice 2. Clitorimegaly 3. Increased Libido C. Menstrual irregularity 1. Amenorrhea 2. Infertility D. Endocrine changes 1. Hypertension 2. Hyperlipidemia 3. Glucose Intolerance E. Skin changes

Congenital Adrenogenital Syndrome Adrenal malfunction has an intrauterine onset, almost simultaneous with the beginning of adrenal glands functioning as an endocrine gland. The clinicodiagnostic criteria: - karyotype 46,ХХ; - the signs of external genitals virilization (clitoromegaly, fusion of the large lips of pudendum, and urogenital sinus persistence – fusion of the two lower thirds of the vagina and urethra, which opens under the enlarged clitoris); - the ovaries and uterus are developed correctly; - advanced sexual development of the heterosexual type; - hypertrichosis; - in consequence of the anabolic action of androgens there takes place the rapid lengthwise growth of tubular bones, distribution of the muscular and fatty tissue by the male type. In girls with congenital AGS the body length reaches 150–155 cm till the age of 10–12 years, children do not grow any more because bone growth plate ossification; - bilateral adrenal hyperplasia shown by US and computer tomography; - high content of 17-ketosteroids (17-KS) in urine, testosterone, 17-OP and DHA in blood; - positive dexamethasone test. The treatment of congenital AGS consists in glucocorticoids administration. The therapy should be continuous. The dose of drugs depends on the age, body weight, and degree. In intensive virilization of the external genital organs there are conducted restorative surgeries.

Pubertal Adrenogenital Syndrome In this from of AGS excessive androgen formation begins simultaneously with sexual development. The clinicodiagnostic criteria: - rapid growth; - athletic body-build (broad shoulders, narrow pelvis, no fat deposits in the buttocks and hips); - hypertrichosis (usually not intensive); - acne, porous oily skin of the face and back; - not infrequently moderate hypoplasia of the small and large lips of pudendum, moderate uterine hypoplasia; - late menarche (after 14–15 years) and irregularities of the ovarian-menstrual cycle. The character of menstrual irregularities (from hypomenstrual syndrome to amenorrhea) and hypertrichosis clearly correlate with hyperandrogenism intensity.

Postpubertal Adrenogenital Syndrome The intensity of clinical manifestations of the disease is determined by hyperandrogenism degree. The clinicodiagnostic criteria: - family history of hypertrichosis noncarrying of pregnancy at early terms; - sterility (may be secondary); - history noncarrying of pregnancy; - late menarche (14–16 years); - hypertrichosis and irregular menstruations beginning from the period of menarche; - virile morphotype traits; - - high content of 17-KS in urine, testosterone, 17-OP and DHA in blood and normalization of these indices after dexamethasone intake.

The Treatment of Pubertal and Postpubertal AGS In order to correct hormonal dysfunction of the adrenal cortex one uses glucocorticoids. Further treatment approach is determined by the aim of the therapy: hypertrichosis inhibition, ovarian-menstrual cycle normalization, or ovulation stimulation. In order to eliminate hypertrichosis there are administered drugs of the antiandrogenic action: - cyproterone acetate (androcur) – 50–150 mg a day from the 1st till the 15th day of themenstrual cycle during 4–6 months; - combined estrogen-gestagen preparation – Diane-35, which contains ethinyl estradiol (0.035 mg) and cyproterone acetate (2 mg); - verospiron (spironolactone) – 25 mg twice a day during 4–6 months. In order to normalize the menstrual cycle there are administered synthetic progestins in the contraceptive regimen during 4–6 months or gestagens in the 2nd phase of the cycle during 4–6 months. After hyperandrogenism correction one induces ovulation against the background of glucocorticoids intake in the same doses. Ovulation induction is provided by clomiphene; if clomiphene is ineffective, gonadotropins are administered.

