ABNORMAL UTERINE BLEEDING - PUBERTAL menorrhagia

Abnormal uterine bleeding

1. PUBERTAL MENORRHAGIA Dr.Sandhiya .K Dr.Sandhya .R 1 St yr PG SVMCH

2. NORMAL MENSTRUATION Cycle length : 24-38 days Mean menstrual blood loss : < 80 ml Duration : <8 days Regularity : Shortest to longest cycle variation <7-9 days

3. NORMAL AND ABNORMAL MENSTRUAL CYCLE International Federation of Gynecology and Obstetrics (FIGO) FIGO AUB System 1

4. Onset of Bleeding Destabilisation of lysosomes and release of proteolytic enzymes {matrix metalloproteinases} into epithelial , stromal and endothelial cells as there is withdrawal of progesterone which is responsible for stabilisation of lysosomes Withdrawal of anti inflammatory effect causing rise in cytokine levels and influx of leucocytes Decrease in tissue factor affecting extrinsic pathway of coagulation Decrease in plasminogen inhibitor , promoting fibrinolysis

5. Arrest of Bleeding By 3 mechanism : Hemostasis by platelet plug formation and clot formation Prostaglandin mediated vasoconstriction Tissue repair – EGF , FGF,VEGF Platelet anti aggregator Platelet aggregator

6. DEFINITION AUB is defined as any bleeding from the genital tract , which is deviation from normal in : - Cyclicity - Duration - Frequency - Quantity And occurs in the absence of pregnancy

7. TYPES OF AUB ACUTE AUB – Episode of uterine bleeding in a women of reproductive age group who is not pregnant and is sufficient quantity to require immediate intervention to prevent further blood loss CHRONIC AUB - Bleeding from uterine body that is abnormal in frequency, regularity, duration and volume that has been present atleast for more than 6 months

8. PREVALENCE OF AUB 18 % Of women in reproductive age group Adolescents 40-60% 50% in perimenopausal women

9. FIGO AUB SYSTEM 2

10. AGEWISE CAUSES OF AUB

11. DIFFERENTIAL DIAGNOSIS OF ADOLESCENT AUB Anovulation Pregnancy related bleeding Exogenous hormones Hematological abnormalities Infections Endocrine or systemic illness Anatomic causes

12. OVULATORY DYSFUNCTION Most common cause of AUB and formerly called as anovulatory DUB Seen in Adolescent girls and perimenopausal women Accounts for all causes of AUB –O Can present as wide spectrum of menstrual irregularities ranging from infrequent ,scanty periods to prolonged and heavy bleeding Results from abnormal functioning of Hypothalamic Pituitary ovarian axis Associated with PCOS, obesity , stress , anorexia or weight loss

13. What happens in normal Ovulatory cycle ? Progesterone controls menstrual bleeding by Stabilising the endometrium – producing key proteins and blocking MMP that degrade extracellular matrix Stimulates tissue factor Stimulating plasminogen activator inhibitor -1 which blocks fibrinolysis and arrest bleeding Increasing synthesis of vasoconstrictor PGs (PGF2a and TXA2)

14. PRESENTATION OF AUB – O HEAVY PROLONGED BLEEDING Due to anovulation there is no midcycle LH surge No ovulation No progesterone production Lack of progesterone Fragile endometrium FOLLICULAR CYST FORMATION Ovarian follicles develop Estrogen is produced but dominant follicle may not develop Insufficient levels of estrogen and failure to trigger LH surge No ovulation or progesterone Persistence of ovarian follicles Follicular cyst formation associated with anovulatory cycles AMENORRHEA F/B PROLONGED AND PROFUSE BLEEDING Estrogen production continues in absence of ovulation Continuous and unopposed estrogen acting on endometrium leading to prolonged amenorrhea When endometrium outgrows its blood supply bleeding occurs

15. Unopposed estrogen action on endometrium unopposed estrogen Proliferative endometrium Hyperplasia without atypia Hyperplasia with atypia Adenocarcinoma

16. ENDOMETRIUM IN OVULATORY DYSFUNCTION : Shows cystic hyperplasia – swiss cheese appearance Characteristics of cystic hyperplasia : 1)Hyperplastic glands and stroma 2)Cystic or irregularly dilated glands 3)Increase in vascularization 4)Thick walled, tortuous and dilated spiral arterioles and veins 5)Infarction and thrombosis of blood vessels 6)Necrosis of superficial endometrium

17. Coagulopathies causing abnormal uterine bleeding: Most common – VON Willebrand disease and thrombocytopaenia. Occurs at menarche. Family history of bleeding disorder is usually present History of easy bruising and prolonged bleeding Use of anticoagulants such as warfarin and drugs that impair platelet function Women on anticoagulants may have a valve replacement,h /o venous thrombosis or APA syndrome Leukaemias Liver disease.

