Some Causes of Ovulatory Dysfunction

Cause	Examples
Hypothalamic dysfunction, structural	Infiltrative disorders of the hypothalamus (eg, Langerhans cell histiocytosis, lymphoma, sarcoidosis, tuberculosis) Irradiation to the hypothalamus Traumatic brain injury Tumors of the hypothalamus
Hypothalamic dysfunction, functional	Cachexia Chronic disorders, particularly respiratory, gastrointestinal, hematologic, renal, or hepatic (eg, Crohn disease, cystic fibrosis, sickle cell disease, thalassemia major, cirrhosis, chronic kidney disease requiring hemodialysis), seizure disorders Dieting Drug abuse (eg, of alcohol, , marijuana, or opioids) Eating disorders (eg, anorexia nervosa, bulimia, orthorexia*) Exercise, if energy required exceeds energy intake Infections (eg, HIV infection, tuberculosis, encephalitis, syphilis) Immunodeficiency Pseudocyesis (false pregnancy) Psychiatric disorders (eg, stress, depression, obsessive-compulsive disorder, schizophrenia) Psychoactive medications Undernutrition
Pituitary dysfunction	Aneurysms of the pituitary Hyperprolactinemia† Idiopathic hypogonadotropic hypogonadism Infiltrative disorders of the pituitary (eg, hemochromatosis, Langerhans cell granulomatosis, sarcoidosis, tuberculosis) Isolated gonadotropin deficiency Kallmann syndrome (hypogonadotropic hypogonadism with anosmia) Postpartum pituitary necrosis (Sheehan syndrome) Traumatic brain injury Tumors of the brain (eg, meningioma, craniopharyngioma, gliomas) Tumors of the pituitary (eg, microadenoma, metastatic carcinoma, endodermal sinus tumor, other pituitary tumors that secrete hormones [eg, ACTH, thyroid-stimulating hormone, growth hormone, FSH, LH]) Space-occupying lesions (eg, empty sella turcica, cerebral arterial aneurysm)
Ovarian dysfunction	Autoimmune disorders (eg, autoimmune oophoritis as may occur in myasthenia gravis, thyroiditis, or vitiligo) Chemotherapy (eg, high-dose alkylating agents) Genetic abnormalities, including chromosomal abnormalities (eg, congenital thymic aplasia, Fragile X syndrome, Turner syndrome [45,X], idiopathic accelerated ovarian follicular atresia) Gonadal dysgenesis (incomplete ovarian development, sometimes secondary to genetic disorders) Irradiation to the pelvis Metabolic disorders (eg, Addison disease, diabetes mellitus, galactosemia [‡]) Ovarian tumors (eg, granulosa-theca cell tumors, Brenner tumors, teratomas, mucinous or serous cystadenomas, Krukenberg tumors, metastatic carcinoma) Viral infections (eg, mumps)
Other endocrine dysfunction	Androgen insensitivity syndrome (testicular feminization) Congenital adrenal virilism (congenital adrenal hyperplasia—eg, due to 17-hydroxylase deficiency or 17,20-lyase deficiency) or adult-onset adrenal virilism§ Cushing syndrome§,¶ Hyperthyroidism Hypothyroidism Obesity (which causes excess extraglandular production of estrogen) Polycystic ovary syndrome True hermaphroditism§ Tumors producing androgens (usually ovarian or adrenal)§¶ Tumors producing estrogens
* Orthorexia is characterized by obsession with eating healthy or organic foods; with associated restrictive behaviors that may result in restriction of nutrients and calories leading to amenorrhea .
† Hyperprolactinemia due to other conditions (eg, hypothyroidism, use of certain medications) may also cause amenorrhea.
‡ Based on Berry GT: Galactosemia and amenorrhea in the adolescent.
§ Females with these disorders may have virilization or ambiguous genitals.
¶ Virilization may occur in Cushing syndrome secondary to an adrenal tumor.
ACTH = adrenocorticotropic hormone; FSH = follicle-stimulating hormone; GnRH = gonadotropin-releasing hormone; LH = luteinizing hormone.

