Secondary Amenorrhea

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Secondary Amenorrhea - Amenorrhea Unmasked

Secondary amenorrhea: Cessation of menses after menarche.

  • Diagnostic Criteria:
    • Previously regular cycles: No menses for ≥3 months.
    • Previously irregular cycles: No menses for ≥6 months.
  • Key Initial Investigations ("Unmasking"):
      1. Exclude Pregnancy: β-hCG test is paramount.
      1. TSH: Screen for thyroid dysfunction.
      1. Prolactin: Detect hyperprolactinemia.
      1. Progestin Challenge Test (PCT): Evaluates estrogen status and outflow tract integrity. If withdrawal bleed occurs, indicates anovulation.

⭐ The most frequent cause of secondary amenorrhea is pregnancy. Secondary Amenorrhea Initial Workup Flowchart

Secondary Amenorrhea - The No-Show Culprits

Defined as absence of menses for >3 months in women with previously regular cycles, or >6 months in women with previously irregular cycles. Always exclude pregnancy first (β-hCG test).

  • Hypothalamic Dysfunction (↓GnRH → ↓FSH, ↓LH, ↓E2)
    • Functional Hypothalamic Amenorrhea (FHA): Stress, excessive exercise (Female Athlete Triad), weight loss (anorexia nervosa).
    • Kallmann Syndrome: GnRH deficiency with anosmia.
  • Pituitary Disorders
    • Hyperprolactinemia: ↑Prolactin (e.g., prolactinoma) inhibits GnRH.
    • Sheehan's Syndrome: Postpartum pituitary necrosis.
    • Empty Sella Syndrome.
  • Ovarian Dysfunction
    • Premature Ovarian Insufficiency (POI): Ovarian failure before age 40 (↑FSH, ↑LH, ↓Estradiol).
    • Polycystic Ovary Syndrome (PCOS): Chronic anovulation, hyperandrogenism.
  • Uterine/Outflow Tract Abnormalities (Normal HPO axis)
    • Asherman's Syndrome: Intrauterine adhesions, often post-instrumentation.
    • Cervical Stenosis.
  • Other Endocrine Disorders
    • Thyroid dysfunction (Hypo- or Hyperthyroidism).
    • Cushing's syndrome.

Key Investigations: β-hCG, TSH, Prolactin, FSH, LH, Estradiol. Progestogen challenge test helps differentiate anovulation from outflow tract obstruction.

Causes of secondary amenorrhea by HPO axis

⭐ Asherman's syndrome, characterized by intrauterine adhesions typically following uterine instrumentation (e.g., D&C), is a key cause of secondary amenorrhea with normal hormonal profiles (FSH, LH, Estradiol).

Secondary Amenorrhea - Star Syndromes Spotlight

Key conditions causing menses absence >3 cycles or >6 months.

  • Polycystic Ovary Syndrome (PCOS)
    • Rotterdam (2/3): Oligo/anovulation, hyperandrogenism (clin/biochem), PCO on USG (string of pearls).
    • Labs: ↑LH/FSH ratio (often >2:1), ↑Testosterone, Insulin Resistance.

    ⭐ In PCOS, the LH:FSH ratio is often >2:1, though not a mandatory diagnostic criterion. Polycystic Ovary Ultrasound: String of Pearls

  • Asherman Syndrome
    • Intrauterine adhesions (IUAs).
    • Cause: Post-curettage, endometritis.
    • Diagnosis: Hysteroscopy (gold standard), HSG.
    • Treatment: Hysteroscopic adhesiolysis.
  • Sheehan Syndrome
    • Postpartum pituitary necrosis.
    • Cause: Severe PPH & hypotension.
    • Features: Failure to lactate, amenorrhea, hypothyroidism, adrenal insufficiency symptoms.
    • ↓Pituitary hormones.
  • Premature Ovarian Insufficiency (POI)
    • Ovarian failure <40 years.
    • Symptoms: Amenorrhea, menopausal (hot flashes).
    • Labs: ↑FSH (>25-40 IU/L on 2 occasions), ↓Estrogen.
    • Karyotype if <30 yrs (e.g., Turner mosaic).

Secondary Amenorrhea - Charting the Course

  • Initial Steps: Exclude pregnancy, assess TSH & prolactin.
  • Progestin Challenge: Differentiates anovulation from hypoestrogenism/outflow issues.
  • Further Evaluation: FSH/LH, estradiol, imaging if needed.

⭐ Asherman syndrome (intrauterine adhesions) is a key cause of secondary amenorrhea with a negative progestin challenge test and no withdrawal bleed after estrogen-progestin challenge, often post-instrumentation (D&C).

High‑Yield Points - ⚡ Biggest Takeaways

  • Secondary amenorrhea: No menses >3 months (regular cycles) or >6 months (irregular cycles).
  • Pregnancy is the most common cause; always perform β-hCG test first.
  • Initial investigations include β-hCG, TSH, and prolactin.
  • Progestin challenge test helps assess endogenous estrogen and outflow tract patency.
  • Asherman syndrome (intrauterine adhesions) and PCOS are important structural and endocrine causes.
  • Functional Hypothalamic Amenorrhea (FHA) is common in athletes or due to stress/low weight.
  • Premature Ovarian Insufficiency (POI) presents with ↑FSH before age 40.

Practice Questions: Secondary Amenorrhea

Test your understanding with these related questions

A middle-aged female presents with increasing visual loss, breast enlargement, and irregular menses. What is the most appropriate investigation to diagnose the underlying condition?

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Flashcards: Secondary Amenorrhea

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_____ syndrome is secondary amenorrhea due to loss and scarring of the basalis layer of the endometrium

TAP TO REVEAL ANSWER

_____ syndrome is secondary amenorrhea due to loss and scarring of the basalis layer of the endometrium

Asherman

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