Testosterone

• Primary Hypogonadism: Treatment of male hypogonadism caused by congenital or acquired testicular failure.
• Secondary Hypogonadism: Hypogonadotropic hypogonadism due to hypothalamic or pituitary dysfunction.
• Delayed Puberty in Males: Induction of puberty in boys with delayed puberty.
• Gender Dysphoria: Hormone replacement therapy for transgender men.
• Breast Cancer: Palliative treatment of inoperable or advanced breast cancer in women.
• Cachexia and Wasting Syndromes: Off-label use to improve body weight and muscle mass in chronic illnesses such as HIV/AIDS or chronic renal failure.
• Osteoporosis: Off-label use to improve bone density in men with testosterone deficiency.
• Anemia: Off-label use for refractory anemia unresponsive to standard treatment.

Adults (Male):

• Hypogonadism Replacement Therapy:
• Intramuscular Injection: Testosterone enanthate or cypionate, 50–400 mg every 2 to 4 weeks.
• Transdermal Gel: Apply 5 to 10 grams daily (delivers 50 to 100 mg testosterone).
• Transdermal Patch: Apply 2.5 to 7.5 mg patch daily.
• Buccal Tablet: 30 mg twice daily.
• Nasal Gel: 11 mg three times daily.
• Delayed Puberty: Start with low doses such as 25–50 mg intramuscularly every 4 weeks, gradually increasing as needed.

Pediatrics:

• Used cautiously for delayed puberty.
• Initial doses typically 25–50 mg intramuscularly monthly, adjusted based on response.

Elderly:

• Use with caution; start with lower doses due to increased risk of cardiovascular and prostate-related adverse effects.

Special Populations:

• Renal and Hepatic Impairment: No specific dose adjustment recommended; careful monitoring advised.

Administration Routes:

• Intramuscular injection, transdermal gel or patch, buccal tablet, nasal gel.

Duration:

• Long-term for hypogonadism; several months for puberty induction.

Testosterone is an endogenous androgen hormone that binds to intracellular androgen receptors in target tissues. Upon binding, the hormone-receptor complex translocates to the cell nucleus, where it regulates gene expression, leading to the development and maintenance of male secondary sexual characteristics, stimulation of protein synthesis, muscle growth, erythropoiesis, and libido. Testosterone is also converted by 5-alpha-reductase into dihydrotestosterone (DHT), a more potent androgen responsible for specific androgenic effects in tissues such as the prostate and skin.

• Absorption: Variable depending on formulation; injectable forms are absorbed rapidly after intramuscular administration, while transdermal formulations provide steady absorption.
• Distribution: Widely distributed; approximately 98% is bound to plasma proteins (mainly sex hormone-binding globulin and albumin).
• Metabolism: Extensively metabolized in the liver via CYP3A4 enzymes. Metabolized to inactive compounds and also converted to DHT and estradiol.
• Elimination: Metabolites excreted primarily in the urine.
• Half-life: Testosterone enanthate and cypionate have a half-life of approximately 4.5 days; transdermal formulations maintain steady levels with daily use.
• Onset of Action: Injectable testosterone produces physiological levels within hours; transdermal forms require consistent daily application.

• Pregnancy: Category X. Testosterone is contraindicated during pregnancy because it can cause fetal harm, including virilization of female fetuses.
• Lactation: Safety during breastfeeding is unknown; testosterone may be excreted in breast milk and could adversely affect the nursing infant.
• Use in pregnant or breastfeeding women is contraindicated unless under strict medical supervision for approved indications.

• Primary Class: Androgen, anabolic steroid.
• Subclass: Natural testosterone and synthetic testosterone esters.

• Known hypersensitivity to testosterone or any component of the formulation.
• Men with breast cancer or known or suspected prostate cancer.
• Pregnancy and lactation.
• Severe hepatic, cardiac, or renal disease (use with caution).
• Hypercalcemia associated with prostate cancer.
• Polycythemia or elevated hematocrit.

• Monitor men for prostate cancer risk; regular PSA testing and digital rectal exams are recommended.
• Caution in patients with cardiovascular disease due to increased risk of thromboembolism, myocardial infarction, and stroke.
• Monitor hematocrit to prevent polycythemia.
• Use with caution in patients with heart failure or hypertension due to potential fluid retention.
• May worsen sleep apnea.
• Monitor liver function; discontinue if signs of hepatotoxicity occur.
• Avoid use in children except for appropriate indications such as delayed puberty.
• Early signs of serious adverse events (chest pain, swelling, jaundice) require immediate medical attention.

• Common:
• Acne and oily skin.
• Injection site reactions (pain, swelling).
• Fluid retention and edema.
• Increased red blood cell count (polycythemia).
• Gynecomastia.
• Mood changes, aggression.
• Serious/Rare:
• Prostate hypertrophy or cancer progression.
• Hepatic dysfunction including cholestasis.
• Cardiovascular events (thrombosis, myocardial infarction, stroke).
• Sleep apnea exacerbation.
• Infertility due to suppression of spermatogenesis.
• Side effects usually develop within weeks to months of therapy.

• CYP3A4 Inducers (e.g., rifampin, phenytoin): May reduce testosterone plasma levels, decreasing efficacy.
• CYP3A4 Inhibitors (e.g., ketoconazole, erythromycin): May increase testosterone levels, raising risk of toxicity.
• Anticoagulants (e.g., warfarin): Testosterone may alter anticoagulant effects; close monitoring of INR is advised.
• Corticosteroids: Concurrent use may increase the risk of edema.
• Insulin and oral hypoglycemics: Testosterone may affect blood glucose control; monitoring is recommended.
• Use with other androgenic agents may enhance androgenic effects and side effects.

• Recent clinical guidelines emphasize confirming symptomatic hypogonadism and low serum testosterone before initiating treatment.
• Increased focus on cardiovascular risk monitoring during testosterone therapy.
• New transdermal and nasal formulations provide more consistent testosterone levels with fewer side effects.
• Recommendations to avoid overuse in elderly men without clear evidence of benefit.
• Enhanced safety monitoring protocols including regular PSA, hematocrit, and liver function tests.

• Store at controlled room temperature between 20°C and 25°C (68°F to 77°F).
• Protect from excessive heat, moisture, and direct sunlight.
• Injectable forms should be kept in their original packaging until use; avoid freezing.
• Transdermal gels and patches should be kept tightly closed and stored away from heat or light.
• Nasal gels should be stored upright and not frozen.
• Follow manufacturer instructions regarding handling and expiration.