Testosterone Injection

Introduction Overview

Generic Name

testosterone injection

Brand Name

Aveed
Delatestryl
Depo-Testosterone
Testosterone Cypionate
Testosterone Enanthate
Testosterone Undecanoate
Xyosted

Dosage Form

Intramuscular injection

Drug Class

Androgens and anabolic steroids

Pharmacokinetics

Testosterone pharmacokinetics encompass absorption, distribution, metabolism, and elimination processes that define its clinical profile.

Absorption:
Testosterone injection is administered intramuscularly, bypassing gastrointestinal absorption degradation seen with oral formulations. Following intramuscular injection, testosterone esters are slowly released from the depot, allowing for sustained absorption into the bloodstream over days to weeks depending on the ester formulation. This depot effect yields prolonged plasma testosterone levels compared to immediate release formulations. The absorption rate is influenced by the specific ester used (e.g., cypionate, enanthate, undecanoate), muscle perfusion, and injection site. Pharma studies have demonstrated peak serum testosterone concentrations occurring within 24 to 72 hours post-injection, followed by a gradual decline, dictating the dosing interval (typically every 2 to 4 weeks).

Distribution:
Upon systemic absorption, testosterone is highly lipophilic and extensively bound to plasma proteins. Approximately 98% of circulating testosterone binds plasma proteins, predominantly sex hormone-binding globulin (SHBG) and albumin. The proportion bound to SHBG is biologically inactive, while the albumin-bound fraction is considered loosely bound and bioavailable. Free testosterone represents roughly 1–3% of total serum levels and is the hormonally active form. Testosterone distributes widely into target tissues including muscle, bone, liver, brain, and reproductive organs. Its volume of distribution varies but is generally reported as moderately low due to the high plasma protein binding.

Metabolism:
Testosterone undergoes extensive first-pass metabolism primarily in the liver but also locally within target tissues. Intramuscular injection circumvents gut and hepatic first-pass metabolism initially but systemic metabolism follows once absorbed. Testosterone is biotransformed primarily via reduction to dihydrotestosterone (DHT) by 5-alpha reductase, which has greater androgenic potency in tissues such as prostate and skin. Aromatization to estradiol by the CYP19 aromatase enzyme occurs in adipose tissue, brain, and bone, contributing to estrogenic effects. Hepatic metabolism involves conjugation reactions (glucuronidation, sulfation) facilitating renal and biliary excretion. Genetic polymorphisms and liver function affect metabolic rates.

Elimination:
Testosterone and its metabolites are primarily eliminated via urine after hepatic metabolism. Conjugated metabolites such as testosterone glucuronide and sulfate are water-soluble and renal excretion accounts for the majority of clearance. A minor fraction of metabolites is excreted via bile into feces. The elimination half-life depends on the ester formulation; testosterone cypionate and enanthate have half-lives of approximately 4.5 days, while testosterone undecanoate may have a half-life extending up to several weeks due to lymphatic absorption. The elimination kinetics enable dosing intervals of every two to four weeks for injections. Factors such as renal or hepatic impairment can influence clearance and plasma levels, necessitating clinical monitoring.

Dosage Forms

Available Dosage Forms:
Testosterone is available in multiple injectable ester forms, each providing distinct pharmacokinetic profiles:
- Testosterone Cypionate injection: commonly supplied in concentrations such as 100 mg/mL or 200 mg/mL for intramuscular use
- Testosterone Enanthate injection: similar concentrations to cypionate, e.g., 200 mg/mL, for intramuscular injection
- Testosterone Undecanoate injection (e.g., Aveed): long-acting intramuscular solution with formulations typically 750 mg/3 mL vial
- Xyosted: subcutaneous injection testosterone enanthate formulation designed for patient self-administration, typically dosed weekly

