II. Precautions

  1. Cardiovascular disease risk with Androgen Replacement is still unclear
  2. Androgen Replacement is not recommended for asymptomatic men or those with normal range Serum Testosterone
  3. Discontinue Testosterone Supplementation if no improvement after 3-6 months
  4. Androgen Replacement may be abused as an Anabolic Aid in sports
    1. Consider completing a Controlled Substance Contract

III. Indications: Men

  1. Depression, Fatigue, muscle wasting in HIV or AIDS
  2. Symptomatic Testicular Failure AND low morning Serum Testosterone levels<300 ng/dl (two levels are recommended)
    1. See Male Menopause
    2. See Hypogonadism
    3. FDA approved for low testosterone due to underlying cause (e.g. pituitary disorder, testicular infection)
      1. Not FDA approved for normal testosterone decline with routine aging
    4. Symptoms
      1. Decreased libido
      2. Erectile Dysfunction (PDE5 Inhibitors are preferred as first-line)

IV. Contraindications

  1. Absolute Contraindications
    1. Breast Cancer
    2. Polycythemia Vera (Hematocrit >54%)
    3. Prostate Cancer or suspicion for active Prostate Cancer (e.g. PSA > 4 mcg/L, ProstateNodules)
  2. Relative Contraindications
    1. Normal Serum Testosterone
    2. Hematocrit >50% (prior to starting Testosterone Replacement)
    3. Fertility desired (Testosterone Replacement decreases spermatogenesis)
    4. Untreated Obstructive Sleep Apnea
    5. Uncontrolled Congestive Heart Failure

V. Effects: Positive

  1. Increases bone density or decreases bone loss (Lumbar Spine, hip)
  2. Increase Lean Body Mass and Muscle Strength
  3. Decrease body fat
  4. Increase serum Hematocrit
  5. Increases sense of well-being, mood (variable effects)
  6. Increases libido

VII. Effects: Disproved Risks for physiologic Androgen Replacement

VIII. Adverse Effects: Cardiovascular Disease Risk (mixed results)

  1. Increased mortality, CVA and MI may be associated with Testosterone Replacement
    1. Vigen (2013) JAMA 310(17):1829-36 [PubMed]
  2. Older studies suggested no increased cardiovascular disease risk
    1. Zmuda (1997) Am J Epidemiol 146:609-14 [PubMed]

IX. Adverse Effects (decreased if Testosterone Level stable)

  1. HDL Cholesterol declines
  2. Increased Prostate Cancer growth
  3. Erythropoesis stimulation related effects
    1. Polycythemia, Thromboembolism and cerebral vascular accident risk
  4. May exacerbate Sleep Apnea
  5. Hepatotoxicity (especially oral preparations)
  6. Behavior and mood changes
    1. Moodiness or irritability
    2. Aggressive behavior
  7. Virilization (Hirsutism, Alopecia, Acne)
  8. Lethargy (low Serum Testosterone fluctuations)
  9. Edema
  10. Gynecomastia

X. Labs: Monitoring while on Testosterone

  1. See Androgen Replacement in Women for monitoring women
  2. Baseline Labs
    1. See Male Hypogonadism
    2. Morning Serum Testosterone level
      1. Confirm low testosterone on 2 different morning Serum Testosterone levels
      2. Consider Free Testosterone and Sex Hormone Binding Globulin (SHBG)
    3. Prostate Specific Antigen (PSA)
    4. Digital Rectal Exam and Prostate examination
    5. Complete Blood Count (or Hematocrit)
    6. Liver Function Tests (if using oral testosterone, which is not recommended)
  3. Monitoring for non-injectable preparations
    1. History and exam
      1. Follow-up at 3-6 months after initiation of therapy, and then annually if stable
    2. Total Serum Testosterone
      1. Obtain 3-6 months after starting therapy, then annually if stable
      2. Goal total Serum Testosterone level 400 to 700 ng/dl
    3. Complete Blood Count
      1. Obtain 3-6 months after starting therapy, then annually if stable
      2. Stop Androgen Replacement if Hematocrit >54%
    4. Prostate Specific Antigen (PSA) and Digital Rectal Exam (DRE)
      1. Indicated if older than age 40 years and baseline PSA >0.6 ng/ml
      2. Obtain PSA, DRE baseline and 3-6 months after initiation of therapy
        1. Refer to urology if >1.4 ng/ml increase within 12 months or Prostate nodularity
    5. Bone Mineral Density
      1. Indicated in men with Osteoporosis or low MechanismFracture
      2. Obtain at 1-2 years after initiation of therapy
    6. Liver Function Tests
      1. If using oral testosterone (which, again, is not recommended)
  4. Monitoring for Establishing Injection Dose
    1. Serum Testosterone at one week post injection
      1. Level above normal: decrease subsequent doses
    2. Serum Testosterone at two weeks post injection
      1. Level below normal: increase injection frequency