Symptoms and Signs

F. General appearance 1. Muscular male body habitus (e.g. Shoulder girdle) 2. Android Obesity G. Miscellaneous Changes 1. Deepening of voice 2. Clitorimegaly 3. Increased Libido H. Menstrual irregularity 1. Amenorrhea 2. Infertility I. Endocrine changes 1. Hypertension 2. Hyperlipidemia 3. Glucose Intolerance J. Skin changes 1. Hirsutism involving face, chin, chest and perineum 2. Alopecia a. Vertex or crown Hair Loss b. Bitemporal Hair Loss may also occur 3. Acanthosis Nigricans (HAIR-AN Syndrome) 4. Oily skin 5. Acne Vulgaris 6. Male sweat changes (malodorous perspiration)

Postpartum Hypopituitarism (Sheehan’s syndrome)

Sheehan’s syndrome develops as a result of necrotic changes in the hypophysis, which appeared against the background of a spasm or intravascular blood coagulation in the vessels of the adenohypophysis after hemorrhages and septic shock during delivery or abortion. The development of these changes is promoted by blood supply peculiarities of the hypophysis, whose anterior lobe weight redoubles, and also ergot preparations, which are widely used in deliveries and bleedings. The factors increasing the risk of this pathology onset is pregnancy complications, particularly gestoses, and repeated frequent deliveries with an interval less than 2 years. The clinical presentation is characterized by a varying degree of endocrine glands hypofunction, most frequently of the thyroid, adrenal, and sexual glands. There are singled out three forms of the syndrome: mild, moderate, and severe. The mild form is characterized by headache, rapid fatigability, chill, and a tendency to hypotension. The moderate form has such signs: depression of the hormonal function of the ovaries (oligomenorrhea, anovulatory sterility) and thyroid gland (sponginess, disposition to edemas, brittleness of nails, dryness of skin, fatigability, hypotension with a tendency to unconsciousness). In the severe form there is noted symptomatology of the total hypofunction of the hypophysis with evident insufficiency of gonadotropin (persisten amenorrhea, hypotrophy of the genital organs and mammary glands), thyrotrophic hormone (myxedema, alopecia, sleepiness, memory impairment), ACTH (hypotension, adynamia, weakness, increased skin pigmentation). The clinicodiagnostic criteria: - characteristic anamnesis (the onset of the disease is connected with hemorrhage or septic shock in delivery/abortion); - clinical signs of endocrine glands hypofunction; - no lactation after delivery;

- the decrease of gonadotropins, ACTH, TSH, Е2, cortisol, Т3, and Т4 in blood. Treatment. There is provided replacement therapy with glucocorticoids and thyrotropic drugs incase of clinical manifestation of hypofunction of corresponding glands. In amenorrhea and olimenorrhea women are administered cyclic hormonal therapy. There are also used anabolic preparations. There should be necessarily provided rational nutrition rich in protein and vitamin therapy. In anemia hemostimulating therapy is provided. The disease is prevented by means of timely treatment of pregnant women with gestoses, prophylaxis of bleedings during pregnancy and delivery, proper resuscitation measures if there is septic shock or hemorrhage in delivery. Postcastration Syndrome

Postcastration syndrome (PCS) is a complex of vegetovascular and metabolic- endocrine disorders, which arise after total or subtotal ovariectomy with or without hysterectomy. PCS is observed in 60–80 % operated women with tumors of the uterus, uterine appendages, and purulent tubo-ovarian masses (Fig. 5). The term “surgical ” is being used in the literature recently. Surgical menopause is termination of the menstrual function because of removal of the ovaries, ovaries and uterus, or only uterus, whereas PCS arises after ovariectomy – total or subtotal castration. Unlike natural menopause, in which ovarian failure is happening slowly during a couple of years, in PCS there arises sudden failure of the steroidogenic ovarian function. PCS develops in 2–3 days after ovariectomy and reaches full growth in 2–3 months and more. At first there prevail neurovegetative and psychoemotional disorders (40–60 %). Urogenital disorders and skin lesions rank second (30–50 %), then come late metabolic disorders (25–40 %) – osteoporosis and cardiovascular diseases, and very late disorders (5–12 %) – Alzheimer’s disease. The diagnostics is not difficult. The diagnosis is given on the basis of anamnestic data and clinical presentation. The treatment is provided subject to extragenital pathology, age, and the volume of operative intervention; it should be complex and include non-medicamental and medicamental therapy, including RHT. The treatment aims to eliminate vegetovascular, psychoemotional, and urogenital symptoms in the postoperative period, and, which is the most important, to provide the prophylaxis of remote effects of estrogen loss (cardiovascular diseases, osteoporosis, Alzheimer’s disease). The therapy with sex hormones should include estrogens and gestagens in the cyclic regimen or combined estrogen-gestagen preparations. Estrogen monotherapy is recommended only after hysteroovoectomy. One should monitor the condition of the mammary glands (US, mammography), endometrium, arterial blood pressure, and the coagulation factors in all the women, who have been administered RHT. The first monitoring is to take place in 1 month after the operation, the second – in 3 months, and then every 6 months. In the complex treatment for PCS one is recommended to use herbal drugs. Climactoplan and climodinon are used most often.