18. Endometrial causes With regular ovulatory cycles and no structural uterine abnormalities HMB is primarily due to disorder at the endometrial level. pathogenesis Alteration in the ratio of PGE:PGF 2alpha Increase in fibrinolytic activity.

19. Clinical evaluation HISTORY : Age Age at menarche Parity Key menstrual parameters - Regularity - Frequency - Duration - Volume Postcoital bleeding Dysmenorrhoea -Congestive - -Spasmodic

20. Dyspareunia Infertility Vaginal discharge Recent abortion IUCD insertion Oral contraceptive/hormone use Symptoms of hypothyroidism\ Symptoms of bleeding disorders Medications

21. PHYSICAL EXAMINATION General Pallor Thyroid BMI Signs of PCOS : - Hirsutism -Acanthosis nigricans -Acne Speculum examination Bimanual examination -size and contour of uterus -Tenderness Fixity Adnexal mass /tenderness

22. INVESTIGATIONS Laboratory tests Haemoglobin Full blood count Bleeding time, Prothrombin time, partial thromboplastin time and peripheral smear Thyroid function test Liver function test Factor assays Cervical Cytology Should be performed in sexually active women to exclude CIN Ultrasonography Sonohysterography - Helpful in diagnosis of intracavitary lesions

23. Endometrial Sampling Women > 45 years – to exclude hyperplasia or carcinoma Women of reproductive age with persistent AUB associated with risk factors such as obesity, PCOS. Hysteroscopy

24. MANAGEMENT OF ABNORMAL UTERINE BLEEDING AIMS : Treatment is individualized based on the following factors Age of the patient Severity of bleeding Etiology or cause Desire for fertility and preservation of uterus Need for contraception Previous treatment details Medical comorbidities

25. GENERAL MEASURES Correction of Anemia Oral iron therapy – Mild to moderate anemia Packed cell transfusion – Profuse bleeding and severe anemia Lifestyle modification Weight reduction Diet Exercise Peripheral estrogen production in adipose tissue will continue if BMI not brought down to near ideal value

26. TREATMENT Anovulatory AUB is the most common cause for Adolescent AUB Patient can be divided into 3 category badsed on the severity of anemia and treated accordingly Mild Anemia Moderate Anemia Severe Anemia

27. MILD ANEMIA (HB 10-11 G/DL) Reassurance Prescribe Hematinics NSAIDS If symptoms persist , cyclical coc prescribed for 3-6 months

28. MODERATE ANEMIA (HB 7-10G/DL ) Prescribe Hematinics Non hormonal therapy 1)NSAIDS – mefenamic acid 500 mg tds 2)Tranexamic acid 500 mg tds Hormonal therapy if patient not responding to non hormonal therapy 1)Cyclical Progesterone ( Medroxy progestrone acetate 10 mg/day from day 5 to day 25 ) 2) Cyclical coc pills for 3-6 months

29. SEVERE ANEMIA (HB <7G/DL ) Admission If patient in Hypovolemic shock – Resuscitate with IV Fluids and blood transfusion Hormonal therapy – to stop acute bleeding

30. MANAGEMENT OF ACUTE AUB More common in Adolescents Exclude coagulation disorders If hemodynamically unstable Transfuse Uterine balloon tamponade Uterine curettage

31. If hemodynamically stable , transfuse if Hb <7 g/dl In acute bleeding , functional layer is lost , estrogen priming is essential Inj. Conjugated estrogen 25 mg IV q4h x 24 hrs reduced to Q6H Oral Progestin after 48 hrs Oral conjugated estrogen 2.5 mg 4 times daily reduced to 3 times and then twice daily Progestin added 48 hrs later High dose COC pill 6 hrly , reduced to 8 hrly then once daily Inj. Proluton depot 500 mg IM stat Tab . Norethisterone 10 mg Q8h reduced to twice daily Inj.tranexamic acid 10mg/kg 8 hrly f/b oral 1g thrice daily for 5 days

