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For further information, see CMDT Part 26-34: Secondary Amenorrhea & Menopause

Key Features

Essentials of Diagnosis

  • Secondary amenorrhea: absence of menses for 3 consecutive months in women who have passed menarche

  • Menopause: termination of naturally occurring menses; usually diagnosed after 12 months of amenorrhea

General Considerations

Causes of secondary amenorrhea

  • High human chorionic gonadotropin (hCG)

    • Pregnancy most common cause

    • Rarely caused by ectopic secretion of hCG by choriocarcinoma or bronchogenic carcinoma

  • Hypothalamic-pituitary causes (low-normal follicle-stimulating hormone [FSH])

  • "Hypothalamic amenorrhea"

    • Idiopathic

    • Stress

    • Strict dieting

    • Vigorous exercise

    • Organic illness

    • Anorexia nervosa

  • Hyperprolactinemia, pituitary tumors, and corticosteroid excess can suppress gonadotropins

  • Hyperandrogenism (low-normal FSH)

    • Polycystic ovarian syndrome

    • Use of anabolic steroids

    • Rarely caused by

      • Adrenal P-450c21 deficiency

      • Ovarian or adrenal malignancy

      • Cushing disease

  • Endometritis (normal FSH)

    • Scarring (Asherman syndrome) occurring spontaneously

    • Following delivery or D&C

    • Tuberculosis or schistosomiasis in endemic areas

  • Early and premature menopause (high FSH) (primary ovarian failure before age 45)

    • Autoimmune

    • XO/XX chromosome mosaicism

    • Bilateral oophorectomy

    • Pelvic radiation therapy

    • Chemotherapy

    • Frequently familial

    • Additional causes

      • Myotonic dystrophy

      • Galactosemia

      • Mumps oophoritis

  • Normal menopause (high FSH) (primary ovarian failure after age 45)


  • Normal age of menopause in the United States is 48–55 years (average 51.5 years)

Clinical Findings

Symptoms and Signs

  • Vasomotor symptoms (hot flushes)

    • Experienced by 60–80% of women

    • May last seconds to many minutes

    • Severity varies; may be most severe at night

    • Median duration of moderate-to-severe hot flushes is about 10 years; tend to continue longer in thin versus obese women and in black versus white women

  • Sleep disturbances, fatigue, insomnia, headache, diminished libido, or joint pains

  • Depression and irritability

  • Urogenital atrophy with vaginal dryness and dyspareunia

  • Some women report mild cognitive impairment, which may be related to decreased cerebral blood flow noted in hypogonadal women, particularly during hot flushes

  • Increased bone osteoclastic activity increases the risk for osteoporosis and fractures

  • Skin becomes more wrinkled

  • Increases in the LDL:HDL cholesterol ratio cause an increased risk for atherosclerosis

  • Perform pelvic examination to check for uterine or adnexal enlargement

Differential Diagnosis

  • Pregnancy

  • Menopause or perimenopause

  • Polycystic ovary syndrome

  • Hypothalamic amenorrhea, eg, stress, weight change, exercise

  • Hyperprolactinemia

  • Hypothyroidism or hyperthyroidism

  • Diabetes mellitus

  • Premature ovarian failure

  • Anorexia nervosa


Laboratory Tests

Premature amenorrhea

  • An elevated hCG indicates pregnancy

  • Laboratory evaluation for nonpregnant women includes

    • Serum prolactin

    • Follicle-stimulating hormone, luteinizing hormone (both elevated in menopause)

    • Thyroid-stimulating hormone

  • Routine testing of kidney and liver function (blood urea nitrogen, serum creatinine, bilirubin, alkaline phosphatase, and alanine aminotransferase) is also performed

  • A serum testosterone level is obtained in hirsute or virilized women

  • Patients with manifestations of hypercortisolism receive a 1-mg overnight dexamethasone ...

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