Review Question - QID 221293

This patient presenting with secondary amenorrhea and a history of rigorous exercise most likely has the female athletic triad. This condition includes functional hypothalamic amenorrhea.

Functional hypothalamic amenorrhea is a condition in which relative caloric deficiency leads to functional disruption of the normal pulsatile release of gonadotropin-releasing hormone (GnRH). This condition can occur due to severe caloric restriction, increased energy expenditure, or increased stress. The decreased GnRH release will result in decreased levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), disruption to estrogen levels, and amenorrhea. A common associated clinical presentation is known as the "female athlete triad," which includes decreased calorie availability or increased energy expenditure through exercise, decreased bone mineral density due to a decrease in estrogen levels, and menstrual dysfunction. Treatment includes increasing caloric intake, behavioral therapy as needed, and possible estrogen replacement therapy.

Ackerman et al. reviews the role of estrogen replacement in improving bone mineral density in patients with functional hypothalamic amenorrhea. They discuss how spine and femoral neck bone mineral density z-scores significantly increased with estrogen replacement. They recommend the use of transdermal estradiol over 12 months in improving bone mineral density in patients with functional hypothalamic amenorrhea.

Figure/Illustration A is a pelvic ultrasound demonstrating an empty uterus with a closed myometrial cavity (red circle). This finding rules out pregnancy as a cause of amenorrhea.

Incorrect Answers:
Answer 1: Anorexia nervosa will often manifest with secondary amenorrhea in women. This patient has a normal BMI and no history of disordered eating. The mechanism of amenorrhea in the setting of anorexia nervosa relates to the same hypothalamic-pituitary-ovarian axis at play in functional hypothalamic amenorrhea wherein the state of energy deficiency from inadequate caloric intake disrupts normal pulsatile GnRH secretion, leading to decreased FSH, LH, estrogen levels, and subsequent amenorrhea.

Answer 3: Hypothyroidism is a cause of secondary amenorrhea wherein abnormal thyroid function can lead to altered levels of sex hormone-binding protein, prolactin, and gonadotropin-releasing hormone, thus causing menstrual dysfunction. This patient does not present with other signs of hypothyroidism, such as fatigue, sensitivity to cold, dry skin, muscle weakness, weight gain, constipation, joint stiffness, or thinning hair.

Answer 4: Polycystic ovary syndrome is a condition often associated with obesity in which hyperinsulinemia or insulin resistance is hypothesized to alter the hypothalamus feedback response, leading to the increased luteinizing hormone to follicle-stimulating hormone ratio, increased androgen levels, and decreased rate of follicular maturation leading to unruptured follicles. Patients will often present with amenorrhea or oligomenorrhea, hirsutism, acne, and decreased fertility.

Answer 5: Pregnancy is a cause of secondary amenorrhea that is less likely in this patient given her lack of sexual history and other associated symptoms such as decreased appetite, nausea, and insomnia. A beta-human chorionic gonadotropin (beta-hCG) test should always be part of the workup for secondary amenorrhea.

Bullet Summary:
Functional hypothalamic amenorrhea is a condition in which caloric restriction, increased energy expenditure through exercise, and/or increased stress leads to a disrupted pulsatile secretion of gonadotropin-releasing hormone with the downstream effect of amenorrhea.