Hyperprolactinaemia or hyperprolactinemia (HP, Chiari – Frommel syndrome).

Prolactin synthesis and secretion by pituitary lactotroph cells is tonically suppressed by hypothalamic dopamine traversing the portal venous system to impinge on lactotroph D2 receptors (3). Factors inducing prolactin synthesis and secretion include estrogen, thyrotropin-releasing hormone, epidermal growth factor, and dopamine receptor antagonists. The isolation of human prolactin in 1970 permitted development of RIAs (4, 5), which enabled identification of hyperprolactinemia as a distinct clinical entity and resulted in distinguishing prolactin-secreting tumors from nonfunctioning adenomas (6).

Prolactin acts to induce and maintain lactation of the primed breast. Nonpuerperal hyperprolactinemia is caused by lactotroph adenomas (prolactinomas), which account for approximately 40% of all pituitary tumors. Hyperprolactinemia may also develop due to pharmacological or pathological interruption of hypothalamic-pituitary dopaminergic pathways and is sometimes idiopathic. Regardless of etiology, hyperprolactinemia may result in hypogonadism, infertility, and galactorrhea, or it may remain asymptomatic (7–9). Bone loss occurs secondary to hyperprolactinemia-mediated sex steroid attenuation. Spinal bone density is decreased by approximately 25% in women with hyperprolactinemia (10) and is not necessarily restored with normalization of prolactin levels.

At autopsy, approximately 12% of pituitary glands are shown to harbor a clinically inapparent adenoma (11). The reported population prevalence of clinically apparent prolactinomas ranges from 6–10 per 100,000 to approximately 50 per 100,000 (12, 13). In an analysis of 1607 patients with medically treated hyperprolactinemia, the calculated mean prevalence was approximately 10 per 100,000 in men and approximately 30 per 100,000 in women, with a peak prevalence for women aged 25–34 yr (14). However, the prevalence of ever-treated hyperprolactinemia was approximately 20 per 100,000 male patients and approximately 90 per 100,000 female patients. In women aged 25– 34 yr, the annual incidence of hyperprolactinemia was reported to be 23.9 per 100,000 person years. Prolactinomas may rarely present in childhood or adolescence. In girls, disturbances in menstrual function and galactorrhea may be seen, whereas in boys, delayed pubertal development and hypogonadism are often present. The treatment options are the same as in adult patients.

Testing for hyperprolactinemia is straightforward, owing to the ease of ordering a serum prolactin measurement. Accordingly, an evidence-based, cost-effective approach to management of this relatively common endocrine disorder is required.

1.1. To establish the diagnosis of hyperprolactinemia, we recommend a single measurement of serum prolactin; a level above the upper limit of normal confirms the diagnosis as long as the serum sample was obtained without excessive venipuncture stress. We recommend against dynamic testing of prolactin secretion for the diagnosis of hyperprolactinemia A prolactin level greater than 500 μg/liter is diagnostic of a macroprolactinoma (17). Although a prolactin level greater than 250 μg/liter usually indicates the presence of a prolactinoma, selected drugs, including risperidone and metoclopramide, may cause prolactin elevations above 200 μg/liter in patients without evidence of adenoma (18). Even minimal prolactin elevations may be consistent with the presence of a prolactinoma, but a non-prolactin-secreting mass should first be considered. However, substantial prolactin elevations can also occur with microadenomas.

