Abnormal Uterine Bleeding District 1 ACOG Medical Student Education Module 2011

What is normal uterine bleeding? Age of patient Frequency Duration Flow

What is normal uterine bleeding? Frequency of menses 21 days (0.5%) to 35 days (0.9%) Age 25, 40% are between 25 and 28 days Age 25-35, 60% are between 25 and 28 days Teens and women over 40’s cycles may be longer apart Munster K et al, Br J Obstet Gynaecology

What is normal uterine bleeding? Duration of menses 2 days to 8 days Usually 4-6 days Hallberg L et al, Acta Obstet Gynecology Scandinavica

What is normal uterine bleeding? Flow/amount of menses Normal volume of menstrual blood loss is 30 cc Hallberg L et al, Acta Obstet Gynecology Scandinavica

Traditional terminologies Menorrhagia Regular intervals, excessive menstrual blood loss amount >80mL Metrorrhagia Irregular intervals, excessive flow and duration Oligomenorrhea Interval longer than 35 days Polymenorrhea Interval less than 21 days Cohen BJB et al, Obstetrical and Gynecologic Survey

Differential diagnosis Pregnancy related complications ectopic, inevitable

Differential diagnosis Disease of the cervix Polyp, ectropian, dysplasia, invasive cancer

Differential diagnosis Disease of the uterus Infection: endometritis Endometrial polyp, adenomyosis, hyperplasia, adenocarcinoma Fibroids One third of patients with symptoms Correlation between the severity of the bleeding and the area of endometrial surface Sehgal N, et al American Journal of Surgery Histologic abnormalities of the endometrium, ranging from atrophy to hyperplasia Deligdish, et al Journal of Clinical Pathology Endometrial venule ectasia Faulkner RL American J of Obstetrics and Gynecology; Farrer-Brown G, et al Journal of Obstetrics and Gynaecology Br Common W

Differential diagnosis Disease of the ovary Germ cell tumors Choriocarcinomas Embryonal carcinoma Sex cord-stromal tumors Granulosa cell tumors(1-2% of all ovarian tumors) Peak incidence between 50 and 55 years of age

Differential diagnosis Thyroid disease Prolactinomas Coagulation defects Renal, liver failure

Differential diagnosis Trauma Foreign bodies

Differential diagnosis Dysfunctional uterine bleeding Anovulatory cycles Loss of normal regulatory mechanism Immaturity Dysfunction Psychiatric medications, stress, anxiety, exercise, rapid weight loss, anorexia nervosa Ovarian failure Obesity PCOS

Evaluation History and physical Labs Pregnancy test CBC TSH Prolactin (Liver function tests) (Coagulation panels) (Androgen profile) Testosterone, DHEAS, Hydroxyprogesterone

Evaluation (cont) Cytopathology Imaging studies Surgical Pap Endometrial biopsy Imaging studies Surgical D&C hysteroscopy

Treatments Medical therapy Surgical therapy Radiologic therapy Hormonal Progestin, estrogen (IV), combination OCPs GnRH agonist Surgical therapy D&C Endometrial ablation Myomectomy/hysterectomy Radiologic therapy Uterine artery embolization (UAE)

Anovulatory Bleeding: Adolescents (13-18 years) Anovulatory bleeding may be normal physiologic process, with ovulatory cycles not established until 1-2 yrs after menarche (immature HPG axis) Screen for coagulation disorders (PT/PTT, plts) May be caused by leukemia, ITP, hypersplenism Consider endometrial bx in adolescents with 2-3 year history of untreated anovulatory bleeding, especially if obese

Anovulatory Bleeding: Management in Adolescents High dose estrogen therapy for acute bleeding episodes (promotes rapid endometrial growth to cover denuded endometrial surfaces): conjugated equine estrogens PO up to 10 mg/d in 4 divided doses or IV 25 mg q 4 hrs for 24 hrs Treat pts with blood dyscrasias for their specific diseases, r/o leukemia Prevent recurrent anovulatory bleeding with: cyclic progestin (i.e. Provera) or low dose (≤ 35 μg ethinyl estradiol) oral contraceptive suppresses ovarian and adrenal androgen production and increases SHBG  decreasing bioavailable androgens

Anovulatory Bleeding: Reproductive Age (19-39 years) Anovulatory bleeding not considered physiologic, evaluation required 6-10% of women have hyperandrogenic chronic anovulation (i.e. PCOS), characterized by noncyclic bleeding, hirsutism, obesity (BMI ≥ 25) Underlying biochemical abnormalities: noncyclic estrogen production, elevated serum testosterone, hypersecretion of LH, hyperinsulinemia. h/o rapidly progressing hirsutism with virilization suggests tumor Lab testing: HCG, TSH, fasting serum prolactin If androgen-producing tumor is suspected, serum DHEAS and testosterone levels If POF suspected, serum FSH Chronic anovulation resulting from hypothalamic dysfunction (dx’d by low FSH level) may be due to excessive psychologic stress, exercise, or weight loss

Anovulatory Bleeding: Reproductive Age (19-39 yrs) When is endometrial evaluation indicated? Sharp increase in incidence of endometrial CA from 2.3/100,000 ages 30-34 yrs  6.1/100,000 ages 35-39 yrs Therefore, endometrial bx to exclude CA is indicated in any woman > 35 yrs old with suspected anovulatory bleeding Pts 19-35 who don’t respond to medical therapy or have prolonged periods of unopposed estrogen 2/2 anovulation merit endometrial bx

Anovulatory Bleeding: Reproductive Age (19-39 yrs) Medical therapies Can be treated safely with either cyclic progestin or OCPs, similar to adolescents. Estrogen-containing OCPs relatively contraindicated in women with HTN or DM contraindicated for women > 35 who smoke or have h/o thromboembolic dz If pregnancy is desired, ovulation induction with clomid is initial tx of choice Can induce withdrawal bleed with progestin (i.e. provera), followed by initiation of therapy with Clomid, 50 mg/d for 5 days, starting b/t days 3 and 5 of menstrual cycle

Anovulatory Bleeding: Later Reproductive Age (40-Menopause) Incidence of anovulatory bleeding increases toward end of reproductive years In perimenopausal women, onset of anovulatory cycles is due to declining ovarian function. Can initiate hormone therapy for cycle control When is endometrial evaluation indicated? Incidence of endometrial CA in women 40-49 years: 36.2/100,000 All women > 40 yrs who present with suspected anovulatory bleeding merit endometrial bx after excluding pregnancy

Anovulatory Bleeding: Later Reproductive Age (40-Menopause) Medical therapy Cyclic progestin, low-dose OCPs, or cyclic HRT are all options Women with hot flashes secondary to decreased estrogen production can have symptomatic relief with ERT in combination with continuous or cyclic progestin

Anovulatory Bleeding: Later Reproductive Age (40-Menopause) Surgical therapy Surgical options include: hysterectomy and endometrial ablation Surgical tx only indicated when medical mgmt has failed and childbearing complete Some studies suggest hysterectomy may have higher long-term satisfaction than ablation Endometrial ablation: NovaSure, thermal balloon YAG laser and rollerball less widely-used currently 45% of women achieve amenorrhea after YAG laser or resectoscope. 12 month post-op satisfaction is 90%. Only 15% of women achieve amenorrhea after thermal balloon ablation, and 1 yr satisfaction rate still 90% Long-term satisfaction with ablation may be lower: in 3-year f/u study, 8.5% of women who had undergone ablation were re-ablated, an additional 8.5% had hyst In a 5-year follow up study, 34% of women who underwent ablation later had a hyst.