Testosterone (Testoviron, Androgel, Natesto) is a male sex hormone that is available as an injection, oral, buccal, dermal (Gel and solution), and a transdermal patch.

Indications of Testosterone (Testoviron, Androgel, Natesto):

• Metastatic breast cancer, IM injection (enanthate):

  • It is recommended for women who are 1 to 5 years postmenopausal and have advanced, inoperable metastatic (skeletal) mammary cancer.
  • In premenopausal women with breast cancer who have benefitted from oophorectomy and have a hormone-responsive tumor, use may be taken into consideration.

• Delayed puberty: IM injection (enanthate), pellet:

  • It is effective in stimulating puberty in carefully selected males with delayed puberty.

• Hypogonadism

  • Hypogonadotropic (congenital or acquired): Gonadotropin or luteinizing hormone-releasing hormone deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation.

    • Use any formulation (Buccal oral Capsule, nasal Gel, transdermal, IM injection (cypionate enanthate undecanoate), transdermal Patch, Pellet, transdermal Solution, or SubQ injection (enanthate)

• Hypogonadism

  • primary (congenital or acquired): Treatment of testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter syndrome, chemotherapy, or toxic damage from alcohol or heavy metals

    • Use any formulation (Buccal oral Capsule, nasal Gel, transdermal, IM injection (cypionate enanthate undecanoate), transdermal patch, Pellet, transdermal solution, or SubQ injection (enanthate):

  • Limitations of use:

    • (Manufacturer's labeling) Age-related hypogonadism (or late-onset hypogonadism) in males has not been proven to be safe or effective.
    • Patients with signs of low testosterone levels and persistently and categorically low morning testosterone readings are advised to get testosterone treatment, according to the Endocrine Society.
    • Men over the age of 65 should receive treatment that is specifically tailored to their needs and only begin after discussing risks and benefits with the patient.

• Off-Label Use of Testosterone in Adults:

  • Hormone therapy for transgender males (female-to-male)

Testosterone (Testoviron, Androgel, Natesto) dose in adults:

Note: Testosterone enanthate IM formulation and testosterone enanthate SubQ formulation are not to be used interchangeably.

Testoviron dose in the treatment of Breast cancer in females:

• Testosterone enanthate: 200 to 400 mg I/M every 2 to 4 weeks.

Testosterone (Testoviron) dose for delayed puberty in males:

• Testosterone enanthate: 50 to 200 mg I/M every 2 to 4 weeks for a limited duration (eg 4 to 6 months).
• Pellet (for subcutaneous implantation): 150 to 450 mg every 3 to 6 months. Dosing is generally at the lower range for a limited duration (eg 4 to 6 months).

Testosterone (Testoviron) dose in hormone therapy in transgender males (female-to-male), monotherapy (off-label):

• testosterone enanthate or testosterone cypionate: 100 to 200 mg I/M every 2 weeks or 50 to 100 mg every week.
• Testosterone undecanoate: 1 g I/M every 6 weeks for the first 2 doses followed by 1 g every 12 weeks.
• SubQ (testosterone enanthate): 50 to 100 mg every week.
• Topical:Gel: Androgel 1.62%: 50 to 100 mg daily.

Testosterone (Testoviron) dose in primary hypogonadism or hypogonadotropic hypogonadism in males:

Note:

• To improve symptoms and return testosterone levels to normal, alter the course of treatment.
• For the majority of individuals, a total testosterone aim in the mid-normal therapeutic range (for example, 450 to 600 ng/dL for most laboratories) is suitable in order to avoid any overtreatment or undertreatment.
• For injectable formulations, 350 to 600 ng/dL is an effective range. (Xyosted manufacturer labeling).
• Dose titration is not necessary if symptoms disappear when testosterone levels are below the recommended target range.
• Buccal: 30 mg twice daily (every 12 hours) applied to the gum region above the incisor tooth.
• IM (testosterone enanthate or testosterone cypionate):
  • Initial: 75 to 100 mg/week or 150 to 200 mg every 2 weeks.
  • dosage range: 50 to 100 mg/week or 100 to 200 mg every 2 weeks.

• Manufacturer labeling:

  • Dosing in the prescribing information may not reflect current clinical practice.
    • 50 to 400 mg IM every 2 to 4 weeks.

  • IM (testosterone undecanoate):

    • Initial: 750 mg followed by 750 mg administered 4 weeks later, then 750 mg administered every 10 weeks thereafter.

  • Intranasal: Testosterone gel: Natesto:

    • 11 mg (2 pump actuation; 1 actuation per nostril) intranasally 3 times daily (6 to 8 hours apart).
    • Total daily dose: 33 mg.

  • Oral capsule: Testosterone undecanoate:

    • Jatenzo:
      • Initial: 237 mg twice daily.
      • Dosage range: 158 to 396 mg b.i.d daily.
    • 40 mg capsule [Canadian product]):
      • Initial: 120 to 160 mg/day in 2 divided doses for 2 to 3 weeks;
      • usual maintenance dose: 40 to 120 mg/day (in divided doses).
    • Pellet (for subcutaneous implantation):
      • 150 to 450 mg every 3 to 6 months.
    • SubQ (testosterone enanthate):
      • Initial: 75 mg once weekly.
      • Dosage range: 50 to 100 mg once weekly.

