Amenorrhea

Background

• Amenorrhea is the absence of menses, categorized as either primary or secondary.
  • Primary amenorrhea is the absence of menarche in females
    • aged ≥ 15 years with normal secondary sexual development (or 5 years after initial breast development, which normally begins before 10 years of age)
    • aged ≥ 13 years with no secondary sexual characteristics
  • Secondary amenorrhea is cessation of menstruation after menarche
    • for 3 consecutive months in women with previously normal menstrual cycle (every 21-45 days)
    • for 6 consecutive months in women with previously irregular menstrual cycle
• Secondary amenorrhea is more prevalent than primary amenorrhea, often affecting female athletes.
• Causes of primary or secondary amenorrhea include pregnancy, functional hypothalamic amenorrhea, (including female athlete triad and weight loss), polycystic ovary syndrome, endocrine disorders, and less commonly genetic and congenital abnormalities.
• The major complication of amenorrhea is infertility, the treatment for which depends on the underlying cause of amenorrhea.

Evaluation

• To differentiate between primary and secondary amenorrhea, ask about onset of menarche, which occurs with normal sexual development by 15 years of age.
• For patients with suspected secondary amenorrhea, ask about
  • symptoms of
    • androgen excess
    • vasomotor instability
    • hyperprolactinemia and abnormal thyroid function
  • history of procedures and conditions that may cause intrauterine synechiae
  • contraceptive use and medication use
  • weight change and eating and exercise habits
• Physical exam should include assessment of internal and external genitalia and evaluate for signs of systemic disease. In cases of primary amenorrhea, assess Tanner stage.
• Initial testing for all patents with amenorrhea should include pregnancy testing and general endocrine workup including levels of thyroid stimulation hormone (TSH), prolactin, and luteinizing and follicle stimulating hormones.
• If evidence of hyperandrogenic state on physical exam, measure serum free and total testosterone and dehydroepiandrosterone sulfate concentrations.
• Consider pelvic ultrasound if gynecological examination is not possible or insufficient to establish presence or absence of uterus, ovaries, and any anatomic defect of the outflow tract.

Management

• Specific treatments depend on the cause of amenorrhea and may or may not result in menarche or resumption of menses.
  • For girls with delayed puberty, consider watchful waiting or short-term, low dose estrogen.
  • For women with polycystic ovary syndrome, normal weight and exercise is the recommended first-line treatment. Also consider hormonal contraceptives, metformin, and insulin-sensitizing agents.
  • For women with functional hypothalamic amenorrhea and related disorders including the female athlete triad, recommend restoration of normal weight through nutritional education and psychological counseling and reduced intensity and duration of exercise.
    • For women with pubertal hormone deficiencies or functional hypothalamic amenorrhea who failed to respond to nonpharmacologic interventions, consider estrogen with cyclic progesterone to induce or restore menses.
    • In women with hypothalamic-pituitary-peripheral axis disorders, consider leptin to restore or regulate menses.
  • Calcium (1,200 mg daily) and vitamin D (at least 800 units daily) supplements are recommended for all women with hypoestrogenic amenorrhea.
• Surgical intervention may be required to treat anatomic causes of amenorrhea such as imperforate hymen or transverse vaginal septum.
• Consider referral to specialist for most cases of primary amenorrhea and in cases where diagnosis or management of secondary amenorrhea is unclear, particularly in women with fertility concerns.