Amenorrhea – Primary
Menarche occurs at an average age of 12.7 years in the U.S. Primary amenorrhea occurs when menarche remains absent at age 16, or if 5 years have passed since the onset of puberty and menarche has not begun.
Differential Diagnosis
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Constitutional delay of puberty
–Most common cause
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Anatomic causes
–Uterine aplasia (Mayer-Rokitansky
syndrome)
–Vaginal aplasia
–Imperforate hymen
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Hypogonadotropic hypogonadism
–Decreased FSH
–Congenital and acquired etiologies
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Congenital hypogonadotropic hypogonadism
–Kallmann syndrome
–Panhypopituitarism
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Aquired hypogonadotropic hypogonadism
–Malnutrition
–Stress
–Anorexia nervosa
–Inflammatory bowel disease
–Celiac disease
–Excessive exercise
–Pituitary tumor (e.g., prolactinoma or
craniopharyngioma)
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Hypergonadotropic hypogonadism
–Increased FSH
–Gonadal dysgenesis (Turner syndrome is the
most common)
–Ovarian failure: Autoimmune oophoritis, galactosemia, effects of chemotherapy or radiation, FSH or LH receptor mutations (rare)
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Abnormal thyroid function
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Androgen insensitivity syndrome
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Congenital adrenal hyperplasia and other causes of hyperandrogenism
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Medications
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Pregnancy
Workup and Diagnosis
- History
–Screen for eating disorders, weight change, colitis, excessive exercise, chronic illnesses, medications
–Family history: Age of menarche, puberty onset, autoimmune disorders, fertility issues
–Puberty history: Age of thelarche (breast development) and pubarche (pubic hair growth); lack of breast development suggests insufficient estrogen (e.g., lack of gonadotropins or ovarian insufficiency/absence)
–Abdominal pain, especially cyclic (imperforate hymen)
–Anosmia or hyposmia (seen with Kallmann syndrome)
–Headaches or visual changes (with pituitary tumors)
–Galactorrhea (with prolactinoma)
–Hirsutism, excessive weight, acne may result from
hyperandrogenism
- Physical exam
–Height, weight, Tanner staging
–Features of Turner syndrome: Short stature, ptosis,
high palate, webbed neck, shield chest, cubitus valgus,
heart murmur, sexual infantilism
–Signs of virilization: Acne and facial hair
–Visual fields and optic discs, goiter
–Striae, galactorrhea, inguinal masses
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Labs: FSH, LH, thyroid function tests, prolactin, testosterone, 17-hydroxyprogesterone, urine hCG
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Karyotype: Turner syndrome, gonadal dysgenesis, or androgen insensitivity syndrome
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Pelvic US, MRI of brain/pituitary for suspicion of pituitary mass or if hypogonadotropic hypogonadism is present with no clear precipitating factor
Treatment
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Underlying chronic illnesses, malnourished states, or hypothyroidism should be treated
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Stop medications causing hyperprolactinemia (e.g., antidepressants, phenothiazines) if safe to do so
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Prolactinomas can be treated medically with a dopamine agonist
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Other pituitary tumors will need treatment according to their specific type
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Patients with ovarian insufficiency or hypogonadotropic hypogonadism need estrogen therapy for breast development, and then should cycle estrogens and progestins to establish menses
