Secondary Amenorrhea

See Also

Definitions

Secondary Amenorrhea
1. Previously regular cycles: 3 months of no Menses
2. Previously irregular cycles: 6 months of no Menses

Causes
Axis Associated

See Hypogonadism
Axis 1: Hypothalamic or Central
1. Anovulation (50% of secondary causes)
2. Post-Hor monal Contraception (Post-Pill Amenorrhea)
3. CNS injury
  1. Traumatic Brain Injury
  2. Meningitis
  3. CNS Neoplasm
4. Functional Hypothalamic Amenorrhea
  1. Eating Disorder (e.g. Anorexia Nervosa)
  2. Malabsorption, Malnutrition or rapid weight loss
Axis 2: Pituitary
1. Hyperprolactinemia (25% of secondary causes)
  1. See Medication Causes of Hyperprolactinemia
2. Sheehan Syndrome (rare)
3. Hypothyroidism (1% of secondary causes): Prolactin-like effect
4. Pituitary infiltration (e.g. Sarcoidosis)
5. Cushing Syndrome
Axis 3: Ovary
1. Polycystic Ovary Syndrome (8% of secondary causes)
2. Premature Ovarian Failure (10% of secondary causes)
3. Oophoritis (rare)
  1. Chemotherapy or Radiation
  2. Infection (e.g. Mumps, Tuberculosis)
Axis 4: Uterus
1. Asherman's Syndrome (5%)
2. Endometritis
3. Cervical stenosis

Causes
Miscellaneous

Other endocrine causes
1. See Hypoandrogenism
2. Adrenal hyperplasia (adult onset)
3. Androgen-Secreting tumor
4. Cushing Syndrome
5. Polycystic Ovary Syndrome
6. Severe Hyperthyroidism
Physiologic causes
1. Pregnancy!
2. Lactation
3. Contraception
4. Menopause
5. Exogenous androgens

Pathophysiology
Mechanisms

Luteal Phase dysfunction
1. Insufficient Progesterone
Anovulation
1. Unopposed Estrogen leads to long cycles
Hypoestrogenemia (Most common)
1. Able to conceive

History

See Amenorrhea

Exam

See Amenorrhea

Labs

Imaging

See Amenorrhea
Pelvic Ultrasound

Evaluation
Based on FSH, LH

See Amenorrhea
Step 0: Evaluate labs in Amenorrhea as above (HCG, Serum LH, Serum FSH, TSH, Serum Prolactin)
1. Pregnancy
2. Hypothyroidism or Hyperthyroidism
3. Hyperprolactinemia (especially if >100 ng/ml)
Step 1: Serum FSH and Serum LH increased
1. Confirm with repeat Serum LH and Serum FSH in one month
2. Additional labs if confirmed elevated Serum LH and Serum FSH
  1. Obtain karyotype for Turner Syndrome if Short Stature
  2. Consider Serum Estradiol
3. Diagnosis
Step 2a: Hyperandrogenism findings
1. Evaluation
  1. Serum Androgens (Serum Testosterone and DHEA-S)
    1. Consider adrenal or ovarian tumor if very high androgen levels or rapid onset of symptoms
  2. 17-Hydroxyprogesterone (at 8 am)
    1. Consider late-onset Congenital Adrenal Hyperplasia
2. Diagnosis (if normal serum androgens and 17-Hydroxyprogesterone)
  1. Polycystic Ovary Syndrome (PCOS)
Step 2b: Pituitary or other CNS Lesion suspected (e.g. Headache, Vision change)
1. Evaluation
  1. Head MRI or Head CT with cone-down sella turcica views
2. Diagnosis
  1. Pituitary Lesion
Step 2c: Functional Hypothalamic Amenorrhea suspected
1. Evaluation
  1. Nutritional History
  2. Eating Disorder history
2. Diagnosis
  1. Femal athlete triad
  2. Poor nutritional status
Step 2d: Structural abnormality suspected
1. Evaluation
  1. Consider Oral Contraceptive cycling trial (failed trial suggests structural abnormality)
  2. Consider Hysteroscopy
2. Diagnosis
  1. Outflow obstruction
  2. Uterine abnormality

Evaluation
Based on Progesterone Challenge

See Amenorrhea
Step 0: Evaluate labs in Amenorrhea as above (HCG, Serum LH, Serum FSH, TSH, Serum Prolactin)
1. Pregnancy
2. Hypothyroidism or Hyperthyroidism
3. Hyperprolactinemia (especially if >100 ng/ml)
Step 1: Progesterone Challenge Test
1. Precaution: Inconsistent results
Step 2a: Any bleeding with Progesterone Challenge Test (within 7 days)
1. Suggests Progesterone insufficiency (Anovulation)
  1. Unopposed Estrogen with risk of Endometrial Cancer
2. Option 1: Treat Anovulation empirically (especially if otherwise asymptomatic)
  1. Provera 10 mg daily for 10 days per month or
  2. Oral Contraceptives
3. Option 2: Check serum Luteinizing Hormone (LH)
  1. Luteinizing Hormone (LH) High
    1. Polycystic Ovary Syndrome
      1. Androgen Excess
      2. Unopposed Estrogen
    2. Management
      1. Progesterone cycling (see above regarding Unopposed Estrogen)
  2. Luteinizing Hormone (LH) Low or Normal
    1. Hypothalamic Amenorrhea
      1. Eating Disorder
      2. Chronic illness
      3. Pituitary Lesion (may present with Headaches and Vision changes)
    2. Evaluation
      1. Check Pituitary MRI or CT (Cone down Sella)
Step 2b: No Bleeding occurs with Progesterone Challenge
1. Ascertain Estrogen Level
  1. Perform Estrogen-Progesterone Challenge Test or
  2. Check Serum Estrogen level
2. Estrogen Normal (no bleeding occurs with OCP)
  1. Suggests uterine bleeding outflow obstruction
  2. Example: abnormal Uterus (e.g. Asherman's Syndrome)
3. Estrogen Low (bleeding occurs with OCP)
  1. Obtain Serum FSH and Serum LH
  2. Serum FSH and Serum LH <5
    1. See Hypogonadotropic Hypogonadism
    2. Hypothalamic origin
    3. Check Pituitary MRI or CT (Cone down Sella)
  3. Serum FSH >20 and Serum LH >40
    1. See Hypergonadotropic Hypogonadism
    2. Suggests ovarian failure
    3. Female Athlete Triad
    4. Premature Ovarian Failure

References