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COPYRIGHT 2006 American Academy of Family Physicians
A thorough history and physical examination as well as laboratory testing can help narrow the differential diagnosis of amenorrhea. In patients with primary amenorrhea, the presence or absence of sexual development should direct the evaluation. Constitutional delay of growth and puberty commonly causes primary amenorrhea in patients with no sexual development. If the patient has normal pubertal development and a uterus, the most common etiology is congenital outflow tract obstruction with a transverse vaginal septum or imperforate hymen. If the patient has abnormal uterine development, mullerian agenesis is the likely cause and a karyotype analysis should confirm that the patient is 46,XX. If a patient has secondary amenorrhea, pregnancy should be ruled out. The treatment of primary and secondary amenorrhea is based on the causative factor. Treatment goals include prevention of complications such as osteoporosis, endometrial hyperplasia, and heart disease; preservation of fertility; and, in primary amenorrhea, progression of normal pubertal development.
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Primary amenorrhea can be diagnosed if a patient has normal secondary sexual characteristics but no menarche by 16 years of age. If a patient has no secondary sexual characteristics and no menarche, primary amenorrhea can be diagnosed as early as 14 years of age. Secondary amenorrhea is the absence of menses for three months in women with previously normal menstruation and for nine months in women with previous oligomenorrhea. Secondary amenorrhea is more common than primary amenorrhea. (1-3)
Pubertal changes typically occur over a three-year period and can be measured using Tanner staging. (4) The normal progression of female puberty is illustrated in Table 1. (4,5) The normal menstrual cycle involves a complex interaction between the hypothalamic-pituitary-ovarian axis and the outflow tract. Any disruption in this interaction can cause amenorrhea.
Evaluation
Physicians should conduct a comprehensive patient history and a thorough physical examination of patients with amenorrhea (Table 2 (2,6-8)). Many algorithms exist for the evaluation of primary amenorrhea; Figure 1 (1,7,9,10) is one example. Laboratory tests and radiography, if indicated, should be performed to evaluate for suspected systemic disease. If secondary sexual characteristics are present, pregnancy should be ruled out. Routine radiography is not recommended, however. (7)
[FIGURE 1 OMITTED]
Figure 2 (1-3,6) is an algorithm for the evaluation of secondary amenorrhea. The most common cause of secondary amenorrhea is pregnancy. After pregnancy is ruled out, the initial work-up should be based on patient history and physical examination findings. Prolactin levels should be checked in most patients. The risk of amenorrhea is lower with subclinical hypothyroidism than with overt disease. However, the effects of subclinical hypothyroidism on menstruation and fertility are unclear, and abnormal thyroid hormone levels can affect prolactin levels; therefore, physicians should consider measuring thyroid-stimulating hormone (TSH) levels. (3,11,12) A study (13) of 127 women with adult-onset amenorrhea showed that 7.5 percent of participants had abnormal prolactin levels and 4.2 percent had abnormal TSH levels.
[FIGURE 2 OMITTED]
If TSH and prolactin levels are normal, a progestogen challenge test (Table 3 (3,14)) can help evaluate for a patent outflow tract and detect endogenous estrogen that is affecting the endometrium. A withdrawal bleed usually occurs two to seven days after the challenge test. (3) A negative progestogen challenge test signifies an outflow tract abnormality or inadequate estrogenization. An estrogen/ progestogen challenge test (Table 3 (3,14)) can differentiate the two diagnoses. A negative estrogen/progestogen challenge test typically indicates an outflow tract obstruction. A positive test indicates an abnormality within the hypothalamic-pituitary axis or the ovaries.
Gonadotropin levels can further help determine the source of the abnormality. Elevated follicle-stimulating hormone (FSH) or luteinizing hormone (LH) levels suggest an ovarian abnormality (hypergonadotropic hypogonadism). Normal or low FSH or LH levels suggest a pituitary or hypothalamic abnormality (hypogonadotropic hypogonadism). Magnetic resonance imaging (MRI) of the sella turcica can rule out a pituitary tumor. Normal MRI indicates a hypothalamic cause of amenorrhea. (3)
Differential...
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