  • Topical Gel:

    • AndroGel 1%:
      • Initial: 50 mg applied once daily in the morning to the shoulder and upper arms or abdomen.
      • Dosage range: 50 to 100 mg/day.
    • Fortesta:
      • Initial: 40 mg once daily in the morning.
      • Apply to the thighs.
      • Dosing range: 10 to 70 mg/day;
      • maximum: 70 mg/day.
    • AndroGel 1.62%:
      • Initial: 40.5 mg applied once daily in the morning to the shoulder and upper arms.
      • Dosage range: 20.25 mg to 81 mg/day;
      • maximum: 81 mg/day.
    • Testim:
      • Initial: 50 mg applied once daily (preferably in the morning) to the shoulder and upper arms.
      • If testosterone concentrations are less than the normal range dosage may be increased from 50 mg to 100 mg once daily;
      • maximum: 100 mg/day.
    • Vogelxo:
      • Initial: 50 mg applied once daily in the morning to the shoulder and/or upper arms.
      • Dosage may be increased to a maximum of 100 mg/day.

  • Solution (Axiron):

    • Initial: 60 mg once daily (dosage range: 30 to 120 mg/day).
    • Apply to the axilla at the same time each morning.
  • Transdermal system (Androderm):
    • Initial: 4 mg/day (as one 4 mg/day patch; do not use two 2 mg/day patches).
    • Dosage range: 2 to 6 mg/day.

• Dosing conversion:

  • The 2.5 mg/day and the 5 mg/day patches have been discontinued in the US; patients may be switched from the 2.5 mg/day patch 5 mg/day patch or the combination (ie 7.5 mg/day) as follows:
    • From 2.5 mg/day patch to 2 mg/day patch.
    • From 5 mg/day patch to 4 mg/day patch.
    • From 7.5 mg daily (one 2.5 mg/day and one 5 mg/day patch) to 6 mg daily (one 2 mg/day and one 4 mg/day patch).

Note:

• Patch change should occur at the next scheduled dosing.
• The early morning testosterone levels should be checked 2 weeks after switching therapy.

Testosterone (Testoviron) dose in children:

Note:

• Age, gender, diagnosis, patient's response to therapy, and appearance of adverse effects are the factors that determine dosage and duration.
• In general total doses > 400 mg/month are not required due to the prolonged action of the drug.

Testosterone (Testoviron) Dose for Constitutional delay of growth and puberty (CDGP):

• Children ≥12 years and Adolescents ≤17 years:

  • Note: Typically not recommended for use before 14 years of age.
  • Initial: Enanthate or cypionate: 50 mg/dose I/M every 2 to 4 weeks for 3 to 6 months; may increase the dose in 25 to 50 mg increments for another 3 to 6 months to effect.
  • maximum dose: 100 mg; typical duration of therapy: 12 months. Additional testing is required if no response or inadequate response is seen after 1 year of treatment.
  • Note: Other regimens have suggested high initial doses and taper downward as puberty progresses.

  • Adolescents ≥18 years:

    • Enanthate: 50 to 200 mg  I/M every 2 to 4 weeks for a limited duration (eg 4 to 6 months)

  • Subcutaneous implant: Pellet:

  • Children ≥12 years and Adolescents:

    • Usual range: 150 to 450 mg I/M every 3 to 6 months;
    • usual duration: 4 to 6 months;
    • dosing typically on the lower end of the range; various regimens have been used.

Testosterone (Testoviron) Treatment dose of Male hypogonadism or hypogonadotropic hypogonadism:

• Enanthate or cypionate:

  • Children ≥12 years and Adolescents ≤17 years:

    • Initiation of pubertal growth:
      • 25 to 75 mg I/M every 3 to 4 weeks gradually titrate dose every 6 to 9 months to 100 to 150 mg monthly;
      • some experts suggest increasing the interval to every 2 weeks at this point; the typical duration of initiation therapy is 3 to 4 years.
    • Maintenance therapy:
      • 200 to 250 mg I/M every 3 to 4 weeks;
      • once expected adult height and adequate virilization are achieved may convert to other testosterone replacement dosage forms (eg patch gel etc).

  • Adolescents ≥18 years:

    • 50 to 400 mg I/M every 2 to 4 weeks or
    • 75 to 100 mg/week or 150 to 200 mg every 2 weeks.

• Undecanoate: Aveed:

  • Adolescents ≥18 years:

    • Initial dose: 750 mg I/M followed by 750 mg administered 4 weeks later, then 750 mg administered every 10 weeks thereafter.

• Subcutaneous implant: Pellet:

  • Fixed dosing:

    • Children ≥12 years and Adolescents:

      • Usual range: is 150 to 450 mg I/M every 3 to 6 months; various regimens have been used

  • Weight-direct dosing: Limited data available:

    • Children ≥12 years and Adolescents <17 years: 8 to 10 mg/kg/dose every 6 months.

• Topical:

  • Adolescents ≥18 years:

    • Buccal: Striant:

      • 30 mg twice daily (every 12 hours) applied to the gum region above the incisor tooth.
      • If serum testosterone levels remain outside of the normal range, it should be stopped.