XI. Dosing: Testosterone Injection (Intramuscular)

  1. Transdermal delivery is preferred over intramuscular
    1. Cardiovascular risks may be higher with injectable
  2. Preparations: Every 2 weeks
    1. Testosterone cypionate (Depo-Testosterone)
    2. Testosterone enanthate (Delatestryl)
    3. Typical Dose: 200 mg IM every 2 weeks ($4 per month)
    4. Range: 50 to 400 mg IM every 2-4 weeks
  3. Preparations: Every 10 weeks
    1. Testosterone undecanoate (Aveed) injectable
    2. Dose: 3-mL (750 mg) Intramuscular Injection
      1. Give once at starting protocol THEN
      2. Give again in 4 weeks THEN
      3. Give every 10 weeks
    3. Adverse effects
      1. Pulmonary-Oil Microembolism (POME) and Anaphylaxis
    4. Precautions
      1. Carries black box warning (regarding POME, Anaphylaxis) and certification for prescribers

XII. Dosing: Testosterone Transdermal (preferred, physiologic)

  1. Background
    1. Serum Testosterone peaks 2 hours post-patch application
    2. Risk of skin-to-skin transmission of testosterone
  2. Testoderm ($72 per month)
    1. Dose: One 4 or 6 mg patch
    2. Apply to shaved Scrotum every 24 hours
    3. Much less irritating than Androderm
  3. Transdermal Testosterone Solution (Axiron)
    1. Dose: 60 mg daily (30 to 120 mg daily)
    2. Apply to axillary area (similar to deodorant)
    3. Risk for transfer to others
  4. Androderm ($98 per month)
    1. Typical dose: 4 mg patch daily
      1. Manufacturer changed dose in 2011
      2. Androderm 2 mg patch (instead of 2.5 mg)
      3. Androderm 4 mg patch (instead of 5 mg)
    2. May cause rash (8% of patients)
    3. Apply to skin every 24 hours
      1. Abdomen
      2. Thigh
      3. Between Shoulder blades
  5. Transdermal Gels
    1. Very expensive ($300/month)
    2. Dosing: Equivalent to 50-100 mg daily
    3. Formulations
      1. Testim 1%
      2. Fortesta
      3. Androgel (Testosterone 1% gel) four pumps (5 grams) topically daily
        1. May cause local skin reaction
        2. Apply to upper arms, Shoulders and Abdomen
        3. Avoid bathing for 5 hours after application
      4. Androgel (Testosterone 1.62% gel) two pumps topically daily
        1. Newer preparation released in 2011
        2. Equivalent to 4 pumps of the 1%
        3. Apply to upper arms, Shoulders, but NOT to Abdomen (due to less absorption)
        4. Avoid bathing for 2 hours after application

XIII. Dosing: Other forms

  1. Testosterone buccal (Striant) 30 mg to gums twice daily
    1. May cause oral irritation
    2. New option less studied than other forms
  2. Testosterone implanted pellets (Testopel)
    1. Dose: 150 to 450 mg implanted SQ every 3-6 months
    2. Used for Delayed Puberty in males
  3. Testosterone intranasal gel (Natesto)
    1. Dose: One actuation (33 mg) in each nostril three times daily
  4. Oral testosterone (not recommended)
    1. Listed for completeness
    2. Not recommended due to hepatotoxicity and less effect
    3. Agents
      1. Methyltestosterone (Android)
      2. Fluoxymesterone (Halotestin)

Images: Related links to external sites (from Bing)

Related Studies (from Trip Database) Open in New Window

Cost: Medications

androderm (on 2/22/2017 at Medicaid.Gov Survey of pharmacy drug pricing)
ANDRODERM 2 MG/24HR PATCH $8.14 each
ANDRODERM 4 MG/24HR PATCH $16.51 each
testim (on 2/22/2017 at Medicaid.Gov Survey of pharmacy drug pricing)
TESTIM 1% (50 MG) GEL Generic $1.80 per gram
androgel (on 4/3/2017 at Medicaid.Gov Survey of pharmacy drug pricing)
ANDROGEL 1%(2.5G) GEL PACKET Generic $2.11 per gram
ANDROGEL 1%(5G) GEL PACKET Generic $1.36 per gram
ANDROGEL 1.62% GEL PUMP $7.27 per gram
ANDROGEL 1.62%(1.25G) GEL PCKT $14.48 per gram
ANDROGEL 1.62%(2.5G) GEL PCKT $7.57 per gram

Ontology: Androderm (C0718531)

Concepts Pharmacologic Substance (T121) , Hormone (T125) , Steroid (T110)
MSH D013739
French Androderm
Italian Testosterone, CEPA, Testosterone, Faulding, Testosterone, Paladin, Androderm, Testosterone, Watson, Testosterone, AstraZeneca
English androderm, Androderm, AstraZeneca Brand of Testosterone, CEPA Brand of Testosterone, Faulding Brand of Testosterone, Paladin Brand of Testosterone, Watson Brand of Testosterone
Norwegian Androderm

Ontology: Testoderm (C0723655)

Concepts Pharmacologic Substance (T121) , Steroid (T110) , Hormone (T125)
MSH D013739
French Testoderm
Italian Testosterone, Ferring, Testosterone, Ortho, Testoderm
English testoderm, Testoderm, Ferring Brand of Testosterone, Ortho Brand of Testosterone
Norwegian Testoderm