ABNORMAL UTERINE BLEEDING

1. Cruz, Rivera, Tai, Veloso ABNORMAL UTERINE BLEEDING

2. Menorrhagia - menses lasting longer than 7 days or exceeding 80 mL of blood loss • Metrorrhagia - intermenstrual bleeding. • menometrorrhagia. • hypomenorrhea - diminished flow or shortening of menses • Oligomenorrhea - intervallonger than 35 days (normal 28 days ± 7 days)

3. withdrawal bleeding refers to the predictable bleeding that often results from abrupt progestin cessation. • Assessment: lack of correlation between patient perception of blood loss and objective measurement • passing clots more than 1.1 inches in diameter and changing pads more frequently than every 3 hours

4. FIGO Classification system for causes of abnormal uterine bleeding in nongravidwomen of reproductive age

6. P- Polyps • Endometrial and endocervical • epithelial proliferations comprise a variable vascular, glandular, and fibromuscular and connective tissue • often asymptomatic, but generally accepted that at least some contribute to the genesis of AUB

7. A- Adenomyosis • presence of endometrial tissue within the uterine wall (myometrium) • Relationship unclear

8. L- Leiomyoma • Benign fibromuscular tumors of the myometrium • submucosal lesions are the most likely to contribute to the genesis of AUB

9. M- Malignancy • Endometrial carcinoma is the most common invasive cancer of the female genital tract • Risks: obesity, diabetes, hypertension, infertility, unopposed estrogen stimulation

10. C- Coagulopathy • Coagulation disorders • von Willebrand's disease • prothrombin deficiency • Platelet deficiency • leukemia, severe sepsis, idiopathic thrombocytopenic purpura, and hypersplenism, can also cause excessive bleeding.

11. O – Ovulatory dysfunction • Unpredictable timing of bleeding and variable amount of flow

12. O - Ovulatory • absence of predictable cyclic progesterone production from the corpus luteum every 22–35 days • later reproductive years: “luteal out-of-phase” events

13. O - Ovulatory • Endocrinopathies • polycystic ovary syndrome, hypothyroidism, hyperprolactinemia, mental stress, obesity, anorexia, weight loss, or extreme exercise such as that associated with elite, athletic training).

14. E - Endometrial • predictable and cyclic menstrual bleeding, and particularly when no other definable causes are identified

15. E - Endometrial • deficiencies in local production of vasoconstrictors such as endothelin-1 and prostaglandin F2α; and/or, • accelerated lysis of endometrial clot because of excessive production of plasminogen activator • increased local production of prostaglandin E2 and prostacyclin (vasodilators)

16. E - Endometrial • deficiencies in the molecular mechanisms of endometrial repair secondary to: • endometrial inflammation or infection; • abnormalities in the local inflammatory response; or aberrations in endometrial vasculogenesis.

17. I - Iatrogenic • Gonadal steroid therapy • breakthrough bleeding (BTB) • Systemically administered single-agent or combination gonadal steroids • impact the control of ovarian steroidogenesis via effects on the hypothalamus, pituitary, and/or ovary itself, and also exert a direct effect on the endometrium.

18. I - Iatrogenic • Poor compliance • Use of anticonvulsants and antibiotics • Cigarette smoking

19. I - Iatrogenic • Tricyclic antidepressants and phenothiazines • Use of anticoagulant drugs (e.g. warfarin, heparin and LMW heparin)

20. N – Not yet classified • Chronic endometritis • Arteriovenous malformations • Myometrial Hypertrophy

21. Management

22. To cut or not to cut?

23. Medical Treatment • Estrogen • Progestogen • NSAIDs • Anti-fibrinolytics agents • Danazol • Gonadotropin-releasing hormone (GnRH) agonists

24. Estrogen • Used for acute management of AUB • Causes rapid endometrial growth • Preferred if endometrial lining is <5mm • Oral Conjugated Equine Estrogen (CEE) • 10 mg/day, administered in 4 divided doses • May also promote platelet adhesiveness (Livioet.al)

