Testosterone Cypionate Injection

• Testosterone Cypionate is a synthetic, slow-acting, long-ester, oil-based injectable form of testosterone, primarily prescribed for treating hypogonadism, which is characterized by low testosterone levels and associated symptoms in males.

• Testosterone was the first synthesized anabolic steroid. Testosterone cypionate was introduced to the U.S. prescription market in the early 1950s under the brand name Depo-Testosterone by Upjohn, now part of Pharmacia & Upjohn.
• It is similar to testosterone enanthate, a slightly longer-acting ester. Testosterone cypionate has primarily been available in the United States, where it is often considered an American-specific medication.

• Testosterone is the primary androgen in the human body, produced naturally in the testis, ovary, and adrenal cortex.
• Therapeutically, testosterone is used to manage hypogonadism, which can be either congenital (present at birth) or acquired (developed later in life).
• Testosterone is also used as a palliative treatment for breast cancer in postmenopausal women, as it helps in managing certain symptoms of the disease.
• FDA Approval: Testosterone was in use as early as 1938 and received FDA approval in 1939. Over the years, various formulations of testosterone have been developed, including injectable forms, transdermal patches, gels, and buccal systems.

• Testosterone derivatives, known as anabolic steroids, have been used both legally and illicitly. Due to their potential for abuse, these substances were classified as controlled substances in the United States in 1991.

• Testosterone is administered parenterally, with regular and delayed-release (depot) dosage forms available. Transdermal patches, gels, implants, and topical solutions have also been developed, with varying dosages tailored for different applications, including hormone replacement therapy in women.

• Ester Function: Esters are organic compounds that, when combined with testosterone, influence the medication’s solubility and half-life in the body. The length of the carbon chain in the ester determines how quickly the medication acts and is metabolized.
• Cypionate Ester: The cypionate ester, characterized by a long carbon chain, is slow-acting, meaning it remains active in the body for an extended period, allowing for less frequent injections compared to shorter esters.

• Sexual Maturation: Testosterone plays a crucial role in sexual development at all life stages, beginning in the fetus, intensifying during puberty, and continuing throughout adulthood. In males, testosterone is primarily produced in the testis, while females produce small amounts in the ovaries. The adrenal cortex also secretes androgens, but in amounts insufficient to maintain male sexual function.
• Synthesis: Endogenous testosterone is synthesized from cholesterol, a key precursor in steroid hormone production.

• Negative Feedback Mechanism: Increased levels of testosterone suppress the release of gonadotropin-releasing hormone (GnRH), which in turn reduces the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). This negative feedback mechanism helps regulate endogenous testosterone production.
• Androgen Action: Testosterone is highly lipid-soluble, allowing it to enter target cells quickly. Once inside, it is converted by enzymes to 5-alpha-dihydrotestosterone (DHT), a more potent androgen. DHT binds to cytosolic receptors, forming a complex that translocates to the nucleus. This complex initiates the transcription of specific genes, leading to cellular changes and androgenic effects.
• Protein Synthesis: Androgens like testosterone stimulate RNA polymerase activity, increasing protein synthesis. These proteins are essential for the normal development of male sexual characteristics, including the growth and maturation of the prostate, seminal vesicles, penis, and scrotum.

• Physical Development: During puberty, testosterone causes a rapid increase in muscle growth, redistribution of body fat, and changes in the larynx and vocal cords, leading to a deeper voice. It also promotes the growth of body hair and beard development.
• Epiphyseal Fusion: Testosterone is responsible for the fusion of the epiphyses (growth plates) in bones, leading to the cessation of growth. It also plays a role in maintaining spermatogenesis, the process of sperm production.

• When endogenous testosterone production is insufficient, as in cases of hypogonadism, exogenous testosterone (such as testosterone cypionate) is administered to maintain normal male growth and development. This external source of testosterone helps achieve the necessary physiological effects when the body cannot produce adequate levels on its own.

