Amenorrhea refers to the absence of menstrual periods. It is classified as primary, if menstrual bleeding has never occurred by age 15 in the absence of hormonal treatment, or secondary, if menstrual periods are absent for >3 months in a woman with previous periodic menses. Pregnancy should be excluded in women of childbearing age with amenorrhea, even when history and physical examination are not suggestive. Oligomenorrhea is defined as a cycle length of >35 days or <10 menses per year. Both the frequency and amount of bleeding are irregular in oligomenorrhea. Frequent or heavy irregular bleeding is termed dysfunctional uterine bleeding if anatomic uterine lesions or a bleeding diathesis has been excluded.
The causes of primary and secondary amenorrhea overlap, and it is generally more useful to classify disorders of menstrual function into disorders of the uterus and outflow tract and different causes for abnormal ovulation (Fig. 178-1).
Anatomic defects of the outflow tract that prevent vaginal bleeding include absence of vagina or uterus, imperforate hymen, transverse vaginal septae, and cervical stenosis.
Women with amenorrhea and low FSH and LH levels have hypogonadotropic hypogonadism due to disease of either the hypothalamus or the pituitary. Hypothalamic causes include congenital idiopathic hypogonadotropic hypogonadism, hypothalamic lesions (craniopharyngiomas and other tumors, tuberculosis, sarcoidosis, metastatic tumors), hypothalamic trauma or irradiation, vigorous exercise, eating disorders, stress, and chronic debilitating diseases (end-stage renal disease, malignancy, malabsorption). The most common form of hypothalamic amenorrhea is functional, reversible gonadotropin-releasing hormone (GnRH) deficiency due to psychological or physical stress, including excess exercise, malnutrition, and anorexia nervosa. Disorders of the pituitary include rare developmental defects, pituitary adenomas, granulomas, postradiation hypopituitarism, and Sheehan’s syndrome. They can lead to amenorrhea by two mechanisms: direct interference with gonadotropin production, or inhibition of GnRH secretion via excess prolactin production (Chap. 171: Disorders of the Anterior Pituitary and Hypothalamus).
Women with amenorrhea and high FSH levels have ovarian failure, which may be due to Turner’s syndrome, pure gonadal dysgenesis, premature ovarian insufficiency, the resistant-ovary syndrome, and chemotherapy or radiation therapy for malignancy. The diagnosis of premature ovarian insufficiency is applied to women who cease menstruating before age 40.
Polycystic ovarian syndrome (PCOS) is characterized by the presence of clinical or biochemical hyperandrogenism (hirsutism, acne, male pattern baldness) in association with amenorrhea or oligomenorrhea. The metabolic syndrome and infertility are often present; these features are worsened with coexistent obesity. Additional disorders with a similar presentation include excess androgen production from adrenal or ovarian tumors and adult-onset congenital adrenal hyperplasia. Hyperthyroidism may be associated with oligo- or amenorrhea; hypothyroidism more typically with metrorrhagia.
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