Dosages for Adults and Adolescents:
For adults and post-pubertal males with hypogonadism:
- Testosterone cypionate/enanthate: 50 to 400 mg injected intramuscularly every 2 to 4 weeks
- Testosterone undecanoate: initial dose 750 mg intramuscularly, repeated at 4 weeks, then every 10 weeks
- Dosing is individualized based on clinical response and serum testosterone levels
For delayed puberty in adolescent males:
- Doses generally lower and titrated carefully to mimic physiologic puberty progression, e.g., 50 mg every 4 weeks, gradually increased

Specific Patient Populations:
- Patients with hepatic or renal dysfunction require careful monitoring due to altered metabolism and elimination
- Use in women is limited; testosterone injections may be employed in certain breast cancers at lower doses under strict supervision
- Off-label use for gender-affirming hormone therapy in transgender males generally involves individualized dosing regimens, often with weekly subcutaneous injections (e.g., Xyosted)
- Frequent monitoring of hematocrit, lipids, liver function, and prostate-specific antigen (PSA) is essential in all populations

Clinical guidelines emphasize the importance of titrated doses to achieve physiological testosterone levels while minimizing adverse effects, adjusting frequency and dose according to pharmacokinetic properties of the ester formulation used.

Mechanism Of Action

Testosterone is the principal endogenous androgen responsible for the development and maintenance of male secondary sexual characteristics and anabolic effects in various tissues. Its mechanism of action involves several molecular and cellular pathways.

At the molecular level, testosterone diffuses across cell membranes due to its lipophilic nature and binds intracellular androgen receptors (AR) located in the cytoplasm. Upon binding, the hormone-receptor complex undergoes conformational change, dissociates from heat shock proteins, and translocates into the nucleus where it acts as a transcription factor. This complex binds androgen response elements (AREs) in the DNA, modulating transcription of target genes involved in protein synthesis, growth, and differentiation. Through this genomic mechanism, testosterone regulates genes responsible for muscle mass, bone density, erythropoiesis, and sexual function.

In some tissues, testosterone is converted by 5-alpha reductase to dihydrotestosterone (DHT), a more potent androgen with higher affinity for the androgen receptor. DHT binding results in stronger androgenic effects, especially in the prostate, skin, and hair follicles, contributing to development of male external genitalia and secondary sex characteristics.

Testosterone also exerts non-genomic actions through membrane-associated receptors and second messenger systems, leading to rapid cellular responses independent of direct gene transcription. These mechanisms include activation of protein kinases and modulation of ion channels, which may impact neuronal excitability, vasodilation, and metabolic regulation.

Clinically, testosterone’s anabolic activity improves muscle strength and mass, while androgenic action supports libido, mood, and male reproductive system maintenance. Comparative to synthetic anabolic steroids, testosterone maintains physiological androgen receptor activation with balanced anabolic and androgenic effects. Clinical studies confirm that testosterone replacement therapy restores serum levels, alleviates hypogonadal symptoms, improves bone mineral density, and supports metabolic homeostasis, validating its critical role and mechanism.

Pharmacological Actions

Restoration and maintenance of male secondary sexual characteristics
Anabolic effects promoting increased muscle mass and strength
Stimulation of erythropoiesis leading to increased red blood cell production
Enhancement of libido and sexual function
Regulation of mood and cognitive functions via central nervous system effects
Promotion of bone mineralization and maintenance of bone density
Influence on lipid metabolism, including modulation of cholesterol levels
Stimulation of spermatogenesis via hypothalamic-pituitary-gonadal axis feedback
Conversion to dihydrotestosterone (DHT) for potent androgenic activity in target tissues
Modulation of protein synthesis through androgen receptor-mediated gene expression
Non-genomic actions affecting cell signaling and vascular tone
Potential immunomodulatory effects
Influence on fat distribution and reduction of adipose tissue
Impact on hair growth patterns via androgen receptor pathways
Regulation of adrenal androgen synthesis