• Children: Testosterone should not be used in children unless explicitly directed by a physician.
• Pregnancy and Breastfeeding: Testosterone is contraindicated in women who are pregnant, trying to conceive, or breastfeeding due to potential adverse effects on the fetus and infant. Testosterone therapy is classified as an FDA pregnancy risk category X.
• Breast Cancer: Men with breast cancer should not use testosterone, as it may exacerbate the condition.
• Prostate Conditions: Testosterone is contraindicated in patients with prostate cancer and should be used cautiously in those with benign prostatic hyperplasia (BPH), as it can worsen symptoms and increase the risk of malignancy.
• Hypersensitivity: Patients with known hypersensitivity to testosterone or any of the excipients in the formulation should avoid this medication. Specific formulations, such as AndroGel and Striant, are contraindicated in patients with soy or soybean hypersensitivity due to their derivation from soy products. Testosterone undecanoate (Aveed) is contraindicated in patients with hypersensitivity to benzyl benzoate, benzyl alcohol, or polyoxyethylated castor oil.
• Athletes: Testosterone use is banned by most athletic organizations due to its performance-enhancing effects.

• Cardiovascular Risks: Testosterone therapy has been associated with an increased risk of severe cardiovascular events such as myocardial infarction (MI) and stroke, especially in older men or those with pre-existing heart conditions. The FDA is investigating this potential link, and healthcare providers should carefully weigh the benefits and risks before initiating therapy.
• Prostate Cancer Surveillance: Patients, particularly elderly men, should be evaluated for prostate cancer before starting testosterone therapy. Regular monitoring for prostate cancer is recommended during treatment.
• Hepatic and Renal Impairment: Testosterone should be used cautiously in patients with liver or kidney disease due to the risk of fluid retention and potential drug accumulation. Edema is a concern in patients with heart disease, including those with heart failure or myocardial infarction.
• Respiratory Risks: Testosterone injections should be administered intramuscularly, not intravenously, to avoid serious respiratory adverse events such as pulmonary oil microembolism (POME) reactions.
• Polycythemia: High doses of testosterone can lead to polycythemia. Patients on testosterone therapy should have regular hemoglobin and hematocrit levels checked to detect this condition.
• Sleep Apnea: Testosterone therapy may exacerbate sleep apnea, particularly in patients with risk factors such as obesity or chronic pulmonary disease.
• Hypercalcemia: Testosterone can induce osteolysis, which may worsen hypercalcemia in patients with metastatic breast cancer.
• Accidental Exposure: Topical testosterone products can be transferred to others through skin contact, leading to unintended effects such as virilization. Precautions should be taken to avoid accidental exposure, particularly with children and women.

• MRI Considerations: Some testosterone transdermal patches contain aluminum, which can overheat during MRI scans and cause skin burns. Patches should be removed before MRI procedures.
• Use in Geriatric Patients: The use of testosterone in elderly patients, particularly for age-related hypogonadism, is controversial due to insufficient safety and efficacy data. According to the Beers Criteria, testosterone is considered a potentially inappropriate medication for geriatric patients due to the risk of cardiac issues and prostate cancer.
• Use in Pediatric Patients: Testosterone use in children should be approached with extreme caution, as it may accelerate bone maturation without sufficient linear growth, potentially compromising adult stature. Accidental exposure to testosterone in children can cause significant adverse effects, including genitalia enlargement and advanced bone age.

• Testosterone undecanoate (Aveed): Due to the risk of POME and anaphylaxis, this formulation is only available through a restricted program called the Aveed REMS Program. Patients must be monitored for at least 30 minutes after administration.
• Intranasal Formulations: Intranasal testosterone (e.g., Natesto) is not recommended for patients with nasal disorders, and its efficacy may be reduced in individuals with rhinitis or nasal congestion.

