1. Abnormal Uterine Bleeding
Naval Medical Center San Diego
Department of Obstetrics and Gynecology
CDR David Furlong, DO, FACOG

2. Introduction 1/3 of all outpatient gyn visits are for AUB
Majority of cases occur just after menarche or in the perimenopausal time period
Among adolescents, AUB is most frequent cause of urgent admission to the hospital
World wide affects 50% of menstruating women
Of the half-million hysterectomies performed in the U.S., 50% or more are for AUB

3. What is normal?
Normal uterine bleeding is defined as menses occurring ever 28 days (+/- 7 days) with a mean duration of 5 days and an average EBL of 30 cc
no more than 80 mL
Soaked tampon or pad is 5ml. Important to make distinction

4. Regulation of Normal Menses Ovary
Late in menses the hypothalamus generates timed pulses of GnRH
This stimulates the anterior pituitary to produce FSH and small amount of LH
FSH recruits a cohort of ovarian follicles
Estradiol is produced and a positive feedback loop increasing FSH until a LH surge occurs triggering ovulation of a dominant follicle (oocyte).

5. Regulation of Normal Menses Endometrium
Rising levels of estradiol cause proliferative growth of the endometrium
Once the LH surge occurs, the ovum is released and the follicle collapses to become the corpus luteum (CL)
The CL produces large amounts of progesterone causing the secretory phase of the endometrium.
If implantation fails to occur, the CL involutes and progesterone is withdrawn causing endometrial collapse and menstruation.

6. Menstrual changes

7. Etiologic Bases of anovulatory bleeding
Estrogen-withdrawal
Results from unexpected decrease in estrogen levels
Examples include:
Iatrogenic after BSO
Recurrent midcycle spotting just before ovulation
Postmenopausal women

8. Etiologic Bases of Anovulatory Bleeding
Estrogen-breakthrough
Chronic stimulation of endometrium
Unopposed proliferation results in insufficient structural support
Parts of the endometrium slough at irregular and unpredictable intervals
PCOS is classic example (No progesterone withdrawal increases risk for endometrial hyperplasia/cancer)
Obesity

9. Etiologic Bases of Anovulatory Bleeding
Progesterone-breakthrough bleeding
Progesterone-to-estrogen ratio is relatively high
Endometrium atrophies and ulcerates due to the lack of estrogen
Use of oral contraceptives is a classic example
Mirena or LNG based IUD
Nexplanon implant

10. Etiologic Bases of Bleeding Progesterone Withdrawal
Normal menstrual physiology

11. Old AUB terms
Oligomenorrhea – menses occurring less than monthly (35 days)
Polymenorrhea – bleeding that occurs more often than 21 days
Menorrhagia – menstrual blood loss greater than >80cc
Metrorrhagia – bleeding between periods
Menometrorrhagia – heavy bleeding that also occurs between periods
Dysfunctional Uterine Bleeding – bleeding related to anovulation or ovulatory disorder

12. New AUB terms by etiology!
PALM:
Structural Causes
Polyp (AUB-P)
Adenomyosis (AUB-A)
Leiomyoma (AUB-L)
Submucosal (AUB-Lsm)
Other myoma (AUB-Lo)
Malignancy & Hyperplasia (AUB-M)
COEIN:
Nonstructural Causes
Coagulopathy (AUB-C)
Ovulatory dysfnc (AUB-O)
Endometrial (AUB-E)
Iatrogenic (AUB-I)
Not yet classified (AUB-N)

13. New AUB terms
Heavy menstrual bleeding
Intermenstrual bleeding

14. Etiology of AUB by age Birth Birth to age 12 Age 13-18 Age 19-39
Estrogen withdrawal
Birth to age 12
Foreign body, infxn, sarcoma botryoides, trauma, ovarian tumor
Age 13-18
Hormonal contraceptives, pregnancy, pelvic infection, coagulopathy or tumors
Age
Pregnancy, structural lesions, anovulatory cycles, hormonal contraception, endometrial hyperplasia
Age 40 to menopause
Anovulatory cycles, endometrial hyperplasia/cancer, endometrial atrophy, leiomyomas
15-24% of wpmen may have a coagulopathy. Suspect it if they have always had heavy menses or family history

15. Evaluation of AUB Medical history Physical examination
Laboratory tests
Diagnostic/Imaging tests
Tissue sampling

16. Medical History Age of menarche and menopause
Menstrual bleeding patterns (menstrual diary is helpful; there’s an APP for that!)
40% of women with blood loss > 80 cc consider their menses light or moderate
14% of women with blood loss < 20 cc consider their menses heavy
Severity of bleeding (clots or flooding; nighttime bed protection)
Pain (severity and treatment)
Medical conditions
Surgical history
Use of medications
Symptoms and signs of possible hemostatic disorder

