Amenorrhea: Causes

Pathogenesis (development of disease)

Primary amenorrhea can be distinguished from secondary amenorrhea.Primary amenorrhea is usually caused by a developmental or hormonal disorder.Secondary amenorrhea is predominantly caused by hormonal disorders. Pregnancy and lactation amenorrhea are considered physiological conditions.

Etiology (Causes)

Biographic causes

  • Genetic burden from parents, grandparents.
    • Genetic diseases
      • Adrenogenital syndrome (AGS) – autosomal recessive inherited metabolic disorder characterized by disorders of hormone synthesis in the adrenal cortex. These disorders lead to a deficiency of aldosterone and cortisol.
      • Hemochromatosis (iron storage disease) – genetic disease with autosomal recessive inheritance with increased deposition of iron as a result of increased iron concentration in the blood with tissue damage.
      • Kallmann syndrome (synonym: olfactogenital syndrome): genetic disorder that can occur sporadically or be inherited in an autosomal-dominant, autosomal-recessive, or X-linked recessive manner; symptom complex consisting of hypo- or Anosmia (decreased to absent sense of smell) in conjunction with testicular or ovarian hypoplasia (defective development of the testis or ovaries, respectively); prevalence (disease frequency) in males 1: 10,000 and in females 1: 50,000.
      • Mayer-von-Rokitansky-Küster-Hauser syndrome (MRKH syndrome or Küster-Hauser syndrome) – genetic disorder with autosomal dominant inheritance; congenital malformation of the female genitalia due to inhibition malformation of the Müller ducts in the second embryonic month. Ovarian function (estrogen and progestin synthesis) is not impaired, allowing normal development of secondary sexual characteristics.
      • Laurence-Moon-Biedl-Bardet syndrome (LMBBS) – rare genetic disorder with autosomal recessive inheritance; according to clinical symptoms is divided into:
        • Laurence-Moon syndrome (without polydactyly, i.e., without the appearance of supernumerary fingers or toes, and obesity, but with paraplegia (paraplegia) and muscle hypotonia/reduced muscle tone) and
        • Bardet-Biedl syndrome (with polydactyly, obesity and peculiarities of the kidneys).
  • Malformations or defects (vaginal and uterine malformations: see below).
  • Intersexuality – persons with male and female sexual characteristics.
  • Hormonal factors
    • Prepuberty
    • Premature Menopause – Premature Ovarian Failure (POF): a woman may enter menopause prematurely when egg reserves are depleted prematurely.
    • The average age for entering menopause (menopause) is currently circa 51 years. However, if the egg reserves are used up prematurely (due to follicular atresia), ovulation will not occur and menstruation may also stop prematurely. If this happens in women under 40 years of age, it is called premature menopause. This occurs in 1-4% of women.
    • Postmenopause
  • Disaster situations

Behavioral causes

  • Consumption of stimulants
    • Alcohol
  • Drug use
    • Amphetamines (indirect sympathomimetic).
    • Heroin
    • LSD (lysergic acid diethylamide/lysergide)
  • Physical activity
    • Competitive sports
  • Psycho-social situation
    • Psychosocial stress
  • Overweight (BMI ≥ 25; obesity).

Disease-related causes

  • Diseases of endocrine organs
    • Adrenal gland
    • Ovary (ovary)
      • Ovarian hypoplasia – underdevelopment of the ovaries due to various conditions such as Turner syndrome (gonadal dysgenesis).
      • Premature menopause/early menopause).
    • Pancreas (diabetes mellitus)
    • Thyroid (e.g., hypothyroidism/ hypothyroidism).
  • Genital causes (uterine and/or vaginal malformations or defects):
    • Gynatresia (malformations of the internal female reproductive organs summarized, in which cavities or ducts of the internal female reproductive organs are occluded by inhibitory malformations):
      • Laurence-Moon-Biedl-Bardet syndrome (LMBBS) (see “Genetic disorders” below).
      • Mayer-von-Rokitansky-Küster-Hauser syndrome (MRKH syndrome or Küster-Hauser syndrome) (see “Genetic disorders” below).
    • Asherman syndrome – loss of the endometrium due to severe inflammation or trauma.
    • Genital tuberculosis
  • Hypothalamic-pituitary disorders
    • Genetic defects (Kallman syndrome) (see “Genetic disorders” below).
    • Functional gonadotropin deficiency (see below extragenital causes).
    • Inflammation in the area of the hypothalamus; hypothalamus tumors.
    • Hypopituitarism (hypofunction of the pituitary gland): eg.
      • Sheehan syndrome (acquired anterior pituitary insufficiency (insufficient hormone production by the anterior lobe of the pituitary gland (pituitary gland)).
      • Pituitary tumors
    • Hyperprolactinemia (elevation of prolactin levels in the blood)/prolactinoma (benign tumor of the anterior lobe of the pituitary gland that produces prolactin) – which usually leads to disruption of follicle maturation (oocyte maturation), resulting in corpus luteum insufficiency, anovulation, and oligomenorrhea/regular menstruation: The interval between bleeding is > 35 days and ≤ 90 days (until amenorrhea/> 90 days); see also under “Hyperprolactinemia due to medications”
  • Ovarian disorders
    • Ovarian insufficiency (loss of function (insufficiency) of the ovary with a disturbance of ovulation; of varying genesis/ origin).
    • Polycystic ovary syndrome (PCO syndrome) – symptom complex characterized by hormonal dysfunction of the ovaries. [about 25% of all women with secondary amenorrhea.]
    • Ovarian hyperandrogenemia (ovary-related overproduction of male hormones).
    • Postmenopause (period of a woman’s life that follows the last menstrual period (menopause)).
  • Extragenital causes
    • Stress
    • Mental stress
    • Competitive sports
    • Diseases

Operations

  • After forced curettage (traumatic amenorrhea) – Asherman syndrome due to destruction of the basalis of the endometrium (endometrium).

Medication

Other causes

  • Gravidity (pregnancy) → pregnancyamenorrhea.
  • Lactation period (breastfeeding phase) → lactationalamenorrhea.
  • Zust. n. Radiatio (radiotherapy).