Therapeutic Or Clinical Uses

Treatment of male hypogonadism due to primary or secondary causes
Induction of puberty in males with delayed puberty
Management of male patients with testosterone deficiency due to genetic disorders or acquired conditions
Palliative treatment of metastatic breast cancer in females
Hormone replacement therapy in transgender men (gender dysphoria)
Treatment of osteoporosis in hypogonadal men to improve bone mineral density
Management of certain anemia types associated with testosterone deficiency
Supportive therapy post-chemotherapy causing hypogonadism
Improvement of quality of life and sexual functioning in men with androgen deficiency
Off-label use in selected cases of chronic debilitating illnesses with catabolic states
Treatment of cachexia in advanced diseases secondary to androgen deficiency
Potential use in male infertility related to hypogonadotropic hypogonadism
Experimental use in certain neurodegenerative diseases for neuroprotective effects
Adjunct in delayed growth conditions related to androgen deficiency
Use in specific cases of transgender hormone therapy aligning physiologic characteristics

Side Or Adverse Effects

Local injection site reactions including pain, swelling, or redness
Gynecomastia (enlargement of male breast tissue)
Polycythemia (increased hematocrit), raising risk of thrombosis
Edema with peripheral swelling and weight gain
Acne and oily skin
Male pattern baldness and increased body or facial hair growth
Sleep apnea exacerbation or new onset
Elevated blood pressure and cardiovascular risks including myocardial infarction and stroke
Prostate enlargement and potential stimulation of occult prostate cancer
Infertility due to suppression of spermatogenesis
Mood changes including aggression, irritability, or depression
Liver function abnormalities, particularly with oral formulations
Virilization symptoms in women such as voice deepening, hirsutism, and clitoral enlargement
Nausea, vomiting, or gastrointestinal discomfort
Pulmonary oil microembolism (POME) with injectable depot forms
Allergic reactions ranging from mild rash to anaphylaxis
Injection site abscess or infection
Decreased testicular size and function with prolonged use
Potential development of dependency and withdrawal syndrome upon cessation

Precautions

Contraindicated in patients with prostate or breast cancer
Screening for prostate cancer prior to and during therapy is essential
Regular monitoring of hematocrit to prevent polycythemia and thrombosis risk
Use cautiously in patients with cardiovascular disease history including coronary artery disease and stroke
Monitor liver and renal function during prolonged therapy
Watch for signs of virilization in female patients receiving therapy
Avoid use in pregnant or breastfeeding women due to teratogenic and toxicity risks
Adjustment or avoidance in patients with untreated sleep apnea
Use with caution in patients with benign prostatic hyperplasia due to possible exacerbation
Monitor lipid profiles to detect adverse changes in cholesterol and triglycerides
Avoid concomitant use with other androgenic drugs to minimize adverse effects
Ensure accurate diagnosis of hypogonadism to prevent inappropriate treatment
Patient education on injection technique and side effects to enhance safety
Monitor psychological status due to potential mood alterations
Cautious use in elderly patients due to increased cardiovascular risks
Frequent lab assessment to guide dose titration and avoid supraphysiologic levels
Educate patients about the risk of misuse and abuse leading to serious health consequences

Warnings

Do not use if pregnant or potentially pregnant due to risk of fetal harm
Avoid use in men with known or suspected prostate or breast cancer
Risk of serious cardiovascular events including heart attack and stroke
Potential to induce pulmonary oil microembolism (POME) with injectable formulations causing severe respiratory symptoms
Misuse or abuse may result in irreversible organ damage and psychological effects
Withdrawal of testosterone therapy can lead to significant symptoms and requires medical supervision
May cause hepatic dysfunction and cholestatic jaundice with certain formulations
Possibility of inducing polycythemia increasing risk for thromboembolic events
May affect glucose tolerance and exacerbate diabetes mellitus
Testosterone use may result in fluid retention and exacerbate hypertension or heart failure
Not indicated for enhancing athletic performance or normal aging
Potential virilization effect in women may be irreversible if treatment continued
Risk of injection site infection or abscess formation
Patients should report symptoms such as chest pain, swelling, dyspnea, or neurological signs promptly
Long-term effects on fertility and reproductive health; contraceptive measures recommended
Should be administered only by trained healthcare professionals due to risks associated with improper use

