Abnormal uterine bleeding

1. Abnormal Uterine Bleeding Prof. M.c.Bansal. MBBS.MS.MICOG.FICOG. Founder Principal & controller; Jhalawar Medical college And Hospital Jhalawar. Ex. Principal & controller; Mahatma Gandhi Medical college And Hospital , Sitapura, Jaipur

2. Normal Menstrual Cycle Menstration is a cyclic physiological phenomena starting at the age of Menarche (10-12years) till establishment of Menopause (45-55 yrs). It is regulated by hypothalmo-pituitary- ovarian hormones secreted in pulsatile and cyclic pattern. Also influenced by endometrial response top these (E& P ) hormones and coagulation cascade. Cycle lenghth-21-35 days , mean menstrual blood loss -30-40 ml , duration of bleeding (period0---2-8 days.

3. Volume of blood flow is assessed by number of pads / tampons used whether the pads are fully/ partially soaked , presence of clots. It can be better assessed by pictorial charts-- Pad Area Soaked 1 st day 2 nd Day 3 rd Day 4 th Day 5 th day 6 th Day 7 th Day X 1 // / / X 5 /// // X20 /// Total Points 89(<1oo)- Normal blood Loss Tampons soaked X1 // // / / x 5 /// D X 15 Total Points ////// 111 Excessive blood loss

4. Pituitary

5. Cyclical Changes in Menstruation

6. ovary

7. Double Cell Theory of Estrogen Production

8. Menstruating Endometrial

9. Proliferative Endometrial

10. Early Secretary Phase ENDOMetrium

11. Late Secretary Phase of Endometrium

12. Arrest of Menstrual bleeding # mechanisms--- 1 Haemostasis by plate let plug and clot formation – starts soon the bleeding starts and open BV are plugged .once Blood vessels are plugged , fibrin deposition occurs ---Fibrinolysis also go hand in hand to balance and keep the blood loss fluid. 2.Prostaglandin Mediation – Archadonic acid and Pg synthetase enzyme produce PGs ---pge2 –vasodilator, PGf2a--- vaso constrictor and Thromboxane – vaso constrictor. Estrogen produce PGE2 and PGF2a in ratio of 1:1 in proliferative phase ; while Progesterone produce PGE2 and PGF2a + thromboxane (a2) in a: 2 ratio in premenstrual phase so balance is shifted towards vasoconstricton which help in contrl of bleeding.

13. Arrest of Menstrual bleeding -- 3. Tissue Repair --- starts from the mouths of open endometrial glands in the denuded areas , endothelium out grows and covers the raw area under the influence of Epithelial Growth Factor ( EGF) and blood vessels regrow due to Vascular endothelial Growth Factor (VEGF). Thus the raw area of remaining basal endometrium is completely epithelized under Estrogen effect.

14. Abnormal uterine bleeding Organic Causes Functional Uterine bleeding(DUB) Deseases Of Genital Tract— Pregnancy related irregularity Abnormal Bleeding from Genital Tract without any demonstrable organic cause. IUCD Related Irregularity Diagnosis is made by excluding organic cause . Benign Conditions-- Altered Hypothalamus-pituitary-ovarian- Fibroids, its polyps Function Endometriosis (external; Adenomyosis Altered endometrial response to Sex Hormones Endometrial Polyp altered proprtion of estrogen and progestrone production and their effect on Endometrial Malignant Lesions phasing may cause DUB. Endometrial Cervical Vaginal Ovarian Systemic Causes =Coagulation disorder , thyroid and liver disease

15. Menstrual Patterns IN DUB Regularity—1. regular ,2 irregular , absent. Frequency---1. frequent < 21 days, 2. Normal 21-35 days,3. Infrequent >35 days. Duration– Normal 2-8 days , Prolong > 8 days .shortened <2 days . Volume – normal 20 -80ml , Heavy > 80 ml, Light < 15 ml

16. Terminology Menorrhagia –Regular cycle with prolonged or heavy flow. Polymenorrhoea – frequent cycles but normal bleeding . Poly menorrhagia – frequent cycles with heavy bleeding . Metrorrhagia ----Inter menstrual Bleeding . Oligomenorrhoea—Infrequent cycle with normal bleeding . Hypomenorrhoea—Regular normal cycle with light Bleeding.

17. Classification of DUB 1. Anovulatory – Metropathia Haemprrhagica. Threshold Bleeding. 2.Ovulatory --- Idiopathic ovulatory Menorrhagia. Luteal Phase Defect.

