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Dysfunctional Uterine Bleeding Dr. ELHAM GHANBARI JOLFAEI MD OB & Gynecologiest Introduction Dysfunctional uterine bleeding (DUB) is • as ABNORMAL uterine bleeding defined demonstrable organic cause, with no extragenital. genital or Diagnosis of EXCLUSION• Patients present with “abnormal uterine • bleeding” DUB occurs most often shortly after • at the end of the menarche and reproductive years. 20% of cases are adolescents– 50% of cases in 40-50 year olds– Introduction DUB is most frequently associated with chronic anovulation. Heavy menses, prolonged menses, or frequent irregular bleeding are the most common complaints. Up to 20% of women will experience irregular cycles in their lifetimes. 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 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. • • • • 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. 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 ◦ ◦ ◦ ◦ ◦ 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 ◦ 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 Cessation of Menses Two main mechanisms: Formation of the platelet plug ◦ important in the functional endometrium Prostaglandin dependent vasoconstriction ◦ important in the basalis layer Menstrual Period Characteristics Abnormal <2d, >7d Normal 4-6 days Duration >80cc 30-35cc Volume <21d, >35 21-35d Cycle length Average Iron loss: 16mg 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% ◦ 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. Causes of DUB The pathophysiology of DUB may also represent ◦ exaggerated FSH release in response to normal levels of GnRH. Causes of DUB After menarche, ◦ normal adult FSH and LH patterns eventually develop with mid-cycle surges and E2 peaks. 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 Differential Diagnosis of Abnormal Uterine Bleeding Organic Reproductive tract disease ◦ Systemic Disease ◦ Iatrogenic causes ◦ Non-organic DUB ◦ “You must exclude all organic causes first!” Reproductive Tract Disease Complications of pregnancy Abortion Ectopic gestation Retained products Placental polyp Trophoblastic disease Reproductive Tract Disease Benign pelvic lesions Leiomyomata Endometrial or endocervical polyps Adenomyosis and endometriosis Pelvic infections Trauma Foreign bodies (IUD, sanitary products) ◦ ◦ ◦ ◦ ◦ ◦ 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 ◦ ◦ ◦ ◦ Systemic Disease Coagulation disorders platelet deficiency ◦ platelet function defect ◦ prothrombin deficiency ◦ Hypothyroidism Liver disease Cirrhosis ◦ Iatrogenic Causes Medications Steroids Anticoagulants Tranquilizers Antidepressants Digitalis Dilantin ◦ ◦ ◦ ◦ ◦ ◦ Intrauterine Devices 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 ◦ 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 ◦ ◦ ◦ ◦ ◦ Step One: Rapid assessment of vital signs ◦ Hemodynamically stable Hemodynamically unstable Step Two: (simultaneous with step 1) Baseline CBC, quantitative beta hCG ◦ 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 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 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 Step Six (Adults): Proliferative endometrium or hyperplasia ◦ without atypia assume DUB manage according to desired fertility Hyperplasia with atypia or CA ◦ treat accordingly Treatment of DUB Goals control bleeding prevent recurrence preserve fertility correct associated conditions induce ovulation in patients who want to conceive ◦ ◦ ◦ ◦ ◦ Treatment of DUB Medical management before Surgical effective methods include: ◦ estrogens, progestins, or both NSAID’s antifibrinolytic agents danazol GnRH agonists 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 ◦ 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 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 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 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 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 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 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 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 ◦ ◦ ◦ ◦ 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 Treatment of DUB Surgical Treatment: (Ablation) Laser ablation ◦ Loop electrode resection ◦ Roller electrode ablation ◦ 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 Treatment of DUB Surgical Treatment Hysterectomy ◦