Dysfunctional Uterine Bleeding

1. Dysfunctional Uterine Bleeding Ding Ding M.D., Ph.D. Department of Obstetrics & Gynecology Ob/Gyn Hospital Fudan Unoversity

2. Introduction DUB 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

3. Introduction • 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. 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

5. Normal Menstrual Cycle

6. 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%

7. 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.

8. 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

9. Ovulatory DUB Luteal phase insufficiency • Shortened menstrual interval(24-26d) • Not easy to conceive baby • Recurrent first-trimester abortion Irregular shedding of endometrium • Prolonged involution of corpus luteum • 5-6th day during menses of the menstrual cycle, the secretory phase endometrium was still seen

10. 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!”

11. 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

12. E E+P Diagnosis • History • BBT • Cervical mucus: no typical fernlike crystal • Sexual hormones evaluation • Ultrasound • D&C: endometrium biopsy • Hysteroscopy

13. Treatment Goals of DUB Adolescent • Control bleeding • Regulate menstrual cycle • Induce ovulation Reproductive age • Stimulate follicle development • Promote corpus luteum function • Induce ovulation Perimenopausal • Control bleeding, reduce volume • Regulate menstrual cycle • Prevent endometrial cancer

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

15. 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

16. 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

17. 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

18. 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

19. 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

20. 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

21. 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

22. 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

23. Treatment of DUB • Surgical Treatment: • Hysteroscopy: Endometrial Biopsy & Ablation • Laser ablation • Loop electrode resection • Roller electrode ablation

24. Treatment of DUB • Surgical Treatment • Hysterectomy • Indication: elder and no demands on bearing babies atypical hyperplasia or EM cancer

25. 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?

26. 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?