Amenorrhea

• Amenorrhea


  The absence of menses
• Primary amenorrhea


  The absence of menarche (first menses) by age 16 or no menstruation by 4 years after thelarche (the onset of breast development)
• Secondary amenorrhea


  The absence of menses for three menstrual cycles or a total of 6 months in women who have previously had normal menstruation
• The prevalence of primary amenorrhea in the United States is 1% to 2%
• Causes of primary amenorrhea

  • Congenital and chromosomal abnormalities
  • Hormonal aberrations
  • Hypothalamic-pituitary disorders
  • Causes of secondary amenorrhea that may present before menarche
• Categories of primary amenorrhea


  • Outflow tract obstruction
  • End-organ disorders
  • Central regulatory disorders
• Imperforate hymen


  • Failure of the hymen to canalize during fetal development, resulting in a solid membrane across the vaginal introitus
  • Prevents egress of menstrual blood or menses
  • Leads to accumulation and dilation of the vaginal vault and uterus by menses, causing pelvic or abdominal pain
• Transverse vaginal septum


  Failure of the Müllerian-derived upper vagina to fuse with the urogenital sinus-derived lower vagina, resulting in an imperforate transverse vaginal septum
• Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome


  Müllerian agenesis or dysgenesis, resulting in complete vaginal agenesis and absence of a uterus or partial vaginal agenesis with a rudimentary uterus and distal vagina
• Testicular feminization (androgen insensitivity syndrome)

  Dysfunction or absence of the testosterone receptor, leading to a phenotypical female with 46,XY chromosomes
• Causes of primary ovarian failure

  • Idiopathic premature ovarian failure
  • Steroidogenic enzyme defects
  • Testicular regression syndrome
  • True hermaphroditism
  • Gonadal dysgenesis
  • Ovarian resistance syndrome (Savage syndrome)
  • Autoimmune oophoritis
  • Postinfection
  • Postoophorectomy
  • Postirradiation
  • Postchemotherapy
• Swyer syndrome


  Congenital absence of the testes in a genotypically male individual, resulting in a phenotypically female appearance
• Kallmann syndrome


  Congenital absence of GnRH and anosmia, due to disrupted migration of GnRH neurons from the olfactory placode to the hypothalamus
• Primary defects of the pituitary are a rare cause of primary amenorrhea, as pituitary dysfunction is usually secondary to hypothalamic dysfunction
• Hemosiderosis can result in iron deposition in the pituitary, leading to destruction of the gonadotrophs that produce FSH and LH
• Diagnosis of primary amenorrhea

  1. Assess presence/absence of uterus

  2. Assess presence/absence of breasts

  3. Perform karyotype

  4. Perform progesterone challenge
• Causes of primary amenorrhea

  • Uterus present
  • Gonadal failure/agenesis in 46,XX
  • Disruption of hypothalamic-pituitary axis
  • Hypothalamic, pituitary, or ovarian pathogenesis
  • Congenital abnormalities of the genital tract
• Congenital abnormalities of the genital tract

  • Imperforate hymen
  • Transverse vaginal septum
  • Vaginal agenesis
• Congenital abnormalities of the genital tract

  • Patent vagina
• Congenital abnormalities of the genital tract

  • Uterus present
  • Breasts absent
• Congenital abnormalities of the genital tract

  • Karyotype: testicular feminization, Müllerian agenesis, 46,XY steroid enzyme defects, pure gonadal dysgenesis, or anorchia
• Progesterone challenge


  Consider as if progesterone challenge negative
• Figure 21-1 Diagnostic flowchart for patients with primary amenorrhea.
• Release of MIF by the testes and in females with Müllerian agenesis. Breast development is dependent on estradiol secretion by the ovaries. Patients who have neither a uterus nor breasts are generally 46,XY males with steroid synthesis defects or varying degrees of gonadal dysgenesis, in which adequate MIF is produced by gonadal tissue but androgen synthesis is insufficient.
• If breasts are present but no uterus, the etiologies can include congenital absence of the uterus (Müllerian agenesis) in the female or testicular feminization in the male. In the latter case, estradiol from direct testicular secretion as well as peripheral conversion of testosterone and androstenedione leads to breast development. The presence of a normal amount and distribution of pubic hair supports Müllerian agenesis, whereas absent or scant pubic hair indicate androgen insensitivity.
• For patients who have a uterus but breast development is absent, the differential includes hypergonadotropic hypogonadism, as seen in gonadal dysgenesis in both sexes, and with defects in steroid pathways in 46,XX patients and hypogonadotropic hypogonadism, which is seen in CNS, hypothalamic, and pituitary dysfunction. A serum FSH level differentiates between these two, with elevation seen in hypergonadotropic hypogonadism.
• The workup for amenorrhea in phenotypic females with the absence of either a uterus or breasts should include a karyotype analysis, followed by testosterone and FSH assays. Further biochemical and hormonal assays may be performed to elucidate specific enzyme defects. Patients with both a uterus and breast development should be evaluated to determine whether there is a patent outflow tract from the uterus. If the vagina, cervix, and uterus are continuous, these can be evaluated as if the patient were presenting with secondary amenorrhea.