Amenorrhea causes

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Kiran Singh, M.D. [2]

Overview

Common causes of amenorrhea include breastfeeding, pregnancy, menopause, and stress.

Causes

Life Threatening Causes

Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated. There are no life-threatening causes of delayed puberty, however complications resulting from untreated delayed puberty are common.

Common Causes

• Breastfeeding
• Menopause
• Pregnancy
• Stress
• Turner syndrome
• Excessive exercise
• Dieting
• Obesity
• Hyperthyroidism
• Hypothyroidism

Less Common Causes

• Genetic disorder
  • Congenital gonadotropin-releasing hormone deficiency
  • GnRH receptor gene mutations
  • Prader-Willi syndrome
  • Congenital thymic aplasia
  • Fragile X syndrome
  • Idiopathic accelerated ovarian follicular atresia
• Infiltrative disorders of the hypothalamus
  • Langerhans cell granulomatosis
  • Lymphoma
  • Sarcoidosis
  • Tuberculosis (TB)
• Irradiation to the hypothalamus

• Traumatic brain injury
• Tumors of the hypothalamus
• Cachexia

• Chronic disorders
  • Crohn disease
  • Cystic fibrosis
  • Sickle cell disease
  • Thalassemia major
• Drug abuse
  • Alcohol
  • Cocaine
  • Marijuana
  • Opioids

• Eating disorders
  • Anorexia nervosa
  • Bulimia

• HIV infection
• Immunodeficiency
• Psychiatric disorders
  • Stress
  • Depression
  • Obsessive-compulsive disorder
  • Schizophrenia
  • Psychoactive drugs

• Malnutrition

• Aneurysms of the pituitary
• Hyperprolactinemia
• Idiopathic hypogonadotropic hypogonadism
• Infiltrative disorders of the pituitary
  • Hemochromatosis
  • Langerhans cell granulomatosis
  • Sarcoidosis
  • TB

• Isolated gonadotropin deficiency
• Kallmann syndrome
• Postpartum pituitary necrosis (Sheehan syndrome)
• Tumors of the brain
  • Meningioma
  • Craniopharyngioma
  • Gliomas

• Pituitary microadenoma
• Autoimmune disorders
  • Autoimmune oophoritis (in myasthenia gravis, thyroiditis, or vitiligo)
• Chemotherapy (eg, high-dose alkylating drugs)

• Gonadal dysgenesis
• Irradiation to the pelvis
• Metabolic disorders
  • Addison disease
  • Diabetes mellitus
  • Galactosemia

• Viral infections (mumps)

• Androgen insensitivity syndrome (testicular feminization)

• Congenital adrenal virilism
• Cushing syndrome
• Drug-induced virilization
  • Androgens
  • Antidepressants
  • Danazol
  • High-dose progestins

• True hermaphroditism

• Tumors producing androgens (ovarian or adrenal)

