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  • Amenorrhea is literally defined as the absence of menses.
  • Primary amenorrhea (seen in approximately 2.5% of the population) is clinically defined as the absence of menses by age 13 years in the absence of normal growth or secondary sexual development, or the absence of menses by age 15 years in the setting of normal growth and secondary sexual development.
    • Traditionally, evaluation was usually initiated by age 16 years if normal growth and secondary sexual characteristics were present, and at age 14 years if absent.
    • Because of secular trends toward earlier menarche over the past half century, the evaluation should begin at age 15 years, the age when more than 97% of girls should have experienced menarche.
    • The decision to evaluate should be made with a full understanding of the patient's clinical presentation.
    • Evaluation should not be delayed in the setting of neurologic symptoms (suggestive of hypothalamic–pituitary lesion) or pelvic pain (suggestive of outflow obstruction).
  • Secondary amenorrhea is clinically defined as the absence of menses for more than 3 cycle intervals, or 6 consecutive months, in a previously menstruating woman.
    • The incidence of secondary amenorrhea can be quite variable, from 3% in the general population to 100% under conditions of extreme physical or emotional stress.
    • Table 54–1 lists the most common causes of secondary amenorrhea.

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Table 54–1. Causes of Secondary Amenorrhea.

Menstruation has long been an important societal marker of female sexual development, as well as one of the most tangible signs of female endocrine and reproductive tract maturation. Regular and spontaneous menstruation requires (1) functional hypothalamic–pituitary–ovarian endocrine axis, (2) an endometrium competent to respond to steroid hormone stimulation, and (3) an intact outflow tract from internal to external genitalia.


The human menstrual cycle is susceptible to environmental influences and stressors. Thus missing a single or occasional menstruation rarely reflects a significant pathology. However, prolonged or persistent absence of menses may be one of the earliest signs of neuroendocrine or anatomic abnormality.


Diagnosing and treating amenorrhea is important because of the implications for future fertility; risks of unopposed estrogen, including endometrial hyperplasia and neoplasia; risks of hypoestrogenism, including osteoporosis and urogenital atrophy; and impact on psychosocial development. Because of their significant overlap in etiology and treatment, primary and secondary amenorrhea are discussed collectively in this chapter.


Pregnancy is the most common cause of amenorrhea and must be considered in every patient presenting for evaluation of amenorrhea. Amenorrhea caused by aberrations of the normal menstrual cycle is discussed in Chapter 4. Chapters 37 and ...

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