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1
Question:

A 17-year-old girl comes to the office for evaluation of irregular menses.  The patient reports irregular menses since menarche at age 13, and her menstrual cycle has become increasingly unpredictable.  Over the past year, she has had 5 menstrual periods.  Her most recent period was 6 weeks ago and it lasted 10 days, with heavy bleeding and large clots.  The patient has also gained 10 kg (22 lb) over the last year and has been unable to lose weight despite changes in her diet.  She has no medical problems and has had no surgeries.  She does not use tobacco, alcohol, or recreational drugs.  Blood pressure is 130/80 mm Hg and pulse is 76/min.  BMI is 28 kg/m2.  Physical examination shows coarse hair along the chin.  There is no thyromegaly or palpable neck masses.  The abdomen is soft and nontender, with no striae or palpable masses.  Deep tendon reflexes of the extremities are normal, and no pedal edema is present.  Hemoglobin is 10.2 g/dL.  TSH and prolactin levels are normal.  A urine pregnancy test is negative.  Which of the following is the best next step for addressing this patient's irregular menses?

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Explanation:

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Polycystic ovary syndrome

Clinical features

  • Androgen excess (eg, acne, male pattern baldness, hirsutism)
  • Oligoovulation or anovulation (eg, menstrual irregularities)
  • Obesity
  • Polycystic ovaries on ultrasound

Pathophysiology

  • ↑ Testosterone levels
  • ↑ Estrogen levels
  • LH/FSH imbalance

Comorbidities

  • Metabolic syndrome (eg, diabetes, hypertension)
  • Obstructive sleep apnea
  • Nonalcoholic steatohepatitis
  • Endometrial hyperplasia/cancer

Treatment options

  • Weight loss (first-line)
  • Oral contraceptives for menstrual regulation
  • Letrozole for ovulation induction

This patient's irregular menses, hirsutism (eg, coarse hair along chin), and weight gain are consistent with polycystic ovary syndrome (PCOS).  Patients with PCOS often have hyperandrogenism, diagnosed either clinically (eg, hirsutism, severe acne, androgenic alopecia) or biochemically (eg, elevated testosterone levels).  Hyperandrogenism, and the subsequent hyperestrogenism (due to peripheral androgen conversion), results in chronic anovulation.  Anovulatory cycles cause irregular menses, decreased progesterone secretion, and uncontrolled endometrial proliferation from unopposed estrogen.  When menstrual periods do occur, they are often associated with heavy bleeding that may result in anemia.

The first-line therapy for menstrual regulation is a combination of weight loss and combined estrogen/progestin oral contraceptives.  Combined oral contraceptives contain progesterone to stimulate endometrial differentiation (ie, limit continued proliferation) and estrogen to stabilize the uterine lining, which restores normal cycles.  In addition, combined oral contraceptives reduce hirsutism by blocking adrenal androgen secretion and increasing production of sex hormone-binding globulin, which binds and decreases free testosterone.

(Choice A)  A CT scan of the adrenal gland can be used in the evaluation of adrenocortical tumors as causes of hyperandrogenism.  Patients with adrenocortical tumors typically have virilization (eg, clitoromegaly, deepening voice), abdominal striae, and elevated dehydroepiandrosterone sulfate levels.

(Choice C)  Letrozole, an aromatase inhibitor, is administered for ovulation induction in PCOS to treat infertility.  It does not regulate menses.

(Choice D)  Leuprolide, a gonadotropin-releasing hormone agonist, is used in the treatment of endometriosis.  Patients with endometriosis have dysmenorrhea, chronic pelvic pain, and no evidence of hyperandrogenism.

(Choice E)  Levothyroxine is used to treat hypothyroidism, which can cause irregular menses, but patients also have elevated TSH levels.  This patient has a normal TSH level.

(Choice F)  Spironolactone, an androgen receptor antagonist, is indicated for treatment of hirsutism; it does not regulate menstrual cycles.

Educational objective:
Polycystic ovary syndrome may present with irregular menses and signs of hyperandrogenism (eg, hirsutism).  Treatment involves weight loss and oral contraceptives containing estrogen and progestin to regulate menstrual cycles.