18. Anovulatory DUB In some adolescent girls and perimenopausal women, Ovarian follicles develop(FSH Stimulation) and produce estrogen in variable amount leading to proliferation of endometrium . Dominant follicle may not develop due to insufficient LH surge – no ovulation—no development of carpus Luteum ---no progesterone --- no secretary changes in endometrium ; estrogen still secreted by follicles (grannulosa cells) . Unopposed estrogenic Stimulation and some time hyper ( super threshold ) level of estrogen results in over growth of endometrium(hyperplasia) ----resulting in prolonged cycle and increased blood loss during period.

19. Anovulatory DUB When endometrium over grow s its blood supply , lack of progesterone causes decrease PGE2 vasodilators initially and Avascular necrosis of functional endometrium occur , endometrium is shade off Lack of vasoconstrictors--- PGf2a and thromboxane results in excessive blood loss which is pain less and prolonged for 20-30days (As irregular shading of endometrium continues for such a long time ). Persistent Follicles under go the formation of follicular cysts.

20. Anovlatory DUB Metropathia Hamorrhagica Accounts for 80% of DUB; at Pubertal and perimenopausal age ,Patient has variable period of amenorrhoea followed by prolong, heavy , painless bleeding . Prroplonged Un opposed Estrogen Proliferative Endometrium Simple Hyperplasia Complex Hyperplasia Complex Hyperplasia with Atypia Adenocarcinoma

21. Endometrium in Metyrpathia Haemorrhagica Usually reveals cystic hyperplasia( simple hyperplasia with out atypia) called swiss cheese appearance . Hyperplastic glands and strauma. Cystic or irregularly dilated glands. Thick walled , tortuous , dilated spiral arterioles and veins. Infarction and thrombosis of blood vessels. Necrosis of functional endometrium .

22. Metropatha Hamorrhagica

23. Progress And Course of Metropathia Haemorrhagica Incidence of malignancy --- simple cystic Hyperplasia---1% Complex hyperplasia with atypia---29% It is further increased in perimenopausal women who are obese, diabetic,on E2 therapy, hypertensive and relatively infertile , H/O Ca endometrium in family and had PCOD. Young Girls who are obese with or with out PCOD are prone to have metropathia Haemorrhagica of early changes which are reversible with progesterone / Ocs therapy.

24. Simple Endometrial hyperplasia

25. Atypia (hyperchromatic, large, variable size and shape Of Nucleus)

26. Endometrial Hyperplasia with Nuclear Atypia

27. Complex Hyperplasia

28. The endometrial adenocarcinoma in the polyp at the left is moderately differentiated, as a glandular structure can still be discerned. Note the hyperchromatism and pleomorphism of the cells, compared to the underlying endometrium with cystic atrophy at the right.

29. Threshold Bleeding This is often seen in peri menopausal women . There is insufficient development of ovarian follicles resulting in low estrogen level not able to sustain endometrium or trigger LH surge ( no ovulation ). Such women can have prolonged and excessive bleeding due to absence of progesterone and lack of PGF2a and thomboxane. Bleeding PV in these women can be controlled with cyclic E2 + P Combination Therapy as both are at low level .

30. Ovulatory DUB More common in women of reproductive age group (21-40 years ) . Accounts for 20% cases of DUB. Patient usually present Cyclic excessive bleeding / premenstrual spotting. Periods are associated with Pain .

31. Idiopathic Adulatory Menorrhagia (DUB ) An alteration in ratio of PGE2 and PGF2a ( vaso dilator : vaso constrictor )occurs in some women despite of ovulation and normal progesterone production from carpus luetium . Increase in PGE receptors in endometrium , reduction in thrombxane production and increased fibrinolytic activity has also been demonstrated in these women . PgF2a causes Dysmenorrhea. HP report of endometrium reveals secrtory changes

32. DUB: Classification, Pathophysiology And Endometrial Changes OVULATORY Idiopathic Ovulatory Menorrhagia Corpus Luteum insufficiency Normal Progesterone Altered PG E : PG F Menorrhagia Secretory Endometrium Reduced Progesterone Reduced PG F2 Premenstrual Spotting (Polymenorrhoea) Irregular ripening ANOVULATORY Metropathica Haemorrhagica Prolonged Oestrogen No Progesterone Reduced PG F2 Amenorrhoea followed by bleeding Hyperplastic Endometrium Threshold Bleeding Low Oestrogen No Progesterone Reduced PG F2 Polymenorrhoea/ Polymenorrhagia Proliferative Endometrium

33. Luteal Phase Defect In adequate Functioning of carpus luteum can result in-- -- in sufficient and erratic production of Progesterone. As well as alteration in the ratio of PGE : PGF ---resulting in irregular and patchy screttory changes in the endometrium Both pathophysiological deficit leads to irregular ripening and or irregular shading of endometrium .

