Skip to Main Content

We have a new app!

Take the Access library with you wherever you go—easy access to books, videos, images, podcasts, personalized features, and more.

Download the Access App here: iOS and Android. Learn more here!

For further information, see CMDT Part 26-35: Secondary Amenorrhea

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 hCG)

    • Hypothalamic-pituitary causes (low or normal FSH)

    • Hyperandrogenism (low or normal FSH)

    • Uterine causes (normal FSH)

    • 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 PRL, 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, Normal

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.