Primary Ovarian Insufficiency

Aka: Primary Ovarian Insufficiency, Premature Ovarian Failure, Hypergonadotrophic Ovarian Failure

advertisement

II. Epidemiology

  1. Incidence: 1% of women

III. Pathophysiology

  1. Follicle depletion or dysfunction resulting in impaired ovarian function

IV. Causes

  1. Idiopathic (>90%)
  2. Chromosomal Abnormality
    1. X-Chromosome abnormality (e.g. Turner Syndrome)
    2. Y-Chromosome presence abnormality
  3. Infection (e.g. Mumps)
  4. Autoimmune Disease directed at Ovary
  5. Empty Sella Syndrome
  6. Chemotherapy or Radiation Exposure related

V. Associated Conditions

  1. FMR1 Gene premutation
    1. Associated with risk of Fragile X Syndrome in children
  2. Thyroid autoimmune disorders
    1. Consider testing for Thyroid autoantibodies
  3. Adrenal autoimmune disorders
    1. Consider testing for adrenal autoantibodies
  4. Turner Syndrome
    1. May present only as Short Stature and Amenorrhea
    2. Obtain karyotype from women with Short Stature and Primary Ovarian Insufficiency
      1. Multi-system implications of Turner Syndrome require surveillance and highlight the importance of testing

VI. Diagnosis

  1. Woman younger than age 40 years old with Amenorrhea or Oligomenorrhea >=4 months AND
  2. Follicle Stimulating Hormone in menopausal range (>25 mIU/ml)
    1. Single FSH >25 mIU/ml is sufficient
    2. Previously required 2 consecutive tests, one month apart (an may still consider)

VII. Symptoms

  1. See Vasomotor Symptoms of Menopause
  2. Hot Flushes
  3. Vaginal Dryness
  4. Amenorrhea

VIII. Labs: First Line

  1. See Secondary Amenorrhea
  2. See Markers of Ovarian Reserve
  3. Anti-Mullerian Hormone
  4. Thyroid Stimulating Hormone
  5. Follicle Stimulating Hormone
    1. Used as part of diagnosis above

IX. Labs: Second-Line Testing for Non-Iatrogenic Causes

  1. Primary Ovarian Insufficiency labs
    1. FMR1 Gene Premutation (fragile-X gene)
    2. 21-Hydroxylase autoantibodies (Autoimmune Adrenalitis and Addison's Disease)
      1. Premature Ovarian Insufficiency secondary to Autoimmune Polyendocrine Syndrome
  2. Karyotype
    1. Turner Syndrome
      1. Monosomy X (45,X)
      2. Mosaicism (e.g. 45,X / 46,XX)
    2. Y Chromatin (Y Chromosome)
      1. Swyer syndrome (46,XY gonadal dysgenesis)
      2. Mosaic Turner Syndrome

X. Labs: Other (as Indicated for secondary cause)

  1. Fasting Serum Glucose
  2. Calcium
  3. Phosphorus
  4. Total Protein
  5. Albumin to globulin ratio
  6. Complete Blood Count (CBC)
  7. Erythrocyte Sedimentation Rate (ESR)
  8. Rheumatoid Factor (RF)
  9. Antinuclear Antibody (ANA)
  10. Thyroid Stimulating Hormone (TSH)
  11. Morning Serum Cortisol Level

XI. Management: Adults

  1. Estrogen Replacement Therapy
    1. Continue until at least average typical Menopause age (e.g. age 50 years old)
    2. Medications
      1. Transdermal Estradiol 100 mcg (or oral forms of Estradiol >=2 mg/day) AND
      2. Progesterone (if intact Uterus)
        1. See Sequential Estrogen Replacement
        2. See Continuous Estrogen Replacement
    3. Efficacy
      1. Reduces Osteoporosis and Fracture risk
      2. Reduces Vasomotor Symptoms of Menopause
      3. Reduces uterine atrophy
  2. Pregnancy
    1. Risk of variable fertility (10% have spontaneous resolution and risk of pregnancy)
      1. Consider combined Hormonal Contraception instead of Estrogen Replacement to prevent pregnancy
    2. Otherwise pregnancy is possible with donor implantation
  3. Osteoporosis Prevention
    1. Calcium Supplementation 1200 mg daily
    2. Vitamin D Supplementation 800 IU daily (or more)
    3. DEXA Scan at baseline and then every 1-3 years
  4. Cardiovascular Disease Prevention
    1. Annual Blood Pressure Measurement
    2. Hyperlipidemia screening every 5 years

XII. Management: Adolescents

  1. Estrogen therapy
    1. Consult pediatric endocrinology
    2. Start at age 11-12 years with phased hormonal dosing
  2. Monitoring
    1. Serum Estradiol
      1. Obtain every 4-6 months
    2. Pelvic Ultrasound
      1. Evaluate for Uterine Size and endometrial thickness
      2. Periodically during induction phase
      3. Repeat at Puberty completion
    3. Wrist XRay
      1. Obtain yearly (until induction completion)
    4. DEXA Scan
      1. Obtain at initiation of hormonal therapy
      2. Repeat every 1-3 years

XIII. References

  1. Klein (2026) Am Fam Physician 114(1): 72-85 [PubMed]
  2. Klein (2013) Am fam Physician 87(11): 781-8 [PubMed]
  3. Nelson (2009) N Engl J Med 360(6): 606-14 [PubMed]

Images: Related links to external sites (from Bing)

These images are a random sampling from a Bing search on the term "Primary Ovarian Insufficiency." Click on the image (or right click) to open the source website in a new browser window. Search Bing for all related images

Related Studies

Related Topics in Endocrinology

advertisement