34. History Taking In DUB Age Age at menarche. Parity. Menstrual History—regularity, frequency, duration of bleeding , Volume of blood loss. Post coital bleeding ? Dysmenorrhoea – spasmodic / congestive . Dyspareunia. O.H.---fertility / infertility/ gravidity / parity etc. Associated Vaginal Discharge . Rescent Abortion / delivery / ectopic pregnancy . IUCD insertion , ocs, hormone therapy/ drugs. Symptoms of thyroid disease. Symptoms of any bleeding disorder.

35. Examination General Physical . Pallor. thyroid. BMI . Signs of PCOD . Speculum Examination. PV examination --- uterine, position, size. Shape surface , consistency ,tenderness and mobility . Furnaces for any anneal mass /tenderness/ indurations

36. Investigations Laboratory Tests  HB , T/DLC, BT. CT, PT , PPT, platelets count , ESR, Fasting Blood Sugar,,T3-T4- TSH.– to know degree of anemia, to exclude coagulation disorders and leukemia's, Diabetes and thyroid disorders. TVS /abdominal USG –to exclude Genital tract lesions like fibroids, endometrial thickening , endometriosis, PCOD , polyps , IUCD pregnancy related conditions anneal mass etc . Soon Historiography– intra cavity lesions like polyp fibroid . Dilatation Curettage--- Endometrial sampling for HPR--- type of endometrial ; secretary , LPD, proliferative / hyperplasia , inflammation like tuberculosis and precancerous or cancer lesion . Hysteroscopy---diagnostic as wells therapeutic use in IUCD sub mucous fibroid , polyps .

37. Endometrial curette

38. Differential Diagnosis—Adolescent---DUB Differential Diagnosis Symptoms and signs Investigations Bleeding Disorder s previous history Present BT, CT , Platelet count , PT APTT Thyroid dysfunction PCOD (hormonal disorder but ovarian enlargement can be detected ) Thyroid enlargement ,Resident of Goiter endemic area, clinical symptoms and signs present. Obesity, Acne , hirsutism,Acanthyosis etc T3 , T4 and TSH profile. USG, FSH/LH ratio ,serum prolactn and SerumE2 level on day 2 of menses.

39. Differential diagnosis in Reproductive Age Group Differential diagnosis Symptoms & Signs Investigations Evacuation of vascicular mole, Post Abortal Bleeding , ch. Ectopic ,Post delivery bleeding , retained IUCD H/o recent abortion , missed period , delivery/ insertion of IUCD / Medical abortion Pill urine Pregnancy test, USG Fibroid Uterus Menorrhagia/ Poly menorrhagia , congestive dysmenorrhea , irregular enlarged uterus but not tender. USG Endometriosis/ Adenomyoma Menorrhagia/ Poly menorrhea , cutting pain during menses / coital pain ,Infertility. Enlarged (Localized in adenomyoma) RV RF Fixed and tender uterus and adenexa/ mass. USG Chronic PID Poly menorrhagia, congestve dysmenorrhoea,leucorrhea chronic pain in lowe abdomen and sacral region. Tender uterus , fixed / restricted mobility , adnexal thickening and tenderness USG

40. Differential Diagnosis In Perimenopausal Age Group Differential Diagnosis Symptoms And Signs Investigations Fibroid Uterus Adenomyosis Multipara, menorrhagia , congestive dysmenorrhea Uterus bossed and irregularly Enlarged firm to hard and not tender. Menorrhagia, multi para , congestive dysmenorrhoea . Uterus regularly enlarged soft and tender USG USG Endometrial Carcinoma Nullipara, obese , hypertensive , delyed menopause , diabetic , family history +/_ , PCOD , Irregular /freuent cycles Fractional Curretage and endometrial HP Examination

41. Treatment General Measures –> Rx of anaemia , life style modification ---weight reduction by diet control and exercise . Definitive Rx-  Medical – 1.Non Hormonal like Antifibrinolytics, PG synthesis inhibitors , Capillary fragility inhibitors. 2. Hormonal ---Progesterone—oral , IM, Progesterone bearing IUCD. Estrogen +progesterone combination. Estrogen only. 3. Others ---Danazoloe , GnRH analoges / Omeloxifene., Testosterone. Surgical-- &c , Endometrial Ablation , Hysterectomy

42. Management Of AUB According to Endometrial TVS

43. Management Of AUB In Endometrial TVS

44. Algorithm for USG based Triage for AUB case

45. DUB management in Reproductive Age Group Abnormal bleeding Clinical Evaluation Normal Abnormal Medical Rx USG Response No Response Rx Accordingly Cont. For USG 3-6 months/ Polyp Normal LNG –IUS Response No Response Hysterectomy hysteroscopic polypoidectomy Endo . Ablation LNG -IUS= Levonorgstrel intra uterine system

46. Management of DUB in Adolescent Girls Abnormal Bleeding Clinical Evaluation ? Bleeding disorder / Thyroid dysfunction/ PCOD NO YES Investigate & Rx Profuse bleeding Moderate Bleeding High Dose Progesterone Cyclical combined Ocs for Followed By E+P combination 3-6 months for 3-6 Months

