Menstrual...................... cycle.pptx

Description about menstrual cycle ...it's phases and disorders

1. Menstrual cycle Department of Obstetrics and Gynecology with the course of postgraduate education

2. The menstrual cycle is the body’s way of preparing for pregnancy. The menstrual cycle is aimed at the monthly maturation of eggs, as well as creating conditions for the normal implantation of a fertilized egg into the endometrium, followed by the progression of pregnancy.

3. Which organs regulate the menstrual cycle? The regulation of the menstrual cycle is an interdependent system. Five levels are involved in the regulation of the menstrual cycle: Cortex . The regulation cascade begins precisely with the brain. Hypothalamus . This is the part of the brain that secretes liberins and statins, hormones that stimulate or inhibit the production of hormones of the next level of regulation - the pituitary gland.

4. Pituitary This is the part of the brain in which all tropic hormones are produced, not only for the reproductive system. It is these hormones that make the ovaries turn on and stimulate the synthesis of sex hormones directly by the female appendages of the uterus. A hormone that stimulates the growth and maturation of follicles (FSH) and LH.

5. Ovaries A paired organ in which, under the stimulating effect of tropic hormones of the pituitary gland, the growth and maturation of follicles occurs. It is in the ovary that sex steroids are produced. They, in turn, exert their multifaceted influence both on the uterus, directly on the endometrium, and on the target organs of the whole organism.

6. Menstruation Shedding of the sloughed endometrium with mucous and blood through the vagina externally, following failure of fertilization or implantation. It gives the most obvious external sign of normal cycle. The cycle depends on changes occurring within the ovaries and fluctuation in the ovarian hormones levels, that are themselves controlled by the pituitary gland and hypothalamus (hypothalamic – pituitary – ovarian axis).

7. NORMAL MENSTRUAL CYCLE What is the mean duration of the MC? Mean 28 days (only 15% of ♀) Range 21-35 What is the average duration of menses? 2-7 days When does ovulation occur? Usually day 14 36 hrs after the onset of mid-cycle LH surge

8. During the course of a normal menstrual cycle: The ovaries go through 3 phases: Follicular. Ovulation. Luteal. The endometrium goes through 3 phases: Proliferative. Secretory. Menstruation.

9. Stages of ovarian follicule development

10. Follicular phase As FSH rises in the early days of the cycle (where estrogen and progesterone are low), this stimulates a cohort of follicles to grow

11. The dominant follicle is the follicle with the most efficient aromatase activity and the highest concentration of FSH induced LH receptors. This follicle will survive the decreasing levels of FSH while other follicles will become atretic. Other factors involved in the regulation of folliculogenesis:Inhibin , activin, IGF1, IGF2.

12. Key Events in the Preovulatory Follicle 1. E2 secretion reaches a threshold to induce LH surge.. 2. Acting through its receptors, LH initiates luteinization and progesterone production in the granulosa layer. 3. The preovulatory rise in progesterone facilitates the positive feedback action of estrogen and may be required to induce the midcycle FSH peak. 4. Rapidly rising estradiol then exerts a POSITIVE feedback effect, upregulating GnRH receptors in the pituitary, causing an OVULATORY SURGE of FSH and LH, triggering ovulation.

13. Ovulation: The dominant follicle is around 20 mm in diameter. LH surge: ovulation follows it by 36 hours. Role of LH: triggers ovulation, resumption of miosis prior to the release of ovum, lutenization of the granulosa cells and formation of corpus luteum.

14. Physical release of the ovum occurs after breakdown of the follicular wall under the influence of LH, FSH and progesterone controlled proteolytic enzymes such as prostaglandins and plasminogen activators. Therefore the use of prostaglandin inhibitors can lead to failure of ovulation.

15. Luteal phase: The remaining granulosa and theca cells will form the corpus luteum. The cells have vacuolated yellow appearance. LH stimulate these cells to form progesterone to stabilize the endometrium. The progesterone has its highest level in the mid luteal phase → suppress FSH and LH. If no pregnancy → luteolysis . With decrease in estrogen, progesterone and inhibin levels, FSH will be released from the negative feedback effect so that there will be gradual increase in FSH level and new cohort of follicles will enter a new cycle.

16. Luteal-Follicular Transition (WHY THE CYCLE OCCURS) The demise of the corpus luteum results in a nadir in the circulating levels of estradiol, progesterone, and inhibin. The decrease in inhibin-A removes a suppressing influence on FSH secretion. The decrease in E2 and progesterone allows a progressive and rapid increase in the frequency of GnRH pulsatile secretion and removal of the pituitary from NEGATIVE FEEDBACK suppression The removal of inhibin-A and E2, as well as increasing GnRH pulses allow increased FSH secretion cf with LH The increase in FSH rescues a ~70 day-old group of follicles from atresia, allowing a dominant follicle to begin to emerge.

17. Endometrial changes during the menstrual cycle: Proliferative phase: Estrogen → the epithelium lining the glands will change from a single layer of columnar cells to pseudostratified epithelium with frequent mitosis. The stroma will be infiltrated by cells from the bone marrow. The endometrial thickness will increase from 0.5 to 3.5 mm at the end of the proliferative phase.

18. Endometrial changes during the menstrual cycle: Secretory phase: Progesterone → the endometrial glands will become tortuous, fluid is secreted in the glandular cells and in the uterine lumen. Progesterone will induce the formation of a temporary layer which is known as the decidua (stromal cells with increased mitotic activity and nuclear enlargement, generation of basement membrane.

19. Prior to menstruation, 3 distinct layers of endometrium can be seen: Basalis. (25%) Stratum spongiosum. (edematous stroma) Stratum compactum. (with prominent decidualized stromal cells)

20. Menstruation: Luteolysis → decreased estrogen and progesterone → vasoconstriction of spiral arterioles and distal ischemia → tissue breakdown and loss of the upper layer along with bleeding from fragments of the remaining arterioles. Vaginal bleeding will cease when the endometrium begin to repair by stromal, glandular regeneration and and angiogenesis. Hemostasis in the uterus differ in that it does not involve clot formation and fibrosis.

21. There are other factors which are involved in vessels constriction, initiating and controlling menstruation; these are prostaglandin F2α, endothelin 1 and platelet activating factor. Progesterone withdrawal → increase endometrial prostaglandin synthesis and decreased prostaglandin metabolism; these prostaglandins may be balanced by the effect of vasodilatation agents such prostacyclin and nitric oxide.

22. Estrogen causes: - Mild myometrial contraction - Rhythmic contraction in the fallopian tube. - Production of thin elastic mucous that attracts sperm. - In the vagina, causes cornifcation of its epithelium with increasing acidity.

23. Progesterone causes: Relaxation of the myometrium. The fallopian tube epithelium to be rich with nutrients for the zygote. Thick cervical mucous. In the vagina decrease cornification.

24. DISORDERS OF MENSTRUAL CYCLE

25. everything that is not the norm, is a DISORDER

26. Classification: depending on the nature of the disorders: absence of menstruation hypomenstrual syndrome hypermenstrual syndrome painful menstruation depending on the regularity of the cycle: with a normal cycle with a broken cycle combined disorders CLINICAL CLASSIFICATION amenorrhoea disfunctional uterine bleeding dismenorrhoea

27. AMENORRHEA(THE ABSENCE OF MENSES) Primary Amenorrhea absence of menses by age 15 in the presence of normal growth and secondary sexual characteristics OR absence of menses by age 13 in complete absence of secondary sexual development Secondary Amenorrhea absence of menses for more than 3 cycle intervals OR 6 consecutive months in women who were previously menstruating

28. Classification of amenorrhoea With dysfunction of the gonads: 1. Gonadal dysgenesis 2. Testicular feminization syndrome 3. Primary ovarian hypofunction AMENORRHOEA “FALSE” AMENORRHOEA “TRUE” AMENORRHOEA PHYSIOLOGICAL PATHOLOGICAL Primary SECONDARY Ovarian dysfunction Hypothalamic dysfunction Pituitary dysfunction Uterine dysfunction Extragonadal: 1. Congenital dysfunction of the adrenal cortex 2. Hypothyroidism 3. Damage to the central nervous system and hypothalamic-pituitaryareas 4. Destruction of the endometrium

29. Gonadal dysgenesis typical form ( Shereshevsky -Turner syndrome) - 45XO karyotype; erased form - the karyotype has a mosaic character, 45XO / 46XX; mixed form - mosaic karyotype with the obligatory presence of the Y chromosome or its segment (the most common karyotype is 45XO / 46XY); pure form ( Swyer's syndrome) - 46XX or 46XY karyotype.

30. Gonadal dysgenesis Typical form ( Shereshevsky -Turner syndrome) ovaries are unable to respond to gonadotropins (one of most common causes of premature ovarian failure) and results in “hypergonadotropic hypogonadism” (high FSH)

31. Gonadal dysgenesis Pure form ( Swyer's Syndrome) Mutations of SRY gene account for many cases  Indifferent gonads fail to differentiate into testes  Lack of testosterone or DHT results in normal external female genitalia  Secondary sex characteristics do not develop

32. Testicular feminization syndrome (Morris syndrome) 46, XY Unable to convert testosterone to DHT no differentiation of male genitalia during fetal development Ambiguous genitalia at birth Undergo virilization at puberty but no enlargement of external genitalia or prostate

33. Primary ovarian hypofunction(Insufficiency ) Premature ovarian failure may be caused by genetic factors such as chromosome abnormalities. It may also occur with certain autoimmune disorders that disrupt the normal function of the ovaries. FSH levels are higher than normal in women with premature ovarian failure.

34. Extragonadal: Congenital dysfunction of the adrenal cortex (adrenal hyperplasia) Congenital adrenal hyperplasia (CAH) encompasses a group of autosomal recessive defects in the enzymes that are responsible for cortisol, aldosterone, and, in very rare cases,  androgen synthesis . All forms of CAH are characterized by low levels of cortisol, high levels of ACTH, and adrenal hyperplasia. The exact clinical manifestations depend on the enzyme defect. The most common form of CAH is caused by a deficiency of 21 β -hydroxylase and manifests with hypotension, ambiguous genitalia, virilization (in the female genotype), and/or precocious puberty (in both males and females). All newborn infants must be screened for 21 β -hydroxylase deficiency by measuring 17-hydroxyprogesterone in a blood sample obtained from a heel prick. CAH treatment involves lifelong glucocorticoid and  fludrocortisone   replacement therapy .

35. Extragonadal: Hypothyroidism Arises as a result of hereditary defects in the biosynthesis of thyroid hormones, infectious-inflammatory and autoimmune processes in the thyroid gland, insufficient intake of iodine in the body. Under conditions of thyroid hormone deficiency, the growth of thyrotrophs producing an increased amount of TSH is enhanced, the function of pituitary cells that produce LH is suppressed, the FSH/LH ratio and prolactin levels increase. There is an underdevelopment of the genital organs and secondary sexual characteristics, a violation of the growth and development of bone tissue. The diagnosis is established on the basis of the determination of TSH, thyroxine, triiodothyronine, and the level of sex hormones in the blood. Against the background of the appointment of thyroid drugs, the menstrual cycle is restored.

36. Extragonadal: Damage to the central nervous system and hypothalamic-pituitaryareas may be of an organic nature (trauma, toxic, infectious lesions, tumors) or of a neuropsychic nature. Amenorrhea often occurs with schizophrenia, manic-depressive psychosis.

37. Extragonadal: Destruction of the endometrium Anomalies in the development of the uterus, including with the Rokitansky- Kustner -Mayer-Hauser syndrome, when the uterus and vagina are presented in the form of thin connective tissue strands, as well as under the influence of damaging factors (endometrial destruction in tuberculosis, or a decrease in the sensitivity of endometrial receptors to the effects of sex hormones).

38. Classification of amenorrhoea With dysfunction of the gonads: 1. Gonadal dysgenesis 2. Testicular feminization syndrome 3. Primary ovarian hypofunction AMENORRHOEA “FALSE” AMENORRHOEA “TRUE” AMENORRHOEA PHYSIOLOGICAL PATHOLOGICAL Primary SECONDARY Ovarian dysfunction Hypothalamic dysfunction Pituitary dysfunction Uterine dysfunction Extragonadal: 1. Congenital dysfunction of the adrenal cortex 2. Hypothyroidism 3. Damage to the central nervous system and hypothalamic-pituitaryareas 4. Destruction of the endometrium

39. SECONDARY PATHOLOGICAL “TRUE” AMENORRHOEA: Hypothalamic dysfunction like the primary one, it can develop as a result of an organic and functional lesion of the central nervous system. This group includes the following states: Psychogenic amenorrhea Anorexia nervosa "False pregnancy" Amenorrhea in neuropsychic diseases Amenorrhea associated with galactorrhea

40. SECONDARY PATHOLOGICAL “TRUE” AMENORRHOEA: Pituitary dysfunction Sheehan syndrome (postpartum hypopituitarism) Simmonds Syndrome Hyperprolactinemia Itsenko -Cushing's disease Acromegaly and gigantism.

41. SECONDARY PATHOLOGICAL “TRUE” AMENORRHOEA: Ovarian dysfunction Premature ovarian failure. Occurs when the ovaries stop functioning as they should before age 40. When this happens, your ovaries don't produce typical amounts of the hormone estrogen or release eggs regularly. This condition is also called premature ovarian failure and often leads to infertility Polycystic ovary syndrome Condition where you have few, unusual or very long periods. It often results in having too much of a male hormone called androgen. Many small sacs of fluid develop on the ovaries. They may fail to regularly release eggs. Resistant ovary syndrome Amenorrhea associated with androgen-producing ovarian tumors Post-castration syndrome

42. SECONDARY PATHOLOGICAL “TRUE” AMENORRHOEA: Uterine dysfunction Tuberculous endometritis Damage to the endometrium due to its rough curettage and removal of the basal layer Damage to the endometrium due to its chemical, thermal burn or cryodestruction Asherman's syndrome (intrauterine synechia) Removal of the uterus.

43. DIAGNOSTICS OF THE LEVEL AND CHARACTER OF DAMAGESYSTEMS OF REGULATION OF MENSTRUAL FUNCTIONIN AMENORRHEA Anamnesis Physical research Gynecological examination: examination of the external genitalia, examination in the mirrors and bimanual abdominal-vaginal or abdominal-rectal examination.

44. DIAGNOSTICS OF THE LEVEL AND CHARACTER OF DAMAGESYSTEMS OF REGULATION OF MENSTRUAL FUNCTIONIN AMENORRHEA The results of the clinical and anamnestic stage of the examination determine the range of additional instrumental and laboratory methods (ultrasound of the pelvic organs, thyroid gland, mammary glands, adrenal glands if indicated. CT with contrast or MRI of the pituitary gland is performed to exclude pituitary tumors in women with hyperprolactinemia with normal thyroid function According to indications, hysteroscopy with histological examination of scrapings, hysterosalpingography, laparoscopy and MRI of the brain are performed) Genetic studies, including karyotyping, consultation with a geneticist. Hormonal studies and functional tests. If necessary, related specialists are involved in the examination of patients: an ophthalmologist (examination of the fundus, peripheral, color visual fields), a therapist, an endocrinologist, a neurologist, a psychiatrist, and a psychologist.

45. TREATMENT OF AMENORRHEA Treatment of patients with amenorrhea is complex and depends on the form of amenorrhea. The basis of treatment is the identification and elimination of the disease that caused amenorrhea. Surgical treatment is indicated for malformations of the genital tract. With atresia of the hymen, a cruciform dissection is performed. With a transverse septum of the vagina, its removal is indicated. In vaginal aplasia, an artificial vagina ( colpopoiesis ) is surgically created. In patients with gonadal dysgenesis and the presence of the Y chromosome, the gonads are removed due to the high risk of their malignancy. For tumors of the central nervous system (including macroprolactinomas), surgical treatment, radiation therapy, or a combination of both are performed.

46. Abnormal uterine bleeding (AUB) Any menstrual bleeding that is either abnormal in volume, regularity, timing, frequency OR Non-menstrual uterine bleeding (IMB, PCB, PMB)

47. Classification Terminology Discription Chronic AUB AUB has been present for the majority of the past 6 months Acute AUB Excessive bleeding that requires immediate intervention to prevent further blood loss May present in the context of existing chronic AUB or might occur without such a history

48. Causes of AUB: FIGO classification New classification system PALM-COEIN: Structural causes : PALM Non-structural causes : COEIN

49. Clinical manifestations Heavy menstrual bleeding   regular, heavy and prolonged menstruation; characteristic of adenomyosis, submucosal uterine fibroids, coagulopathy, endometrial hyperplasia; Intermenstrual bleeding   against the background of a regular cycle; characteristic of endometrial polyps, chronic endometritis, focal endometrial hyperplasia; Prolonged menstrual bleeding irregular prolonged and (or) profuse bleeding, more often occurring after menstruation delays, characteristic of ovarian dysfunction, hyperplasia, precancer and endometrial cancer).

50. DIAGNOSTICS OF ABNORMAL UTERINE BLEEDINGS The algorithm for diagnosing AUB is carried out in 2 stages. At stage 1 , the presence of AUB is confirmed based on the truth of the patient's complaints. It is known that 40-50% of women with complaints of heavy menstruation do not have menorrhagia, 25% of women without complaints have blood loss of more than 80 ml. Currently, the following methods for assessing menstrual blood loss are used: • Clinical indicators of uterine bleeding • 90-day menstrual diary • Semi-quantitative method - pictograms of menstrual blood loss • Quantitative alkaline-hematin method (FDA).

51. DIAGNOSTICS OF ABNORMAL UTERINE BLEEDINGS At the 2nd stage , a differential diagnostic search is carried out with the diagnosis of AUB and clarification of its cause using clinical, laboratory and instrumental research methods. Clinical examination of the patient includes history taking, physical examination, general and gynecological examination. Laboratory diagnostics includes: • exclusion of possible pregnancy; • exclusion of pathology of the cervix; • screening for anemia; • exclusion of disorders of the blood coagulation system ( coagulogram ), consultation of a hematologist; • hormonal examination is carried out with an irregular rhythm of menstruation and the risk of hypothyroidism; • testing for chlamydial infection. Instrumental research methods using visualization methods: • ultrasound of the pelvic organs (transvaginal and (or) abdominal); • saline infusion sonohysterography and diagnostic hysteroscopy;• direct biopsy under vision control.

52. TREATMENT OF ABNORMAL UTERINE BLEEDING Treatment of AUB: 1. It is determined by the clinical situation (intensity of AUB, acute or chronic), the etiology of bleeding, the woman's desire to maintain reproductive function, the need for contraception, concomitant extragenital pathology. 2. Should affect the pathogenetic link. 3. When selecting therapy, one should take into account its effectiveness, safety, side effects, level of evidence, registration of indications.Treatment of AUB is carried out in 3 stages: Complex hemostatic therapy. Prevention of recurrent bleeding and regulation of MC. Rehabilitation of impaired reproductive function in case of reduced fertility or infertility.

53. Treatment. Medical. Non-hormonal Antifibrinolytics Tranexamic acid 50%↓ in blood loss NSAIDS Mefenamic acid 30-40% ↓ in loss Significant ↓ in dysmenorrhoea

54. Treatment. Medical. Hormonal Mirena IUS Levonorgestrel Causes endometrial atrophy Blood loss ↓ by up to 90% 30% will be amenorrhoeic at 12 months Provides contraception ↓ in number of hysterectomies Progesterone (Cyclic) From day 5 to 26 in a cyclical manner From day 15 or 19 to day 26 of the cycle Cyclical progesterone for 21 days Significant reduction in menstrual blood loss Combined oral contraceptive

55. Treatment. Surgical Minimally invasive (uterine preserving) Endometrial resection Endometrial ablation Myomectomy in cases of fibroid Polypectomy Hysterectomy Laparoscopic Open Vaginal

56. Dysmenorrhea Dysmenorrhea, defined as painful cramps that occur with menstruation, is the most common gynecologic problem in women of all ages and races, and one of the most common causes of pelvic pain. Estimates of the prevalence of dysmenorrhea vary widely (16.8% to 81%), and rates as high as 90% have been recorded. Symptoms typically begin in adolescence and may lead to school and work absenteeism, as well as limitations on social, academic, and sports activities.

57. Classification Primary dysmenorrhea is a cyclic pathological process that occurs from the moment of menarche or 1.5–2 years after the establishment of ovulatory cycles. More often it is functional in nature, not associated with pathological changes in the internal genital organs. Secondary dysmenorrhea is organic in nature, due to gynecological diseases: external and internal genital endometriosis, malformations of the uterus and vagina, inflammatory diseases and tumors of the uterus and its appendages, adhesions in the pelvis, varicose veins of the pelvis. It is observed more often after 30 years. In its course, dysmenorrhea can be compensated , in which the severity of pathological symptoms do not change over time, and decompensated , when there is an increase in the intensity of the pain syndrome during menstruation over time

58. Pathophysiology

59. Clinical features  Usually occurs during the first 1–3 days of  menstruation Spasmodic, crampy  pain  in the lower abdominal and/or pelvic midline (often radiating to the back or thighs)  autonomic, vegetative-vascular, emotional-mental, metabolic-endocrine disorders and symptoms of an inflammatory response Normal   pelvic examination

60. Severity of dysmenorrhea

61. Diagnosis of dysmenorrhea The complex of diagnostic measures for dysmenorrhea is aimed at finding organic causes of pain in the lower abdomen, not associated with menstruation, and includes: • Anamnesis • Presence and parity of factors. • Diagnostic test with NSAIDs that inhibit prostaglandin synthetase • Assessment of mental and emotional state. • Special gynecological examination, smear microscopy for flora, vaginoscopy - according to indications. • Ultrasound • Hormonal study of peptide and steroid hormones • Electroencephalography (EEG) and rheoencephalography (REG), echo and electrocardiography. • If necessary, laparoscopy and hysteroscopy. • According to indications: consultations of the therapist, endocrinologist, neuropathologist, psychologist.

62. Treatment of dysmenorrhea Symptomatic treatment: pain relief (e.g.,  NSAIDs ), topical application of heat Hormonal contraceptives (e.g., combined oral contraceptive pill, IUD with progestogen) Venotonics The patient needs to follow a regimen with good rest, a diet with an increase in consumption of vitamin-rich foods on perimenstrual days and the exclusion of products based on milk and coffee. Therapeutic physical culture, psychotherapy, sedative therapy with herbal preparations (tincture of motherwort, peony, valerian, herbal teas).

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