Abnormal uterine bleeding

1. ABNORMAL VAGINAL BLEEDING FAHAD ZAKWAN

2. What is normal vaginal bleeding ? Normal vaginal bleeding is the periodic blood that flows as a discharge from the woman's uterus . Normal vaginal bleeding is also called menorrhea . The process by which menorrhea occurs is called menstruation .

3. Unless pregnancy occurs, the cycle ends with the shedding of part of the inner lining of uterus, which results in menstruation. The time of the cycle during which menstruation occurs is referred to as menses . The menses occurs at approximately four week intervals, representing the menstrual cycle. Menarche is the time in a girl's life when menstruation first begins. Menopause is the time in a woman's life when the function of the ovaries ceases. The average age of menopause is 51 years old.

4. MENSTRUATION Shading of the upper layers of the endometrium Stratum compactum Stratum spongiosum Stratum basalis

5. Menstruation is normally under Endocrine Control Hypothalamus - GnRH Pituitary – LH & FSH Ovary – OESTROGEN & PROGESTERON = Effect of the uterus

6. Endometrium responds to the ovarian hormones which causes proliferation and on withdraw=Bleeding ( Menses )

7. Thus Normal Menstruation Results from fluctuations in the circulating levels of estrogen and progesterone . Estrogen causes increased blood flow to the endometrium A significant correlation exists between plasma Estradiol and endometrial blood flow, with both increasing in the days preceding ovulation.

8. Estradiol and progesterone levels decrease several days prior to the onset of menses. Endometrial blood flow decreases Endometrial height decreases and vascular stasis occurs. Tissue ischemia occurs. Arterial relaxation Sloughing of the endometrium. Uterine bleeding occurs

9. NORMALLY Frequency of menses 21 days (0.5%) to 35 days (0.9 %) Average 28 days Duration of menses 2 days to 8 days Usually 4-6 days

10. Flow/amount of menses Average blood loss with menstruation is 35-80cc. 95% of women lose <60cc.

11. What is abnormal vaginal bleeding ?

12. Any deviation in normal frequency , duration and amount of blood flow in women of reproductive tract in reproductive age

13. In order to determine whether bleeding is abnormal, and its cause, as a doctor you must consider these three questions: Is the woman pregnant? What is the pattern of the bleeding? Is she ovulating or not?

14. 1. Pregnancy related AVB Much of the abnormal vaginal bleeding during pregnancy occurs so early in the pregnancy that the woman doesn't realize she is pregnant. Therefore, irregular bleeding that is new may be a sign of very early pregnancy, even before a woman is aware of her condition.

15. Vaginal bleeding during pregnancy can also be associated with complications of pregnancy, such as: Spontaneous abortion Ectopic pregnancy Placental previa Abruptio placenta Trophoblastic disease Puerperal complications

16. 2. Abnormal Bleeding Patterns Polymenorrhoea: frequent (<21 d) menstruation, at regular intervals. can be caused by certain sexually transmitted diseases (STDs) (such as chlamydia or gonorrhea) that cause inflammation in the uterus. This condition is called pelvic inflammatory disease. Endometriosis is a condition of unknown cause that can lead to pelvic pain and polymenorrhea. Sometimes, the cause of polymenorrhea is unclear, in which case the woman is said to have dysfunctional uterine bleeding.

17. Menorrhagia: Excessive (>80 ml) & / or prolonged menstruation, at regular intervals Metrorrhagia : Excessive (>80 ml) & / or prolonged menstruation at irregular intervals. Hypomenorrhoea : scanty menstruation. Oligomenorrhea: infrequent menstruation (>35 d)

18. Menometrorrhagia : both menorrhagia and metrorrhagia can be due to benign growths in the cervix, such as cervical polyps. Metrorrhagia can also be caused by infections of the uterus ( endometritis ) and use of birth control pills ( oral contraceptives ). Sometimes does not have an identifiable cause. Perimenopause is the time period approaching the menopausal transition . It is often characterized by irregular menstrual cycles, including menstrual periods at irregular intervals and variations in the amount of blood flow. Menstrual irregularities may precede the onset of true menopause (defined as the absence of periods for one year) by several years.

