Abnormal Uterine Bleeding

2. Abnormal Uterine Bleeding District 1 ACOG Medical Student Education Module 2011

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

4. 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

5. 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

6. 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

7. 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

8. Differential diagnosis • Pregnancy related complications • ectopic, inevitable

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

10. 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

11. 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

12. Differential diagnosis • Thyroid disease • Prolactinomas • Coagulation defects • Renal, liver failure

13. Differential diagnosis • Trauma • Foreign bodies

14. 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

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

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

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

18. 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

19. 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

20. 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

21. 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

22. 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

23. 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

24. 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

25. 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.