Anovulatory Bleeding

Aka: Anovulatory Bleeding, Metrorrhagia

1. See Also
   1. Menstrual Cycle
   2. Abnormal Uterine Bleeding (Dysfunctional Uterine Bleeding)
   3. Abnormal Uterine Bleeding Causes
   4. Anovulatory Bleeding (Metrorrhagia)
   5. Ovulatory Bleeding (Menorrhagia)
   6. Uterine Bleeding in Pregnancy
   7. First Trimester Bleeding
   8. Late Pregnancy Bleeding
   9. Endometrial Cancer Screening
   10. Oral Contraceptive-Related Uterine Bleeding Management
   11. Postmenopausal Bleeding
   12. Amenorrhea
   13. Lower GI Bleed
   14. Hematuria
2. Epidemiology
   1. Anovulation causes 90% Dysfunctional Uterine Bleeding
   2. Age breakdown of Anovulatory Bleeding
      1. Women over age 40 years represent 50% of this group
      2. Adolescent women represent 20% of anovulatory group
   3. Common at the extremes between Menarche and Menopause
      1. Menarche: First 2-3 years with irregular cycles (immature hypothalamic-pituitary-ovarian axis)
      2. Perimenopause: Up to 8 years prior to Menopause
3. Associated Conditions
   1. Endometrial Cancer
      1. Unopposed Estrogen Relative Risk: 3 fold
      2. See Endometrial Cancer for evaluation indications
4. Pathophysiology
   1. Anovolution results in no LH surge and no formation of a corpus luteum
      1. Progesterone is not produced
      2. Estrogen continues to stimulate endometrium (Unopposed Estrogen) for a prolonged period
   2. Unopposed Estrogen (Progesterone deficiency)
      1. Excessive endometrial proliferation, instability and variable timing of bleeding
      2. Risk of Endometrial Hyperplasia and Endometrial Cancer
   3. See Menses
   4. See Menstrual Cycle
5. Causes
   1. Immature Hypothalamic-Pituitary-Ovarian axis
      1. Frequently seen in Adolescents
      2. Follicle Stimulating Hormone released
         1. Stimulates Unopposed Estrogen release
         2. Lacks Luteinizing hormone (LH) surge
            1. No Ovulation
            2. Progesterone deficiency
         3. Results in breakthrough bleeding
   2. Polycystic Ovary Syndrome (Stein Leventhal Syndrome)
      1. Most common cause (6-10% of Abnormal Uterine Bleeding cases)
   3. Pending ovarian failure (Peri-Menopause)
      1. Common for up to 8 years prior to Menopause
   4. Body Habitus and Nutritional Status
      1. Obesity
      2. Very low calorie diets
      3. Eating disorder (e.g. Anorexia)
   5. Intense Exercise (Female Athlete Triad)
      1. Norepinephrine affects Luteinizing hormone (LH) pulse
   6. Psychological stress
   7. Medical disorders
      1. Diabetes Mellitus (uncontrolled)
      2. Hypothyroidism or Hyperthyroidism
      3. Hyperprolactinemia
   8. Medications
      1. Anti-Seizure medications (especially Valproic Acid or Depakote)
         1. Related to associated weight gain and Hyperandrogenism
      2. Antipsychotics
         1. Related to serum Prolactin level increase
         2. Typical Antipsychotics (Haloperidol, chlorpromazine, thiothixene)
         3. Atypical Antipsychotics (Clozapine, Risperidone)
6. Symptoms
   1. Change in Amount and Frequency of Menstrual Bleeding
      1. General
         1. Irregular, typically infrequent menstrual periods
         2. Progesterone deficiency
      2. Low Levels of Unopposed Estradiol or Estrogens
         1. Lighter and Less Frequent Menses
      3. High Levels of Unopposed Estradiol or Estrogens
         1. Prolonged periods of Amenorrhea
         2. Heavy Withdrawal Bleeding
   2. Lack of premenstrual signs
      1. Progesterone absent: no bloating or Breast Pain
7. Differential Diagnosis
   1. Pregnancy
   2. Immature Hypothalamic-Pituitary-Ovarian axis (Adolescent)
   3. Uncontrolled Diabetes Mellitus
   4. Eating Disorder (e.g. Anorexia)
   5. Hyperthyroidism
   6. Hypothyroidism
   7. Hyperprolactinemia
   8. Medications (see causes above)
   9. Perimenopause
   10. Polycystic Ovary Syndrome
8. Precautions
   1. Recurrent Anovulation causes endometrial abnormalities in 14% of cases
      1. Endometrial Hyperplasia
      2. Endometrial Cancer
   2. High risk groups
      1. See Endometrial Cancer Risks (Unopposed Estrogen)
      2. Adolescents rarely get Endometrial Cancer
         1. However, 2-3 years of recurrent Anovulation and morbid Obesity warrants evaluation
9. Exam
   1. Observe for systemic or structural disease
   2. See Dysfunctional Uterine Bleeding causes
   3. Observe for signs of Hyperandrogenism or Polycystic Ovary Syndrome
      1. Hirsutism
      2. Obesity
10. Labs
    1. Initial
       1. Urine Pregnancy Test (hCG)
       2. Thyroid Stimulating Hormone (TSH)
       3. Serum Prolactin
    2. Additional labs to consider
       1. Complete Blood Count (CBC)
       2. Glucose to Insulin Ratio
          1. Abnormal in Polycystic Ovary Syndrome
11. Indications: Abnormal bleeding requiring evaluation
    1. Recurrent anovulatory cycles
    2. Perimenopause
       1. Increased bleeding volume or duration of bleeding
       2. Menstrual periods more often than every 21 days
       3. Postcoital bleeding
       4. Intermenstrual bleeding
    3. Adolescents (especially if morbidly obese)
       1. More than 3 months between cycles or
       2. More than 3 years of irregular cycles
12. Protocol
    1. See Dysfunctional Uterine Bleeding for overall evaluation
    2. See Endometrial Cancer Screening
    3. Postmenopause
       1. See Postmenopausal Bleeding
       2. See Endometrcial cancer for evaluation indications
    4. Age >35 years or Endometrial Cancer Risk Factors
       1. See Endometrial Cancer Screening for complete evaluation protocol
       2. Endometrial Biopsy
          1. Required in most cases
          2. If negative then treat with Metrorrhagia Management
       3. Consider Transvaginal Ultrasound
          1. Reassuring if endometrial stripe <5 mm
          2. Does not replace Endometrial Biopsy in high risk patient
    5. Age <35 years and no Endometrial Cancer Risk Factors
       1. Trial of hormone supplementation
          1. See Metrorrhagia Management
          2. Oral Contraceptive (no higher than 35 mcg of Ethinyl Estradiol)
          3. Cyclic Progesterone
             1. Provera 10 mg daily for 10-14 days per month
       2. If results in normal cycles then
          1. Discontinue after 3-6 months
          2. If abnormal bleeding then Oral Contraceptive
       3. Indications for Endometrial Cancer Screening (as done for protocol above for those over age 35 years)
          1. Persistent Abnormal Uterine Bleeding despite hormonal supplementation
          2. Long-standing Unopposed Estrogen
          3. Endometrial Cancer Risk Factors
    6. Indications for referral
       1. See Endometrial Cancer Screening
       2. Desired Fertility
       3. Unresolved uterine bleeding
13. Management
    1. See Metrorrhagia Management
    2. See Endometrial Cancer Screening
14. References
    1. Nelson (1997), Fam Prac Recert 19(8):14
    2. Buchanan (2009) Am Fam Physician 80(10): 1075-88
    3. Sweet (2012) Am Fam Physician 85(1): 35-43