    • Dermal:

      • Gel:
        • AndroGel 1%:
          • 50 mg is applied once daily in the morning to the shoulder and upper arms or abdomen. The dosage may be increased to a maximum of 100 mg.
          • Dose adjustment based on serum testosterone levels:
            • Less than normal range: Increase dose from 50 mg to 75 mg or from 75 mg to 100 mg once daily.
            • Greater than normal range: The dose should be decreased and if consistently above normal at 50 mg daily, it should be stopped.
        • AndroGel 1.62%:
          • 40.5 mg applied once daily in the morning to the shoulder and upper arms;
          • dose range: 20.25 to 81 mg.
          • Maximum daily dose: 81 mg/day.
          • Dose adjustment based on serum testosterone levels:
            • >750 ng/dL: Decrease dose by 20.25 mg/day.
            • 350 to 750 ng/dL: Maintain current dose.
            • <350 ng/dL: Increase dose by 20.25 mg/day.
        • Fortesta:
          • 40 mg once daily in the morning.
          • Apply to the thighs.
          • Dosing range: 10 to 70 mg/day.
          • Dose adjustment based on serum testosterone levels:
            • ≥2,500 ng/dL: Decrease dose by 20 mg/day.
            • ≥1,250 to <2,500 ng/dL: Decrease dose by 10 mg/day.
            • ≥500 and <1,250 ng/dL: Maintain current dose.
            • <500 ng/dL: Increase dose by 10 mg/day.
        • Testim:
          • 50 mg is applied once daily (preferably in the morning) to the shoulder and upper arms.
          • If serum testosterone concentrations are less than the normal range dosage may be increased from 50 mg to 100 mg once daily;
          • The maximum daily dose: is 100 mg/day.
        • Vogelxo:
          • 50 mg applied once daily to the shoulder and/or upper arms.
          • Dosage may be increased up to a maximum daily dose: of 100 mg/day.
          • Dose adjustment based on serum testosterone levels:
            • If the level is less than the normal range: Increase the dose from 50 mg to 100 mg once daily.

    • Solution:

      • Axiron:
        • 60 mg once daily;
        • dosage range: 30 to 120 mg/day.
        • Apply to the axilla at the same time each morning; do not apply to other parts of the body.
        • Dose adjustment based on serum testosterone levels:
          • >1,050 ng/dL: Decrease 60 mg/day dose to 30 mg/day;
          • if levels >1,050 ng/dL persist after dose reduction: discontinue therapy
          • <300 ng/dL: Increase 60 mg/day dose to 90 mg/day or increase 90 mg/day dose to 120 mg/day
    • Transdermal system: Androderm:
      • Initial: 4 mg/day (as one 4 mg/day patch; do not use two 2 mg/day patches). Dose adjustment based on testosterone levels:
        • >930 ng/dL: Decrease dose to 2 mg/day
        • 400 to 930 ng/dL: Continue 4 mg/day
        • <400 ng/dL: Increase the dose to 6 mg/day (as one 4 mg/day and one 2 mg/day patch)

• Dosing conversion of transdermal patches:

  • If needed patients may be switched from the 2.5 mg/day 5 mg/day and 7.5 mg/day patches as follows.
  • Patch change should occur at their next scheduled dosing.
  • Early morning testosterone levels should be checked 2 weeks after switching therapy:
    • • From 2.5 mg/day patch to 2 mg/day patch.
      • From 5 mg/day patch to 4 mg/day patch.
      • From a 7.5 mg/day patch to a 6 mg/day patch (one 2 mg/day and one 4 mg/day patch).
  • Intranasal: Testosterone gel: Natesto: 11 mg (2 pump actuation; 1 actuation per nostril) intranasally 3 times daily (6 to 8 hours apart). Total daily dose: 33 mg.

• Dose adjustment based on testosterone levels:

  • Less than normal range:

    • Consider alternative treatment if consistently <300 ng/mL.

  • Greater than normal range:

    • Discontinue if consistently >1,050 ng/mL.

Testosterone (Testoviron, Androgel, Natesto) treatment dose of Multiple pituitary hormone deficiencies (with microphallus):

• Infants:

  • Enanthate or cypionate:
    • 25 mg I/M every 4 weeks for 3 months;
    • may repeat for another second course if necessary.

Pregnancy Risk Category: X

• Benzyl alcohol, which can pass the placenta, is a component of certain goods.

• Use is not advised for women who are trying to get pregnant or during pregnancy.

• Fetal exposure reveals various degrees of virilization.

• Due to the possibility of subsequent exposure, all children and women should avoid skin-to-skin contact with anybody who has administered testosterone topically.

• Large dosages of testosterone can inhibit spermatogenesis, which could have permanent effects.

• Treatment for hypogonadotropic hypogonadism is not advised for men who want to become fathers.

Testosterone use during breastfeeding:

• Testosterone excretion occurs in breast milk.
• Most products are contraindicated while breastfeeding.
• The distribution of testosterone in breast milk was evaluated following the use of the subcutaneous pellet in a breastfeeding woman.
• Prior to therapy, milk concentrations of testosterone were 96 pg/mL.
• Following SubQ implantation of the 100 mg pellet, milk samples ranged from 88 pg/mL (day 2) to 100 pg/mL (day 7 [morning]).
• Reported maternal serum samples ranged from <100 pg/mL (baseline), 2830 pg/mL (day 2), and 1,480 pg/mL (day 7 [morning]).
• In the breastfeeding male infant after 7 months of continuous maternal therapy, no adverse effects were noted.
• Milk production is suppressed by high levels of endogenous maternal testosterone, such as those caused by certain ovarian cysts.
• Maternal serum testosterone levels generally fall following pregnancy and return to normal once breastfeeding is stopped.