25. Estrogen • IV Estrogen • Several hours needed to induce mitotic activity (DeVore, et.al) • No great advantage to oral estrogen

26. Estrogen and Progestin • Estrogen + progestin (high dose) after bleeding has stopped • Most acute heavy bleeding episodes is due to anovulation • Progestin addition: Medroxyprogesterone acetate (MPS) 10mg OD • Estrogen and Progestin are given for 7-10 days then stopped

27. Estrogen and Progestin • OCPs that contain estrogen and progestin • Four tablets of an oral contraceptive containing 50 μg of estrogen q 24 h in divided doses • Not as effective as high doses of CEE

28. Progestogen • Slows down endometrial growth by organizing and supporting endometrial tissue • Organized slough to basalis layer stops bleeding quickly • Stimulates arachidonic acid formation in endometrium • Opposes effects of anovulation • Menometrorrhagia – MPA 10mg/day for 10 days monthly

29. Progesterone-releasing IUD • needs to be reinserted annually • rapid diffusion of progesterone through polysiloxone • Levonorgestrol-releasing intrauterine system (LNG-IUS) • duration of action: more than 5 years • Increases hemoglobin • Decreases dysmenorrhea • Reduces blood loss secondary to fibroids and adenomyosis • Good alternative to hysterectomy

30. NSAIDs • Ideal for decreased endometrial bleeding • Stop prostaglandin pathway • Allow thromboxane formation (for platelet aggregation) • NSAIDs blocks • Thromboxane formation • Prostaglandin pathway • More effective in ovulating women

31. Curretage • If bleeding does not cease within 24 hours  consider curretage • Invasive and fast • For volume-depleted and anemic patients • Thick endometrium ( >10-12 mm) • Anatomic problem

32. Antifibrinolytic Agents • Examples: ε-Aminocaproic acid (EACA), tranexamic acid (AMCA), and para-aminomethylbenzoicacid (PAMBA) • Study by Nilsson and Rybo • significant reduction in blood loss after treatment with EACA, AMCA, and oral contraceptives, and use of each of these agents resulted in about a 50% reduction in MBL • greatest reduction in blood loss with antifibrinolytic therapy occurred in women who exhibited the greatest MBL

33. Antifibrinolytic Agents • Preston et al • AMCA reduced MBL by 45%, but there was a 20% increase with norethindrone • side effects (in decreasing order of frequency): nausea, dizziness, diarrhea, headaches, abdominal pain, and allergic manifestations *much more common with EACA than with AMCA

34. Antifibrinolytic Agents • Produce a reduction in blood loss • Can be used by ovulating women with menorrhagia • Best combined with other agents like oral contraceptives for greater effect • Use limited by side effects • Mostly GI • Minimized by reducing dose and use to first 3 days of bleeding • Contraindications: Renal failure and pregnancy

35. Antifibrinolytic Agents • Ergot – Not recommended • Rarely effective • High incidence of side effects: nausea, vertigo, abdominal cramps • Nilsson and Rybo no reduction in blood loss among 82 women with menorrhagia who were treated with methylergobaseimmaleate

36. Androgenic Steroids (Danazol) • MBL markedly reduced in studies from more than 200 mL to less than 25 mL with increased interval between bleeding episodes • Most common side effects: weight gain and acne (Reduction of dosage from 400 to 200 mg daily decreased the side effects but did not alter the reduction in blood loss)

37. Androgenic Steroids (Danazol) • Dockeray et al  Danazol was more effective in reducing MBL, 60% compared with 20% for mefenamicacid but side effects were more severe with Danazoland occurred in 75% of patients • Appears to be more effective than placebo, progestogens, oral contraceptives and NSAIDs. However, side effects were 7x greater as compared to NSAIDS and 4x more when compared with progestogens • Expensive with moderate side effects