• Gestational trophoblastic disease

Causes by Organ System

Cardiovascular	Hamosiderosis, heart disease
Chemical/Poisoning	Alcoholism, Alcohol poisoning, Lead poisoning, Mercury poisoning, Morphine poisoning
Dental	No underlying causes
Dermatologic	Systemic lupus erythematosus
Drug Side Effect	Antidepressants, Antipsychotics, Chemotherapy, Combined oral contraceptive pill, Cyclophosphamide, Epirubicin, Ethanol, Fluoxymesterone, Medroxy-progesterone acetate, Metoclopramide, Nandrolone, Spironolactone, Stanozolol
Ear Nose Throat	No underlying causes
Endocrine	Acromegaly, 5-alpha-reductase deficiency, Achard-Thiers syndrome, Addison's disease, Adrenal cortex tumours, Adrenal gland disorders, Adrenocortical hyperplasia, Ahumada-Del Castillo syndrome, Androgen insensitivity syndrome, Anorexia nervosa, Anovulation, Anterior pituitary failure, Arrhenoblastoma, Autoimmune adrenalitis, Breastfeeding, C21-hydroxylase deficiency, Chiari-Frommel syndrome, Congenital adrenal hyperplasia , Conn syndrome, Constitutional delay of puberty, Corpus luteum cyst, Cortisone reductase deficiency, Cretinism, Cushing's disease, Cushing syndrome, Diabetes mellitus, Dystrophia adipose-genitalis, Eating disorders, Empty sella syndrome, Exogenous androgen use, Female athlete syndrome, Forbes-Albright syndrome, Frohlich's syndrome, FSH receptor deficiency, Galactorrhea, Galactorrhoea-hyperprolactinaemia, GnRH deficiency, Hyperprolactinaemia, Hyperthyroidism, Hypogonadism, Hypogonadotropic hypogonadism, Hypopituitarism, Hypothyroidism, Incomplete androgen insensitivity, Kallmann syndrome, Laron syndrome , Masculinization disorders, Mayer-Rokitansky syndrome, Menopause, Mullerian aplasia, Mullerian dysgenesis, Multiple endocrine neoplasia type 1, Myxoedema, Obesity, Ovarian failure, Ovarian insufficiency due to FSH resistance, Familial ovarian insufficiency, Panhypopituitarism, Perimenopause, Pituitary apoplexy, Pituitary dwarfism, Pituitary infarct, Pituitary tumour, Polycystic ovary syndrome, Premature ovarian failure, Prolactinoma, Pseudoamenorrhea, Pseudocyesis, Rapid weight loss, Sheehan syndrome, Simmonds' disease, Stein-Leventhal syndrome, Testicular feminization syndrome, Testosterone, Thyrotoxicosis, Underweight, Weight gain, XY female
Environmental	Climate change
Gastroenterologic	Anorexia nervosa, Autoimmune hepatitis, Bearn-Kunkel syndrome, Celiac disease , Cystic fibrosis, Eating disorders,Hemosiderosis, Hepatocellular carcinoma, Inflammatory bowel disease, Liver cirrhosis, Malabsorption syndrome, Rapid weight loss, Weight gain
Genetic	18p minus syndrome, Agenesis of lower vagina, Androgen insensitivity syndrome, C21-hydroxylase deficiency, Celiac disease, Chromosome 15q duplication syndrome, Chromosome 17p - partial deletion , Cortisone reductase deficiency, Defect in sry gene, Cystic fibrosis, Down's syndrome, FGFR1 mutation, Galactose-1-phosphate uridyltransferase deficiency, Gonadal dysgenesis, Kal1 mutation, Kallmann syndrome, Laurence-Moon-Biedl syndrome, Mayer-Rokitansky syndrome, Ovarian insufficiency - familial, Prader-Willi syndrome , PROKR2 mutation, Tetrasomy X, Triple X syndrome, Turner syndrome, Werner syndrome, XY female
Hematologic	Anemia, Hemosiderosis, Hodgkin's disease, Leukemia
Iatrogenic	Antidepressants, Antipsychotics, Chemotherapy, Combined oral contraceptive pill, Cyclophosphamide, Epirubicin, Ethanol, Fluoxymesterone, Medroxy-progesterone acetate, Metoclopramide, Nandrolone, Spironolactone, Stanozolol
Infectious Disease	Mumps, Tuberculosis
Musculoskeletal/Orthopedic	No underlying causes
Neurologic	Brain tumor, Craniopharyngioma, Dystrophia adipose-genitalis, Empty sella syndrome, Frohlich's syndrome, Glioma, Hypothalamic tumor, Meningioma, Ovarioleukodystrophy, Traumatic brain injury
Nutritional/Metabolic	Dietetic deficiency, Galactose-1-phosphate uridyltransferase deficiency, Low weight, Malabsorption syndrome, Malnutrition, Obesity, Proprotein convertase 1,3 deficiency, Rapid weight loss, Underweight, Vitamin A embryopathy, Weight gain
Obstetric/Gynecologic	Anovulation, Asherman syndrome, Autoimmune hepatitis, Autoimmune oophoritis, Cervical closure, Combined oral contraceptive pill, Complications from D&C procedure, Corpus luteum cyst, Defect in SRY gene, Ectopic pregnancy, Endometrial scarring, FSH receptor deficiency, Germinoma, Granulosa-cell tumor, Hematocolpos, Hematometra, Hematosalpinx, Hydatidiform mole, Hypogonadism, Hysterectomy, Imperforate hymen, Mayer-Rokitansky syndrome, Menopause, Mullerian aplasia, Mullerian dysgenesis, Ovarian cancer, Ovarian failure, Ovarian insufficiency due to FSH resistance, Ovarian insufficiency - familial, Ovarioleukodystrophy, Ovary damage, perimenopause, Polycystic ovary syndrome, Pregnancy, Premature ovarian failure, Pseudoamenorrhea, Pseudocyesis, Reproductive disorders, Sheehan syndrome, Stein-Leventhal syndrome, Tubal ligation syndrome, Uterine aplasia, Vaginal agenesis, vaginal closure, vaginal septum, Virilizing ovarian tumor, XY female
Oncologic	Granulosa cell tumor, Hepatocellular carcinoma, Hodgkin's disease, Hypothalamic tumor, Leukemia, Meningioma, Ovarian cancer, Prolactinoma, Virilizing ovarian tumor
Ophthalmologic	No underlying causes
Overdose/Toxicity	Alcohol poisoning, Lead poisoning, Mercury poisoning, Morphine poisoning
Psychiatric	Alcoholism, Anorexia nervosa, Anxiety, Bulimia, Depression, Eating disorders, Emotional turmoil, Excessive exercise, Female athlete syndrome, Grief, Insanity, Ovarioleukodystrophy, Primary affection disorder, Stress
Pulmonary	Cystic fibrosis, Tuberculosis
Renal/Electrolyte	Chronic renal failure, Denys-Drash syndrome, Hypokalaemic distal renal tubular acidosis, Nephritis, Systemic lupus erythematosus
Rheumatology/Immunology/Allergy	Autoimmune adrenalitis, Autoimmune hepatitis, Autoimmune oophoritis, Celiac disease, Systemic lupus erythematosus
Sexual	No underlying causes
Trauma	Traumatic brain injury
Urologic	Frasier syndrome
Miscellaneous	Cranial irradiation, Chronic illness, Radiotherapy

