Primary (hypergonadotropic) hypogonadism |
Testicular disorders (primary gonadal failure) |
Undescended testes |
Acquired bilateral torsion of testes |
Orchitis (e.g. mumps orchitis)/cryptorchidism |
Vanishing-testes syndrome (congenital anorchism or prepubertal functional castrate) |
Seminiferous tubule dysgenesis (Klinefelter syndrome) |
Pure gonadal dysgenesis (46XX and 46XY) |
Sweyer syndrome (phenotypic female with gonads and genitalia identical to gonadal dysgenesis) |
Noonan (Boonevie-Ullrich) syndrome |
Hemochromatosis |
Impaired Leydig cell activity |
Inborn errors of testosterone biosynthesis |
Leydig cell hypoplasia |
Testicular unresponsiveness (LH receptor failure?) |
Androgen-resistant states and enzyme defects |
Testicular feminization (absence of androgen receptors) |
Incomplete androgen insensitivity (Reiffenstein syndrome) |
5-Reductase deficiency |
External testicular insults |
Trauma |
Radiation treatment |
Chemotherapy |
Autoimmune syndromes (e.g. anti-Leydig cell antibody-associated disorders) |
Sertoli-cell only syndrome |
Secondary (hypogonadotropic) hypogonadism |
GnRH deficiency |
Hypothalamic lesions |
Tumors |
Encephalitis |
Granuloma |
Abscess |
Craniopharyngioma |
Isolated GnRH deficiency |
Idiopathic (Kallmann syndrome or fertile-eunuch syndrome) |
Prader-Willi syndrome |
Lawrence-Moon-Bardet-Biedl syndrome |
Alström syndrome |
Fertile-eunuch syndrome |
Familial cerebellar syndrome |
Hyperprolactinemia |
Prolactinoma |
Certain drugs |
Hemochromatosis |
Neurosarcoid |
Myotonic dystrophy |
Pituitary disorders (gonadotrophin deficiency) |
Isolated LH deficiency |
Pasqualini syndrome |
Eunuchoidism |
Absent secondary sexual characteristics |
Oligospermia |
Tumors |
Pituitary infarction, apoplexy |
Empty sella syndrome |
Hemochromatosis |
Cranial trauma with or without pituitary-stalk transection |
Irradiation |
Hypophysitis |
FSH=follicle-stimulating hormone; GnRH=gonadotropin-releasing hormone; LH, luteinizing hormone.
Sources: AACE guidelines[2] and Rehman et al.[4]
Cytotoxic agents |
Spironolactone |
Corticosteroids, ketoconazole, aminoglutethimide, ethanol |
Decrease Leydig-cell testosterone production |
Anticonvulsants, hepatic microsomal liver enzyme inducers |
Augment testosterone metabolism |
Gonadotropin-releasing hormone agonists, estrogens, anabolic steroids, psychotropic medications, post-transplant immunosuppressants, corticosteroids, ethanol |
Reduce gonadotropin secretion |
Adapted with permission from Hameed et al.[3]
A Seftel, Department of Urology, Case Western Reserve University, Cleveland, OH, USA
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