19. Hypomenorrhoea: scanty menstruation . An overactive thyroid function ( hyperthyroidism ) or certain kidney diseases can both cause hypomenorrhea . Oral contraceptive pills can also cause hypomenorrhea .

20. Premenstrual spotting: light bleeding preceding menses Post coital spotting: vaginal bleeding within 24h of intercourse

21. Intermenstual bleeding: episodes of uterine bleeding between regular menstruations Women who are ovulating normally can experience light bleeding (sometimes referred to as "spotting") between menstrual periods. Hormonal birth control methods (oral contraceptive pills or patches) as well as IUD use for contraception may sometimes lead to light bleeding between periods. Psychological stress, certain medications such as anticoagulant drugs, and fluctuations in hormone levels may all be causes of light bleeding between periods. Other conditions that cause abnormal menstrual bleeding, or bleeding in women who are not ovulating regularly (see below) can also be the cause of intermenstrual bleeding.

22. 3. Is the woman ovulating ? Usually , the ovary releases an egg every month in a process called ovulation . Normal ovulation is necessary for regular menstrual periods. There are certain clues that a woman is ovulating normally including regular menstrual intervals, vaginal mucus discharge halfway between menstrual cycles, and monthly symptoms including breast tenderness, fluid retention, menstrual cramps , back pain , and mood changes . If necessary, doctors will order hormone blood tests ( progesterone level), daily home body temperature testing, or rarely, a sampling of the lining of the uterus (endometrial sampling) to determine whether or not a woman is ovulating normally.

23. On the other hand, signs that a woman is not ovulating regularly include: prolonged bleeding at irregular intervals after not having a menstrual period for several months, excessively low blood progesterone levels in the second half of the menstrual cycle, lack of the normal body temperature fluctuation during the time of expected ovulation. Sometimes , a doctor determines that a woman is not ovulating by using endometrial sampling with biopsy.

24. Hx, PE, Preg test Preg test POS Preg test NEG Pregnant Location Viability GA Dating Non-uterine bleeding NON PREGNANT Uterine bleeding Cervix Vagina Anus Urethra Abnormal Vaginal Bleeding

25. 2. Non-Uterine Conditions CERVIX Cervix Neoplasms: Squamous cell carcinoma Adenocarcinoma Polyps Condyloma Neoplasia Infections: cervicitis (chlamydia, gonorrhea, mycoplasma hominis) Benign cervical ectropion: Exposed columnar epithelial cells on ectocervix Red appearance; bleeds to touch

26. 2. Non-Uterine Conditions VAGINA Vaginal inflammation Atrophic vaginitis Severe vaginal trichomoniasis Trauma/ foreign body Vaginal wall laceration Hymeneal ring tear/laceration Vaginal foreign body (esp. pre- menarchal bleeding) Vaginal neoplasms Squamous cell cancer

27. 2. Non-Uterine Conditions URETHRA (post-void bleeding) Urethral caruncle (outgrowth) Squamous or transitional cell cancer ANUS (bleeding after wiping) External or internal hemorrhoid Anal fissure Genital warts Squamous cell cancer

28. Hx, PE, Preg test Preg test POS Preg test NEG Pregnant Location Viability GA Dating Non-uterine bleeding Pelvic Exam Uterine bleeding Cervix Vagina Anus Urethra Abnormal Vaginal Bleeding ( Oligo ) Anovulation Iatrogenic Ovulatory

29. Uterine Bleeding Polyp Adenomyosis Leiomyoma Malignancy Coagulopathy Infections Thyroid dz LPD Structural Non-Structural Idiopathic Ovulatory Iatrogenic Anovulatory Abnormal Vaginal Bleeding: Standard Definitions

