A 19-year-old woman comes to the office for evaluation of amenorrhea. The patient underwent menarche at age 12, and she previously had menses regularly every 25-28 days. However, for the past year, her menses have been irregular, and her last menstrual period was 3 months ago. The patient has no significant medical history, eats mainly fruits and vegetables, and exercises regularly at a local gym. On further questioning, she expresses concern about being overweight and asks for suggestions on cutting down her caloric intake. BMI is 18 kg/m2. The patient is thin and has dry skin covered by fine, downy hair. A pregnancy test is negative. Which of the following laboratory findings are most likely present in this patient?
Show Explanatory Sources
Amenorrhea is categorized as primary (no onset of menarche by age 15) or secondary (no menses for ≥3 months in premenopausal patients with previously regular menses). This patient has secondary amenorrhea, which usually occurs due to endocrine dysfunction (eg, hypothalamic-pituitary-ovarian axis dysfunction, thyroid disorder), pregnancy, or intrauterine adhesions (ie, Asherman syndrome).
This patient's distorted body image (feeling overweight despite underweight BMI), restricted diet, exercise regimen, dry skin, and lanugo (fine hair indicating inadequate caloric intake) suggest anorexia nervosa, a common cause of functional hypothalamic amenorrhea (FHA). The pathophysiology of FHA is incompletely understood but is thought to arise due to diminished adipose tissue stores, which reduce circulating leptin levels. In response, the hypothalamus decreases the amplitude and frequency of pulsatile gonadotropin-releasing hormone (GnRH) release, leading to low GnRH levels, decreased pituitary LH and FSH secretion, low circulating estrogen levels, anovulation, and amenorrhea (Choices C and E).
In addition to anorexia nervosa, FHA can also occur when caloric expenditure is out of proportion to intake, such as in female athletes (eg, distance runners, dancers) or patients with chronic illness, particularly those with low adipose stores. FHA is a form of hypogonadotrophic (low LH and FSH) hypogonadism (low estrogen). Therefore, potential complications in young patients include reduced peak bone mass, which may lead to early-onset osteoporosis.
(Choice A) Low circulating estrogen levels despite increased GnRH and FSH secretion are consistent with a primary ovarian disorder (eg, primary ovarian insufficiency [POI], menopause). POI is associated with Turner syndrome and prior chemoradiation, not anorexia nervosa.
(Choice B) Pituitary dysfunction, which includes anatomic (eg, prolactinoma) and functional disorders (eg, hypopituitarism due to infarction [Sheehan syndrome]), can cause hypogonadotropic hypogonadism and amenorrhea characterized by increased GnRH, low FSH and LH, and low estrogen. However, prolactinomas typically present with additional clinical features (eg, bilateral galactorrhea), and Sheehan syndrome is usually associated with prior hemorrhage, particularly obstetric hemorrhage.
Educational objective:
Functional hypothalamic amenorrhea is a common cause of secondary amenorrhea and occurs due to decreased amplitude and frequency of pulsatile gonadotropin-releasing hormone release from the hypothalamus, which in turn leads to low FSH, LH, and estrogen levels. Causes include anorexia nervosa (eg, distorted body image, restricted diet, lanugo), excessive strenuous exercise, and chronic illness.