Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.

A 24-year-old woman is evaluated for irregular menses and infertility. She reports having had normal puberty but having irregular menses until she started taking an oral contraceptive pill.

She has been unable to become pregnant since marrying 1 year ago despite regular intercourse and discontinuing the oral contraceptive pill; during the past year, she has menstruated three times. The patient has never had acne or facial hair. She was a track athlete in high school and college and still enjoys distance running, typically running 50 miles per week. There is no family history of infertility or an endocrine disorder.

On physical examination, blood pressure is 100/68 mm Hg, pulse rate is 52/min, and BMI is 16. Visual fields are full to confrontation. The patient has small breasts without galactorrhea and no facial hair or acne. Pubic hair is normal.

Laboratory studies:

Human chorionic gonadotropin	Negative for pregnancy
Prolactin	16 ng/mL (16 µg/L)
Follicle-stimulating hormone	2 mU/mL (2 U/L)
Thyroid-stimulating hormone	1.2 µU/mL (1.2 mU/L)

Which of the following is the most appropriate next step in management?

A) Clomiphene therapy
B) Pelvic ultrasonography
C) Progestin withdrawal challenge
D) Weight gain and decreased exercise

Answer and critique

The correct answer is D) Weight gain and decreased exercise. This item is available to MKSAP 15 subscribers as item 66 in the Endocrinology and Metabolism section.

This patient should stop or reduce exercising and gain some weight to restore normal menses and fertility. Hypothalamic amenorrhea (or oligomenorrhea, in this patient’s case) involves disordered gonadotropin release and may be the result of a tumor or infiltrative lesion (such as lymphoma or sarcoidosis) but more commonly is functional. The usual functional causes are stress, excessive loss of body weight or fat, excessive exercise, or some combination thereof; BMI is typically less than 17. Diagnosis of functional hypothalamic amenorrhea is one of exclusion, and the minimal evaluation includes a pregnancy test and measurement of serum prolactin, thyroid-stimulating hormone, and follicle-stimulating hormone levels to rule out prolactinoma, thyroid problems, and ovarian failure, respectively. If a functional etiology is still suspected, decreased exercise, improved nutrition, and attention to emotional needs are helpful adjuncts to restore normal menses and fertility.

Although clomiphene can be used to induce ovulation and pelvic ultrasonography can be used to assess reproductive anatomy, the pretest probability of functional hypothalamic amenorrhea is sufficiently high that conservative treatment should be recommended first.

If results of the initial laboratory assessment are normal, the next step in evaluation of patients with amenorrhea is the progestin withdrawal challenge. Menstrual flow on progestin withdrawal indicates relatively normal estrogen production and a patent outflow tract. However, this patient already has occasional menses, so even if she does have progestin withdrawal bleeding, the test result would be of limited value.

Key Point

• Functional hypothalamic amenorrhea, which is usually caused by excessive loss of body weight or fat or excessive exercise, is a diagnosis of exclusion.

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