Dysfunctional Uterine Bleeding

Darren Farley, M.D. Department of Obstetrics and Gynecology UKSM-Wichita

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

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. Intermenstrual bleeding: bleeding of variable amounts occurring between regular menstrual periods.

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 40s 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 vasopressin endothelin histamine

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

Duration Volume Cycle length Normal 4-6 days 30-35cc 21-35d Abnormal <2d, >7d >80cc <21d, >35

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 NSAIDs 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 OCPs 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 OCPs
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 OCPs

healthy non-smokers, free of vascular disease

Treatment of DUB
Other options
NSAIDs
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, OCPs, or NSAIDs 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