Testosterone (Testoviron, Androgel, Natesto) Dose adjustment in renal disease:

• There are no dosage adjustments provided in the manufacturer’s labeling.
• It can lead to edema formation. Testosterone cypionate is contraindicated in serious renal disease.

Testosterone (Testoviron, Androgel, Natesto) Dose adjustment in liver disease:

• There are no dosage adjustments provided in the manufacturer’s labeling.
• It can lead to edema formation. Testosterone cypionate is contraindicated in serious hepatic disease.

Common Side Effects of Testosterone (Testosviron):

• Genitourinary:

  • Increase Prostate-Specific Antigen
  • Benign Prostatic Hypertrophy
•  

• Cardiovascular:

  • Hypertension

• Dermatologic:

  • Skin Blister

• Hematologic & Oncologic:

• • Increased Hematocrit

• Local:

  • Application site pruritis.

Rare Side Effects of Testosterone (Testoviron):

• Cardiovascular:

  • Peripheral Edema
  • Peripheral Vascular Disease

• Central Nervous System:

  • Emotional Lability
  • Altered Sense Of Smell
  • Nervousness
  • Abnormality In Thinking
  • Anxiety
  • Body Pain
  • Anosmia
  • Headache
  • Procedural Pain
  • Depression
  • Chills
  • Confusion
  • Fatigue
  • Paresthesia
  • Insomnia
  • Aggressive Behavior
  • Vertigo
  • Irritability
  • Sleep Apnea
  • Stinging Sensation

• Dermatologic:

  • Acne Vulgaris
  • Crusted Skin
  • Excoriation Of Skin
  • Contact Dermatitis
  • Bulla
  • Erythema
  • Hyperhidrosis
  • Alopecia
  • Skin Rash
  • Pruritus
  • Xeroderma

• Endocrine & Metabolic:

  • Decreased HDL Cholesterol
  • Increased Thyroid Stimulating Hormone Level
  • Increased Plasma Estradiol Concentration
  • Decreased Libido
  • Hyperlipidemia
  • Hypokalemia
  • Increased Serum Triglycerides
  • Gynecomastia
  • Hot Flash
  • Weight Gain

• Gastrointestinal:

  • Gingivitis
  • Oral Irritation
  • Decreased Appetite
  • Dysgeusia
  • Gastroesophageal Reflux Disease
  • Gastrointestinal Hemorrhage
  • Increased Appetite
  • Nausea
  • Diarrhea
  • Gingival Pain
  • Abdominal Pain
  • Gingival Swelling
  • Toothache
  • Oral Mucosa Changes

• Genitourinary:

  • Testicular Atrophy
  • Prostatic Disease
  • Hypogonadism
  • Mastalgia
  • Impotence
  • Pelvic Pain
  • Urinary Incontinence
  • Testicular Disease
  • Urinary Frequency
  • Breast Hypertrophy
  • Prostatitis
  • Urinary Tract Infection
  • Dysuria
  • Hematuria
  • Difficulty In Micturition
  • Ejaculatory Disorder
  • Prostate Induration
  • Spontaneous Erections

• Hematologic & Oncologic:

  • Anemia
  • Polycythemia
  • Prostate Carcinoma
  • Increased Hemoglobin

• Hepatic:

  • Increased Serum Bilirubin
  • Abnormal Hepatic Function Tests

• Local:

  • Bruising At Injection Site
  • Application-Site Erythema
  • Application-Site Reaction
  • Pain At Injection Site
  • Application-Site Induration
  • Application-Site Vesicles
  • Bleeding At Injection Site
  • Erythema At Injection Site
  • Application-Site Edema
  • Application-Site Irritation
  • Application-Site Rash
  • Local Skin Exfoliation
  • Application-Site Burning

• Neuromuscular & Skeletal:

  • Back Pain
  • Myalgia
  • Limb Pain
  • Hemarthrosis
  • Arthralgia
  • Increased Creatine Phosphokinase In Blood Specimen
  • Asthenia
  • Abnormal Bone Growth

• Renal:

  • Increased Serum Creatinine
  • Polyuria

• Respiratory:

  • Nasopharyngitis
  • Rhinorrhea
  • Bronchitis
  • Upper Respiratory Tract Infection
  • Epistaxis
  • Nasal Discomfort
  • Dry Nose
  • Nasal Congestion
  • Nasal Mucosa Swelling
  • Sinusitis
  • Cough

Side effects of Testoviron (Frequency Undefined):

• Cardiovascular:

  • Exacerbation of Hypertension

• Central Nervous System:

  • Hostility

• Hepatic:

  • Hepatic Adenoma

• Gastrointestinal:

  • Gingival Recession

• Local:

  • Induration at the Injection Site

Contraindications to Testosterone (Testoviron):

• Pregnancy
• Breast carcinoma in males
• prostate malignancy

Androderm, Axiron, Fortesta, Natesto, Striant, Testim, Vogelxo: Additional contraindication:

• Women planning for conception
• Breastfeeding women

Testosterone undecanoate (oral): Additional contraindications:

• Hypersensitivity to any component of the formulation
• Men with hypogonadal conditions that are not associated with structural or genetic etiologies (eg, age-related hypogonadism).

