II. Causes

  1. Primary (Testicular) Hypogonadism (High LH, high FSH)
    1. Congenital
      1. Klinefelter's Syndrome
      2. 5-alpha reductase deficiency
      3. Myotonic dystrophy
      4. Cryptorchidism (Undescended Testicle)
      5. Hemochromatosis
      6. FSH or LH receptor gene mutation
    2. Acquired
      1. Orchiectomy
      2. Bilateral Orchitis (mumps, Gonorrhea, Chlamydia)
      3. Drug or Toxin induced Hypogonadism
        1. Alcohol
        2. Heavy metals (e.g. Hemochromatosis)
        3. Chemotherapy
      4. HIV Infection or AIDS
      5. Hypothyroidism
      6. Radiation or Trauma to Testicless
      7. Testicular Torsion
  2. Secondary (Central) Hypogonadism (Low LH, low FSH)
    1. Congenital
      1. Kallmann Syndrome
      2. Fertile Eunuch Syndrome
      3. Prader-Willi Syndrome
    2. Acquired
      1. Pituitary Adenoma or Prolactinoma
      2. Craniopharingioma
      3. Pituitary surgery
      4. Intracranial radiation (sella radiation)
      5. Chronic Opioid use
      6. Sleep deprivation
      7. Surgery or Trauma
  3. Mixed Cause Hypogonadism
    1. Male Menopause (Normal Physiologic response to aging)
      1. Testosterone Levels normally starting declining after age 40 years old
      2. Testosterone Levels are low in 50% of age >80 years old
    2. Obesity
    3. Type II Diabetes Mellitus
    4. Chronic Obstructive Pulmonary Disease (COPD)
    5. Chronic Kidney Disease
    6. Cirrhosis
    7. HIV Infection or AIDS

III. Symptoms

  1. Sexual Dysfunction
    1. Decreased libido (erectile function often intact)
    2. Decreased sexual activity
  2. Decreased facial and body hair
  3. Decreased Muscle Strength and decreased muscle mass
  4. Fatigue, low energy or lethargy
  5. Depressed mood
  6. Mild Cognitive Impairment
  7. Increased visceral fat
  8. Hot Flashes or sweats

IV. Signs

  1. Prepubertal Onset
    1. Hypoplastic penis and Testes
    2. Thin, smooth skin
    3. Voice does not deepen
    4. Female distribution of pubic hair
    5. Absence of beard
    6. Poor muscle development
    7. Long limbs
    8. Broad hips
    9. Gynecomastia
  2. Postpubertal Onset
    1. Testicular atrophy (small Testes) and pallor
    2. Reduced body hair
    3. Increased visceral fat
    4. Decreased libido
    5. Decreased spontaneous Erection or Impotence
    6. Infertility
    7. Decreased muscle mass, physical strength or physical work performance
    8. Decreased Bone Mineral Density (low impact Mechanism for Fracture)
    9. Increased body fat or Body Mass Index (BMI)

V. Imaging

  1. Prepubertal delay in epiphyseal closure

VI. Labs

  1. Serum Androgens
    1. Testosterone
      1. Decreased in all cases (<300 ng/dl or 10.4 nmol/L)
      2. Obtain in the morning (or within 2 hours of awakening) due to circadian variation
    2. Leutinizing Hormone (LH)
      1. Primary Testicular Failure: High LH
      2. Central failure: Low LH
    3. Follicle Stimulating Hormone (FSH)
      1. High level suggests irreversible Hypogonadism
    4. GnRH
  2. Secondary cause
    1. Urine 17-Ketosteroids
  3. Secondary effects of Hypogonadism
    1. Complete Blood Count
      1. Anemia (normocytic and normochromic)

VII. Diagnosis

  1. Precautions
    1. Do not evaluate for Hypogonadism in patients without signs or symptoms
    2. Questionnaires (e.g. Aging Males Symptoms) are inadequate alone to indicate Hypogonadism testing
      1. Emmelot-Vonk (2011) Clin Endocrinol 74(4): 488-94 [PubMed]
  2. Protocol: Symptoms and signs suggestive of Hypogonadism
    1. Morning Total Testosterone decreased (<300 ng/dl)
      1. Confirm with a second morning Total Testosterone
      2. If borderline Total Testosterone, consider additional testing
        1. Consider Free Testosterone
        2. Consider Sex Hormone Binding Globulin (SHBG), affected by aging, Obesity, Diabetes Mellitus
    2. Additional testing if low testerone confirmed
      1. Obtain LH and FSH levels, and interpret as below
  3. Primary Hypogonadism (Testicular)
    1. Leutinizing Hormone (LH) elevated
    2. Follicle Stimulating Hormone (FSH) elevated
    3. Testosterone Level decreased (<300 ng/dl)
    4. Consider chromosomal testing in early age-onset Hypogonadism
  4. Secondary Hypogonadism (Central)
    1. Leutinizing Hormone (LH) decreased
    2. Follicle Stimulating Hormone (FSH) decreased
    3. GnRH may be decreased
    4. Testosterone Level decreased (<300 ng/dl)
    5. Consider pituitary evaluation (Serum Prolactin, Brain MRI)
    6. Consider drug-induced (Alcohol, Chemotherapy) or systemic causes of Hypogonadism
  5. Eliminate other causes
    1. Urine 17-Ketosteroids normal

