Testosterone Troches

Testosterone troches are a form of oral testosterone that dissolves in the mouth and is absorbed through the mucous membranes. They provide an alternative to other testosterone delivery systems like injections, gels, and patches.

• Historical Use: Testosterone, the primary androgen in the body, has been used therapeutically since 1938 and was FDA-approved in 1939.
• Controlled Substance: Testosterone and its derivatives were classified as controlled substances in 1991 due to their potential for misuse.
• FDA Approvals: Testosterone cream, developed as AndroGel by Uniumed Pharmaceuticals and approved by the FDA in 2000, is a popular treatment for testosterone deficiency. Other brands include Testogel (UK) and Testim (U.S.), along with various generic versions.

• Delivery System: Testosterone troches are absorbed through the oral mucosa, offering a non-invasive alternative to injections.
• Absorption: Like transdermal gels and injections, the effectiveness of testosterone troches can be influenced by the application site. For topical applications like creams and gels, optimal absorption occurs when applied to densely muscled areas due to the higher density of capillaries, which facilitates rapid absorption into the bloodstream.

• Therapeutic Use: Testosterone is used to manage hypogonadism (congenital or acquired) and is also used for palliative treatment in postmenopausal women with breast cancer.
• Benefits: It helps address various hypogonadic conditions, including mood, energy levels, and sexual dysfunction. Additionally, it can be used in treating injury-related conditions, such as those from severe burns or accidents.

• Source: Produced from cholesterol and secreted primarily by the testes in males and in smaller amounts by the ovaries in females.
• Role in Development:
  • Fetal Development: Essential for sexual differentiation in the fetus.
  • Puberty: Drives the development of secondary sexual characteristics and physical changes.
  • Adult Function: Maintains male sexual function and other physiological processes throughout life.

• Negative Feedback Mechanism: Increased levels of testosterone decrease the secretion of:
  • Gonadotropin-Releasing Hormone (GnRH): Reduces endogenous testosterone production.
  • Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH): Critical in regulating reproductive functions.

• Lipid Solubility: Testosterone’s high lipid solubility allows it to rapidly enter target cells.
• Enzymatic Conversion: Inside the cells, testosterone is converted to 5-alpha-dihydrotestosterone (DHT).
• Receptor Binding: Testosterone forms a complex with cytosolic androgen receptors. This complex then translocates to the nucleus, where it influences gene expression.

• RNA Polymerase Stimulation: Testosterone stimulates RNA polymerase, leading to increased protein production.
• Proteins and Development:
  • Sexual Development: Stimulates growth and maturation of sexual organs such as the prostate, seminal vesicles, penis, and scrotum.
  • Pubertal Changes: Promotes muscle growth, body fat redistribution, voice deepening, beard and body hair growth, and epiphyseal fusion (which terminates linear bone growth).

• Spermatogenesis: Essential for the production and maintenance of sperm.
• Overall Growth and Development: When endogenous testosterone is insufficient, exogenous testosterone is used to support normal growth and development.

• Cancer: Contraindicated in individuals with:
  • Prostate Cancer: Testosterone can stimulate cancerous tissue growth.
  • Breast Cancer in Men: Similar concerns about stimulating cancerous tissue.
• Pregnancy: Testosterone is contraindicated due to potential harm to the fetus (FDA pregnancy risk category X). Women of childbearing potential should use contraception.
• Lactation: Topical testosterone formulations are contraindicated during breastfeeding. Other formulations should also be avoided.

