A 16-year-old girl comes to the office for a pre-participatory school sports examination. She plays on her high school soccer team and also frequently competes in local beauty pageants. The patient follows strict dietary limitations and exercises strenuously 2 hours a day. Onset of menses was at age 13, but her last menstrual period was 8 months ago. She otherwise feels well. Her height is 165 cm (5 ft 5 in) and her weight is 45.3 kg (100 lb), with a BMI of 16.6 kg/m². Physical examination shows a pale and thin girl with fine hair around her trunk, but the remainder is otherwise normal. Urine pregnancy test is negative. Which of the following is the most likely mechanism of her amenorrhea?

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11ec160b_3aaf_9797_9249_a5a4e620980e_MD0001_00 Amenorrhea can be categorized as primary (failure of menarche prior to age 15) or secondary (cessation of menstruation in premenopausal women who previously have had menses). Secondary amenorrhea can be due to hypothalamic, pituitary, ovarian, uterine, or other endocrine (eg, thyroid) disorders. This patient has secondary amenorrhea associated with low body weight, frequent strenuous exercise, and lanugo (fine hair indicating inadequate caloric intake), suggesting functional hypothalamic amenorrhea (FHA). FHA is commonly seen in competitive athletes, dancers, fashion models, and others who maintain very low body weights. The underlying pathophysiology of FHA is incompletely understood but appears to involve reduced circulating leptin levels as a result of diminished adipose tissue stores. The decrease in leptin levels inhibits pulsatile gonadotropin-releasing hormone (GnRH) release from the hypothalamus, causing decreased pituitary LH and FSH secretion, low circulating estrogen levels, and amenorrhea. (Choice A) Like FHA, hyperprolactinemia can cause secondary amenorrhea by suppressing normal GnRH release in the hypothalamus. Affected women may also develop galactorrhea. However, this patient's low body weight, caloric restriction, and strenuous exercise regimen are more consistent with FHA. (Choice B) Hyperthyroidism can cause irregular menses or amenorrhea, along with weight loss. However, this patient has no other features to suggest a thyroid disorder (eg, goiter, temperature intolerance, diarrhea, hair loss). (Choices D and E) The amenorrhea in patients with FHA stems from a deficiency in hypothalamic GnRH release, rather than a problem with the pituitary or ovaries; this patient has no other features of hypopituitarism. Educational objective: Functional hypothalamic amenorrhea results from loss of pulsatile gonadotropin-releasing hormone release from the hypothalamus and is caused by weight loss, strenuous exercise, systemic illness, or abnormal eating habits. Loss of cyclic gonadotropin release leads to a decrease in LH and FSH secretion from the pituitary, which in turn causes low circulating estrogen levels. __________ References: Functional hypothalamic amenorrhea: current view on neuroendocrine aberrations. (http://www.ncbi.nlm.nih.gov/pubmed/18224538)

A 16-Year-Old Girl Comes to the Office for a Pre-Participatory