Some Etiologies of Ovulatory Dysfunction
Etiology | Examples |
|---|---|
Hypothalamic dysfunction, functional | Inadequate calorie intake due to dieting, orthorexia*, eating disorders (eg, anorexia nervosa, bulimia), undernutrition (eg, due to food insecurity), restricted eating*, disordered eating*, or malabsorption Excessive calorie expenditure (if calories used exceed calorie intake) due to exercise or hypermetabolic states Metabolic disturbances (eg, associated with obesity, aging) Emotional stress Psychiatric disorders (eg, depression, obsessive-compulsive disorder, schizophrenia) Chronic disease, particularly gastrointestinal, renal, or hepatic (eg, Crohn disease, celiac disease, chronic kidney disease requiring hemodialysis, cirrhosis, sickle cell disease, cystic fibrosis, thalassemia major, or seizure disorders) Some medications, including psychoactive medications (eg, antipsychotics, antidepressants) and antiepileptics Misuse of some substances (eg, alcohol, opioids) Infections (eg, HIV infection, encephalitis, syphilis) |
Hypothalamic dysfunction, genetic or structural | Genetic disorders (eg, idiopathic gonadotropin-releasing hormone deficiency [also referred to as idiopathic hypogonadotropic hypogonadism or Kallman syndrome], monogenic obesity syndromes [eg, Prader-Willi syndrome], congenital hypopituitarism) Infiltrative inflammatory disorders of the hypothalamus (eg, Langerhans cell histiocytosis, sarcoidosis, tuberculosis) Neoplasms of the hypothalamus (eg, lymphoma, craniopharyngiomas, gliomas, metastatic disease) Irradiation to the hypothalamus |
Pituitary dysfunction | 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]) Other brain tumors (eg, meningioma, glioma, ependymoma) Irradiation of the pituitary Space-occupying lesions (eg, empty sella turcica, cerebral arterial aneurysm) Infiltrative disorders of the pituitary (eg, hemochromatosis, Langerhans cell granulomatosis, sarcoidosis, tuberculosis) Hyperprolactinemia (primary or secondary to other endocrinologic disorders [eg, thyroid disease], medications, or other substances) Genetic or developmental disorders (eg, idiopathic gonadotropin-releasing hormone deficiency, hypoplastic pituitary gland) Postpartum pituitary infarction and necrosis (Sheehan syndrome) Traumatic brain injury |
Ovarian dysfunction | Autoimmune disorders (eg, autoimmune oophoritis associated with myasthenia gravis, thyroiditis, or vitiligo) Gonadal dysgenesis due to genetic abnormalities, including chromosomal abnormalities (eg, congenital thymic aplasia, Fragile X syndrome, Turner syndrome [45,X], idiopathic accelerated ovarian follicular atresia) Metabolic disorders (eg, Addison disease, diabetes mellitus, galactosemia [†]) Viral infections (eg, mumps) Chemotherapy (eg, high-dose alkylating agents) Irradiation to the pelvis Ovarian tumors (eg, granulosa-theca cell tumors, Brenner tumors, teratomas, mucinous or serous cystadenomas, Krukenberg tumors, metastatic carcinoma) |
Other endocrine dysfunction | Androgen insensitivity syndrome (testicular feminization) Congenital adrenal hyperandrogenism (congenital adrenal hyperplasia—eg, due to 17-hydroxylase deficiency or 17,20-lyase deficiency) or adult-onset adrenal hyperandrogenism§ Ovotesticular difference of sexual development (formerly called true hermaphroditism)§ Tumors producing androgens (usually ovarian or adrenal)‡ Drug-induced virilization (eg, by androgens, antidepressants, danazol, or high-dose progestins)§Drug-induced virilization (eg, by androgens, antidepressants, danazol, or high-dose progestins)§ Obesity (which causes excess extraglandular production of estrogen) Tumors producing estrogens or tumors producing human chorionic gonadotropin (gestational trophoblastic disease) |
* Orthorexia is characterized by obsession with eating healthy foods, with associated restrictive behaviors that may result in restriction of nutrients and calories leading to amenorrhea. Restricted eating is a conscious effort to limit food intake, often driven by the desire to lose weight or control eating habits. Disordered eating describes unhealthy eating behaviors that do not meet the criteria for a specific eating disorder diagnosis. † Berry GT. Galactosemia and amenorrhea in the adolescent. Ann N Y Acad Sci. 2008;1135:112-117. doi:10.1196/annals.1429.038 ‡ Krassas GE. Thyroid disease and female reproduction. Fertil Steril. 2000;74(6):1063-1070. doi:10.1016/s0015-0282(00)01589-2 § Females with these disorders may have virilization or ambiguous genitals. | |
ACTH = adrenocorticotropic hormone; FSH = follicle-stimulating hormone; GnRH = gonadotropin-releasing hormone; LH = luteinizing hormone. | |