32. Nonhormonal - Antifibrinolytics - PG synthetase inhibitors - Capillary fragility inhibitors Hormonal - Progestin only – oral,injectable and intrauterine systems - Oestrogen -progestin combinations - Oestrogen -only Others - Danazol - GnRH analogues - Ormeloxifene MEDICAL MANAGEMENT OF AUB

33. ANTIFIBRINOLYTICS In women with HMB , increased fibrinolytic activity has been demonstrated Antifibrinolytics – Epison aminocaproic acid and tranexamic acid leads to 50%reduction in blood loss More effective than PG Synthetase inhibitors Tranexamic acid Doasage : 1 g thrice daily for first 3-4 days It is well tolerated and is the first line of management in women with cyclic heavy bleeding and normal sized uterus (AUB – E )

34. PG SYNTHETASE INHIBITORS Bleeding in AUB is also mediated through PGs drugs that reduce the synthesis of PG help in reducing bleeding Acts by inhibiting cyclo oxygenase mediated conversion of arachidonic acid to PGs and by biding to PG receptor thereby blocking them Drugs include NSAIDS , Ibuprofen , Naproxen and Mefenamic acid Dosage : Mefenamic acid 500mg three times a day Reduce menstrual blood loss by 25-40 % Second line of treatment of AUB – E Used along with tranexamic acid as first line treatment

35. CAPILLARY FRAGILITY INHIBITORS Ethamsylate reduces capillary fragility have not shown to reduce bleeding significantly in women with AUB and are not recommended

36. HORMONAL TREATMENT Oral progestins Injectable progestogens Progestrone intrauterine device Estrogen – progestin combination Estrogens Other drugs

37. Oral progestins Medroxyprogestrone acetate Norethisterone Norethindrone These are used to arrest bleeding and regulate cycle To arrest bleeding in women with acute HMB – Norethisterone 10 mg 6 hourly for 24-48 hrs f/b 10 mg 1-1-1 10 mg 1-0-1 10 mg 1-0-0 for 21 days After withdrawal bleeding 5-10 mg from day 5 to 25 for 3-6 cycles Medroxyprogestrone acetate 10 mg 6 th hourly Norethindrone 5mg 6 th hourly

38. Cont’d Women who are currently bleeding with irregular menses Oral progestin 5-10 mg day 15-25 If not controlled and in women with endometrial hyperplasia progestogen cyclically from day 5-25 Menstrual blood loss is reduced by 30%

39. Injectable progestogens Injectable progestogens – depot medroxyprogestrone acetate (150 mg ) every 3 months can be used in women with anovulatory cycles or hyperplastic endometrium Bleeding can be irregular and unpredictable and some may have amenorrhea

40. Progesterone intrauterine device Most commonly used progesterone intrauterine device is LNG-IUS . Reduce blood loss by 95% and is as effective as endpometrial ablation LNG delivers 20 mcg of levonorgestrol Mechanism : cause glandular atrophy and stromal decidualisation and prevents endometrial cancer LNG –IUS effective in ovulatory dysfunction , AUB-E and coagulopathies Device has to changed every 3 years in case of used for HMB For contraception – changed every 5 years

41. Estrogen – progestin combination First line treatment in women with HMB, irregular and intermenstrual bleeding bleeding reduces by 60-70% Available low dose preparation contains 20 or 30mcg ethinylestradiol and 50-75mcg progestogen (levonorgestrel, norethisterone ) Used in cyclical fashion (21 days ) or as extended pills for 3 months

42. Estrogens Estrogen alone are seldom used in treatment of AUB –O Ocassionaly young girls with anovulatory bleeding may present with atropic endometrium as endometrium is completely shed Atrophic endometrium does not respond to progestin unless primed with estrogen Conjugated equine estrogen 25 mg iv 6 th hrly Ethinyl estradiol 50 mcg daily for 5 days Should be followed by estrogen progestin combination or progestin alone in the usual dose for rest of cycle

43. Danazol – antigonadotropin Dose – 100-200 mg daily dose in AUB –E SIDE EFFECT :Weight gain and acne Not often used in management of AUB GnRH analogue – cause amenorrhea by inhibiting pituitary production of gonadotropins S/E: Hot flushes Reduction in bone mineral density when used for >6 months Injection given monthly in a dose of 3.6 mg IM Ormeloxifen (Saheli )– Selective estrogen receptor modulator Reduction in bleeding when used as 60 mg twice weekly for 12 weeks

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