30. Ovulatory Bleeding CONDITIONS Low estrogen Cervical CA Endometrial CA Fibroids Polyps Inflammation Lacerations

31. Ovulatory Bleeding CONDITIONS Much less common—5-10% Usually underlying prostaglandin imbalance (DUB) Defects in local endometrial hormonal hemostasis Structural lesions Leiomyoma, adenomyosis , polyps Systemic disease Liver dz , renal failure, bleeding disorder

32. Estrogenic (DUB) Hypo-Estrogenic Ovulatory Iatrogenic Anovulatory Physiologic Menarche Peri - menopause Anatomic Androgenic Systemic Dz Hypothalamic Pituitary Ovarian Hyperplasia EM Cancer PCOS CAH Cushings Renal Liver Uterine Bleeding Abnormal Vaginal Bleeding: Standard Definitions

33. Iatrogenic Causes of AVB Intra-uterine device Oral and injectable steroids Psychotropic drugs

34. Anovulatory Bleeding 90-95% of reproductive age Cause: systemic hormonal imbalance Hypothalamic Pituitary Ovarian Always a relative progestin-deficient state.

35. Anovulatory Bleeding With anovulation a corpus luteum is NOT produced and the ovary thereby fails to secrete progesterone. However, estrogen production continues, resulting in endometrial proliferation and subsequent AUB.

36. Postmenopausal bleeding. Bleeding from the genital tract 12 months after the cessation of menses. Causes: hypoestrogenism , vaginal and endometrial atrophy, vaginal, cervical and uterine cancers, urethral caruncle , cervical polyps, uterine fibroids. Vulvar tumors, vulvovaginitis . estrogen and progesterone hormone therapy Differential diagnosis: causes of bladder and rectal bleeding which can be confused with vaginal bleeding

37. Vaginal bleeding during or after sexual intercourse Vaginal bleeding may occur during or after sexual intercourse for a number of reasons including: Injuries to the vaginal wall or introitus (opening to the vagina) during intercourse Infections (for example, gonorrhea, chlamydia, yeast infections) can be a cause of vaginal bleeding after intercourse.

38. lowered estrogen levels in peri -menopausal or postmenopausal women may cause the lining of the vagina to become thinned and easily inflamed or infected, and these changes can be associated with vaginal bleeding after intercourse. Anatomical lesions, such as tumors or polyps on the cervix or vaginal wall may lead to vaginal bleeding during or after intercourse.

39. Genital Trauma Commonly due to vigorous voluntary/involuntary sexual activity Associates with Sex toys Posterior fornix is most common area injured

40. adenomyoses Caused by endometrial glands growing into myometrium May cause menorrhagia and dysmenorrhea at the time of menstruation Treatments are analgesics for pain – surgery may be needed for severe bleeding refectory to medical therapy

41. leiomyoma Fibroids – smooth muscle cell tumors - responsive to estrogen, usually multiple Size increases in first part of pregnancy and at times with OCP use Size decreases with menopause Fibroids are usually found during manual exam or by ultrasound If acute degeneration or torsion occurs – patients will present with acute abdomen symptoms on physical exam Treatment is NSAIDs, progestins, GNRHs, or surgery if indicated Uterine artery embolization is a new promising therapy

42. Blood Dyscrasias Menstrual bleeding may be excessive and be the presenting symptom of a bleeding disorder Treatment includes antifibrinolytics and OCPs. OCPs increase levels of factor VIII and vWF factor Desmopressin (DDAVP) – increases release of factor VIII and vWF In these groups NSAIDs are not helpful and may cause increased bleeding

43. Polycystic Ovary Syndrome PCOS – caused by hyperandrogenism and anovulation without disease of adrenal or pituitary glands Triad usually seen – obese, hirsutite , oligomenorrhea Menses are heavy and prolonged Other characteristics – alopecia, increased androgens, increased LH and FSH and acne Therapy – OCPs – low doses or cyclic progestins