Cause

Examples

Hypothalamic dysfunction, structural

Infiltrative disorders of the hypothalamus (eg, Langerhans cell histiocytosis, lymphoma, sarcoidosis, tuberculosis)

Irradiation to the hypothalamus

Traumatic brain injury

Tumors of the hypothalamus

Hypothalamic dysfunction, functional

Cachexia

Chronic disorders, particularly respiratory, gastrointestinal, hematologic, renal, or hepatic (eg, Crohn disease, cystic fibrosis, sickle cell disease, thalassemia major, cirrhosis, chronic kidney disease requiring hemodialysis), seizure disorders

Dieting

Drug abuse (eg, of alcohol, , marijuana, or opioids)

Eating disorders (eg, anorexia nervosa, bulimia, orthorexia*)

Exercise, if energy required exceeds energy intake

Infections (eg, HIV infection, tuberculosis, encephalitis, syphilis)

Immunodeficiency

Pseudocyesis (false pregnancy)

Psychiatric disorders (eg, stress, depression, obsessive-compulsive disorder, schizophrenia)

Psychoactive medications

Undernutrition

Pituitary dysfunction

Aneurysms of the pituitary

Hyperprolactinemia†

Idiopathic hypogonadotropic hypogonadism

Infiltrative disorders of the pituitary (eg, hemochromatosis, Langerhans cell granulomatosis, sarcoidosis, tuberculosis)

Isolated gonadotropin deficiency

Kallmann syndrome (hypogonadotropic hypogonadism with anosmia)

Postpartum pituitary necrosis (Sheehan syndrome)

Traumatic brain injury

Tumors of the brain (eg, meningioma, craniopharyngioma, gliomas)

Tumors of the pituitary (eg, microadenoma, metastatic carcinoma, endodermal sinus tumor, other pituitary tumors that secrete hormones [eg, ACTH, thyroid-stimulating hormone, growth hormone, FSH, LH])

Space-occupying lesions (eg, empty sella turcica, cerebral arterial aneurysm)

Ovarian dysfunction

Autoimmune disorders (eg, autoimmune oophoritis as may occur in myasthenia gravis, thyroiditis, or vitiligo)

Chemotherapy (eg, high-dose alkylating agents)

Genetic abnormalities, including chromosomal abnormalities (eg, congenital thymic aplasia, Fragile X syndrome, Turner syndrome [45,X], idiopathic accelerated ovarian follicular atresia)

Gonadal dysgenesis (incomplete ovarian development, sometimes secondary to genetic disorders)

Irradiation to the pelvis

Metabolic disorders (eg, Addison disease, diabetes mellitus, galactosemia [‡])

Ovarian tumors (eg, granulosa-theca cell tumors, Brenner tumors, teratomas, mucinous or serous cystadenomas, Krukenberg tumors, metastatic carcinoma)

Viral infections (eg, mumps)

Other endocrine dysfunction

Androgen insensitivity syndrome (testicular feminization)

Congenital adrenal virilism (congenital adrenal hyperplasia—eg, due to 17-hydroxylase deficiency or 17,20-lyase deficiency) or adult-onset adrenal virilism§

Cushing syndrome§,¶

Hyperthyroidism

Hypothyroidism

Obesity (which causes excess extraglandular production of estrogen)

Polycystic ovary syndrome

True hermaphroditism§

Tumors producing androgens (usually ovarian or adrenal)§¶

Tumors producing estrogens

* Orthorexia is characterized by obsession with eating healthy or organic foods; with associated restrictive behaviors that may result in restriction of nutrients and calories leading to amenorrhea .

† Hyperprolactinemia due to other conditions (eg, hypothyroidism, use of certain medications) may also cause amenorrhea.

‡ Based on Berry GT: Galactosemia and amenorrhea in the adolescent.

§ Females with these disorders may have virilization or ambiguous genitals.

¶ Virilization may occur in Cushing syndrome secondary to an adrenal tumor.

ACTH = adrenocorticotropic hormone; FSH = follicle-stimulating hormone; GnRH = gonadotropin-releasing hormone; LH = luteinizing hormone.

In these topics

Amenorrhea