Abnormal Uterine Bleeding

Disorders of the Menstrual Cycle
• Amenorrhea
• Dysmenorrhea
• Premenstrual Syndrome




 Definitions
• Menorrhagia: heavy or prolonged uterine bleeding that occurs at regular intervals. Some sources define further as the loss of ≥ 80 mL blood per cycle or bleeding > 7 days.
• Hypomenorrhea: periods with unusually light flow, often associated with hypogonadotropic hypogonadism (athletes, anorexia). Also may be associated with Asherman’s syndrome
• Metrorrhagia: irregular menstrual bleeding or bleeding between periods
• Menometrorrhagia: metrorrhagia associated with > 80 mL
• Polymenorrhea: frequent menstrual bleeding. Strictly, menses occur q 21 d or less
• Oligomenorrhea: Menses are > 35 d apart. Most commonly caused by PCOS, pregnancy, and anovulation

Differential Diagnosis
• Structural
– Cervical or vaginal laceration
– Uterine or cervical polyp
– Uterine leiomyoma
– Adenomyosis
– Cervical stenosis/Asherman’s (hypomenorrhea)
• Hormonal
– Anovulatory bleeding
– Hypogonadotropic hypogonadism
– Pregnancy
– Hormonal Contraception (i.e. OCPs, Depo-Provera)
• Malignancy
– Uterine or Cervical cancer
– Endometrial hyperplasia (potentially pre-malignant)
• Bleeding disorders
– von Willebrand’s Disease, Hemophilia/Factor deficiencies, platelet disorders


Workup

• History
– Timing of bleeding, quantity of bleeding, menstrual hx including menarche and recent periods, associated sxs, family hx of bleeding disorders

• Physical
– R/o vaginal or cervical source of bleeding. Bimanual may reveal bulky uterus/discrete fibroids
– Assess for obesity, hirsutism, stigmata of thyroid disease (hypothyroidism associated with anovulation), signs of hyperprolactinemia (visual field testing, galactorrhea)
– Pap smear
– Endometrial biopsy, if appropriate

• Pregnancy Test

• Imaging
– Pelvic ultrasound
– Sonohystogram or hysterosalpingogram

• Surgical
– Hysteroscopy
– D & C


Normal Ovulatory Cycle
• Follicular development à ovulation (d14) à corpus luteal function à luteolysis
• Endometrium is exposed to:
– ovarian production of estrogen à
(proliferation)
– Combination of estrogen and progesterone à
(secretory phase)
– Estrogen and progesterone withdrawal
(desquamation and repair)


Anovulatory Bleeding
• Corpus luteum is not produced
– Ovary fails to secrete progesterone, although estrogen production continues
– Result is continuous, unopposed E stimulation of endometrium:
• endometrial proliferation without P-induced differentiation / stabilization
– Endometrium becomes excessively vascular without stromal support à fragility and irregular endometrial bleeding


Etiologies
• Hyperandrogenic anovulation (PCOS, CAH, androgen-producing tumors)
• Hypothalamic dysfunction (stress, anorexia, exercise)
• Hyperprolactinemia
• Hypothyroidism
• Primary pituitary disease
• Premature ovarian failure
• Iatrogenic (secondary to radiation or chemo)

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 progestogen (i.e. Provera)
or
• low dose (≤ 35 μg ethinyl estradiol) oral contraceptive
– suppresses ovarian and adrenal androgen production and increases SHBG à 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 virilizationà 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 à 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 progestogen 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 progestogen (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

Medical therapy
• Cyclic progestogen, 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 progestogen


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.