The causes are: the Hypothalamic nuclei lesion due to rheumatism, systemic autoimmune diseases, severe infections, focal poor blood circulation of the hypothalamic area, pituitary tumors, causing excessive release of certain hormones or compression of the hypothalamic nuclei, postpartum period on the background of long-term breastfeeding. Scientists have observed that the Chiari –Frommel syndrome predominantly occurs in women with a history of childbirth.

Patients with large nonfunctioning pituitary tumors, craniopharyngiomas, or granulomatous infiltration of the hypothalamus can develop hyperprolactinemia because of pituitary stalk compression or dopaminergic neuronal damage. In 226 patients with histologically confirmed nonfunctioning pituitary macroadenomas, a prolactin level greater than 94 μg/liter reliably distinguished between prolactinomas and nonfunctioning adenomas (36).

Dopamine agonist therapy lowers prolactin levels and improves symptoms in patients with stalk compression, but it is not definitive therapy for a nonfunctioning adenoma. Fewer than 10% of patients with idiopathic hyperprolactinemia ultimately are found to harbor a microadenoma, and progression from a microadenoma to a macroadenoma is rare (37). Spontaneous normalization of prolactin levels occurs in approximately 30% of patients with idiopathic hyperprolactinemia (38). It is important to determine whether patients with hyperprolactinemia also have acromegaly (39) because prolactin is elevated in up to 50% of patients with GH-secreting tumors (6).

The symptoms include: Symptoms of neurogenic character (headaches, visual disturbances, sweating, hot flashes, sleep disturbances, emotional lability, irritability), the increase of both mammary glands (it is possible to palpate enlarged lobules), galactorrhea ( the discharge of milk from the breast that is not associated with breast-feeding, maybe both moderate and abundant), the absence of menstrual function and menstruation, obesity of different degree or, conversely, lack of body weight, hirsutism - excessive hair growth, reduced pigmentation areola area of the , atrophic changes in the mucous membranes and the entire structure of the external genitalia, infertility.

The investigations should include: X-ray examination or any kind of tomography of the skull (the focus is on the area of sella, where the pituitary gland and the hypothalamus is located), ultrasound examination of pelvic organs and , cytological and histological examination of vaginal and uterine smears, Blood analysis for levels of sex hormones (FSH, LH, prolactin-releasing hormone, estrogen, progesterone), urine for the of sex hormones and their metabolites.

Treatment: In case the cause is the pituitary tumor the surgical treatment is needed, if the disease appeared in the classic version and is associated with the destruction of the primary nuclei of the hypothalamus, such patients are subject of conservative medical correction by hormones. For the treatment of infertility special measures are not required because, in case the hyperprolactinemia is treated the ability to fertilize is restored. Management of drug-induced hyperprolactinemia

In a symptomatic patient with suspected drug-induced hyperprolactinemia, we suggest discontinuation of the medication for 3 d or substitution of an alternative drug, followed by remeasurement of serum prolactin . Discontinuation or substitution of an antipsychotic agent should not be undertaken without consulting the patient's physician. If the drug cannot be discontinued and the onset of the hyperprolactinemia does not coincide with therapy initiation, we recommend obtaining a pituitary magnetic resonance image (MRI) to differentiate between medication-induced hyperprolactinemia and symptomatic hyperprolactinemia due to a pituitary or hypothalamic mass

Verapamil causes hyperprolactinemia in 8.5% of patients , presumably by blocking hypothalamic dopamine. Opiates and cocaine act through the μ-receptor to cause mild hyperprolactinemia . The role of estrogen in causing hyperprolactinemia is controversial . Twelve to 30% of women taking higher estrogen-containing oral contraceptives may have a small increase in serum prolactin, but this finding is rarely an indication for therapy .

Patients with drug-induced hyperprolactinemia must evaluate the merits of their current medication program with their physicians. Assessment should include the availability of alternative medications—such as antipsychotic agents with lower dopamine antagonist potency or aripiprazole, an atypical antipsychotic with both dopamine agonist and dopamine antagonist activity that can lower prolactin and reverse hyperprolactinemia-related side effects —and their relative merits and downsides, and the potential adverse impact of ongoing hyperprolactinemia.

In recommending against the use of dopamine agonists, we are placing a low value on avoiding the adverse consequences of hyperprolactinemia due to medications that cannot be replaced or discontinued, a low value on forgoing the potential benefits of dopamine agonists, and a high value on avoiding adverse effects of such therapy, including psychosis exacerbation.

