Amenorrhea

Basics

Description

  • Transient, intermittent or permanent absence of menses
  • Primary amenorrhea:
    • Absence of menses at age 15 with normal growth and secondary sexual characteristics or at age 13 with complete absence of secondary sexual characteristics (ie, breast development)
  • Secondary amenorrhea:
    • Absence of menses for more than 3 mo in a patient with prior regular menstrual cycles or 6 mo in patients with irregular menses
    • More common than primary amenorrhea
    • Pregnancy is the most common cause

Etiology

  • Primary:
    • Congenital abnormalities:
      • Complete androgen insensitivity syndrome
      • 5-α reductase deficiency
      • 17-α hydroxylase deficiency
    • Hypothalamic–pituitary disorder
    • Chromosomal abnormalities:
      • Turner syndrome
    • Imperforate hymen
  • Secondary:
    • Pregnancy, breastfeeding, postpartum state
      • Ectopic and molar pregnancies
    • Intrauterine adhesions (Asherman syndrome)
    • Hypothalamic–pituitary–ovarian axis dysfunction
    • Polycystic ovarian syndrome (PCOS)
    • Endocrinopathies
      • Hypothyroidism
      • Hyperthyroidism
    • Metabolic
      • Obesity
      • Starvation or anorexia nervosa
      • Intense exercise
    • Medications:
      • Oral contraceptives
      • Antipsychotics
      • Antidepressants
      • Calcium channel blockers
      • Chemotherapeutic agents
      • Digitalis
      • Marijuana
    • Autoimmune disorders
    • Premature ovarian failure
    • Menopause

Diagnosis

Signs-Symptoms

History

  • Menarche and menstrual history
  • Sexual activity
  • Exercise, weight loss
  • Chronic illness
  • Anorexia nervosa
  • Medications
  • Previous CNS radiation or chemotherapy
  • Family history
  • Infertility
  • Contraception use
  • Galactorrhea:
    • Pituitary tumor
  • Hirsutism/acne:
    • PCOS
    • Cushing syndrome
    • Hyperandrogenism
  • Illicit drug use:
    • Effect on prolactin
  • Headaches or vision changes:
    • CNS tumor
  • Temperature intolerance, palpitations, skin changes, diarrhea, tremor
    • Thyroid

Physical Exam

  • Low estrogen:
    • Atrophic vaginal mucosa
    • Mood swings, irritability
  • High androgen:
    • Truncal obesity
    • Hirsutism
    • Acne
    • Male-pattern baldness
  • Thyroid exam:
    • Tachycardia, goiter, hyperhidrosis–hyperthyroidism
    • Bradycardia–hypothyroidism
  • Pelvic/genital exam
    • Underdeveloped or ambiguous genitalia
  • Tanner staging

Essential Workup

Pregnancy test

Diagnostic Tests And Interpretation

Lab

  • If pregnancy test is negative, no further testing is needed emergently
  • Thyroid-stimulating hormone level if concern for thyroid disorder
  • Basic metabolic panel, Magnesium, Phosphorus if concern for anorexia nervosa
  • May send luteinizing hormone, follicle stimulating hormone, and prolactin for follow-up by gynecology or primary care physician

Imaging

  • Pelvic ultrasound as indicated for ectopic pregnancy workup
  • Magnetic resonance imaging of the brain with and without contrast if concern for intracranial mass

Diagnostic Procedures/Surgery

None needed emergently

Differential Diagnosis

  • Pregnancy
  • Mullerian agenesis:
    • Congenital malformation of the genital tract
    • Normal breast development without menarche
    • Associated with:
      • Fused vertebrae
      • Urinary tract defects
  • Transverse vaginal septum
  • Imperforate hymen
  • Complete androgen insensitivity syndrome
  • Asherman syndrome:
    • Intrauterine synechiae
    • Due to gynecologic instrumentation
  • Primary ovarian insufficiency
  • Hypothalamic/Pituitary
  • Prior CNS infection, trauma, or autoimmune destruction of pituitary
  • Anorexia nervosa
  • Depression
  • Prolactinoma or suprasellar mass
  • Polycystic ovary syndrome
  • Medication adverse effect
  • Contraceptive use
  • Thyroid disease:
    • Hyperthyroid more likely than hypothyroid
  • Adrenal disease

Treatment

Prehospital

If amenorrhea is the result of pregnancy, stabilize patient as appropriate for pregnancy

Ed Treatment/Procedures

  • Manage pregnancy as indicated, referral to OB/Gyn for follow-up
  • Review medications
  • Manage anorexia nervosa and depression as indicated, refer for follow-up
  • Surgical referral to pediatric gynecology for imperforate hymen
  • Manage thyroid disorders as indicated

Medication

Defer for gynecology evaluation

Follow-Up

Disposition

Admission Criteria

Admit if ectopic pregnancy cannot be ruled out

Discharge Criteria

Discharge with appropriate referral

Issues For Referral

Referral to gynecology

Follow-Up Recommendations

Gynecology follow-up is recommended

Pearls And Pitfalls

  • Pregnancy is the most relevant etiology of amenorrhea in the emergency department:
    • Urine pregnancy test (UPT) may give false negative with low urine specific gravity
    • UPT sensitivity for β-hCG level may vary depending on type/manufacturer
    • High concern for amenorrhea due to pregnancy, specifically an ectopic, may warrant a qualitative serum pregnancy test
  • Anorexia nervosa is an important consideration in patients with amenorrhea, particularly in adolescents
  • Hyperprolactinemia from use of antipsychotic drugs is a common etiology of amenorrhea in psychiatric patients
  • Consider suprasellar mass or prolactinoma in patients with headache or bitemporal hemanopsia

Additional Readings

  1. Heiman DL. Amenorrhea. Prim Care. 2009;36:1–17.  [PMID:19231599]
  2. Klein DA, Poth MA. Amenorrhea: an approach to diagnosis and management. Am Fam Physician. 2013;87:781–788.  [PMID:23939500]
  3. Nawaz G, Rogol AD, Jenkins SM. Amenorrhea. [Updated 2024 Feb 25]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan. https://www.ncbi.nlm.nih.gov/books/NBK482168/
  4. Patrice Committee of the American Society for Reproductive Medicine. Current evaluation of amenorrhea. Fertil Steril. 2006;86:S148–S155.  [PMID:17055812]
  5. Rosenberg HK. Sonography of the pelvis in patients with primary amenorrhea. Endocrinol Metab Clin N Am. 2009;38:739–760.
  6. Santoro N. Update in hyper- and hypogonadotropic amenorrhea. J Clin Endocrinol Metab. 2011;96:3281–3288.  [PMID:22058375]

Authors

Michael H. Morgan

Harshit Singh