Patients should consult with their healthcare provider to fully understand the risks and benefits of testosterone therapy and to ensure it is appropriate for their specific medical condition. Regular monitoring and adherence to safety guidelines are essential to mitigate potential adverse effects.

• Diabetes Medications: Testosterone can affect blood glucose control.
• Blood Thinners (Warfarin): Increased anticoagulant action; monitor INR and prothrombin time.
• Steroids (e.g., prednisone, cortisone): Increased risk of edema, especially with cardiac or hepatic disease.
• Cyclosporine: Potential for increased plasma concentrations and nephrotoxicity.
• CYP3A4 Inhibitors (e.g., fluconazole, voriconazole): Increased testosterone levels.
• Goserelin and Leuprolide: Concomitant use is relatively contraindicated.
• Hepatotoxic Medications: Increased risk of liver damage.
• Erythropoiesis-Stimulating Agents (e.g., epoetin alfa): Monitor for adverse reactions due to increased blood viscosity.
• 5-alpha Reductase Inhibitors (e.g., finasteride, dutasteride): Antagonistic to androgens.

• Warfarin: Testosterone can increase the anticoagulant action, requiring more frequent monitoring of INR and prothrombin time.
• Cyclosporine: Androgens may increase cyclosporine plasma concentrations, risking nephrotoxicity.
• Corticosteroids: Concomitant use with androgens may increase edema risk, particularly with fludrocortisone.
• Goserelin and Leuprolide: These inhibit steroidogenesis, making concurrent androgen use counterproductive.
• Hepatotoxic Medications: Increased hepatotoxicity risk when combined with androgens.
• Erythropoiesis-Stimulating Agents: Androgens can amplify the response to epoetin alfa, potentially leading to adverse effects due to increased blood viscosity.
• 5-alpha Reductase Inhibitors: These have antiandrogenic effects, which can counteract androgens.
• Saw Palmetto: Antiandrogenic effects may antagonize the actions of androgens.
• Fluconazole and Voriconazole: These can increase testosterone concentrations due to CYP3A4 inhibition.
• Conivaptan: As a potent CYP3A4 inhibitor, it may increase testosterone plasma concentrations.
• Ranolazine: Coadministration with testosterone may increase ranolazine absorption.
• Ambrisentan: Coadministration with testosterone may increase oral absorption, requiring close monitoring.
• Oxyphenbutazone: Elevated concentrations when combined with testosterone.
• Propranolol: Testosterone can increase the clearance of propranolol.
• Dabigatran: Increased serum concentrations with testosterone, especially in severe renal impairment.
• Afatinib: Increased exposure when coadministered with testosterone.
• Intranasal Testosterone (Natesto): Unknown interaction potential with other intranasal drugs.
• Oxymetazoline: Does not significantly impact the absorption of intranasal testosterone.

• Insulin Resistance: Low testosterone is associated with insulin resistance.
• Improvement in Glycemic Control: Exogenous androgens can reduce fasting plasma glucose and HbA1c levels.
• Monitor Glycemic Control: Patients with diabetes on androgens should be closely monitored for changes in glycemic control.

• Herbs and Supplements: Interaction potential with herbs like Saw palmetto, which have antiandrogenic effects.
• Alcohol and Illegal Drugs: These can interact with testosterone therapy.

Note: Always provide a complete list of all medications, supplements, and lifestyle habits to your healthcare provider to ensure safe and effective management of testosterone therapy and to avoid potential interactions.

Testosterone therapy can lead to a variety of adverse reactions and side effects, particularly when used in prolonged or high doses. These side effects can vary based on gender, age, and the specific testosterone formulation used.

