This week, we are sharing another USMLE® Step 1-style practice question to test your knowledge of medical topics. Today’s case focuses on a 16-year-old girl with a history of menarche at age 13 presents with amenorrhea for the last 5 months. She has joined the gymnastics team at school and is trying to lose weight. Her parent is concerned about her eating habits, and the patient reports being afraid of gaining weight and dissatisfaction with her body. Physical examination reveals hair loss on the head, Tanner stage V breasts, and soft, unpigmented hair growth over the arms. Which of the following hormonal changes is most likely responsible for this patient’s amenorrhea? Can you figure it out?
A 16-year-old girl is brought to the physician by her parent due to the absence of consistent menstrual cycles. The patient has not had any menstrual cycles for the last 5 months. Menarche occurred at age 13. She has recently joined the gymnastics team at school and is trying to exercise and lose weight. Her parent is worried about her eating habits because she has been eating less to lose weight even though she is already thin. The patient tells the physician she is afraid of gaining weight and that she “does not like how her body looks.” Her BMI is 17.4 kg/m2. On physical examination, hair loss is noticed on the head, and the breasts are Tanner stage V. There is growth of soft, unpigmented hair over the arms. Which of the following hormonal changes is most likely responsible for this patient’s amenorrhea?
| Gonadotropin-Releasing Hormone (GnRH) | Luteinizing hormone (LH) | Estrogen | |
| A. | Decreased | Decreased | Decreased |
| Gonadotropin-Releasing Hormone (GnRH) | Luteinizing hormone (LH) | Estrogen | |
| B. | Increased | Increased | Decreased |
| Gonadotropin-Releasing Hormone (GnRH) | Luteinizing hormone (LH) | Estrogen | |
| C. | Normal | Normal | Normal |
| Gonadotropin-Releasing Hormone (GnRH) | Luteinizing hormone (LH) | Estrogen | |
| D. | Increased | Decreased | Decreased |
| Gonadotropin-Releasing Hormone (GnRH) | Luteinizing hormone (LH) | Estrogen | |
| E. | Increased | Increased | Increased |
Scroll down to find the answer!
The correct answer to today’s USMLE® Step 1 Question is…
| Gonadotropin-Releasing Hormone (GnRH) | Luteinizing hormone (LH) | Estrogen | |
| A. | Decreased | Decreased | Decreased |
Before we get to the Main Explanation, let’s look at the incorrect answer explanations. Skip to the bottom if you want to see the correct answer right away!
Incorrect answer explanations
The incorrect answers to today’s USMLE® Step 1 Question are…
| Gonadotropin-Releasing Hormone (GnRH) | Luteinizing hormone (LH) | Estrogen | |
| B. | Increased | Increased | Decreased |
Incorrect: These labs are seen in patients with primary ovarian insufficiency; however, this patient’s amenorrhea is likely a complication of anorexia nervosa, in which calorie restrictions result in decreased GnRH release, with subsequent decreases in LH and estrogen, and resultant anovulation.
| Gonadotropin-Releasing Hormone (GnRH) | Luteinizing hormone (LH) | Estrogen | |
| C. | Normal | Normal | Normal |
Incorrect: The patient in this vignette is most likely suffering from anorexia nervosa, wherein there is decreased GnRH, LH, and estrogen.
| Gonadotropin-Releasing Hormone (GnRH) | Luteinizing hormone (LH) | Estrogen | |
| D. | Increased | Decreased | Decreased |
Incorrect: These labs indicate a pituitary pathology causing amenorrhea. This patient’s presentation is most consistent with anorexia nervosa, which causes a different set of laboratory abnormalities.
| Gonadotropin-Releasing Hormone (GnRH) | Luteinizing hormone (LH) | Estrogen | |
| E. | Increased | Increased | Increased |
Incorrect: This patient has amenorrhea, indicating decreased gonadotropic hormones, not increased.
Main Explanation
This patient is most likely experiencing amenorrhea due to calorie restriction and weight loss secondary to an underlying diagnosis of anorexia nervosa. Anorexia nervosa is an eating disorder characterized by low body weight, a distorted body image, and an intense fear of gaining weight accompanied by aggressive weight-loss behaviors (e.g., calorie restriction, excessive exercising).
Anorexia nervosa is associated with multiple complications in almost every organ in the body due to malnutrition and weight loss. Because of the calorie restriction and starvation, protein and fat catabolism results in atrophy in the brain, heart, intestines, muscles, and kidneys. In addition, hormonal disturbances are common in patients with anorexia. Due to severe malnutrition, the hypothalamic-pituitary-gonadal axis is often disturbed in both males and females. Patients with anorexia have decreased GnRH release, leading to decreased LH and FSH, which subsequently decreases estrogen and testosterone. This hormonal disturbance leads to infertility, decreased sexual function, and amenorrhea in females. Amenorrhea in females with anorexia nervosa is one of the most common manifestations of the condition.
In addition, patients tend to have high cortisol and an elevated growth hormone (GH), while insulin-like growth factor-1 is low, indicating GH resistance. Finally, these patients often have thyroid hormone disturbances similar to a euthyroid sick syndrome, in which T3 is low but TSH is normal. T4 is usually variable.
Other complications of anorexia include:
- Gastrointestinal: constipation, bloating, elevated liver enzymes
- Neurological: confusion, altered mental status
- Dermatological: hair loss, lanugo hair growth (growth of soft, unpigmented hair), dry scaly skin
- Hematological: pancytopenia
- Musculoskeletal: muscle atrophy, osteopenia, osteoporosis
Major Takeaway
Amenorrhea is commonly seen in female patients with anorexia nervosa. Calorie restriction results in disruption of the hypothalamic-pituitary-gonadal axis, which is characterized by decreased gonadotropin-releasing hormone (GnRH) release, resulting in low luteinizing hormone (LH) production, low estrogen levels, and anovulation.
References
Mehler, P. S., & Brown, C. (2015). Anorexia nervosa – medical complications. Journal of eating disorders, 3, 11. https://doi.org/10.1186/s40337-015-0040-8
Moore CA, Bokor BR. Anorexia Nervosa. [Updated 2020 Nov 23]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459148/ _________________________
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