Amenorrhea, Secondary

Key Features

• Defined as the absence of menses for 3 consecutive months in women who have passed menarche

• Menopause is defined as the terminal episode of naturally occurring menses; it is a retrospective diagnosis, usually made after 12 months of amenorrhea (see Menopause, Normal)

• Causes of secondary amenorrhea include

  • Pregnancy (high human chorionic gonadotropin [hCG])

  • Hypothalamic-pituitary causes (low or normal FSH)

  • Hyperandrogenism (low or normal FSH)

  • Uterine causes (normal FSH)

  • Premature ovarian failure

  • Menopause (high FSH)

• Menopause

  • Normal menopause refers to primary ovarian failure that occurs after age 45 (see Menopause, Normal)

  • Early menopause

    • Refers to primary ovarian failure that occurs before age 45

    • Affects approximately 5% of women

  • Premature menopause is primary ovarian failure that occurs before age 40

    • Occurs in about 1% of women

    • About 30% of such cases are due to autoimmunity against the ovary

    • X chromosome mosaicism accounts for 8% of cases of premature menopause

    • Ovarian failure is usually irreversible

    • Other causes include surgical bilateral oophorectomy, radiation therapy for pelvic malignancy, and chemotherapy

• Compared to women with normal menopause, women with premature menopause have a

  • 50% increased risk of coronary disease

  • 23% increased risk for stroke

  • 12% increased overall mortality

Clinical Findings

• Secondary "hypothalamic" amenorrhea

  • May be caused by stressful life events such as school examinations or leaving home

  • May also be the result of strict dieting, vigorous exercise, organic illness, or anorexia nervosa

  • Intrathecal infusion of opioids causes amenorrhea in most women

• Hyperandrogenism (with low-normal FSH)

  • Rare causes of secondary amenorrhea include adrenal P450c21 deficiency, ovarian or adrenal malignancies, and Cushing syndrome

  • Anabolic steroids also cause amenorrhea

• Uterine causes (with normal FSH)

  • Infection of the uterus commonly occurs following delivery or D&C but may occur spontaneously

  • Endometritis due to tuberculosis or schistosomiasis should be suspected in endemic areas

  • Endometrial scarring may result, causing amenorrhea (Asherman syndrome)

  • Vaginal estrogen effect is normal

Diagnosis

• Elevated hCG overwhelmingly indicates pregnancy

  • Rare false-positive results can occur from ectopic hCG sources (eg, choriocarcinoma or bronchogenic carcinoma)

• Hypothalamic amenorrhea: regular evaluations and a progestin withdrawal test about every 3 months to detect loss of estrogen effect

• Prolactin elevation may cause amenorrhea

• Corticosteroid excess suppresses gonadotropins

• Elevated serum levels of testosterone

• Premature menopause

  • Serum prolactin, FSH, and LH (both elevated in menopause), and TSH

  • Hyperprolactinemia or hypopituitarism (without obvious cause) should prompt an MRI study of the pituitary region

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

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

Treatment

• Nonpregnant women without any laboratory abnormality may receive a 10-day course of a progestin (eg, medroxyprogesterone acetate, 10 mg/day orally); absence of withdrawal menses typically indicates a lack of estrogen or a uterine abnormality

• See Menopause, ...