Amenorrhea, Secondary & 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)

Demographics

• 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

Diagnosis

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 ...