44. DYSFUNCTIONAL UTERINE BLEEDING Accounts 60 % of AVB D efined as ABNORMAL uterine bleeding with no demonstrable organic cause, genital or extragenital. Patients present with “abnormal uterine bleeding” DUB occurs most often shortly after menarche and at the end of the reproductive years. 20% of cases are adolescents 50% of cases in 40-50 year olds

45. causes of dub The main cause of DUB is anovulation resulting from altered neuroendocrine and/or ovarian hormonal events. In premenarchal girls, FSH > LH and hormonal patterns are anovulatory . The pathophysiology of DUB may also represent exaggerated FSH release in response to normal levels of GnRH

46. MANAGEMENT OF ABNORMAL VAGINAL BLEEDING

47. A. History Personal history (a) Age: The commonest age incidence for carcinoma of uterus is 55-70 years while that for carcinoma of the vulva is 60-70 years. (b) parity: some tumours are more common among nulliparae e.g. endometrial and ovarian carcinoma. Present history Ask about the Onset, frequency, duration, cyclic vs.acyclic , severity Pain, change from menstrual pattern (calendar) Age, parity, marital status, sexual hx , contraception medications, dates of pregnancies symptoms of pregnancy and reproductive tract disease

48. Past history Oestrogen therapy. diseases as diabetes mellitus, hypertension and blood diseases as leukemia. Endometrial carcinoma is more common in diabetic hypertensive patients. Family history Carcinoma of the body of the uterus and ovary have a familial tendency

49. B. General Examination (I) Signs of anaemia. (2) signs of bleeding disorders. (3) presence of cachexia. (4) examination of heart and chest for secondaries . (5) estimation of blood pressure

50. C Abdominal Examination For a pelvi -abdominal mass and ascites which is common with ovarian malignancy. D . Pelvic Examination To detect a local cause for bleeding. The urethra and anal canal are excluded as being the source of bleeding.

51. E. Special Investigations sonography . It excludes the presence of an ovarian tumour or alesion in the uterus as endometrial carcinoma . TAS : can exclude pelvic masses, pregnancy complications TVS : More informative than TAS. Measurement of the endometrial thickness is not a replacement for biopsy. All endometrial carcinoma in postmenopausal with endometrial thickness>4 mm (Osmers,1990)

52. TVS is recommended in: 1. Weight >90 Kg 2. Age > 40 yrs 3. Other risk factors for endometrial hyperplasia or carcinoma e.g. infertility, nulliparity , family history of colon or endometrial cancer, exposure to unopposed estrogen (Grade B)

53. 2. Cervical smear . Taken in absence of bleeding to detect the presence of malignant cells which may come from the cervix, endometrium, tubes, or ovaries.

54. 3. Endometrial biopsy. It must be done in every case of postmenopausal bleeding, as is the only sure method to exclude endometrial carcinoma.

55. Indications: Between 20 & 40 If endometrial thickness on TVS is >12mm, endometrial sample should be taken to exclude endometrial hyperplasia (Grade A). Failure to obtain sufficient sample for H/P does not require further investigation unless the endometrial thickness is >12 mm (Grade B) Aim : diagnosis of the type of the bleeding

56. 4. Biopsy is taken from any suspected lesion in the vulva, vagina, or cervix.

57. 5. Laboratory tests. These are done according to the clinical findings and include: a. Complete blood count. b. Platelet count, bleeding time, coagulation time, estimation of clotting factors if a bleeding disorder is suspected.

58. Choices of investigations are extensive Selection should be tailored to suspected causes from the history and physical examination

59. Egs . diagnostic tests are used to evaluate abnormal vaginal bleeding The diagnostic test will depend upon the diagnosis reached. A pregnancy test is routine if the woman is premenopausal. A blood count may be done to rule out anaemia resulting from excessive blood loss. A Pap smear is also done to rule out cervical cancer . While the Pap smear is being obtained, samples might be taken from the cervix to test for the presence of infections such as chlamydia or gonorrhea. A pelvic ultrasound is often performed based on the woman's medical history and pelvic examination .