47. DUB Management in Perimenopausal age group Abnormal Uterine Bleeding clinical Evaluation Risk Factors for Hyperplasia , carcinoma , irregular acyclic Bleeding NO Yes Low Dose OCS USG, Fractional Curretage, endometrial HP examination Atypical Hyperplasia Simple Hyperplasia Hysterectomy Low Dose Ocs / cyclical Progesterone

48. Drugs used in RX of DUB NonHormonal Drugs Dose Antifibrinolytic Tranexamic Acid 500mg tid/qid for 3-5 days PG synthetase Inhibitors Mefenamic Acid 500mg tid for 3-5days. Capillary Fragility inhibitors Ethamsylate 500mg qid for 4-5 days

49. Hormone therapy in DUB Hormone Dose PROGESTEROGENS— Norethisterone / Medroxipogesterone/ Duphaston—to arrest bleeding-----------  Cyclically---------------------- 10mg 6hrly for24-48 hrs follwed by 10 mg /day for 15-25 days 10mg daily from 10 th -25 th day for 3-6 cycles. Estrogen + Progesterone combintion Ethinyl estradiol + norethysterone / norgestrel/ 20-30 ug + o.5-0.75mg cyclically daily starting on 4 th day to 25 th day of cycle –for 3-6 cycles. Estrogen only---Ethinylestradiol 50ug /day for 5 days danzole 100-200mg /day for 3-6 months. GnRH Analoges Ormiloxifene 3.6mg IM once in 4 weeks 60mg twice weekly for 12 weeks

50. Progesterone Intra Uterine System The commonly used progesterone is Levonorgestrel bearing IUCD (LNG-IUS). It can reduce the blood loss up to 90%. It is effective contraceptive too( 5years). It is as effective as endometrial ablation avoiding surgical management like hysterectomy. LNG-IUS delivers 20 ug levonorgestrel daily to endometrium . It causes glandular atrophy and stromal decidualization. It has minimal action on Hypothalmo-pituitary –ovarian axis. Nosystemic side effect.

51. LNG –IUS

52. Surgical Treatment of DUB Conservative  -Dilatation & Curretage—routine / Fractional -Endometrial ablation. Redical -Hysterectomy Total Pan Hysterectmy. Total with unilateral salping overiotomy/ shalpingo oophrectomy.

53. Endometrial Ablation Ablation means == elimination Indication  failed medical therapy . Young women desires to preserve uterus. Poor surgical risk for hysterectomy (non carcinoma lesion of endometrium) 2. Contra Indications Desire for fertility Large uterine cavity -- <12cm. Endometrial hyperplasisia with Atypia. Suspected malignancy of genital tract. Multiple or large fibroids/ nonfunctional ovarian cysts.

54. Endometrial ablation Techniques First Generation Techniques  Endometrial laser . Trans cervical resection . Roller wall electro coagulation . Second generation Techniques Thermal Ballon Ablation . Microwave ablation . Radiofrequency induced ablation . Hydrotherma ablation . Electrode mash Cryo Ablation . Laser interstitial therapy.

55. Thermo Ablation Of Endometriun

56. Cryo ablation of Endometrium

57. Disadvantages of !st generation Ablation Technique . Require skilled person. Require long training. Require general anasthesia. More chances of uterine perforation and fluid over load. Long term results of Ablation--- 30% women remain amenorrhi0ec . 40-50 % women have reduced bleeding during their menstrual periods. 10-20 % women reqquire hysterectomy due to failure e.g. no relief from bleeding.

58. Hysterectomy Indications Endometrial hyperplasia with atypia. Failed Medical therapy in women over the age of 40-45. Failed endometrial Ablation. Other pelvic pathology that needs surgery

59. Summary of DUB management Age Group USG Endometrial Sampling Medical Management syrgery Adolescent Abdominal to rule out any organic cause Seldom done Usually sffice Seldom Reproductive frequetly done abd / TVS may be required as per TVS report Always 1 st line Secod line of RX Perimenopausal Abd / TVS Should be done Mostly 1 st line of Rx Some time !st Line Of Rx

60. Key Points AUB can be due to organic disease or functional disorder. It can occur in any age group –adolescent/ reproductive or perimenopausal . Dub is diagnose by exclusion of organic lesions by clinical and investigatory methods. Drug Rx (non hormonal –then hormonal should be given first as majority of cases will get desired response. LNG –IUS has revolutionized the medical management and has reduced the need of surgical Rx. If medical management fails – endometrial ablation can be done. If there are contra indication for Ablation and or it fails hysterectomy can be done in Perimenopausal women . Rx of DUB Is to Be Individualized Approach