Dysfunctional Uterine Bleeding

Ding Ding M.D., Ph.D. Department of Obstetrics & Gynecology

Ob/Gyn Hospital

Fudan Unoversity

IntroductionDUB is defined as ABNORMAL uterine bleeding absence of demonstrable structural or organic pathology. It is usually with hormonal disturbances due to hypothalamic-pituitary-ovarian axis (HPOA) dysregulation.

Diagnosis must be made by exclusion.DUB occurs most often shortly after menarche and at the end of the reproductive years.

•20% of cases are adolescents•50% of cases in perimenopausal years

Introduction

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.

Normal Menstrual Cycle Follicular phase

14 days (varies)• Dominant follicle develop with greatest number of

granulosa cells and FSH receptors Ovulation

• 30-36 hours after LH surge Luteal phase

• LH surge to menses• Persists 14 days (constant)

Menses

Involution of corpus luteum

Decrease progesterone and estrogen

20-60 cc of dark blood containing endometrial tissue

Normal Menstrual Cycle

Pathophysiology Two types: anovulatory and ovulatory

Most women with DUB do not ovulate (70-80%).• In theses women, there is continuous E2 production

without corpus luteum formation and progesterone production.

• Adolescent: 20%• Perimenopausal years: 50%

Ovulatory DUB occurs most commonly at the reproductive age.• 20-30% of DUB• Incidence in these patients may be as high as 10%

Anovulatory DUBEtiology

Psychological stress Body weight (obesity, anorexia, or a rapid change) Endocrine: 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  Neoplasm, Drugs It may be otherwise idiopathic.

Endometrial Hyperplasia

Chronic anovulatory, persistently elevated estrogen levels, uninterrupted by progesterone

Proliferative Disorder: earliest pathology Simple Hyperplasia: 1% will develop EM cancer

Complex Hyperplasia: 3%

Atypical Hyperplasia: precarcinoma

15% will develop EM cancer

In fact, 17-51% cases are associated with EM cancer

Ovulatory DUB

Luteal phase insufficiency• Shortened menstrual interval(24-26d)• Not easy to conceive baby• Recurrent first-trimester abortionIrregular shedding of endometrium• Prolonged involution of corpus luteum• 5-6th day during menses of the

menstrual cycle, the secretory phase endometrium was still seen

Differential Diagnosis Organic • Reproductive tract cancer• Endometrial cancer• Cervical cancer • Less frequently:

vaginal, vulvar, fallopian tube cancers estrogen secreting ovarian tumors

• granulosa-theca cell tumors

• Systemic Disease: Coagulation disorders, liver • Ectopic pregnancy, abortion or trophoblastic disease• Pelvic infections

“You must exclude all organic causes first!”

Evaluation History

• Onset, frequency, duration, cyclic vs.acyclic, severity• Pain, change from menstrual pattern (calendar)• Age, parity, marital status, sexual hx, contraception• medications, pregnancies• symptoms of pregnancy and reproductive tract

disease

Physical Exam• pelvic exam• pap smear

Diagnosis

History BBT Cervical mucus: no typical fernlike crystal Sexual hormones evaluation Ultrasound D&C: endometrium biopsy Hysteroscopy

E

E+P

Treatment Goals of DUB

Adolescent• Control bleeding• Regulate menstrual cycle• Induce ovulationReproductive age• Stimulate follicle development• Promote corpus luteum function• Induce ovulationPerimenopausal• Control bleeding, reduce volume• Regulate menstrual cycle• Prevent endometrial cancer

Treatment of DUB

Medical management before Surgical• effective methods include:

estrogens, progestins, or both antifibrinolytic agents danazol GnRH agonists

Treatment of DUB Acute bleeding

• Estrogen therapy High dose estrogens: adolescent Oral conjugated 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 Recurrent bleeding episodes

• Sequential therapy: Estrodial+Progesterone

estrodial 1.25mg/d*21d , last 10d add MPA 10mg/d

• combination OCP’s one tablet per day for 21 days

• intermittent progesterone 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 (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

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

• 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: perimenopausal women• 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

• 3 months later, 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 or OCP’s to prevent recurrence

Treatment of DUB Surgical Treatment: Hysteroscopy:

Endometrial Biopsy & Ablation

• Laser ablation

• Loop electrode resection

• Roller electrode ablation

Treatment of DUB

Surgical Treatment• Hysterectomy• Indication:

elder and no demands on bearing babies

atypical hyperplasia or EM cancer

Case presentation1

15 y.o. girl menarche 13 y.o. Heavy bleeding for 10 days Hb 105g/L, WBC & plt normal

Following examination?

Diagnosis?

Management?

Case presentation2

50 y.o. woman, 1-0-1-1 Heavy bleeding for 8 days Urine HCG(-) Ultrasound: endometrium 12mm, ovaries(-) TCT: normal (two months ago)

Following examination?

Diagnosis?

Management?