A 19-year-old woman comes to the office due to a 6-month history of amenorrhea. Menarche occurred at age 11, and her menstrual cycles were regular until 9 months ago. The patient has had no changes in vision or recent weight loss. She has no medical conditions or previous surgeries. The patient is in her first semester of college, where she has transitioned to collegiate-level soccer. She is taking extra classes and exercising with her team twice daily. The patient is sexually active, has no history of sexually transmitted infection, and uses condoms for contraception. She does not use tobacco, alcohol, or recreational 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 adnexa are not palpable. Pregnancy test result is negative. Prolactin and TSH levels are normal. A 10-day challenge with medroxyprogesterone acetate is initiated; no menstrual bleeding occurs. Compared to the general population, this patient is at greatest risk for which of the following?
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This athlete with increased life stressors, intensive exercise, new-onset secondary amenorrhea, and normal prolactin and TSH levels most likely has functional hypothalamic amenorrhea (FHA) (ie, hypogonadotropic hypogonadism).
Patients with FHA have decreased gonadotropin-releasing hormone (GnRH) secretion due to relative calorie deficiency (from increased energy expenditure and/or reduced calorie intake) and stress (from strenuous exercise and/or chronic illness). Decreased GnRH secretion leads to abnormal gonadotropin (FSH/LH) pulses and a low estrogen level. The low estrogen level can be confirmed with a progesterone challenge test (eg, medroxyprogesterone acetate); 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 because there is no endometrial lining to shed.
Patients with estrogen deficiency are at risk of decreased bone mineral density despite the bone-building effects of physical activity. Estrogen inhibits osteoclastic-mediated bone resorption, and decreased estrogen leads to increased bone resorption. Although estrogen repletion can offset bone loss, increasing calorie intake and/or decreasing exercise is a more effective way to increase bone density.
(Choice B) A failed progesterone challenge test can indicate intrauterine adhesions (eg, Asherman syndrome) in a patient with prior uterine instrumentation (eg, dilation and curettage). Patients with a history of tubal surgery or pelvic inflammatory disease are at increased risk for ectopic pregnancy. This patient has none of these risk factors.
(Choice C) Endometrial hyperplasia is a risk for those with unopposed estrogen stimulation from chronic anovulation, which occurs with 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 anovulation.
(Choice E) Patients with FHA have decreased estrogen levels but no vasomotor symptoms (eg, hot flashes, night sweats) or vaginal atrophy due to low basal levels of estrogen produced by the normal (yet unstimulated) ovaries. Patients with amenorrhea, vasomotor symptoms, and vaginal atrophy are more likely to have primary ovarian insufficiency.
Educational objective:
Functional hypothalamic amenorrhea results from suppression of the hypothalamic-pituitary-ovarian axis by strenuous exercise, calorie restriction, increased stress, or chronic illness. Patients are at risk for decreased bone mineral density due to estrogen deficiency.