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 cancer cervix – Polyp, ectropian, dysplasia, invasive

Differential diagnosis

• Disease of the adenocarcinoma – Fibroids uterus – Infection: endometritis – Endometrial polyp, adenomyosis, hyperplasia, • 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 tumors) ovary – Germ cell tumors • Choriocarcinomas • Embryonal carcinoma – Sex cord-stromal tumors • Granulosa cell tumors(1-2% of all ovarian – 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 • PCOS » Psychiatric medications, stress, anxiety, exercise, rapid weight loss, anorexia nervosa • Ovarian failure • Obesity

Evaluation

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

Evaluation

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

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)

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, • 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

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 • In perimenopausal women, onset of anovulatory cycles is due to declining • 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

Anovulatory Bleeding:

Later Reproductive Age (40 progestin 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

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.