• General Health Conditions:
  • Breathing Problems While Sleeping: Risk of exacerbating sleep apnea.
  • Diabetes: Can affect glucose control; monitor blood glucose levels closely.
  • Heart Disease: Increased risk of cardiovascular events, especially in older adults or those with existing conditions.
  • Kidney Disease: Caution due to potential drug accumulation and effects on renal function.
  • Liver Disease: Use with caution; may lead to fluid retention and exacerbate liver issues.
  • Lung Disease: Caution in patients with chronic pulmonary conditions.
  • Prostatic Hypertrophy: May worsen symptoms of benign prostatic hypertrophy and increase risk of malignancy.
• Age Considerations:
  • Elderly: Testosterone therapy is generally not recommended for age-related hypogonadism due to insufficient safety data. The Beers Criteria consider it a potentially inappropriate medication for older adults.
  • Children and Adolescents: Use with extreme caution due to potential effects on bone maturation and growth.
• Potential Drug Interactions and Side Effects:
  • Flammability: Topical gels and solutions are flammable; avoid exposure to fire, flame, and smoking.
  • Polycythemia: Risk of elevated red blood cell count; monitor hemoglobin and hematocrit levels.
  • Edema: May cause fluid retention; use with caution in patients with pre-existing edema or cardiovascular issues.
• Special Populations:
  • Pregnant and Breastfeeding Women: Contraindicated due to risks to the fetus and infant.
  • Females: Not recommended due to potential for virilization and lack of controlled evaluations.
• Administration Specifics:
  • Testosterone Undecanoate: Associated with serious reactions. Administer carefully and monitor for at least 30 minutes post-injection. Use only in certified settings with emergency capabilities.
  • Intranasal Formulations: Not recommended for those with a history of nasal disorders or recent nasal trauma. Delayed treatment in cases of rhinitis or congestion.
• Handling and Accidental Exposure: To minimize risk of accidental exposure, wash hands thoroughly after application, cover the application site, and remove medication if contact with others is anticipated. If exposure occurs, wash the area immediately with soap and water.

• Anticoagulants:
  • Warfarin: Testosterone may increase warfarin’s anticoagulant effect, raising the risk of serious bleeding. Frequent monitoring of INR and prothrombin time is recommended, and dose adjustments may be necessary.
• Diabetes Medications:
  • Insulin and Oral Antidiabetic Agents: Testosterone may improve glycemic control in patients with diabetes by reducing fasting plasma glucose and HbA1c. However, it’s important to monitor blood glucose levels regularly, as both hypoglycemia and hyperglycemia can occur.
• Corticosteroids:
  • Prednisone, Cortisone: Co-administration with testosterone may increase the risk of edema, especially in patients with underlying cardiac or hepatic conditions. Caution is advised.
• Cyclosporine:
  • Cyclosporine: Testosterone may increase plasma levels of cyclosporine, raising the risk of nephrotoxicity. Monitor for signs of kidney damage.
• 5-alpha Reductase Inhibitors:
  • Dutasteride, Finasteride: These medications counteract the effects of testosterone and should not be used simultaneously with androgens.
• Saw Palmetto:
  • Saw Palmetto Extracts: May have antiandrogenic effects that could counteract testosterone’s actions. Use with caution.
• Fluconazole and Voriconazole:
  • Fluconazole: May increase testosterone concentrations due to CYP3A4 inhibition. Voriconazole may have a similar effect. The clinical significance is unclear.
• P-glycoprotein Substrates:
  • Ranolazine: Co-administration with testosterone, a P-glycoprotein inhibitor, may increase ranolazine absorption. Monitor for adverse effects.
  • Ambrisentan: Increased absorption and potential side effects when coadministered with testosterone.
• Oxyphenbutazone:
  • Oxyphenbutazone: May lead to elevated concentrations of oxyphenbutazone. Monitor for adverse effects.
• Propranolol:
  • Propranolol: Testosterone may increase the clearance of propranolol. Monitor for reduced efficacy of propranolol.
• Dabigatran:
  • Dabigatran: Increased dabigatran serum concentrations and risk of adverse effects. Avoid coadministration in patients with severe renal impairment.
• Afatinib:
  • Afatinib: Testosterone may increase afatinib exposure. Dose adjustment may be necessary if adverse effects occur.
• Intranasal Medications:
  • Intranasal Testosterone (e.g., Natesto): Avoid co-administration with other intranasally administered drugs due to unknown interaction potential.

• Hepatic Enzyme Interactions:
  • Cytochrome P450 (CYP) 3A4: Testosterone is a substrate for CYP3A4, which may affect the metabolism of other drugs processed by this enzyme.
  • P-glycoprotein Transport: Testosterone is both transported by and inhibits P-glycoprotein. This can affect the absorption and efficacy of other P-glycoprotein substrates.
• