SECONDARY AMENRRHOEA pptxSECONDARY AMENRRHOEA pptx

HwLRH

1. SECONDARY AMENORRHOEA By DR PAH unit Department of OBGY Seth GSMC and KEMH

2. DEFINITION Primary amenorrhea- No menses by age 14 in the absence of growth or development of secondary sexual characteristics or by age 16 regardless of the presence of normal growth and development of secondary sexual characteristics Secondary amenorrhea- In a woman, who have menstruated previously, no m enses for an interval of time equivalent to a total of at least three previous cycles or no menses over a 6-month period

3. Primary amenorrhea prevalence – 0.3 % Secondary amenorrhea prevalence – 3% Between 10-20% women complaining of infertility have amenorrhea

4. BASIC FACTORS FOR ONSET AND CONTINUATION OF NORMAL MENSTRUATION Normal female chromosomal pattern(46XX) Coordinated hypothalamo -pituitary axis Anatomical presence and patency of the outflow tract Responsive endometrium Active support of the thyroid and adrenal glands

5. HYPOTHALAMO-PITUITARY-OVARIAN AXIS DOPAMINE

6. Etiology of secondary amenorrhoea Physiological causes-pregnancy(most common), lactation, menopause Iatrogenic-oral and injectable contraceptives, post radiotherapy and chemotherapy Systemic causes- chronic medical illness

7. HYPOTHALAMIC FACTORS Psychogenic shock, stress, anorexia nervosa, strenous exercise. Trauma : accidents, radiotherapy or surgery Infections: tuberculosis Tumors: Craniopharyngioma , meningioma, sarcoid granuloma

8. Prolactinoma Acromegaly Sheehan syndrome Non functioning adenoma Lymphocytic hypophysitis Vasculitis Granulomatous lesions PITUITARY FACTORS

9. Polycystic ovarian syndrome Premature ovarian failure Resistant ovarian syndrome(Savage’s syndrome) Hyper-estrogenic state : persistent follicle sin metropathia , Feminizing tumor of the ovary(Granulosa cell tumor ) OVARIAN FACTORS

10. Masculinizing tumour of the ovary( Sertoli-Leydig cell tumour ) Hypo-estrogenic state like ablation of the ovaries or pelvic radiation Infection- mumps ( oophoritis ), tubo -ovarian abscess Toxins-smoking, galactosemia , chemotherapy Auto-immune disorders

11. ENDOCRINAL FACTORS hyperprolactinemia Adrenal tumours or hyperplasia Cushing syndromes thyroid disorders

12. UTERINE AND CERVICAL FACTORS Tubercular endometritis Post radiation Synechaiae – dilatation and curettage, asherman syndrome Surgery Cervical stenosis

13. UTERINE FACTORS

14. ASHERMAN SYNDROME First described by Joseph Asherman in 1948 and called “Amenorrhea traumatica ”.

15. Causes - Intsrumentation of uterine cavity(mcc) Abdominal/ hysteroscopic myomectomy or metroplasty Uterine artery embolization Infections like tuberculosis, schistosomiasis

16. Presentation Dysmenorrhoea Hypomenorrhoea / amenorrhoea Recurrent pregnancy loss infertility

17. Diagnosis History of instrumentation, uterine operation, infections Scanty or no withdrawal bleeding after progesterone, estrogen treatment TAS/TVS- thin , hyperechoeic and often irregular endometrial echo seen Saline infusion sonogram and hysterosalpingogram are more specific Hysteroscopy provides definitive diagnosis

18. Hysteroscopic diagnosis

19. Management Operative hysteroscopy and adhesiolysis –method of treatment risk for rescarring is high-insertion of an intrauterine balloon catheter which is left inside for 7-10 days keep the walls of uterine cavity separated during the healing process

20. High doses of exogenous estrogens for 4 weeks post surgery followed by progestins for a week leads to return of functional endometrium in 52-80% Recurrence rate - 60% If a woman conceives - increased risk of placenta accreta , placenta previa , preterm labour , PPH. Recent development in the management- use of endometrial uterine stem cells

21. Ovarian factors

22. Polycystic ovarian syndrome 6-10% in women in reproductive age group Aka Leventhal syndrome Most common endocrine disorder in female of reproductive age group Develops when chronic anovulatory state persists MCC of hyperandrogenism , hirsutism, anovulatory infertility in developed countries

23. Rotterdam diagnostic criteria- atleast 2 of the below to diagnose PCOS Olgio /anovulation Hyperandrogenism (excluding other causes of androgen excess )-clinical/biochemical Polycystic ovaries(either 12 or more follicles or increased ovarian volume more than 10 cc)

24. Ultrasound features in PCOS- More than 10 discrete follicles Less than 10mm in diameter arranged peripherally Increased ovarian volume but less than 10 cc Hyperechogenic central stroma Necklace appearance Ovarian changes seen in PCOS Surface area of ovary doubled Number of growing and atretic follicles doubled Thickness of tunica increased by 50% Cortical stromal thickness increased by 1/3rd Oyster shell appearance

25. Biochemical changes in PCOS Hyperinsulinemia Hyperandrogenism Hyperprolactinemia Hyperlipidemia Hyperestrogenemia Hyper secretion of LH Low FSH Low progesterone Low serum SHBG

26. Pathophysiology Abnormal Gonadotropin secretion and action-increased LH, low normal FSH (intrinsic hypothalamic dysfunction, abnormal feedback signal- increased GnRh pulse frequency) hyperinsulinemia and obesity- increased insulin causes ovarian androgen production, inhibits hepatic SHBG production

27. Investigations Increased LH/FSH ratio E1 increased Increased androstenedione,testosterone,and DHEAS, DHT Decreased SHBG, progesterone Hormonal profile

28. Metabolic profile Insulin resistance- fasting insulin is increased >25µIU/mL and insulin levels after 2hrs post glucose challenge(75g)> 300µIL/mL HbA1C Lipid profile SGOT/SGPT Fasting insulin levels Ultrasonography

29. Complications Anovulatory infertility Increased risk of spontaneous abortions Endometrial hyperplasia and carcinoma Diabetes mellitus Gestational diabetes Cardiovascular abnormalities Obstructive sleep apnea

30. Treatment Lifestyle modification Weight reduction Insulin sensitizers like metformin OCPs for menstrual cycle regularization Ovulation induction for management of infertility Ovarian drilling

31. Premature ovarian failure Cessation of ovarian functions, accompanied by raised basal levels of FSH,LH accompanied by decreased levels of estrogen before age of 40 years Incidence is 1 in 100 in women less than 40 years of age 1 in 1000 in women less than 30 years of age

32. CAUSES OF PREMATURE OVARIAN FAILURE Genetic causes Pure gonadal dysgenesis 46 XX/46XY Structural aberrations:45XO,45XO/46XX(mosaics) Enzyme deficiency : Galactosemia,17- α hydroxylase deficiency Defects in the gonadotropon action and structures: α and β subunit defect,receptor defect Familial : fragile X syndrome , FSH receptor mutation(resistant ovary syndrome)

33. Toxins Radiation (20GY) Chemotherapy Smoking Infection : mumps oophoritis , tubo -ovarian abscesses

34. Autoimmune disorders Graves disease Hashimoto thyroiditis Addisons disease Diabetes Hypoparathyroidism Myasthenia gravis Idiopathic thrmbocytopenic purpura Hemolytic anemia Pernicious anemia Rheumatoid arthritis

35. Gonadotrpin resistant ovary(Savage syndrome)- due FSH receptor dysfunction Clinical features- 46XX female,normally developed secondary sexual characteristics and high gonadotropin levels Surgery

36. Fragile X syndrome Inactivation of FMR1 gene on long arm of X chromosome due to more than 200 copies of CGG triplets and is a cause of X linked mental retardation Female carriers of this have CGG between 60 and 200 and do not have mental retardation but have premature ovarian failure PERRAULTS SYNDROME Autososmal recessive disease characterized by premature ovarian failure and neurosensory hearing loss

37. Galactosemia Autosomal recessive disorder of galactose metabolism Deficiency of enzyme GALT Rare cause of POF Affected women have fewer primordial follicles due to cumulative toxicity of galactose metabolites on germ cell migration and survival

38. Hormonal changes in POF FSH >30mIU/ml and decreased levels of estrogen Hormonal levels should be measured on 2 occasions more than 4-6 weeks apart to confirm the diagnosis If FSH levels are always greater then the LH levels,it suggests almost nil ovarian activity

39. Symptoms

40. Pituitary factors

41. Hyperprolactinemia Consistent elevation of fasting serum prolactin in excess of 25ng/ml in the absence of pregnancy and lactation. One third of women with secondary amenorrhoea have hyperprolactinemia

42. PROLACTIN SECRETION IN THE ANTERIOR PITUITARY DOPAMINE GABA SOMATOSTATIN PYROGLUTAMIC ACID ENDORPHINS ESTRADIOL ENCPHALINS GONADOTROPIC RELEASING HORMONE HISTAMINE SEROTONIN SUBSTANCE P THYROTRPIN RELEASING HORMONE VVIP

43. CAUSES OF HYPERPROLACTINEMIA PHYSIOLOGICAL- Pregnancy Post partum period Sleep Stress Nipple stimulation Sexual intercourse

44. PATHOLOGICAL CAUSES OF HYPERPROLACTINEMIA Hypothalamic diseases- tuberculosis, arachnoid cyst, craniopharyngioma , cystic glioma , Cysticercosi sarcoidosis etc Pituitary diseases Acromegaly Hypothyroidism Prolactinoma Tuberculosis Cushings syndrome Addisons disease 1.Metabolic causes Cirrhosis Renal failure Starvation 2. Diseases of chest wall like burns herpes Drugs Methyldopa Cimetidine Opiates Reserpine Anti depressants Phenothiazines Metaclopromide Ectopic production -pituitary tissue in the pharynx,bronchogenic carcinoma,renal cell carcinoma Gonadoblastoma,ovarian dermoid

45. Prolactin causes- Supression of pulsatile release of GnRH Reduces granulosa cell number and FSH binding Interferes with FSH action in production of estrogen Prevents luteinization Reduces progesterone secretion in luteal phase

46. Investigations Thyroid function tests Blood urea creatinine Liver function tests Visual field tests MRI

47. T reatment Depends on the cause Correct thyroid dysfunction If drug induced, stop the drug intake For normalisation of prolactin levels Bromocriptine Cabergoline Pregolide quinagolide

48. Mechanism of action – dopamine agonists Side effects Dizziness Light headedness Orthostatic hypotension Headache Abdominal pain Nausea Fatigue Parasthesia 12% women have severe side effects

49. Trans sphenoidal surgery Radiotherapy -complications of surgery Pan hypo pituitarism CSF leak Meningitis Diabetes insipidus

50. Sheehan syndrome Life threatening blood loss during childbirth, leading to severe hypotension and ischemic damage to pituitary gland Criteria for diagnosis- history of blood loss, inability to produce breast milk, irregular or absent menses, low or absent levels of pituitary hormones Treatment- replacement of hormones produced by pituitary gland

51. Hypothalamic factors

52. Eating disorders anorexia nervosa Increase in neuropeptide (released in response to starvation) which inhibits gonadotropin secretion and causes amenorrhea Reduced leptin levels inhibit GnRH pulse generation

53. Exercise induced amenorrhea Increases endorphins level and inhibit GnRH release Increases IGFBP-1 which leads to supression in GnRH release

54. Stress induced amenorrhea Increases CRH levels in the body CRH increases endogenous opioids Inhibits GnRH release