Aveed: Additional contraindications:

• Hypersensitivity to testosterone undecanoate, castor oil, benzyl benzoate
• breastfeeding women
• women planning for pregnancy

Testosterone enanthate (IM injection): Additional contraindications:

• Hypersensitivity to any component of the formulation
• Women planning for conception

Depo-Testosterone: Additional contraindications:

• Hypersensitivity to testosterone cypionate
• Severe hepatic or renal impairment
• Severe cardiac disease

Testosterone enanthate (SubQ injection): Additional contraindications:

• Hypersensitivity to any component of the formulation
• Women planning for conception
• Men with hypogonadal conditions that are not associated with structural or genetic etiologies.

Canadian labeling: Additional contraindication (not in the US labeling):

• Androderm: Hypersensitivity to any component of the formulation
• Females
• Skin contact in pregnant or breastfeeding women.
• Documentation of allergenic cross-reactivity for androgens is limited.
• However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Warnings and Precautions

• Hypercalcemia:

  • In patients with cancer or prolonged immobility, it can lead to hypercalcemia.
•  

• Blood pressure increases: [US Boxed Warning]:

  • Bot oral and S/C preparations can raise blood pressure.
  • These effects have been reported with other testosterone products as well.
  • Bp should be checked before starting therapy, at approximately 3 to 6 weeks and periodically thereafter.
  • Antihypertensive therapy might be required in some cases.

• Oligospermia:

  • Spermatogenesis can be suppressed by higher doses leading to oligospermia.
  • Dose reduction or withdrawal is required.

• Breast cancer:

  • The risk of breast cancer is increased with prolonged (>10 years) parenteral testosterone for male hypogonadism.

• Cardiovascular events:

  • The use of testosterone, according to certain studies, raises the risk of adverse cardiovascular events such as nonfatal MI, stroke, or cardiovascular death.
  • According to the FDA, males who have low testosterone levels that are caused by particular medical conditions (such as disorders of the testicles, pituitary gland, or brain) and have been confirmed by laboratory testing may receive testosterone.
  • AACE/ACE recommends basing testosterone replacement after a complete diagnostic evaluation on the signs and symptoms and testosterone concentrations rather than the underlying cause.
  • The use of testosterone treatment should be avoided in males who have had a MI or stroke during the preceding six months.
  • Cardiovascular risk factors must be assessed before to beginning treatment, and cardiovascular events must be monitored during treatment.

• Gynecomastia:

  • May cause gynecomastia, which may persist in patients treated for hypogonadism.
•  

• Dyslipidemia:

  • Use caution with a history of MI or coronary artery disease, as derangements in lipid levels can occur.

• Hepatic effects:

  • Serious hepatic effects including, peliosis hepatis, hepatic neoplasms, cholestatic hepatitis, and jaundice can occur with prolonged therapy.
  • Multiple hepatic adenomas can occur with long-term intramuscular testosterone enanthate.
  • In case of signs or symptoms of hepatic dysfunction, therapy should be stopped.

• Polycythemia:

  • Increased hematocrit is seen with therapy.
  • In patients with hematocrit >48% or >50% if living at higher altitudes, therapy should be withheld.
  • Therapy should be stopped if hematocrit exceeds 54% and can be started with low doses.

• Priapism:

  • Priapism or excessive sexual stimulation can be seen which needs dose reduction or withdrawal.

• Prostate cancer:

  • The risk of prostate malignancy is increased with therapy.
  • Withhold therapy pending urological evaluation in patients with a palpable prostate nodule or induration, PSA >4 ng/mL, or PSA >3 ng/mL in men at high risk of prostate cancer.

• Venous thromboembolism:

  • Testosterone is known for causing venous thromboembolic events, including deep vein thrombosis (DVT) and pulmonary embolism (PE).
  • Patients can present with dyspnoea, pain, edema, warmth, and erythema in the lower extremity, therapy should be stopped.
  • Use in hypogonadal men with thrombophilia is not recommended.

• Depression:

  • The risk of depression and suicidal ideation is increased with testosterone.
  • Evaluate patients with new-onset or worsening depression, anxiety, mood changes, or suicidal ideation or behavior.

• Benign prostatic hyperplasia (BPH):

  • Therapy can lead to worsening BPH, therapy should be stopped if urethral obstruction occurs.
  • It is not recommended in patients with severe lower urinary tract symptoms ([AUA]/International Prostate Symptom Score [IPSS] >19) Ref.

• Renal impairment:

  • Use with caution in patients with renal impairment; testosterone may cause fluid retention;
  • Testosterone cypionate is contraindicated in serious renal impairment.
•  

• Diseases exacerbated by fluid retention:

  • Testosterone can exacerbate fluid retention and cardiac impairment in patients with the fluid load.
  • In men with poorly controlled heart failure, therapy should not be given.

• Hepatic impairment:

  • Use with caution in patients with hepatic impairment; testosterone may cause fluid retention;
  • Testosterone cypionate is contraindicated in serious hepatic impairment.

• Sleep apnea:

  • Male patients with risk factors (eg, obesity or chronic lung disease) can develop sleep apnoea with therapy.
  • If there is untreated obstructive sleep apnea, therapy should be withheld.