38. GnRH Agonists • Possible to inhibit ovarian steroid production with GnRHagonists (not based on any large scale studies) • Due to expense and side effects, use for menorrhagia caused by ovulatory DUB  limited to women with severe MBL who fail to respond to other methods of medical management and wish to retain their childbearing capacity • Will help prevent bone loss if used with an estrogen and/or progestin (add-back therapy)

39. Dilatation and Curettage • Can be diagnostic and is therapeutic for immediate management of severe bleeding • Markedly excessive uterine bleeding with possible hypovolemia quickest way to stop acute bleeding (Treatment of choice for hypovolemia from DUB) • Preferred to stop acute bleeding in women older than 35 (higher incidence of pathologic findings)

40. D&C • Rarely curative for DUB • Temporary cure for chronic anovulation  removes hyperplastic endometrium but has no effect on underlying pathology • Not useful for ovulating women with menorrhagia * Nilsson and Rybo  No difference or an in increase in MBL 1 month S/P D&C

41. D&C • Indications: • Acute bleeding that results in hypovolemia • Older women (Higher risk for endometrial neoplasia) Otherwise: Medical therapy after ruling out organic disease via endometrial biopsy, sonohysteroscopy or diagnostic hysteroscopy

42. Endometrial Ablation • Laser photovaporization of the endometrium for menorrhagia • Minimum endometrial regeneration • Causes varying degrees of uterine contraction, scarring and adhesion formation but complications are minor and uncommon • Erian  56% amenorrhea, 38% reduced menses, 7% no reduction requiring 2nd treatment with good response • Cochrane database  preoperative GnRH agonists or danazol is beneficial

43. Endometrial Ablation • Laser photovaporization • Nd-YAG laser (expensive) • Electrocautery by urologic resectoscope through a hysteroscope (Transcervical resection) • Magos et al  30% amenorrhea, 90% improvement in 1 treatment group

44. Endometrial Ablation • Thermal destruction via electrocautery through a ball-end electrode attached to a urologic resectoscope • Larger contact area, better fit into cornual area and easier contact with tissue as compared to loop electrode • Outpatient procedure with general anesthesia • Preop endometrial suppresion with at least 1 month danazol, GnRH analogues or progestin • Paskowitz 60% decreased bleeding • Easier to learn and equipment less expensive

45. Endometrial Ablation • Thermal balloon • Does not require pretreatment regimens or hysteroscopy training • Local anesthesia Meyer et al  Thermal balloon and rollerball – 80% return to normal bleeding

46. Endometrial ablation • VestaBlate new balloon device with a silicone inflatable electrode carrier • Hydrotherablator  heated free fluid system • Does not allow passage of fluid into fallopian tubes • May be used with endometrial distortions including fibroids • 35% amenorrhea, 87% decreased blood flow • Novasure  3D bipolar device and generator with suction

47. Endometrial ablation • Microwave, Cryoablation, Photodynamic therapy • Becoming more popular for women with menorrhagia without uterine lesions who are unresponsive to medical therapy • Alternative to hysterectomy (Less cost, mortality, days in hospital) • For women contraindicated for hysterectomy or those with ovulatory DUB who don’t want to take medication • Not for those who want to maintain their reproductive capacity

48. Endometrial ablation • Complications: fluid overload, uterine hemorrhage, uterine perforation, thermal damage to adjacent organs, and hematometria • When ablation extends too deep, opening up uterine vessels and exposing adjacent tissues to thermal injury

49. Endometrial ablation • Should be restricted to women with heavy MBL in the absence of organic distress • Should destroy all of the endometrium but only the superficial myometrium to reduce posttreatment problems • Suggested that the surgeon should perform 15 supervised procedures before being credentialed

50. Hysterectomy • Decision should be made on an individual basis • For women with other indications for hysterectomy like leiomyomas or uterine prolapse • Only for persistent ovulatory DUB after all medical therapy has failed and with excessive amount of MBL by direct measurement or that causes abnormally low serum ferritin