• Feminization: Prolonged testosterone therapy can cause feminization in males, including gynecomastia (breast enlargement) and mastalgia (breast pain), especially in those with liver disease. These effects are usually reversible.
• Sexual Side Effects: Testosterone therapy can lead to changes in libido (both increases and decreases). In some cases, it can cause priapism (prolonged erections) or impotence. Benign prostatic hyperplasia (BPH) and prostate abnormalities have been reported, along with increased prostate-specific antigen (PSA) levels, which may signal prostate issues.
• Urinary and Reproductive Effects: Prostate disorders, nocturia (frequent urination at night), and other urinary symptoms are associated with testosterone therapy. It can also inhibit spermatogenesis, leading to decreased fertility.
• Cardiovascular Risks: There is ongoing investigation into the possible increased risk of severe cardiovascular events (e.g., myocardial infarction, stroke) associated with testosterone use, particularly in older males or those with pre-existing heart conditions.
• Fluid Retention and Blood Pressure: Testosterone can cause fluid retention, leading to peripheral edema (swelling). It may also impact blood pressure, potentially leading to hypertension.

• Virilization: Women receiving testosterone may experience virilization, which includes symptoms like acne, hirsutism (excess body hair), deepening of the voice, and clitoral enlargement. If not discontinued early, some effects may become irreversible.
• Menstrual Irregularities: Testosterone can disrupt the menstrual cycle, leading to amenorrhea (absence of menstruation) or oligomenorrhea (infrequent menstruation).
• Pregnancy Risks: Testosterone exposure during pregnancy can cause fetal harm, leading to varying degrees of virilization in the fetus.

• Dermatological Reactions: Application site reactions (e.g., erythema, pruritus, rash) are common with topical testosterone products. Acne and seborrhea are also reported due to increased sebaceous gland activity.
• Hepatic Dysfunction: Testosterone can lead to liver issues, including elevated liver enzymes, cholestatic jaundice, or even life-threatening conditions like peliosis hepatis.
• Psychiatric and Neurological Effects: Some patients report mood alterations, including depression, anxiety, and aggression. Headaches, abnormal dreams, and insomnia have also been noted.
• Gastrointestinal and Musculoskeletal Issues: GI problems like diarrhea and vomiting, along with musculoskeletal pain and back pain, have been observed in some patients.
• Metabolic Effects: Testosterone can influence lipid profiles, potentially leading to hypercholesterolemia or hypertriglyceridemia. It also stimulates erythropoiesis, which can cause polycythemia (increased red blood cells), potentially leading to complications like dizziness, fatigue, or clotting issues.

• Regular monitoring of liver function, lipid profiles, hematocrit, and PSA levels is recommended for patients on long-term testosterone therapy. Dose adjustments or discontinuation may be necessary based on these parameters or the occurrence of adverse effects.

In conclusion, while testosterone therapy can be beneficial, it carries significant risks that require careful consideration and ongoing monitoring by healthcare professionals.

• Contraindicated: Testosterone is classified as a Category X medication, meaning it is contraindicated during pregnancy due to the risk of adverse effects on the fetus.
• Contraception: Women of childbearing potential should use adequate contraception while undergoing testosterone treatment to prevent pregnancy.
• Use During Labor: There is no established safety or efficacy for the use of testosterone during labor or obstetric delivery.

• Contraindicated: Testosterone topical solutions, transdermal patches, and gels are contraindicated in breastfeeding women.
• Avoidance Recommended: Other testosterone formulations should also be avoided during breastfeeding.
• Risk: The distribution of testosterone into breast milk has not been well-studied, but significant exposure could have adverse androgenic effects on the infant and potentially interfere with lactation.

Testosterone should not be used during pregnancy or breastfeeding due to potential risks to the fetus or infant and the lack of established safety. Alternative methods to breastfeeding are advised for lactating women receiving testosterone therapy.

Store this medication at 68°F to 77°F (20°C to 25°C) and away from heat, moisture and light. Keep all medicine out of the reach of children. Throw away any unused medicine after the beyond use date. Do not flush unused medications or pour down a sink or drain. NOTE: Warming and shaking the vial should redissolve any crystals that may have formed during storage temperatures lower than recommended.