Testosterone: Drug Interaction

Monitoring parameters:

• Before treatment:

  • Confirm hypogonadism by measuring serum total testosterone on at least 2 separate mornings following overnight fasting.
  • BP
  • Hemoglobin and hematocrit (withhold initial treatment with hematocrit >48% or >50% in males living at higher altitudes)
  • Liver function tests
  • Lipid profile
  • Withhold therapy until urological assessment in individuals with a palpable prostate nodule or induration or if PSA >4 ng/mL or if PSA >3 ng/mL in men at high risk of prostate cancer. PSA and prostate exam in males 55 to 69 years of age or 40 years of age and at elevated risk for prostate cancer.

• During treatment:

  • the heart rate (3 to 6 weeks after initiation or dosage adjustments, and periodically thereafter).
  • Hemoglobin and hematocrit should be checked every three to six months, then every year after that. If the hematocrit is over 54%, treatment should be halted.
  • Serum glucose (may be decreased by testosterone, monitor patients with diabetes).
  • Liver function tests
  • Lipid profile
  • Urine and serum calcium and signs of virilization in women treated for breast cancer.
  • Evaluate males for the response to treatment and adverse events 3 to 12 months after initiation and then annually
  • Monitoring for cardiovascular events closely during therapy.

  • Prostate-specific antigen (PSA):

    • In men 55 to 69 years of age or ≥40 years of age and at increased risk for prostate cancer, PSA and prostate exam at 3 to 12 months, then as recommended based on current prostate cancer screening guidelines.
    • Withhold treatment pending urological evaluation if there is a confirmed increase in PSA of >1.4 ng/mL from baseline, a confirmed PSA >4.0 ng/mL, or prostatic abnormality or substantial worsening of LUTS.

  • Bone mineral density:

    • Prepubertal children:
      • Radiologic examination of wrist and hand every 6 months.
    • Hypogonadal men with osteoporosis or low trauma fracture:
      • Monitor after 1 to 2 years of therapy.

  • Testosterone (free):

    • Free testosterone should be measured in patients with conditions associated with increased or decreased SHBG, or in patients with total testosterone concentrations in the borderline zone around the lower limit of the normal range (eg 200 to 400 ng/dL).

  • Testosterone (total):

    • General recommendations:
      • 3 to 6 months after starting therapy (formulation-dependent), at 12 months, then every 6 to 12 months.

Testosterone Formulation-specific monitoring:

• Buccal Testosterone:

  • Striant:

    • Examine application area of gums; total serum testosterone 4 to 12 weeks after initiating treatment, prior to a morning dose.
    • Discontinue therapy if the total serum testosterone is consistently outside of the normal range.

• Testosterone Injection:

  • Testosterone enanthate IM injection:

    • Measure testosterone level midway between injections.

  • Testosterone cypionate injection:

    • Measure testosterone level midway between injections.

  • Testosterone enanthate SubQ injection:

    • Measure total testosterone trough levels after 6 weeks of dosing, after 6 weeks following a dose adjustment, and periodically during therapy.
    • Trough concentrations should be measured 7 days after the most recent dose.

  • Testosterone undecanoate (Aveed):

    • After the injection, keep an eye on the patient for 30 minutes. If a major POME response or anaphylaxis occurs, there should be adequate therapy available.
    • Testosterone levels should be measured right before each successive injection, and the dosage interval should be changed to keep nadir levels in the low-mid range.
    • Alternatively, you might measure in the middle of each 10-week injection.

• Intranasal Testosterone:

  • Natesto:

    • Measure testosterone periodically, 1 month after starting therapy.
    • If the total serum testosterone is consistently outside of the normal range, therapy should be stopped.

• Oral Testosterone capsule:

  • Jatenzo:

    • Measure testosterone 6 hours after the morning dose beginning one week after starting therapy or after dosage adjustments and then periodically thereafter;
    • 40 mg capsule [Canadian product]:
      • Measure testosterone 5 hours after a dose.

• Pellet (for subcutaneous implant):

  • Testopel:

    • Measure testosterone at the end of the dosing interval.

• Topical Testosterone:

  • Note:

    • With topical gel or solution, serum concentrations might fluctuate significantly; single readings may not always match typical testosterone levels, making dose modifications difficult to predict.

  • AndroGel 1%:

    • Serum testosterone levels in the morning (pre-dose) two weeks after the commencement of treatment or dosage modifications.

  • AndroGel 1.62%:

    • Serum testosterone levels in the morning (pre-dosage) 14 and 28 days after commencing therapy or following dose modifications, as well as on an ongoing basis.

  • Androderm:

    • Morning serum testosterone levels (following application the previous evening) 14 days after the start of therapy or dose adjustments.

  • Axiron:

    • Serum testosterone levels can be measured 2 to 8 hours after application and after 14 days of starting therapy or dose adjustments.

  • Fortesta:

    • Serum testosterone levels can be measured 2 hours after application and after 14 and 35 days of starting therapy or dose adjustments.

  • Testim:

    • Morning (pre-dose) serum testosterone levels 2 weeks after the start of therapy or dose adjustments.

  • Vogelxo:

    • Morning (pre-dose) serum testosterone 2 weeks after initiation of therapy.

Hormone therapy in transgender males (female-to-male):

routine testing for cancer and other diseases in all tissues, just like in non-transgender people. After the first year, serum testosterone levels should be checked annually or twice a year. During therapy, make sure male testosterone levels stay within the normal range.

How to administer Testosterone (Testoviron, Androgel, Natesto)?