60. If something in the patient's (or her family's) medical background or physical examination raises suspicion , tests to rule out blood clotting disorders may be done. Sometimes, a blood sample can be tested to evaluate thyroid function , liver function , or kidney function abnormalities. A blood test for progesterone levels or daily body temperature charting may be recommended to verify that the woman ovulates. If the doctor suspects that the ovaries are failing, such as with menopause, blood levels of follicle-stimulating hormone (FSH) may be tested. Additional blood hormone tests are done if the doctor suspects polycystic ovary, or if excessive hair growth is present.

61. TREATMENT Treatment for irregular vaginal bleeding depends on the underlying cause. Treatment Goals includes: control bleeding prevent recurrence preserve fertility correct associated conditions induce ovulation in patients who want to conceive

62. If the cause of bleeding is DUB Medical management is the preferred initial treatment, especially if the woman desires future fertility and there is no associated pelvic pathology Selection of treatment depends primarily on whether it is used to stop acute or heavy bleeding, or to control recurrent episodes

63. Medical management recommended before Surgical effective methods include: estrogens, progestins, or both NSAID’s antifibrinolytic agents ( trenexemic acid) danazol GnRH agonists

64. Acute bleeding Estrogen therapy Oral conjugated equine estrogens 10mg a day in four divided doses treat for 21 to 25 days medroxyprogesterone acetate, 10 mg per day for the last 7 days of the treatment if bleeding not controlled, consider organic cause OR 25 mg IV every 4 to 12 hours for 24 hours, then switch to oral treatment as above. Bleeding usually diminishes within 24 hours

65. Commonly used oestrogen agents are Conjugated estrogens given IV in 25mg doses every 6 hours should be effective in controlling heavy bleeding. This is followed by PO estrogen. For less severe bleeding, PO Premarin ® 1.25mg, 2 tabs QID until bleeding ceases.

66. Acute bleeding can be managed by estrogen which promotes rapid regrowth of the endometrium over denuded epithelial surfaces. It also causes proliferation of the endometrial ground substance and stabilizes lysosomal membranes. There are no studies that indicate IV estrogen acts quicker or is more effective than high dose oral estrogen. After treatment is finished, all medications are stopped and the patient is allowed to have withdrawal bleeding. This can be heavy so warn patients, but it is rarely prolonged

67. Acute bleeding (continued) High dose estrogen-progestin therapy use combination OCP’s containing 35 micrograms or less of ethinylestradiol four tablets per day treat for one week after bleeding stops may not be as successful as high dose estrogen treatment

68. Recurrent bleeding episodes combined OCP’s one tablet per day for 21 days Mechanism of action: endometrial suppression Side effects; headache, migraine, weight gain, breast tenderness, nausea, cholestatic jaundice, hypertension, thrombotic episodes

69. intermittent progestin therapy medroxyprogesterone acetate, 10mg per day, for the first 10 days of each month higher doses and longer therapy my be tried if no initial response prolonged use of high doses is associated with fatigue, mood swings, weight gain, lipid changes

70. Progestational Agents commonly used include Cyclic medroxyprogesterone 2.5-10mg daily for 10-14 days Continuous medroxyprogesterone 2.5-5mg daily Progesterone in oil, 100mg every 4 weeks DepoProvera ® 150mg IM every 3 months Levonorgestrel IUD (5 years)

71. Recurrent bleeding episodes (continued) Progesterone releasing IUD - mirena avoids side effects must be reinserted annually Levonorgestrel IUD 80% reduction of blood loss at 3 months 100% reduction at 1 year found to be superior to antifibrinolytic agents and prostaglandin synthetase inhibitors

