What is the algorithm for diagnosing amenorrhea with normal puberty and uterus present?

Updated: Oct 14, 2019
  • Author: Kristi A Tough DeSapri, MD; Chief Editor: Richard Scott Lucidi, MD, FACOG  more...
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Obtain a pregnancy test. If the pregnancy test result is positive, refer the patient to the appropriate specialist. If the pregnancy test result is negative, obtain TSH, prolactin, FSH, and LH levels.

If the TSH level is elevated, the diagnosis is hypothyroidism. If the prolactin level is elevated, the diagnosis is hyperprolactinemia. Causes of hyperprolactinemia include prolactinoma, CNS tumors, and medications. MRI is indicated.

If the FSH level is low, obtain a MRI of the brain. If MRI findings are abnormal, consider hypothalamic disease, pituitary disease, or pituitary tumor. If MRI findings are normal, proceed with clinical evaluation to exclude chronic disease, anorexia nervosa, marijuana or cocaine use, and social or psychological stresses.

If FSH is elevated, premature ovarian failure is the diagnosis. Obtain a karyotype. If the karyotype is abnormal, mosaic Turner syndrome may be present. If the karyotype is normal (46,XX), the cause is premature ovarian failure. An association with fragile X syndrome may be observed. [53] If fragile X syndrome is present, family members should be offered genetic testing.

Consider premature ovarian failure due to the following:

  • Autoimmune oophoritis

  • Exposure to radiation or chemotherapy

  • Resistant ovary syndrome

  • Karyotype abnormality (Turner syndrome)

  • Multiple endocrine neoplasm (MEN) syndrome

If TSH, prolactin, and FSH levels are within reference range, perform a progestin challenge test. If withdrawal bleeding occurs, consider anovulation secondary to PCO syndrome. If no withdrawal bleed occurs, proceed with estradiol (E2) priming, followed by a progestin challenge.

If the challenge does not induce menses, consider Asherman syndrome, outlet obstruction, or endometrial thinning secondary to elevated androgens (PCO syndrome) or hypothalamic amenorrhea with decreased estrogen production.

If the challenge induces menses, a hypothalamic dysfunction with low circulating E2 is present. An acquired hypothalamic cause of amenorrhea after puberty has been achieved is a diagnosis of exclusion. The FSH and LH levels may be low or may be below the reference range. The causes include eating disorders, caloric restriction, exercise, stress, and medications.

If hirsutism and/or acne are present, check testosterone, dehydroepiandrosterone sulfate (DHEAS), and 17-hydroxy (17-OH) progesterone level. If the testosterone and DHEAS levels are within the reference range or are moderately elevated, perform a progesterone challenge. If withdrawal bleeding occurs, the diagnosis is PCOS. If the 17-OH progesterone level is elevated, the diagnosis is adult-onset adrenal hyperplasia.

If the testosterone level or DHEAS is 2 or more times higher than the reference range, consider PCOS, hyperthecosis, or an androgen-secreting tumor of the ovary or adrenal gland

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