Causes in Alphabetical Order

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Causes of Amenorrhea Based on Classification

Primary Amenorrhea

• 17 beta-hydroxysteroid dehydrogenase deficiency
• Agonadism
• After trauma
• Anorexia Nervosa
• Anovulation
• Complete androgen insenstivity syndrome
• Constitutional bradygenesis
• Constitutional delay of puberty
• Diabetes Mellitus
• Early infantile brain damage
• Gonadal dysgenesis
• Homozygous adrenogenital syndrome
• Hymenal atresia
• Hyperandrogenism
• Hypothalamic and pituitary tumors

  • Hyperprolactinemia / Prolactin-secreting tumors
  • Dysgerminoma
  • Craniopharyngioma

• Idiopathic gonadotropin deficiency
• Kallmann's Syndrome
• Mayer-Rokitansky-Hauser Syndrome
• Mullerian dysgenesis
• Outflow tract disorders
• Pituitary insufficiency

  • Pituitary schistosomiasis
  • Pituitary tuberculosis
  • Empty Sella Syndrome

• Polycystic Ovary Syndrome
• Post-hormonal contraceptive Amenorrhea
• Severe systemic diseases
• Swyer's Syndrome
• Testicular feminization
• Turner's Syndrome
• Uterine atresia
• Uterine hypoplasia
• Vaginal atresia / gynatresia

Secondary Amenorrhea

• 5-alpha-reductase deficiency
• Addiction
• Addison's Disease
• Adrenocortical insuffiency
• After curettage
• After hysterectomy
• After radiation (can be reversed)
• Adrenal tumors
• Anovulation
• Asherman's Syndrome
• Autoimmune diseases
• Body building (and use of androgens)
• Castration (radiation or surgical)
• Central nervous system tumor (CNS)
• Cervical stenosis
• Change of environment
• Complete and incomplete androgen insensitivity
• Congenital adrenal hyperplasia
• Craniocerebral trauma
• Cushing's Syndrome
• Depression
• Diabetes Mellitus
• Drug Side Effect- Chlorpromazine, Desogestrel and Ethinyl Estradiol, Docetaxel, Epirubicin hydrochloride, Ethynodiol diacetate and ethinyl estradiol, Fluoxymesterone, Histrelin, Iloperidone, Loxapine, Medroxyprogesterone, Norgestimate and Ethinyl estradiol, Norgestrel and Ethinyl estradiol, Sertraline, Methyltestosterone, Olanzapine, Pramipexole, Prochlorperazine, Tiagabine, Trifluoperazine
• Encephalitis
• Enzymatic defects in testosterone biosynthesis
• Exposure to maternal androgens in utero
• Extreme obesity
• During chemotherapy
• Functional hypothalalmic Amenorrhea due to:

  • Stress
  • Eating disorders
  • Excessive exercise
  • Weight loss

• Gonadotropin deficiency in tumors
• Hormone-active ovarian tumor
• Hermaphroditism
• Heterozygous adrenogenital syndrome
• Hyperprolactinemia
• Hyperthyroidism
• Hypothyroidism
• Hysterectomy
• Imprisonment
• Meningitis
• Mullerian anomalies
• Myotonic dystrophy
• Pituitary insufficiency
• Polycystic ovary syndrome
• Post-hormonal contraception
• Post-infection (mumps, severe pelvic inflammatory disease)
• Postoerative gonadotropin deficiency
• Pregnancy
• Premature menopause
• Prolactinoma
• Sheehan's Syndrome
• Stress
• Testicular feminization
• Transsexuality when taking androgens
• Turner's Syndrome
• Uterine cavity sclerosis

  • Uterine Schistosomiasis
  • Abortion
  • Severe generalized infections of the pelvis
  • Post uterine surgery
  • Overzealous or repeated uterine curettage
  • Tuberculosis endometritis