A 29-year-old nulligravid woman comes to the office because she has not menstruated since stopping her birth control. Menarche was at age 14, and she had irregular, heavy menstrual periods from age 14-16. The patient then took combination oral contraceptives until 6 months ago. Since stopping her medication, she has had more frequent headaches and increasing acne but has had no weight changes, pelvic pain, or abnormal hair loss or growth. The patient is a high school teacher and coaches the cross-country and track teams. She runs recreationally and eats a well-balanced diet. She does not use tobacco, alcohol, or illicit drugs. Vital signs are normal and BMI is 22 kg/m². A few open comedones are seen on the forehead. The remainder of the physical examination, including pelvic examination, is normal. Urine pregnancy test is negative and pelvic ultrasound is normal. Which of the following is the best next step in evaluation of this patient?

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11ec25c8_d996_d41f_bc81_9965427734da_MD0003_00 This patient has secondary amenorrhea, defined as amenorrhea for ≥3 months in women with previously regular menses (or ≥6 months in women with previously irregular menses). Most women have return of spontaneous menses within 1-3 months after cessation of oral contraceptives; those who do not have a return of menses (as with this patient) require further evaluation (Choice C). The most common cause of secondary amenorrhea is pregnancy, followed by hypothalamic-pituitary-ovarian (HPO) axis dysfunction (eg, functional hypothalamic amenorrhea, primary ovarian insufficiency) and endocrine abnormalities that affect the HPO axis (eg, pituitary or thyroid dysfunction). Therefore, initial evaluation is with a pregnancy test followed by serum FSH, TSH, and prolactin levels, which help differentiate between the causes of secondary amenorrhea. The results of this initial testing determine the next steps in evaluation (eg, karyotype analysis, imaging). (Choice A) Karyotype analysis is performed in patients with primary ovarian insufficiency (POI), as POI is associated with chromosomal abnormalities (eg, Turner syndrome, fragile X syndrome). However, the diagnosis of POI is made with an elevated FSH level (to postmenopausal levels) in women age <40 who have oligo- or amenorrhea. (Choice B) Prolactinomas can cause secondary amenorrhea and frequent headaches (as in this patient). However, an MRI of the pituitary is performed after patients are found to have elevated prolactin levels. In addition, this patient's headache is nonspecific and could be related to estrogen fluctuations after discontinuation of her oral contraceptives. (Choice D) Serum 17-hydroxyprogesterone is elevated in nonclassic (adult-onset) congenital adrenal hyperplasia (21-hydroxylase deficiency), which can cause abnormal uterine bleeding and hyperandrogenism (eg, severe acne, hirsutism). Although this patient has acne, it is likely due to the cessation of hormonal contraception, which typically worsens acne (due to the anti-androgenic properties of contraceptives). In addition, this patient's acne is mild and likely represents a normal variant. Educational objective: Secondary amenorrhea is amenorrhea for ≥3 months in women with previously regular menses (or ≥6 months in women with previously irregular menses). Initial evaluation includes a pregnancy test, followed by serum prolactin, TSH, and FSH level testing. References: Amenorrhea: an approach to diagnosis and management. (http://www.ncbi.nlm.nih.gov/pubmed/23939500) Using an algorithmic approach to secondary amenorrhea: avoiding diagnostic error. (http://www.ncbi.nlm.nih.gov/pubmed/23588065) Neuroendocrine causes of amenorrhea-an update. (http://www.ncbi.nlm.nih.gov/pubmed/25581597)

A 29-Year-Old Nulligravid Woman Comes to the Office Because She