Dysfunctional Uterine Bleeding

1. Dysfunctional Uterine Bleeding Darren Farley, M.D. Department of Obstetrics and Gynecology UKSM-Wichita

2. Introduction Dysfunctional uterine bleeding (DUB) is defined as ABNORMAL uterine bleeding with no demonstrable organic cause, genital or extragenital. Diagnosis of EXCLUSION 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

3. Introduction • DUB is most frequently associated with chronic anovulation. • Heavy menses, prolonged menses, or frequent irregularbleeding are the most common complaints. • Up to 20% of women will experience irregular cycles in their lifetimes.

4. Goals • Define common terms • Briefly review normal menstruation • Discuss etiologies of DUB • Review the differential diagnosis for abnormal bleeding • Discuss the evaluation of abnormal uterine bleeding • Discuss the treatment of DUB

5. Definitions • Menorrhagia (hypermenorrhea): prolonged (>7 days) and/or excessive (>80cc) uterine bleeding occurring at REGULAR intervals. • Metorrhagia: uterine bleeding occurring at completely irregular but frequent intervals, the amount being variable. • Menometorrhagia: uterine bleeding that is prolonged AND occurs at completely irregular intervals. • Polymenorrhea: uterine bleeding at regular intervals of less than 21 days. • Intermenstrual bleeding: bleeding of variable amounts occurring between regular menstrual periods.

6. Definitions • Oligomenorrhea: uterine bleeding at regular intervals from 35 days to 6 months. • Amenorrhea: absence of uterine bleeding for > 6 months. • Postmenopausal bleeding: uterine bleeding that occurs more than 1 year after the last menses in a woman with ovarian failure.

7. Normal Menstruation • Life Cycle • Menarche • 5-7 years of relatively long cycles • Increasing regularity of cycles • In the 40’s cycles begin to increase in length with increasing episodes of anovulation (2-8 years “perimenopause”) • Menopause (average age = 52) • Characteristics • By age 25, 40% of women have cycles between 25-28 days • Age 25-35, 60% of women have 25-28 day cycles. • Overall 15% have 28 day cycles • .5% have cycles < 21days • .9% have cycles >35 days

8. 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. • These vasodilatory and vasoconstrictive effects are mediated by substances like: • acetylcholine • vasopressin • endothelin • histamine

9. Normal Menstruation • 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 • In women with DUB secondary to anovulation, endometrial blood flow is variable and follows no orderly pattern

10. Cessation of Menses • Two main mechanisms: • Formation of the platelet plug • important in the functional endometrium • Prostaglandin dependent vasoconstriction • important in the basalis layer

11. Menstrual Period Characteristics NormalAbnormal Duration 4-6 days <2d, >7d Volume 30-35cc >80cc Cycle length 21-35d <21d, >35 Average Iron loss: 16mg

12. Pathophysiology • Two types: anovulatory and ovulatory • Most women with DUB do not ovulate. • In theses women, there is continuous E2 production without corpus luteum formation and progesterone production. • Ovulatory DUB occurs most commonly after the adolescent years and before the perimenopausal years. • Incidence in these patients may be as high as 10%

13. 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.

14. Causes of DUB • The pathophysiology of DUB may also represent exaggerated FSH release in response to normal levels of GnRH.

15. After menarche, normal adult FSH and LH patterns eventually develop with mid-cycle surges and E2 peaks. Causes of DUB

16. Causes of DUB • In perimenopausal women, the mean length of the cycle is shorter compared to younger women. • Shortened follicular phase • Diminished capacity of follicles to secrete Estradiol • Other disorders commonly causing DUB • Alterations in the life span of the corpus luteum. • Prolonged (Halbans syndrome) • Variable function or premature senescence in patients WITH ovulatory cycles • Luteal phase insufficiency

17. Differential Diagnosis of Abnormal Uterine Bleeding • Organic • Reproductive tract disease • Systemic Disease • Iatrogenic causes • Non-organic • DUB “You must exclude all organic causes first!”

