A 19-year-old woman comes to the office with a 6-month history of amenorrhea. Menarche occurred at age 11 and her menstrual cycles were regular until 9 months ago. The patient has no changes in vision or recent weight loss. She has no medical problems or previous surgeries. She eats a high-protein/low-fat diet and is a collegiate soccer player. The patient is sexually active and has no history of sexually transmitted infections. She does not use tobacco, alcohol, or illicit drugs. Blood pressure is 120/70 mm Hg and pulse is 78/min. BMI is 20 kg/m². On pelvic examination, the uterus is small, mobile, and nontender. The adnexae are not palpable. A pregnancy test is negative. Prolactin and TSH levels are normal. No menstrual bleeding occurred after a 10-day challenge with medroxyprogesterone acetate. Compared to the general population, this patient is at greatest risk for which of the following?

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11ec25c8_d99d_d813_bc81_7d6626bdbeb9_MD0003_00 An athletic patient with secondary amenorrhea, a negative pregnancy test, and normal prolactin and TSH levels has a clinical picture consistent with the diagnosis of functional hypothalamic amenorrhea. A progestin challenge test (eg, medroxyprogesterone acetate) can be performed to confirm low estrogen levels; the presence of estrogen causes proliferation of the endometrium, with subsequent sloughing after the withdrawal of progesterone. Patients without adequate estrogen will have no or minimal bleeding as there is no endometrial lining to shed. Patients with functional hypothalamic amenorrhea will demonstrate signs and symptoms of hypoestrogenemia (eg, infertility, breast atrophy). They also have decreased bone mineral density despite physical training due to the low estrogen levels offsetting the bone-building effects of exercise. Estrogen regulates the breakdown of bone by osteoclasts; in its absence, increased bone resorption occurs. Although estrogen repletion can offset bone loss, increasing caloric intake and/or decreasing exercise is a more effective means of increasing bone density. (Choice B) A failed progestin challenge test can indicate intrauterine adhesions (eg, Asherman syndrome) in a patient with a history of uterine instrumentation (eg, dilation and curettage) or endometritis, neither of which has occurred in this patient. Patients with a history of tubal surgery or pelvic inflammatory disease are at increased risk of ectopic pregnancy. A patient with intrauterine adhesions is at increased risk of infertility or recurrent abortions. (Choice C) Endometrial hyperplasia is a risk for those with unopposed estrogen stimulation from anovulatory diseases such as polycystic ovary syndrome (PCOS). Patients with PCOS will have withdrawal bleeding after a progesterone challenge test due to high levels of estrogen causing endometrial proliferation. (Choice D) A risk factor for epithelial ovarian cancer is repeated ovulation; trauma to the ovarian surface with each ovulatory cycle can result in malignant transformation. This patient has a decreased risk of ovarian cancer due to her anovulation. (Choice E) Patients with functional hypothalamic amenorrhea have decreased estrogen levels but no vasomotor symptoms (eg, hot flashes, night sweats). In patients with amenorrhea and vasomotor symptoms, another etiology (eg, primary ovarian insufficiency) should be investigated. Educational objective: Functional hypothalamic amenorrhea is due to suppression of the hypothalamic-pituitary-ovarian axis by strenuous exercise, caloric restriction, or chronic illness. Patients are at risk for decreased bone mineral density due to estrogen deficiency. References: Functional hypothalamic amenorrhea: current view on neuroendocrine aberrations. (http://www.ncbi.nlm.nih.gov/pubmed/18224538)

A 19-Year-Old Woman Comes to the Office with a 6-Month