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

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

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

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).

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 If implantation fails to occur, the CL involutes and progesterone is withdrawn causing endometrial collapse and menstruation.

Menstrual changes

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

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

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

Etiologic Bases of Bleeding Progesterone Withdrawal Normal menstrual physiology

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

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)

New AUB terms Heavy menstrual bleeding Intermenstrual bleeding

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 19-39 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

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

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

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

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

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

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

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!!

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

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.

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

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

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

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

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

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

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

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

Questions?