A 25-year-old woman comes to the office due to amenorrhea. The patient has had no changes in vision, cold or heat intolerance, or abnormal vaginal discharge. Her last menstrual period was 2 months ago. Menarche was at age 12; her menstrual cycles are normally 28 days long with 3-4 days of light bleeding. Medical history is significant for type 1 diabetes mellitus and a seizure disorder. Three months ago, the patient was hospitalized for generalized tonic-clonic seizures and phenytoin was added to her medication regimen. She has had no seizure activity since. Blood glucose levels are well controlled with insulin. She is sexually active and uses estrogen/progestin combination oral contraceptives. Four years ago, the patient underwent dilation and curettage for the termination of a pregnancy which was complicated by hemorrhage requiring a blood transfusion. She has no history of sexually transmitted infections and her last Pap test was normal. She does not use tobacco, alcohol, or illicit drugs. Temperature is 36.7 C (98.1 F), blood pressure is 110/60 mm Hg, pulse is 76/min, and respirations are 12/min. BMI is 22 kg/m². There is minimal facial acne. Visual fields are intact. The thyroid is nonenlarged with no palpable masses. The breasts are mildly tender to palpation; there are no masses or expressed nipple discharge. The abdomen is soft and nontender, with no palpable masses. Pelvic examination shows a mobile uterus with no adnexal masses. Which of the following is the most likely cause of this patient's symptoms?

Question

Quizplus · Accepted Answer

Explanation: The most common cause of secondary amenorrhea is pregnancy. This patient's recent change in antiepileptics, coupled with signs of increased estrogen (eg, breast tenderness) on examination, makes pregnancy due to oral contraceptive pill (OCP) failure the most likely scenario. Numerous commonly used antiseizure medications (eg, phenytoin, carbamazepine, ethosuximide, phenobarbital, topiramate) decrease the efficacy of OCPs by inducing cytochrome P450 system in the liver and lead to increased OCP metabolism, thus decreasing contraceptive efficacy. Alternate antiseizure medications that do not increase OCP metabolism include gabapentin and valproate. Long-acting reversible methods of contraception (eg, intrauterine device, etonogestrel implant) are not affected by P450 induction agents. They are preferred in patients of reproductive age who have seizure disorders, especially as some antiepileptics (eg, phenytoin) are associated with fetal cardiac, facial, and genitourinary malformations. (Choice B) Intrauterine adhesions (eg, Asherman syndrome) can occur after uterine instrumentation (eg, dilation and curettage) and endometritis. The typical presentation is cyclic abdominal pain and secondary amenorrhea immediately following the procedure; it is unlikely in this patient due to a history of regular menses following her dilation and curettage. (Choice C) Ovarian insufficiency is associated with autoimmune disease (eg, type 1 diabetes mellitus) and can present with secondary amenorrhea. However, it is typically associated with hypoestrogenism (eg, vaginal dryness, hot flashes) rather than signs of increased estrogen (eg, breast tenderness). (Choice D) Pituitary gland infarction (eg, Sheehan syndrome) can occur due to hypotension and massive hemorrhage; this classically occurs postpartum. Patients can have amenorrhea; however, additional features of panhypopituitarism, including hypothyroidism (eg, cold intolerance) and adrenal insufficiency (eg, electrolyte abnormalities, hyperpigmentation), are present. (Choice E) Polycystic ovary syndrome is a common cause of irregular menses but is typically associated with hirsutism and obesity. This patient's normal hair growth and BMI make this diagnosis unlikely. Educational objective: The most common cause of secondary amenorrhea is pregnancy. Medications that induce the cytochrome P450 system (eg, antiepileptics) can reduce oral contraceptive efficacy and result in unplanned pregnancy. References: Predictors of unintended pregnancy in women with epilepsy. (http://www.ncbi.nlm.nih.gov/pubmed/28122902) Counseling by epileptologists affects contraceptive choices of women with epilepsy. (http://www.ncbi.nlm.nih.gov/pubmed/27829186)

A 25-Year-Old Woman Comes to the Office Due to Amenorrhea