Deep IM injections should be made into the gluteal muscles.

Testosterone undecanoate:

• Inject into the gluteus medius
• Alternate injections between the left and right buttocks
• It is important to avoid intravascular injections, superior gluteal and sciatic nerve, as they can cause pulmonary oils micro-embolism.

Intranasal gel:

• It can also be administered intramuscularly thrice daily.
• You should give the doses 6-8 hours apart, preferably at the exact same time every day.
• Before starting therapy, it is important to clean the nose.
• Invert the pressure and then pressurize the prime pump before first use.
• You should insert the actuator into the nostrils and let it reach the base of your nose.
• Tip the nose so that the tip touches the nostril's lateral wall.
• You should press it slowly until the pump stops. Then, remove the gel from the nose and wipe the tip to transfer the gel to the lateral side.
• You should press the nostrils at the point below the bridge of your nose. After the administration, you should gently massage the area.
• Hands should be washed with soap and warm water if gel is on them.
• In severe cases of rhinitis, alternate therapy is recommended.

Oral Testosterone:

• Application to the Buccal:

  • Two times daily, one mucoadhesive should be applied to the buccal area.
  • Gently push the curved side against the upper gum.
  • To ensure adhesion, hold the buccal system in place and press down for 30 seconds on the outer lip.
  • The buccal system should stick to the gum until it is removed.
  • It should be rotated so that the mouth is on opposite sides.
  • Replace the buccal system if it falls out.
  • You can replace the system with a new buccal system if it falls out in the first 8 hours. Then, continue dosing for 12 hours starting from the time the first system was placed.
  • After 8 hours of dosing, the system may become out of place. A new buccal system can be used. It will remain in place for 12 hour, and then it can resume with the next scheduled dosing.
  • As it absorbs moisture, the system will mold gum to its desired shape.
  • It is not recommended to chew or swallow the buccal system.
  • The buccal system cannot be dissolved, so it should be gently removed, by sliding down from the gum. Avoid scratching.
  • Before applying a new system, it should be removed.

• Oral capsule:

  • Take one tablet each morning and one in the evening along with your meals.
  • 40 mg capsule [Canadian Product]
    • Take it with breakfast and dinner.

• Subcutaneous implant:

  • It must be surgically implanted using a strict sterile procedure.

• Subcutaneous injection:

  • Only inject it in the abdomen.
  • Do not give IV or IM.

• Topical gel and solution

  • General Information:

    • The solution and gels containing alcohol are flammable.
    • Avoid smoking, fires, and flames until the air is dry.
    • After skin-to-skin contact at the application site, testosterone can be transferred to another individual.
    • To reduce secondary exposure, it is important to strictly follow the application instructions.
    • To minimize the risk of contamination, hands should be washed well after applying gel or solution. The application site should also be covered with clothing.
    • Secondary exposure, in addition to skin-toskin contact, has been reported after exposure to secondary items.
    • Secondary exposure should be treated with soap and water immediately.
    • Doses and application locations for topical testosterone products cannot be interchanged.

  • Instructions for product-specific administration:

    • AndroGel 1%:

      • Clean, dry, intact skin should be applied to the area around the abdomen, shoulder, and upper arms each morning.
      • It shouldn't be used on the genitals or chest, back, axillae, knees, or chest.
      • After opening the packet, squeeze the contents into your palm and apply immediately to the site.
      • You can also squeeze a small portion onto your palm and apply it to another area until you have used the whole packet.
      • After application, it is best to avoid swimming, showering, and washing the site.
      • Once the gel has dried, cover the application area with clothing.
      • Prime the multidose pump three times before you use it.
      • Each actuation contains 12.5 mg testosterone
      • The pump can be used to deliver the gel directly to the application site or into the palm of your hand.

    • AndroGel 1.62%:

      • Each morning, apply clean, dry skin to the area around the shoulder and upper arms. Then, cover the area with a short-sleeved t-shirt.
      • It should not be used on the abdomen, genitals or chest.
      • After opening the packet, squeeze the contents into your palm and apply immediately to the site.
      • You can also squeeze a small portion onto your palm and apply it to the skin. Repeat this process until you have applied the entire packet.
      • After application, it is best to avoid swimming, showering, and washing the site.
      • Once the gel has dried, cover the application site with clothing.
      • Prime the multidose pump three times before you use it.
      • Each actuation contains 20.25mg of testosterone
      • The gel can be applied directly to the site of application by using the pump or delivered to the palm of your hand before application.

    • Axiron:

      • Use the applicator to apply clean, dry, intact skin to an area of the axilla each morning.
      • It shouldn't be used on other parts of your body.
      • After application, swimming or washing should be avoided.
      • Before you use the applicator pump, prime it by pressing it three times.
      • After priming, place the nozzle on the applicator cup. Once the pump is fully depressed, the liquid will enter the cup.
      • Each pump actuation delivers testosterone 30 mg.
      • The cup should not contain more than 30mg at a time.
      • If the solution is not absorbed, the applicator should be held straight up.
      • Avoid rubbing skin with your fingers or hands.
      • If more than one 30-mg dose is required, the process should be repeated. Roll-on antiperspirants and deodorants should also be used prior to testosterone.
      • Cover the area with clothing once it is dry.
      • The applicator should then be washed under running water, and dried with a towel.

