The history and physical examination should guide theinvestigation. An outflow tract obstruction should be ruled outin adolescents with primary amenorrhea, abdominal pain, andsecondary sexual characteristics. An abdominal mass resulting from accumulated blood may be present. Low outflowtract obstructions, such as an imperforate hymen, are visibleon examination. An endocrine evaluation is indicated for girlswith primary amenorrhea without secondary sexual characteristics and an unremarkable history and physical examination.Elevated follicle-stimulating hormone (FSH) and luteinizinghormone (LH) indicate primary ovarian insufficiency, whichmay reflect ovarian dysgenesis or ovarian agenesis and warrantsa karyotype. Turner syndrome is a common cause, but other chromosomal anomalies, fragile X premutation carriers, andautoimmune etiologies should be ruled out. Low levels of FSHand LH suggest hypothalamic dysfunction, which may be dueto physiologic immaturity (often familial), isolated gonadotropin deficiency, or hypogonadotropic hypogonadism (chronicillness, low body weight, stressful life events). Additional hormone evaluation includes thyroid-stimulating hormone andprolactin. Hypothyroidism is a common cause of menstrualdysfunction. A prolactinoma, although rare, must be ruled out.
Girls with secondary amenorrhea have secondary sexual characteristics. The most common causes are pregnancy, anorexia/stress (low LH, FSH, and estradiol), and polycystic ovary syndrome (PCOS). In PCOS there may be symptoms of androgen excess, such as acne and hirsutism, and weight gain and, with insulin resistance, acanthosis. If hirsutism or virilization is present, free and total testosterone, androstenedione, and dihydroepiandrosterone sulfate should be measured to rule out ovarian or adrenal tumors. A normal 17-hydroxyprogesterone level rules out late-onset congenital adrenal hyperplasia. PCOS is diagnosed with two of the following: infrequent menstrual bleeding or secondary amenorrhea, clinical or biochemical hyperandrogenism, and polycystic morphology of ovaries on ultrasound. Estradiol may be normal or low; and androgens, including dihydroepiandrosterone sulfate, may be elevated, although not to the extent that a tumor produces. Patients may have impaired glucose tolerance or hypercholesterolemia.
In a patient with amenorrhea (primary or secondary), normalsecondary sex characteristics, negative pregnancy test, normalprolactin and thyroid-stimulating hormone, and no evidence of outflow tract obstruction, the total effect of estrogen on theuterus (rather than a single point estradiol level) can be determined by a progesterone withdrawal test. To achieve this, 5 to 10 mg of medroxyprogesterone (depending on body weight)is given daily for 5 days. If the uterus is normal and primed byestrogen (an intact hypothalamic-pituitary-gonadal axis) withno outflow tract obstruction, there should be bleeding within 1week after the last progesterone tablet. If there is bleeding, theamenorrhea is secondary to anovulation. If there is no progesterone withdrawal bleeding, the uterus has been insufficientlyexposed to estrogen, and there is systemic estrogen deficiency.