VIII. Management

  1. See Androgen Replacement
  2. Precautions: Erectile Dysfunction
    1. Phosphodiesterase-5 Inhibitors (PDE5, e.g. Viagra) is the first-line treatment
    2. Androgen Replacement may be considered in low testosterone if PDE5 Inhibitors fail
    3. Avoid Androgen Replacement in Erectile Dysfunction when Testosterone Levels are normal

IX. Complications of untreated Hypogonadism

  1. Osteoporosis
  2. Diminished Muscle Strength and other androgen effects

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Ontology: Testicular hypogonadism (C0151721)

Definition (MSH) Eunuch-like state in which the male individual has non-functional TESTES.
Concepts Disease or Syndrome (T047)
MSH D005058
ICD10 E29.1
SnomedCT 190557004, 88918002, 267486007, 30187002, 154713003, 48723006
French Défaillance testiculaire, Insuffisance testiculaire SAI, Hypogonadisme testiculaire, Eunuchoïdisme, Hypergonadisme masculin
Italian Eunucoidismo, Insufficienza testicolare, Ipogonadismo maschile, Ipogonadismo testicolare, Insufficienza testicolare NAS
Dutch testiculair hypogonadisme, testiculair falen NAO, eunuchoïdisme; hypogonadotroop, hypogonadisme; man, hypogonadisme; testiculair, hypogonadotroop; eunuchoïdisme, testiculair; hypogonadisme, eunuchoïdisme, hypogonadisme man, testiculair falen
German Hodeninsuffizienz NNB, testikulaerer Hypogonadismus, Eunuchoidismus, Hodeninsuffizienz, Hypogonadismus des Mannes
Portuguese Insuficiência testicular NE, Hipogonadismo testicular, Eunucoidismo, Hipogonadismo no homem, Insuficiência testicular
Spanish Hipogonadismo testicular, Insuficiencia testicular NEOM, hipogonadismo testicular, hipogonadismo testicular (concepto no activo), insuficiencia testicular, eunucoidismo, eunucoidismo (concepto no activo), hipogonadismo masculino (trastorno), hipogonadismo masculino, Eunucoidismo, Hipogonadismo masculino, Insuficiencia testicular
Japanese 精巣機能不全NOS, 類宦官症, 男性性腺機能低下, 精巣機能不全, 精巣性性腺機能低下症, セイソウキノウフゼン, ダンセイセイセンキノウテイカ, セイソウキノウフゼンNOS, セイソウセイセイセンキノウテイカショウ, ルイカンガンショウ
English HYPOGONADISM, MALE, testicular failure (diagnosis), testicular failure, hypogonadotropic eunuchoidism (diagnosis), hypogonadotropic eunuchoidism, Hypogonadism male, Testicular hypogonadism NOS, hypogonadism males, male hypogonadism, failure testicular, hypogonadism male, Testicular failure NOS, Hypogonadism, Male, Eunuchoidism (disorder), Testicular hypogonadism (disorder), Hypogonadism - male, Hypogonadism (in males), Eunuchoidism hypogonadism, Male hypogonadism, Testicular failure, Eunuchoidism, hypogonadism, Male hypogonadism (disorder), eunuchoidism; hypogonadotropic, eunuchoidism, hypogonadism; male, hypogonadism; testicular, hypogonadotropic; eunuchoidism, testicular; hypogonadism, Eunuchoidism, NOS, Male hypogonadism, NOS, Testicular hypogonadism, NOS, Testicular failure, NOS, Eunuchoidism NOS, Hypogonadotropic eunuchoidism, Eunuchoidism, Testicular hypogonadism
Czech Mužský hypogonadismus, Eunuchoidismus, Testikulární selhání, Testikulární selhání NOS, Testikulární hypogonadismus
Hungarian Férfi hypogonadismus, Testicularis hypogonadismus, Testicularis elégtelenség k.m.n., Eunuchoidismus, Testicularis elégtelenség
Norwegian Eunukoidisme, Hypogonadisme, mannlig, Evnukoidisme, Mannlig hypogonadisme