72. Immature hypothalamic-pituitary axis progestin therapy by itself for 10 days every month or every other month until full maturity of the axis provides effective therapy. Older perimenopausal women cyclic progestin therapy prevents development of endometrial hyperplasia low dose OCP’s healthy non-smokers, free of vascular disease

73. Other options NSAID’s cyclooxygenase inhibitors inhibits prostacyclin formation administered throughout the duration of bleeding or for the first 3 days of menses. treatment results in a sustained reduction in blood loss so side effects tend to be mild most effective in ovulatory DUB

74. Other options inhibitors of fibrinolysis EACA (epsilon- aminocaproic acid) AMCA ( tranexamic acid) PABA (para- aminomethybenzoic acid) use limited by side effects nausea, dizziness diarrhea, headaches abdominal pain allergic manifestations

75. Danazol androgenic steroid 200mg and 400 mg daily doses for 12 weeks studied 200mg dose as effective as 400 mg androgenic side effects: weight gain, acne side effects minimized with 200mg dose 100 mg not effective, expensive

76. Mechanism; inhibits the release of pituitary Gnt & has direct suppressive effect on the endometrium Side effects: headache, weight gain, acne, rashes, hirsuitism , mood & voice changes, flushes, muscle spasm, reduced HDL, diminished breast size. Rarely: cholestatic jaundice. It is effective in reducing blood loss but side effects limit it to a second choice therapy or short term use only (Grade A)

77. GnRH agonists treatment results in medical menopause blood loss returns to pretreatment levels when discontinued treatment usually reserved for women with ovulatory DUB that fail other medical therapy and desire future fertility use add back therapy to prevent bone loss secondary to marked hypoestrogenism Side effects; hot flushes, sweats, headache, irritability, loss of libido, vaginal dryness, lethargy, reduced bone density.

78. If the cause of the bleeding is lack of ovulation (anovulation), you may prescribe either progesterone to be taken at regular intervals, or an oral contraceptive, which contains progesterone, to achieve a proper hormonal balance. Such treatment dramatically decreases the risk of uterine cancer in women who do not ovulate.

79. If the cause of irregular vaginal bleeding is a precancerous change in the lining of the uterus progesterone medications may be prescribed to reduce the buildup of precancerous uterine lining tissues in an attempt to avoid surgery .

80. When a woman has been without menses for less than six months and is bleeding irregularly, the cause may be menopausal transition. During this transition, a woman is sometimes offered an oral contraceptive to establish a more regular bleeding pattern, to provide contraception until she completes menopause, and to relieve hot flashes. A woman who is found to be menopausal as the cause of her irregular bleeding may also receive menopause counseling if she has troubling symptoms.

81. If the cause of irregular vaginal bleeding is polyps or other benign growths these are sometimes removed surgically to control bleeding because they cannot be treated with medication.

82. If the cause of bleeding is infection antibiotics are necessary depending on the infection accuired Eg . doxycycline 200mg on first day then 100mg daily for 5/7 Metronidazole 400mg tds 5/7 Amoxillin 500mg tds 5/7

83. Surgical treatment Endometrial ablation Methods: I. Hysteroscopic : 1. Laser 2. Electrosurgical: a. Roller ball b. Resection II.Non-hysteroscopic : 1. Thermachoice 2. Microwave.

84. Indications for surgical treatment 1. Failure of medical treatment 2. Family is completed 3. Uterine cavity <10 cm 4. Submucos fibroid <5 cm 5. Endometrium is normal or low risk hyperplasia.

85. Complications of hysteroscopic methods 1. Uterine perforation 2. Bleeding 3. Infection. 4. Fluid overload 5. Gas embolism

86. Hysterectomy Indications: 1. Failure of medical treatment 2. Family is completed Routes: 1. Abdominal 2. Vaginal 3. Laparoscopic

87. Advantages: 1. Complete cure 2. Avoidance of long term medical treatment 3. Removal of any missed pathology Disadvantages: 1.Major operation 2.Hospital admission 3.Mortality & morbidity

88. THANK YOU for your attention!!!