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  • amenorrhea is not usually a common ED presentation as most are managed by general practitioners but nevertheless it may need consideration in the ED setting, usually in terms of whether a patient is pregnant or not, or in the Mx of episodes of menorrhagia / PV bleeding.
  • in evolutionary terms, most women were probably amenorrhoeic for most of their lives as they were either prepubertal, pregnant, lactating or post-menopausal, or during times of famine or stress, they became amenorrhoeic through a functional hypothalamic mechanism to avoid becoming pregnant at high risk times. Indeed, unnecessary loss of protein and iron through menses would not be an evolutionary advantage.
  • a critical body fat level must be present to have a functioning reproductive system.
    • women who mainly eat raw food rather than cooked have increasing high rates of amenoorrhoea (50% if never eat cooked food), cooking starch or meat foods softens food making it easier to digest, and also increases the amount of energy that can be absorbed from the meal by 30-50% and dramatically reduces the amount that reaches the colon and becomes fermented by colonic bacteria
  • normal menses occurs as a result of failure to become pregnant after ovulation.
  • ovulation is controlled by GnRH produced by the hypothalamus and resultant pulsed release of FSH and LH from the anterior pituitary which act upon the ovary to produce ovulation.
  • the ovaries produce inhibin and activin which feedback to the anterior pituitary, and oestrogens and progestogens which feedback to both the anterior pituitary and the hypothalamus (negative feedback in luteal phase, and positive feedback in follicular phase).
  • regular menses is a sign that the ovaries are producing normal amounts of estrogen, androgens, and progesterone. These sex hormones play an important role in building and maintaining bone mass and preventing osteoporosis.
  • late menarche has been associated with a 3-fold increase in the risk of wrist fracture.


  • prepubertal
  • pregnancy
  • lactation
  • menopause
  • hypogonadotropic hypogonadism:
    • progesterone based contraceptives such as implants
    • functional hypothalamic amenorrhoea:
      • a reversible form of GnRH deficiency commonly triggered by stressors such as:
        • excessive exercise:
          • the female athletic triad is characterized by disordered eating, amenorrhoea, and osteoporosis.
          • ~50% of such exercising women are likely to become amenorrhoeic
        • nutritional deficits and eating disorders (often occurs when body weight falls below 48kg for an average height person)
        • rapid weight loss
        • low BMI, raw foodists
        • psychological stress, depression
        • severe chronic disease
        • recreational and psychotropic drug use
      • susceptibility appears to relate to heterozygous mutations in certain genes which are involved in idiopathic hypogonadotropic hypogonadism - a congenital form of GnRH deficiency1).
    • hyperprolactinaemia:
      • hyperprolactinemia is associated with suppression of the GnRH from the hypothalamus, and persistent hyperprolactinemia is most commonly caused by pituitary microadenoma
      • nipple stimulation including that associated with dermatoses
    • pituitary causes:
      • GnRH receptor mutations - generally have low FSH and oestradiol levels and high LH levels
      • pituitary microadenoma causing persistent hyperprolactinaemia - remember the pressure effects on the optic chiasm and result possible visual field defects
      • pituitary damage from brain injury, irradiation or tumours
      • empty sella syndrome, pituitary infarct
      • haemochromatosis
      • sarcoidosis
    • rarely, congenital idiopathic hypogonadotropic hypogonadism or Kallman syndrome (associated with anosmia)
  • ovarian causes:
    • primary insufficiency (eg. Turner's syndrome)
    • premature ovarian failure and premature menopause - effects 1 in 10,000 by age 20yrs, 1 in 1,000 by age 30yrs, 1 in 250 by age 35yrs and 1 in 100 by age 40yrs; 6% of cases are associated with Fragile X premutation, 3-4% are due to autoimmune causes.
    • gonadal dysgenesis - have significantly elevated FSH levels due to the absence of ovarian follicles and reduction in negative feedback on FSH from estradiol and inhibin A and B.
  • imperforate hymen
  • primary amenorrhoea:
    • ie. failure of menses to occur by age 16 years but should be Ix if no menses by age 13 years and no evidence of secondary sex characteristics developing
    • absent uterus:
      • check karyotype: if 46XX then Mullerian agenesis, etc, if 46XY then consider androgen insensitivity syndrome, vanishing testes syndrome or 5 alpha reductase deficiency.
    • uterus present:
      • FSH and LH < 5IU/L:
        • hypogonadotropic hypogonadism (28% of cases - see above)
      • FSH > 20 IU/L and LH > 40 IU/L:
        • hypergonadotropic hypogonadism (48% of cases):
          • check karyotype: if 46XX then consider premature ovarian failure, if 46XO then Turner's syndrome
NEJM Jan 20 2011 364:3
amenorrhoea.txt · Last modified: 2020/01/31 23:13 (external edit)