Management of prolactinoma

We recommend dopamine agonist therapy to lower prolactin levels, decrease tumor size, and restore gonadal function for patients harboring symptomatic prolactin- secreting microadenomas or macroadenomas . We recommend using cabergoline in preference to other dopamine agonists because it has higher efficacy in normalizing prolactin levels, as well as a higher frequency of pituitary tumor shrinkage .

Prolactinomas are associated with galactorrhea, sexual dysfunction , and decreased bone density if gonadal steroids are reduced . When a prolactinoma is present, serum prolactin levels generally parallel the size of the tumor. However, a prolactinoma may be associated with any level of prolactin. Serum prolactin in patients with macroadenomas is usually higher than in patients with microadenomas. In 46 men with prolactinomas, serum prolactin was elevated at a mean 99 μg/liter (range, 16–385 μg/liter) in 12 patients with microadenomas vs. a mean of 1415 μg/liter (range, 387– 67,900 μg/liter) in 34 patients with macroprolactinomas .

Materials for self-control:

TESTS

1.Which the hormonal imbalance underlies the galactorrhea syndrome? A. hyperprolactinemia B. increasing of all gonadotropins hormones C. increasing secretion of Tireotropin hormone D. increased level of progesterone E. decreased production of 17 – ketosteroids

2.To hypothalamic amenorrhea does not belong: A. amenorrhea at a syndrome Shikhane B. psychogenic amenorrhea C. amenorrhea at false pregnancy D. amenorrhea at adipozogenital dystrophy E. amenorrhea at a syndrome Kiary-Frommel

3. Diagnostics of virile syndrome must include: determination of 17-ketosteroids level curettage of walls colposcopy culdocentesis biopsy

4. Pathogenesis of this disease is connected with necrosis of pituitary gland: Shikhane's syndrome Shershevscy-Terner syndrome adrenogenital syndrome Shtain-Levental syndrome nothing above

5. The postcastrative syndrome develops after: removing of ovaries the carried of endocrine diseases removing of uterus introduction of large doses of hormons violation of pituitary function

6. Which hormone provides lactation process: prolactin estrogen cortizol insulin all are correct 7. The young woman 20 years old, whose delivered a year ago, Shihan' syndrome was the diagnosis of the doctor. What you need for confirmation of the diagnosis? research level of gonadotropic hormones, pituitary tomography hysteroscopy culdoscopy laparoscopy all of the above

8. In 13 months after the first labor a 24-year-old woman complains of amenorrhea. Cesarian section was conducted as a result of premature detachment of normally posed placenta. Hemorrhage has made low fidelity of 2000 ml due to breakdown of coagulation of blood. Choose the most suitable investigation. determination of the level of gonadotropin ultrasound of organs of a small pelvis progesteron test computer tomography of the head determination of the contents of testosteron-depotum in blood serum

9. In the woman of 24 years about earlier normal menstrual function, cycles became irregular, according to tests of function diagnostics - anovulatory. The contents of prolactin in blood is boosted. Choose the most suitable investigation: computer tomography of the head determination of the level of gonadotropins uSI of organs of small pelvis progesterone assay determination of the contents of testosteron-depotum in blood serum

10. A woman consulted a therapeutist about fatigability, significant , weakness, loss of appetite. She has had amenorrhea for 8 months. A year ago she born a full-term child. Haemorrhage during labour made up 2 l. She got blood and blood substitute transfusions. What is the most probable diagnosis? Sheehan's syndrome Stein-Leventhal syndrome Shereshevsky-Turner's syndrome homological blood syndrome vegetovascular dystonia

TASKS 1. The young woman 20 years old, whose delivered a year ago, Shihan' syndrome was the diagnosis of the doctor. What you need for confirmation of the diagnosis? 2. A 30-year-old patient consulted a doctor about menstruation absence for 2 years after labour, loss of hair, body weight loss. The labour was complicated by a haemorrhage caused by uterus hypotonia. Objectively: the patient is asthenic, external genitals are hypoplastic, the uterus body is small and painless. The appendages are not palpaple. What is the most likely diagnosis?