Contraindication

Known hypersensitivity to testosterone or any component of the formulation
Men with prostate cancer or suspected prostate carcinoma
Male breast cancer patients
Pregnant or nursing women due to potential teratogenic effects and toxicity
Severe liver disease leading to impaired drug metabolism
Severe kidney disease impacting drug elimination
Serious cardiovascular conditions posing high risk during androgen therapy
Patients with known hypercalcemia, especially if associated with breast cancer
Individuals with polycythemia or uncontrolled erythrocytosis
Patients with uncontrolled hypertension or severe heart failure
In patients with thrombophilic conditions or history of thromboembolism without adequate anticoagulation
Concurrent use with other androgens or anabolic steroids contraindicated
Presence of severe pulmonary pathology that can be worsened by oil-based injections
Patients with untreated sleep apnea requiring advanced management
Active or unstable psychiatric disorders that may be exacerbated by hormone therapy

Drug Interactions

Anticoagulants (e.g., warfarin, Coumadin, Jantoven) – testosterone may alter coagulation parameters increasing bleeding risk
Anti-inflammatory drugs such as oxyphenbutazone can interact affecting metabolism and efficacy
Corticosteroids – concurrent use may increase risk of edema
Insulin and oral antidiabetic agents – testosterone may affect glucose metabolism and glycemic control
Cytochrome P450 enzyme inducers or inhibitors may alter testosterone metabolism
Other anabolic steroids or androgens – additive androgenic effects and toxicity risks
Drugs affecting liver enzyme activity, e.g., anticonvulsants, can impact testosterone plasma levels
Alcohol – combined hepatotoxicity risk
Opioids may suppress the hypothalamic-pituitary-gonadal axis, counteracting testosterone effects
Drugs that prolong QT interval – testosterone’s cardiac effects may exacerbate arrhythmia risks
Medications affecting lipid metabolism may have altered profiles when combined with testosterone
Herbal supplements like St. John’s Wort may induce hepatic enzymes and reduce testosterone efficacy
Potential interaction with drugs altering protein binding, affecting free testosterone fractions
Diuretics – combined electrolyte disturbances risk
Immunosuppressants may have altered efficacy or toxicity profiles during testosterone therapy

Preparations Of The Drug

Testosterone Cypionate Injection: oil-based solution available typically at 100 mg/mL or 200 mg/mL concentrations for intramuscular administration
Testosterone Enanthate Injection: injectable ester in oily vehicle, commonly dosed at 200 mg/mL for intramuscular use
Testosterone Undecanoate (Aveed): long-acting intramuscular depot injection supplied as 750 mg/3 mL vial intended for less frequent dosing
Xyosted: subcutaneous testosterone enanthate injection designed for patient self-administration with prefilled syringes
Depot-Testosterone: brand of testosterone cypionate for intramuscular injection
Topical gels (e.g., AndroGel) and patches (e.g., Androderm) are available but outside the injectable formulation scope
Buccal and nasal testosterone formulations exist for alternative administration routes though less commonly used
Testosterone pellets for subcutaneous implantation provide continuous delivery over months
Various generic formulations that comply with FDA standards for injectable testosterone esters
Formulations require sterile handling and storage according to manufacturer guidelines
Intramuscular preparations are designed for deep muscle injection to ensure depot formation and slow release
Solutions may contain oil-based vehicles like castor oil or sesame oil to facilitate depot characteristics
Preparations vary in excipients contributing to stability and absorption profile
Dosage forms supplied in single-use vials or prefilled syringes
Manufacturers provide detailed instructions for administration technique and dosing intervals