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Testicular Failure

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Testicular Failure, Hypogonadism in Men, Testicular Hypogonadism, Male Hypogonadism, Testosterone Deficiency

  • See Also
  1. Hypogonadism
  2. Androgen Decline in the Aging Male
  • Definitions
  1. Testosterone Deficiency
    1. Symptomatic, persistently low Serum Testosterone
  • Epidemiology
  1. Prevalence increases with age
    1. Age 50 to 59 years old: 12%
    2. Age >=80 years old: 49%
  • 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 Primary Hypogonadism
        1. Heavy Metals (e.g. Hemochromatosis)
        2. Chemotherapy
        3. Androgen Synthesis Inhibitors (e.g. Spironolactone, Antifungals)
      4. HIV Infection or AIDS
      5. Hypothyroidism
      6. Radiation or Trauma to Testicless
      7. Testicular Torsion
      8. End Stage Renal Disease
  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. Drug or Toxin Induced Secondary Hypogonadism
        1. Alcohol Use Disorder
        2. Anabolic Steroids
        3. Chronic Opioid use
        4. Marijuana used disorder
      3. Craniopharingioma
      4. Pituitary surgery
      5. Hyperprolactinemia
      6. Intracranial radiation (sella radiation)
      7. Sleep deprivation
      8. Surgery or Trauma
  3. Mixed Cause Hypogonadism
    1. Male Menopause or Andropause (Normal Physiologic response to aging)
      1. Testosterone Levels normally start 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
  • Symptoms
  1. Sexual Dysfunction
    1. Decreased libido (erectile function often intact)
    2. Decreased spontaneous Erections
    3. 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
  • Signs
  1. Prepubertal Onset
    1. Hypoplastic penis
    2. Small Testes (<5 ml)
    3. Thin, smooth skin
    4. Voice does not deepen
    5. Female distribution of pubic hair
    6. Absence of beard
    7. Poor Muscle development
    8. Long limbs
    9. Broad hips
    10. 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)
  • Imaging
  1. Prepubertal delay in epiphyseal closure
  • Labs
  1. Serum Androgens
    1. Serum 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
      3. Confirm Testosterone Deficiency with a repeat Serum Testosterone
    2. Serum Leutinizing Hormone (LH)
      1. Primary Testicular Failure: High LH
      2. Central failure (e.g. Pituitary Adenoma): Low LH
        1. Check Prolactin if LH is low
    3. Serum Follicle Stimulating Hormone (FSH)
      1. High level suggests irreversible Hypogonadism
  2. Secondary cause
    1. Urine 17-Ketosteroids
  3. Secondary effects of Hypogonadism
    1. Complete Blood Count
      1. Anemia (normocytic and normochromic)
      2. Baseline Hematocrit >48% is a contraindication for starting Testosterone Replacement
        1. Hematocrit >54% while on Testosterone Replacement is an indication to stop
  • 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. However validated tools (e.g. ADAM) can aid diagnosis
      2. 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
  • Management
  1. See Androgen Replacement
  2. Precautions: Erectile Dysfunction
    1. Phosphodiesterase-5 Inhibitors (PDE5 Inhibitors, 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
  • Complications of untreated Hypogonadism
  1. Osteoporosis
  2. Diminished Muscle Strength and other androgen effects
  • References
  1. Heidelbaugh (2024) Am Fam Physician 109(6): 543-9 [PubMed]
  2. Petering (2017) Am Fam Physician 96(7): 441-9 [PubMed]
  3. Mulhall (2018) J Urol 200(2):423-32 +PMID: 29601923 [PubMed]