    • Fortesta:

      • Cleanse the skin with clean, dry skin daily at morning.
      • It should only be used on the genitals and other parts of your body.
      • Apply the gel to each thigh with one finger.
      • After application, swimming, showering or washing the site should not be done for more than 2 hours.
      • Before you use the pump, prime it by placing the canister upright on the floor. Each pump actuation delivers testosterone 10 mg. The total testosterone dose should be divided among the thighs.
      • Cover the area with clothing once it is dry.

    • Try it:

      • Clean, dry skin should be applied once daily to the area around the shoulder and upper arms. The area will be covered with a t-shirt with a shorter sleeve.
      • It shouldn't be used on the abdomen or genitals.
      • After opening the tube, squeeze the entire contents into your palm and apply immediately to the site.
      • After application, it is best to avoid swimming, showering, and washing the site.
      • After the gel has dried, cover the application area with clothing.

    • Vogelxo:

      • Cleanse intact skin daily, at the same time every morning.
      • It shouldn't be used on the abdomen or the genitals.
      • After opening the packet, squeeze the contents into your palm and apply immediately to the site.
      • If two doses are necessary, apply one dose to each upper arm or shoulder.
      • After submitting your application, you should not swim, shower, or wash the site for more than 2 hours.
      • After the gel has dried, cover the application area with clothing.
      • If you are using a multi-dose pump, prime the pump three times and fully depress the pump mechanism.
      • Each actuation contains testosterone 12.5 mg.

• Transdermal patch

  • After the pouch is removed, apply to your skin.
  • Use the same night cream to dry the skin in the abdomen, back, upper arms and thighs.
  • It shouldn't be used on bony areas, or any other parts of the body subject to prolonged pressure when sitting or sleeping.
  • It shouldn't be used on oily, damaged or irritated skin.
  • Rotating administration sites is a good idea. Allow 7 days for multiple applications to the same place.
  • After application, swimming, showering or washing the site must be avoided for at least three hours.
  • After removing the affected area, mild skin irritation can be treated with OTC Hydrocortisone Cream.
  • To reduce irritation, a small amount of triamcinolone Acetonide 0.1% cream can be applied to the skin. However, the ointment shouldn't be used.
  • All unused or broken patches made by adhesing ends should be replaced in a sealed pouch or container.

Mechanism of action of Testosterone (Testoviron, Androgel, Natesto):

Testosterone is needed for stimulating growth and development of the male sex organs and maintenance of secondary sex characteristics in androgen-deficient males.

Duration (route and ester dependent):

• IM: Cypionate and enanthate esters: 2 to 4 weeks.
• Undecanoate: 10 weeks.
• Transdermal gel: 24 hours.

Absorption:

• Transdermal gel: 10% of the applied dose.

Protein binding:

• 98%; bound to sex hormone-binding globulin (40%) and albumin.

Metabolism:

• Hepatic; forms metabolites, including dihydrotestosterone (DHT) and estradiol (both active).

Bioavailability:

• Oral capsule: Jatenzo: Absolute bioavailability not reported;
• relative bioavailability decreased 25% when taken with a lower fat content meal (eg, 15 g) versus higher fat content meal (eg, ≥30 g).
• 40 mg capsule [Canadian product]: 7% (absolute bioavailability).

Half-life elimination:

• Variable: 10 to 100 minutes.
• Testosterone cypionate: 8 days.

Time to peak:

• IM (undecanoate): 7 days (median; range: 4 to 42 days).
• Intranasal: 40 minutes.
• Transdermal system: 8 hours (range: 4 to 12 hours);
• Buccal system: 10 to 12 hours;
• Oral capsule: Jatenzo: 2 to 4 hours.
• 40 mg capsule [Canadian product]: 4 to 5 hours.
• SubQ (enanthate): 11.9 hours (median; range: 5.8 to 168.7 hours) following weekly administration for 12 weeks.

Excretion:

• Urine (90%; 40 mg oral capsule [Canadian product]: 45% to 48%);
• feces (6%).

International Brands of Testosterone:

• Androderm
• AndroGel
• AndroGel Pump
• Aveed
• Axiron
• Depo-Testosterone
• Fortesta
• Natesto
• Striant
• Testim
• Testopel
• Vogelxo
• Vogelxo Pump
• Xyosted
• Andriol
• Androderm
• AndroGel
• Axiron
• Delatestryl
• Depo-Testosterone
• Natesto
• PMSTestosterone Enhanthate
• PMS-Testosterone Undecanoate
• TARO-Testosterone
• Testim
• Andriol
• Androderm
• AndroForte
• Androgel
• Andromen
• Andropatch
• Aquaviron
• Axiron
• Depo-Test
• Depo-Testosterone
• Intrinsa Patch
• Itnogen
• Jenasteron
• Lowtiyel
• Nebido
• Omnadren
• Primoniat Depot
• Primoteston Depot
• Primotestone Depot
• Proviron Depot
• Reandron
• Sustanon
• Testarzon
• Testex
• Testim
• Testocaps
• Testoderm
• Testogel
• Testom
• Testopatch
• Testosteron Ferring
• Testosteronum propionicum
• Testotop
• Testoviron
• Testoviron Depot
• Testoviron-Depot
• Tostran
• Tostrex
• Tostrex Gel
• Virormone
• Vivrone
• Y45

Testosterone Brand Names in Pakistan: