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Diagnosis

Females who have menstrual cycles lasting longer than 45 days and/or amenorrhea for three or more months should be evaluated for FHA. Differentiating FHA from the irregular menstrual patterns seen in adolescents during the initial years after menarche due to immaturity of the HPO axis can be challenging. However, studies have shown that even during this period, the length of a menstrual cycle does not exceed 45 days. Furthermore, healthy girls with normal BMI (18.5–24.9 kg/m 2) should develop regular menstrual cycles (every 28 +/- 3–5 days) within 1–2 years after menarche. FHA is a diagnosis of exclusion, because the diagnosis can only be made when menstruation has ceased in that absence of organic or anatomic pathology, and thus the evaluation should be used to rule out organic causes of amenorrhea (e.g., pregnancy, thyroid disorders, inflammatory bowel disease, etc.) Endocrinologic etiologies of the thyroid, pituitary, and adrenal glands, ovarian failure, and hyperandrogenism including polycystic ovarian syndrome (PCOS) must be excluded before a diagnosis of FHA can be given. A GnRH stimulation or challenge test should be used to identify FHA as the cause hypogonadotropic hypogonadism in women presenting with symptoms, as hypothalamic dysfunction due to delayed-onset puberty or other pituitary disease will not respond to exogenous GnRH. Hypothalamic disorders are differentiated when GnRH administration results in abnormal increases of gonadotropins. Combined pituitary and hypothalamic impairment is differentiated when there is a decreased or absent response to GnRH secretion; as a result, it impossible to determine if the observed low levels of FSH/LH are due to hypothalamic or pituitary dysfunction, and pulsatile GnRH administration with cyclomate is required to diagnose this distinction (pulsatile LH-RH challenge).