Amenorrhea - classification Anatomic Defects Ovarian Failure Chronic anovulation with estrogen present Chronic anovulation with estrogen absent

Anatomic Defects (outflow tract) Anatomic Defects A. Labial agglutination/fusion B. Imperforate hymen C. Transverse vaginal septum D. Cervical agenesis – isolated E. Cervical stenosis – iatrogenic F. Vaginal agenesis – isolated G. Müllerian agenesis (Mayer-Rokitansky syndrome) H. Complete androgen insensitivity (T. fem) I. Endometrial hypoplasia or aplasia – congenital J. Asherman’s syndrome (intrauterine synechiae)

Ovarian failure (hypergonadotropic hypogonadism) A.Gonadal agenesis B.Gonadal dysgenesis 1. Abnormal karyotype a. Gonadal dysgenesis 45, X b. Mosaicism 2. Normal karyotype a. Pure Gonadal dysgenesis i. 46, XX ii. 46, XY (Swyer’s syndrome) C. Ovarian enzymatic deficiency 1. 17α-Hydroxylase deficiency 2. 17,20-Lyase deficiency 3. Aromatase deficiency

Ovarian failure Ovarian failure - continued D. Premature ovarian failure 1. Idiopathic – premature aging 2. Injury a. Mumps oophoritis b. Radiation c. Chemotherapy 3. Resistant ovary a. Idiopathic b. Mutations of FSH receptor c. Mutations of LH receptor 4. Autoimmune disease 5. Galactosemia

Chronic anovulation, estrogen present Chronic anovulation with estrogen present A. PCOS 1. Hyperthecosis B. Adrenal disease 1. Cushing’s syndrome 2. Adult-onset CAH C. Thyroid disease 1. Hypothyroidism 2. Hyperthyroidism D. Ovarian tumors 1. Granulosa-theca cell tumors 2. Brenner tumors 3. Cystic teratomas 4. Mucinous/serous cystadenomas 5. Krukenberg tumors

Chronic anovulation, estrogen absent (hypogonadotropic hypogonadism) A. Hypothalamic 1. Tumors a. Craniopharyngioma b. Germinoma c. Hamartoma d. Hand-Schüller-Christian disease e. Teratoma f. Endodermal sinus tumors g. Metastatic carcinoma 2. Infection and other disorders a. Tuberculosis b. Syphilis c. Encephalitis/meningitis d. Sarcoidosis e. Kallman’s syndrome f. Idiopathic hypogonadotropic hypogonadism g. Chronic debilitating disease

Chronic anovulation, estrogen absent A. Hypothalamic 3. Functional a. Stress b. Weight loss/diet c. Malnutrition d. Psychological eating disorders (anorexia nervosa, bulimia) e. Exercise f. Pseudocyesis

Chronic anovulation, estrogen absent (hypogonadotropic hypogonadism) B. Pituitary 1. Tumors a. Prolactinomas b. Other hormone-secreting pituitary tumors (corticotropin, thyrotropin, growth hormone) c. Nonfunctional tumors (craniopharyngioma) d. Metastatic carcinoma 2. Space-occupying lesions a. Empty sella syndrome b. Arterial aneurysm 3. Necrosis a. Sheehan’s syndrome b. Panhypopituitarism 4. Inflammatory/infiltrative a. Sarcoidosis b. Hemochromatosis c. Lymphocytic hypophysitis 5.Gonadotropin mutations (FSH) 6.GnRH receptor mutations

Initial workup of amenorrhea 1. History and physical examination (clinical evaluation of estrogen status) 2. R/O pregnancy 3. Measure plasma FSH, prolactin, TSH 4. Progestin administration