By Dr. Sahar Al-Suwailem Consultant OB-Gyn, KFMC WSH Gyn-Lapascopy

1. By Dr. Sahar Al-Suwailem Consultant OB-Gyn, KFMC – WSH Gyn-Lapascopy

3. Abnormal Uterine Bleeding Heavy regular menstrual bleeding (Menorrhagia) Irregular menstrual bleeding Irregular bleeding Inter menstrual bleeding Post coital bleeding Oligomenorrhoea and Amenorrhoea DUB – heavy prolonged flow with or without breakthrough bleeding it may occur with or without ovulation

4. Despite improved education and the media, most women don’t know how much they should lose, and 1 in 3 think they are heavier than normal 30ml (6 teaspoons) - (range 20-60ml) Last 5 days (range 3-8 days) 90% of bleeding in first 3 days What is normal ?

5. Greater than 80mls Teens and perimenopause Commonest in 40–44 years olds (20%) Any bleeding which affects the physical, psychological or social welfare of the patient What is a Heavy Period?

6. Abnormal Uterine Bleeding - WHY? Exact pathophysiology still not known Basis of excessive bleeding? Endocrine abnormality: estrogen - progesterone imbalance (usually estrogen dominance) Deficiency in clotting mechanism Altered prostaglandin synthesis in favor of E2 than F2?.

8. Cycle Regular vs. irregular i.e. ovulatory vs. anovulatory Heaviness Flooding Pain Timing and severity PMT “suggestive of ovulatory cycle” History tells all – back to basics

9. These symptoms may indicate different pathologies and management pathways: Intermenstrual bleeding Post coital bleeding Pelvic pain Pressure symptoms Offensive discharge Dyspareunia E.g. polyps or submucous fibroids are present in 25 to 50% of women with irregular bleeding Why consider HMB separately from IMB or PCB?

10. Differential Diagnosis of Noncyclic Uterine Bleeding Anovulation Uterine leiomyoma Endometrial polyp Endometrail hyperplasia or carcinoma Cervical or vaginal neoplasia Endometritis Adenomyosis Bleeding associated with pregnancy Bleeding associated with pueperium Coagulopathies (von Willebrand’s disease, platelet abnomalities thromboytopenic purpura) Iatorgenic causes and medications Systemic diseases (Thyroid, Hyperprolactinemia)

11. Abdominal and pelvic examination with visualization of the cervix, a smear or swabs if appropriate and a bimanual assessment BMI Sign of excess androgen CBS ± ferritin ± coagulation if appropriate TV ultrasound Endometrial thickness Enlarged uterus ? cause Diagnosis

12. Endometrial sampling All women over 40 years of age Women with high risk of endometrial cancer: nulliparity with history of infertility, obesity = 90 kg, PCO, family history of endometrial and colonic cancer, and on tamoxifen therapy Women who has no improvement in her bleeding pattern following a course of therapy of three months Diagnosis – cont.

13. Saline sonohysterography R/o intrauterine masses during TVS Curettage 10 to 25% D&C alone does not uncover endometrial pathology Risk of anesthesia Risk of perforation Hysteroscopy directed biopsy Endometrial culture Diagnosis – cont.

14. Your history and examination will reveal 3 categories of patients For patients with normal bleeding who are happy you can reassure, or address their other concerns If you suspect a problem refer to AUB clinics If straightforward HMB discuss the options The Discussion

15. A U B - Management Options

16. Medical Treatment for AUB Hormonal Es+Pr (COCP) Progestogens Norethisterone? MPA LNG IUS Danazol GnRHa Estrogen Androgens + Estrogen Non-Hormonal ANTIFIBRINOLYTICS TRANEXAMIC ACID (TA) NSAIDs Mefenamic acid (MA) Naproxen,Ibuprofen, Aspirin

17. Antifibrinolytics Tranexamic acid Anti-prostaglandins – NSAID Mefenamic acid Ibuprofen Medical treatments: Non Hormonal

18. When period are regular / ovulatory When women trying to conceive When women request medication that is non-hormonal When awaiting investigation or other definitive treatment When to use non-hormonal medication

19. Antifibrinolytics Competitive inhibitor of plasminogen activator Reduce MBL 34-59% (based an 10 randomized placebo-controlled trails) Low risk of side-effects - gastrointestinal No effects of coagulation within healthy vessels Non Hormonal Short half life - take regularly 1 gm every 6 hours Tranexamic acid (cyclokapron)