17. Physical Examination General physical Pelvic examination Obesity
Signs of PCOS (hirsutism and acne)
Signs of thyroid disease (thyroid nodule)
Signs of insulin resistance (acanthosis nigricans of the neck)
Signs of a bleeding disorder (ecchymosis, petechia, skin pallor or swollen joints)
Galactorrhea
Pelvic examination
External
Speculum with pap test, if needed
Bimanual

18. Laboratory Evaluation
Pregnancy test
CBC
TSH
GC/CT
Targeted screening for bleeding disorders (if indicated)
Prolactin (oligo or amenorrhea)

20. Diagnostic/Imaging Tests
Transvaginal ultrasonography
Useful, low cost initial screening test
Remember your patient! Peds or virginal adolescent consider abdominal u/s or Gyn referral
Endometrial thickness is not helpful or validated for premenopausal women
Saline Infusion Sonohystogram
Gyn performed. Targeted for intracavitary lesions

21. Tissue Sampling Office endometrial biopsy
45 yo
35-44 yo for significant risk
Obesity
PCOS
Failed medical management
Persistent AUB
Hysteroscopy directed endometrial sampling (office/operating room via dilatation and curettage)
Risk of hyperplasia/malignancy is 19% >45 and 6% <44 yo. Primary patient population with hyperplasia/malignancy is postmenopausal

22. Treatment of AUB MEDICAL THERAPY FIRST LINE SECOND LINE
Lifestyle modifications
NSAIDs
Progestins (oral, injectable, intrauterine)
Combined hormonal contraceptives
SECOND LINE
IV or high dose estrogens (inpatient)
Continuous combined hormonal contraceptive
GnRH agonists
Antifibrinolytics (tranexamic acid)
Premedication of menses with NSAIDs; cyclic or continuous OCPs; high dose(tapering) OCPs. SUPPLEMENT WITH IRON!!

23. Treatment of AUB Cyclooxygenase (COX) – inhibitors
Within the endometrium, cyclooxygenase (COX) converts arachidonic acid into prostaglandins
NSAIDs reduce MBL by 20-50%
Premedication with Naprosyn starting 3 days prior to menses is effective
REMEMBER: 70% of blood loss occurs in first 2 days of menses

24. Treatment of AUB Progestins
Can be administered cyclic, continuous or as IUD
Cyclic progestins useful for anovulatory bleeding
Continuous progestins (Provera, Depo provera or Norethindrone) can produce amenorrhea
Mirena IUD/LNG IUD system
Reduce volume of bleeding by 80-90%, amenorrhea 40% at 12 months
75% of pts chose to continue it compared to 20% of oral norethindrone
60-80% of pts canceled hysterectomy due to satisfaction with IUD.

25. Treatment of AUB Combined Oral Contraceptives
Useful for ovulatory and anovulatory bleeding
Reduces menstrual volume by about 50%
Acute bleeding may be treated with a taper

26. Treatment of AUB Parenteral estrogens
Acute bleeding in adolescent girls usually results from anovulation
IV Estrogen (25mg IV Q 4 hours)  then give progestins
PO Estrogen (2.5 mg po Q 4-6 hours for 14 – 21 days)  then give progestins
Note: Once bleeding stops give progestins for 7-10 days

27. Treatment of AUB GnRH Agonist (Lupron)
Useful for leiomyomas, ovulatory and anovulatory bleeding
Induces amenorrhea and can shrink uterine volume by 40-60%
Note: Gonadotropin “flare” may induce bleeding and/or cramping >14 days after starting therapy

28. Treatment of AUB Tranexamic Acid (TXA/Lysteda) Inhibits fibrinolysis
Reserved for severe heavy menstrual bleeding and postpartum hemorrhage
1300mg PO TID for 5 days at start of menses
Contraindication in VTE history

29. Treatment of AUB: Supplement to anemia
Iron
Average woman ingests enough dietary iron to replace menstrual blood loss up to 60 mL per month.
Oral iron replacement can be sufficient at 325mg every other day with less side effects

30. Treatment of AUB Surgical treatment Endometrial Ablation Hysterectomy
(Note: In acute setting dilation and curettage may be useful until to stop bleeding)
Multiple methods of ablation: novasure, HTA, cryoablation

31. Treatment of AUB Endometrial ablation
90% of patients are satisfied at 12 months
50% amenorrhea at 12 months
At 5 years, 80% had no further surgery and 90 % had not had a hysterectomy
*Mirena IUD and novasure had similar patient satisfaction scores at 3 years

32. Treatment of AUB Hysterectomy Most common surgical treatment for AUB
550,000 hysterectomies performed each year in U.S.
40% performed for AUB
50% of uterine specimens show no uterine abnormality

33. Questions?