II. Definitions
- Testosterone Deficiency
- Symptomatic, persistently low Serum Testosterone
III. Epidemiology
-
Prevalence increases with age
- Age 50 to 59 years old: 12%
- Age >=80 years old: 49%
IV. Causes
- Primary (Testicular) Hypogonadism (High LH, high FSH)
- Congenital
- Klinefelter's Syndrome
- 5-alpha reductase deficiency
- Myotonic Dystrophy
- Cryptorchidism (Undescended Testicle)
- Hemochromatosis
- FSH or LH receptor gene mutation
- Acquired
- Orchiectomy
- Bilateral Orchitis (mumps, Gonorrhea, Chlamydia)
- Drug or Toxin induced Primary Hypogonadism
- HIV Infection or AIDS
- Hypothyroidism
- Radiation or Trauma to Testicless
- Testicular Torsion
- End Stage Renal Disease
- Congenital
- Secondary (Central) Hypogonadism (Low LH, low FSH)
- Congenital
- Kallmann Syndrome
- Fertile Eunuch Syndrome
- Prader-Willi Syndrome
- Acquired
- Pituitary Adenoma or Prolactinoma
- Drug or Toxin Induced Secondary Hypogonadism
- Alcohol Use Disorder
- Anabolic Steroids
- Chronic Opioid use
- Marijuana used disorder
- Craniopharingioma
- Pituitary surgery
- Hyperprolactinemia
- Intracranial radiation (sella radiation)
- Sleep deprivation
- Surgery or Trauma
- Congenital
- Mixed Cause Hypogonadism
- Male Menopause or Andropause (Normal Physiologic response to aging)
- Testosterone Levels normally start declining after age 40 years old
- Testosterone Levels are low in 50% of age >80 years old
- Obesity
- Type II Diabetes Mellitus
- Chronic Obstructive Pulmonary Disease (COPD)
- Chronic Kidney Disease
- Cirrhosis
- HIV Infection or AIDS
- Male Menopause or Andropause (Normal Physiologic response to aging)
V. Symptoms
-
Sexual Dysfunction
- Decreased libido (erectile function often intact)
- Decreased spontaneous Erections
- Decreased sexual activity
- Decreased facial and body hair
- Decreased Muscle Strength and decreased Muscle mass
- Fatigue, low energy or lethargy
- Depressed mood
- Mild Cognitive Impairment
- Increased visceral fat
- Hot Flashes or sweats
VI. Signs
- Prepubertal Onset
- Hypoplastic penis
- Small Testes (<5 ml)
- Thin, smooth skin
- Voice does not deepen
- Female distribution of pubic hair
- Absence of beard
- Poor Muscle development
- Long limbs
- Broad hips
- Gynecomastia
- Postpubertal Onset
- Testicular atrophy (small Testes) and pallor
- Reduced body hair
- Increased visceral fat
- Decreased libido
- Decreased spontaneous Erection or Impotence
- Infertility
- Decreased Muscle mass, physical strength or physical work performance
- Decreased Bone Mineral Density (low impact mechanism for Fracture)
- Increased body fat or Body Mass Index (BMI)
VII. Imaging
- Prepubertal delay in epiphyseal closure
VIII. Labs
- Serum Androgens
- Serum Testosterone
- Decreased in all cases (<300 ng/dl or 10.4 nmol/L)
- Obtain in the morning (or within 2 hours of awakening) due to circadian variation
- Confirm Testosterone Deficiency with a repeat Serum Testosterone
- Serum Leutinizing Hormone (LH)
- Primary Testicular Failure: High LH
- Central failure (e.g. Pituitary Adenoma): Low LH
- Check Prolactin if LH is low
- Serum Follicle Stimulating Hormone (FSH)
- High level suggests irreversible Hypogonadism
- Serum Testosterone
- Secondary cause
- Urine 17-Ketosteroids
- Secondary effects of Hypogonadism
- Complete Blood Count
- Anemia (normocytic and normochromic)
- Baseline Hematocrit >48% is a contraindication for starting Testosterone Replacement
- Hematocrit >54% while on Testosterone Replacement is an indication to stop
- Complete Blood Count
IX. Diagnosis
- Precautions
- Do not evaluate for Hypogonadism in patients without signs or symptoms
- Questionnaires (e.g. Aging Males Symptoms) are inadequate alone to indicate Hypogonadism testing
- However validated tools (e.g. ADAM) can aid diagnosis
- Emmelot-Vonk (2011) Clin Endocrinol 74(4): 488-94 [PubMed]
- Protocol: Symptoms and signs suggestive of Hypogonadism
- Morning Total Testosterone decreased (<300 ng/dl)
- Confirm with a second morning Total Testosterone
- If borderline Total Testosterone, consider additional testing
- Consider Free Testosterone
- Consider Sex Hormone Binding Globulin (SHBG), affected by aging, Obesity, Diabetes Mellitus
- Additional testing if low testerone confirmed
- Obtain LH and FSH levels, and interpret as below
- Morning Total Testosterone decreased (<300 ng/dl)
-
Primary Hypogonadism (Testicular)
- Leutinizing Hormone (LH) elevated
- Follicle Stimulating Hormone (FSH) elevated
- Testosterone Level decreased (<300 ng/dl)
- Consider chromosomal testing in early age-onset Hypogonadism
-
Secondary Hypogonadism (Central)
- Leutinizing Hormone (LH) decreased
- Follicle Stimulating Hormone (FSH) decreased
- GnRH may be decreased
- Testosterone Level decreased (<300 ng/dl)
- Consider pituitary evaluation (Serum Prolactin, Brain MRI)
- Consider drug-induced (Alcohol, Chemotherapy) or systemic causes of Hypogonadism
- Eliminate other causes
- Urine 17-Ketosteroids normal
X. Management
- See Androgen Replacement
- Precautions: Erectile Dysfunction
- Phosphodiesterase-5 Inhibitors (PDE5 Inhibitors, e.g. Viagra) is the first-line treatment
- Androgen Replacement may be considered in low Testosterone if PDE5 Inhibitors fail
- Avoid Androgen Replacement in Erectile Dysfunction when Testosterone Levels are normal
XI. Complications of untreated Hypogonadism
- Osteoporosis
- Diminished Muscle Strength and other androgen effects