20. Is not contraceptive Does not reduce dysemenorrhoea Does not regulate the cycle Only recommended for 4 days Tranexamic acid – “drawbacks”

21. PG synthesis inhibitors (via inhibition of cyclo-oxygenase) Reduce MBL 16-49% Reduce dysmenorrhoea (70%) Few side-effects ? Asthma Can be used with other medications Mefenamic acid, Ibuprofen (NSAID)

22. Need to be told to take them regularly Many think they are painkillers Side-effects Asthmatics Not contraceptive Do not regulate the cycle No evidence regarding effectiveness in the presence of fibroids NSAIDs - “drawbacks”

23. HMB may present in absence of organic pathology Disruption of the hypothalamo–pituitary–ovarian endometrial axis leads to failure of ovulation and progesterone induced secretory change Bleeding results from endometrial instability and is less defined, heavier and often less regular than that to progesterone withdrawal Pattern seen particularly at menarche and perimenopause Medical treatment – Hormonal

24. Mode of action: High local progestogen concentration Induces endometrial atrophy Low systemic absorption with small effect on ovulation Licensed use: 5 years High Contraceptive efficacy Levonogestrel IUS

25. RCTs: MBL reduction 71-96% Benefit may take 6/12 Low incidence of side effects Majority satisfied (OR 0.61) and will continue (OR 0.73) Levonogestrel IUS – cont.

26. Synthetic oestrogen and progestogen combinations Act on HPO axis to suppress ovulation but balanced effect on endometrium – bleed on withdrawal One RCT (n=45) using 30 mcgEE showed MBL reduction of 43% Non-contraceptive benefits e.g. Good cycle control Reduction in breast pain, dysmenorrhoea Combined Oral Contraceptives (COC)

27. The likely mechanism of action is that is induces endometrial atrophy Luteal phase norethisterone (day 19-26) does not affect MBL RCT of 15mg NET from day 5-26 shows: MBL reduction 83% (LNG IUS=94%) Satisfaction 22% (LNG IUS=66%) RCT shows cyclic progestins to be ineffective in controlling regular heavy bleeding compared to NSAID and tranexamic acid (IA) Oral Progestogens

28. Neither product is licensed for HMB Injected /depot progestogens

29. Mimics action of natural GnRH but with much longer half-life Initial stimulation then block FSH &LH production Profound hypogonadism results Used clinically for Perimenopusal women Oestrogen dependent lesions (e.g. fibroids) Data drawn from fibroid studies Gonadotrphin Releasing Hormone analogue (GnRH–a)

30. Reduction in MBL with 89% amenorrhoea Use alone is associated with significant side effects due to hormone deficiency Add-back therapy reduces adverse effects and benefit is not lost Gonadotrphin Releasing Hormone analogue (GnRH–a)

31. Danazol Danazol inhibits secretion of pituitary gonadotrophins and also has androgenic, anti-oestrogenic, and anti-progestogenic activity It reduces excessive menstrual bleeding by up to 80% [NZ, 1998; RCOG, 1999] It is poorly tolerated, due to androgenic side effects of weight gain, hirsutism, acne, mood changes, and occasionally deepening of the voice, which may be irreversible It should generally only be used selectively, following specialist advice [NZ, 1998; RCOG, 1998]

32. Investigate to exclude pathology Hormonal manipulation essential to regulate the cycle Luteal phase progestogen may be useful (5 mg bd from day 19-26 ) Otherwise COC or Mirena Compliance limited by side effects and back of efficacy in regard to decrease in MBL Irregular Bleeding

33. Review in 3 months ? Continue treatment ? Change treatment / add second therapy ? Refer The review

34. Treatment for Menorrhagia (AUB) Current Recommendation

35. Treatment for Menorrhagia (AUB) Current Recommendation – cont.

36. Treatment for Menorrhagia (AUB)Current Recommendation – cont.

38. Heavy menstrual bleeding is more than 80 ml, but we should treat the patient and her concern as well as the bleeding Take a good history Do CBC U/S is the imaging of choice Explain the option and document your consultation In summery

39. Choice is based on: Fertility status Need for contraception Presence of dysmenorrhoea Adverse effects profile Women’s preference Try Pharmaceutical treatment first unless there is a reason to refer If at first you don’t succeed, try a secand line therapy before referring unless there is any suspicion In summery – cont.