Updated: 11/29/2021

Secondary Amenorrhea

Review Topic
  • Snapshot
    • A 22-year-old female presents with increased hair growth. She reports having to shave frequently above the lip, chin, chest, and lower back. She also states not having her menses over a period of four months. Prior to this, she had a regular menses. The patient's weight is 168 lbs (76.2 kg) and height 5 feet and 1 inch (154.9 cm). On physical examination, there is increased hair above the lip and chin area. There is also acne on the cheeks and forehead. Hyperpigmented plaques of the skin are found in the back of the neck. Bilateral enlarged ovaries are palpated on pelvic examination. β-hCG is negative and LH:FSH is 3. (Polycystic ovarian syndrome)
    • Absence of menses > 3 months in those with regular menses or absence of menses > 6 months in those with irregular menses
  • Etiology
    • pregnancy (most common)
    • hypothalamic dysfunction
      • e.g., functional hypothalamic amenorrhea, benign or malignant hypothalamic tumors, and systemic illness
        • functional hypothalamic amenorrhea
          • also known as functional hypothalamic GnRH deficiency
            • excludes pathological disease
          • risk factors
            • eating disorders, excessive exercise, and stress
        • hypothalamic tumors include
          • craniopharyngiomas
        • infiltrative disease affecting the hypothalamus include
          • Langerhans cell histiocytosis and sarcoidosis
    • pituitary dysfunction
      • e.g., prolactin-secreting pituitary adenoma and pituitary infarct (Sheehan syndrome)
    • thyroid disorder
      • e.g., hypothyroidism and severe hyperthyroidism
    • polycystic ovarian syndrome (most common reproductive disorder in women)
    • ovarian dysfunction
      • e.g., primary ovarian insufficiency and ovarian malignancy
    • uterine disorders
      • e.g., Asherman syndrome
    • obesity
  • Presentation
    • Symptoms and physical examination findings will be dependent on the etiology of secondary amenorrhea
      • e.g., patient with eating disorder (functional hypothalamic amenorrhea), hirsutism, or obesity (polycystic ovarian syndrome)
    • History
      • e.g., eating disorder, excessive exercise, hyperandrogenism, visual defects, vaginal dryness, and hot flashes
    • Physical Exam
      • e.g., body mass index, acne, hirsutism, acanthosis nigricans, vitiligo, galactorrhea, and signs of estrogen deficiency on pelvic examination
  • Studies
    • β-hCG
      • best initial test
    • Follicle-stimulating hormone (FSH), prolactin (PRL), and thyroid-stimulating hormone (TSH)
      • order after ruling out pregnancy
      • assesses primary ovarian insufficiency, hyperprolactinemia, and thyroid abnormalities (e.g., severe hyperthyroidism and hypothyroidism)
    • Testosterone
      • should be ordered if there is evidence of hyperandrogenism
    • Progesterone challenge test
      • presence of withdrawal bleeding suggests
        • endogenous estrogen exposure
      • absence of bleeding suggests
        • hypoestrogenism or outflow tract obstruction
    • Estrogen-progesterone challenge test
      • presence of withdrawal bleeding suggests
        • inadequate estrogen
          • next step is ordering an FSH
      • absence of bleeding suggests
        • outflow tract obstruction or scarring of the endometrium
  • Differential Diagnosis
    • Pregnancy
    • Contraceptive use
    • Excessive exercise/physical stress
    • Refer to introduction for causes of secondary amenorrhea
  • Treatment
    • Treatment depends on etiology of disease
      • as a rule of thumb, treat underlying pathology
      • examples include
        • functional hypothalamic amenorrhea
          • lifestyle modification
            • e.g., decreasing exercise and increasing caloric intake in patients with exercise excess
        • primary ovarian insufficiency
          • estrogen and progresterone therapy
        • Asherman syndrome
          • hysteroscopic lysis of adhesions
            • afterwards, place patient on estrogen therapy to stimulate regrowth of the endometrium
  • Complications
    • Infertility
    • Decreased bone density in patients with inadequate estrogen
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Questions (4)

(M2.GN.17.4867) A 23-year-old woman presents to her primary care physician due to amenorrhea. The patient states that historically she has her period once every three months but recently has not had it at all. Otherwise, she has no other complaints. The patient recently started college and is a varsity athlete for the track team. She works part time in a coffee shop and is doing well in school. The patient is not sexually active and does not drink alcohol, use illicit drugs, or smoke. She has no significant past medical history and occasionally takes ibuprofen for headaches. Her temperature is 99.5°F (37.5°C), blood pressure is 100/55 mmHg, pulse is 50/min, respirations are 10/min, and oxygen saturation is 98% on room air. On physical exam, you note a young, lean, muscular woman in no acute distress. Which of the following is the most likely long-term outcome in this patient?

QID: 109607

Endometrial cancer












Anorexia nervosa



M 8 D

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