18. Reproductive Tract Disease • Complications of pregnancy • Abortion • Ectopic gestation • Retained products • Placental polyp • Trophoblastic disease

19. Reproductive Tract Disease • Benign pelvic lesions • Leiomyomata • Endometrial or endocervical polyps • Adenomyosis and endometriosis • Pelvic infections • Trauma • Foreign bodies (IUD, sanitary products)

20. Reproductive Tract Disease • Malignant pelvic lesions • Endometrial hyperplasia • Endometrial cancer • Cervical cancer • Less frequently: • vaginal,vulvar, fallopian tube cancers • estrogen secreting ovarian tumors • granulosa-theca cell tumors

21. Systemic Disease • Coagulation disorders • platelet deficiency • platelet function defect • prothrombin deficiency • Hypothyroidism • Liver disease • Cirrhosis

22. Iatrogenic Causes • Medications • Steroids • Anticoagulants • Tranquilizers • Antidepressants • Digitalis • Dilantin • Intrauterine Devices

23. Evaluation • History • 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 • Physical Exam • pelvic exam • pap smear

24. Evaluation • Tests • Choices are extensive • Not practical or cost effective to do every test • They are not used as general screening tests for all women with DUB. • Selection should be tailored to suspected causes from the history and physical • Stepwise process should be considered

25. Step One: • Rapid assessment of vital signs • Hemodynamically stable • Hemodynamically unstable • Step Two: (simultaneous with step 1) • Baseline CBC, quantitative beta hCG

26. Step Three (adolescents): • Low risk for intracavitary or cancerous lesion • High coagulopathy risk • coagulation profile • if abnormal, further testing and consultation is warranted • If screen is normal, a diagnosis of anovulatory DUB is assumed and appropriate therapy begun

27. Step Four (Adults): • Transvaginal ultrasound • Lesion present • biopsy • hysteroscopy • No lesion • High risk for neoplasia • endometrial biopsy • Low risk for neoplasia • can assume DUB and treat

28. Step Five (Adults): • Secretory endometrium • >50% have polyp or submucosal fibroid • next step is dx hysteroscopy • lesion present • biopsy/excision • lesion absent • consider systemic disease • assume DUB and treat if disease absent

29. Step Six (Adults): • Proliferative endometrium or hyperplasia without atypia • assume DUB • manage according to desired fertility • Hyperplasia with atypia or CA • treat accordingly

30. Treatment of DUB • Goals • control bleeding • prevent recurrence • preserve fertility • correct associated conditions • induce ovulation in patients who want to conceive

31. Treatment of DUB • Medical management before Surgical • effective methods include: • estrogens, progestins, or both • NSAID’s • antifibrinolytic agents • danazol • GnRH agonists

32. Treatment of DUB • 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

33. Treatment of DUB • 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

34. Treatment of DUB • Recurrent bleeding episodes • combination OCP’s • one tablet per day for 21 days • 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

35. Treatment of DUB • Recurrent bleeding episodes (continued) • Progesterone releasing IUD • 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

36. Treatment of DUB • 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

37. Treatment of DUB • 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

38. Treatment of DUB • 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

39. Treatment of DUB • 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

40. Treatment of DUB • 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

41. Treatment of DUB • Surgical Treatment • Dilation and Curettage • quickest way to stop bleeding in patients who are hypovolemic • appropriate in older women (>35)to exclude malignancy but is inferior to hysteroscopy • follow with medroxyprogesterone acetate, OCP’s, or NSAID’s to prevent recurrence

42. Treatment of DUB • Surgical Treatment: (Ablation) • Laser ablation • Loop electrode resection • Roller electrode ablation

43. Treatment of DUB • Surgical Treatment: (Ablation) • Thermal balloon ablation • Microwave ablation • Electromagnetic ablation • poor follow up • Intracavitary radiotherapy (case report) • was common treatment in past • used in a patient who failed medical treatment with multiple contraindications for surgery • chose radiation secondary to complications with a previous D&C and the cost of long term GnRH agonist therapy

44. Treatment of DUB • Surgical Treatment • Hysterectomy