See also Menorrhagia and Polycystic Ovary Syndrome

I. Differential dx of abnormal uterine bleeding

  1. Trauma (laceration, foreign body, IUD)
  2. Inflammation/infection
  3. Anatomic/structural (polyps, Uterine Leiomyomata ("fibroids"), cancer anywhere along reproductive tract)
  4. Endometriosis/adenomyosis
  5. PREGNANCY!!!!
  6. Hypo- or hyperthyroidism
  7. Bleeding disorder (quantitative or qualitative platelet defect; coagulopathy)
  8. Meds (OCPs, phenothiazines, corticosteroids, dig; heroin causes amenorrhea)

II. "Dysfunctional uterine bleeding" (DUB) refers to irregular bleeding or menorrhagia associated with anovulation. Endometrium is subject to essentially unopposed estrogenic stimulation. Causes of anovulation include:

  1. Systemic disease (liver, renal) can affect metabolism of sex steroids
  2. Endocrinopathies
  1. Uncontrolled DM (?)
  2. Cushing's sd.
  3. Addison's
  4. Hyperprolactinemia
  5. Hormone-secreting ovarian or adrenal tumor
  1. Meds, e.g. phenothiazines (hypothalamic depressant effect), OCP's and other sex steroids
  2. Obesity
  3. Polycystic Ovary Syndrome
  4. Dieting, stress, exercise, weight loss

III. Clinical/epidemiologic features of DUB

  1. Tends to occur at extremes of reproductive years, due to fact that ovarian progesterone production starts later and stops earlier in life than estrogen production
  2. Carries increased risk of endometrial hyperplasia & Ca

IV. Approach to abnormal uterine bleeding

  1. Good history, including:
    1. Sx of pituitary tumor (HA, diplopia, galactorrhea)
    2. Sx of hyperandrogenism (male pattern hair loss, hirsutism, acne)
    3. Sx of estrogen w/d (hot flashes)
    4. Personal or family h/o bleeding tendencies
  2. Diagnostic testing
    2. Check Hb level; platelets/coags
    3. Thyroid function testing
    4. Pap and cervical cultures to evaluate for cervicitis
  3. Evaluating for ovulation in premenopausal women
    1. Basal body temperature charting (rises 0.3-1.0' C post ovulation)
    2. Serum progesterone > 9.5nmol/l 7d before next expected menses tends to suggest ovulation
  4. Tissue sampling
    1. Endometrial biopsy
    2. Dilatation/curettage (with or without hysteroscopy)
      1. An approach with endometrial biopsy + saline sonohysterography was found to have sensitivity of 97% for abnormalities compared with hysteroscopy-guided D & C in a study of 113 women 25-69yo with persistent uterine bleeding despite medical therapy (Am. J. Obs. Gyn. 186:858, 2002--JW)
  5. Endovaginal ultrasound--May not be an adequate substitute for endometrial biopsy
  1. In a meta-analysis of 35 studies involving 5,892 women who underwent endovaginal u/s then endometrial bx, a threshold of 5mm to define abnormally thick endometrium on u/s yielded 96% sensitivity for Ca and 92% sensitivity for any endometrial disease. Higher false-positive rate for u/s in women on HRT (JAMA 280:1510, 1998--JW)
  2. However, in a subsequent study, endovaginal u/s had poor sensitivity (67-73% depending on endometrial thickness threshold) for abnormalities on endometrial biopsy in postmenopausal women with abnormal bleeding, none of whom had any findings on bx more serious than hyperplasia w/o atypia (Menopause 6:201, 1999--AFP)
  3. Note that in women who do not have vaginal bleeding, use of hormone replacement therapy is ass'd with significantly greater endometrial thickness than in women not using HRT (ibid.)
  4. In a meta-analysis of 9 studies (total 3813 women) assessing ultrasound for identifying endometrial Ca in postmenopausal women with vaginal bleeding, the "ROC" characteristics of endometrial thickness were such that a 50% FPR would result in sensitivity of 96% and a 10% FPR would result in a 63% sensitivity (Obs. Gyn. 99:663, 2002--JW)

V. Tx of abnormal uterine bleeding (see also "Menorrhagia")

  1. Emergent surgical intervention (usually dilatation and curettage) if unstable
  2. Iron supplementation
  3. Hormonal treatment:
  1. If acute or heavy bleed, tx should contain estrogen; if chronic, should be progestin only or combined estrogen/progestin (OCP's or Premarin/Provera)
  2. Options:
  1. If very heavy, IV Premarin 25mg Q4h, max 3 doses, then Premarin 1.25-2.5mg PO QD plus Provera 10mg QD, for 7-10 more days
  2. Cyclic Premarin (0.625-1.25 QD) plus Provera (10mg QD 14d/mo) if perimenopausal
  3. Combined OC's, 1 pill up to QID x 3-5d to stop bleeding, then finish pack at 1 QD
  4. Premarin 1.25 QD for 7-10d
  5. Medroxyprogesterone acetate e.g. 20mg TID x 7d progesterone in oil 100-200mg IM x1
  6. Clomiphene
  7. Progestin-only OCP or IUD
  8. Depo-Provera 150mg Q3 mo
  1. Surgery, e.g. hysterectomy
  2. Surgical vs. hormonal treatment
    1. 63 premenopausal women 30-50yo with abnormal uterine bleeding unresponsive to cyclic medroxyprogesterone acetate randomized to hysterectomy vs. "expanded" medical treatment (summary doesn't specify). At 6mos, hysterectomy group had sig. greater improvements in mental health, physical sx, sexual desire, and pain-free intercourse. At 2y, all outcomes were the same except for greater improvements in sexual desire in the hysterectomy group. (JAMA 291:1447, 2004--JW)
    2. In a trial of 63 women with abnormal uterine bleeding unresponsive to cyclic medroxyprogesterone randomized to continued medical treatment vs. hysterectomy, improvements in quality of life at 6mo and 2y were sig. greater in the surgery group ("Medicine or Surgery" ("MS") Trial; JAMA 291:1447, 2004--AFP)
  3. See under Uterine Leiomyomata for discussion of treatments specific to that condition
(Sources include Core Content Review of Family Medicine, 2012)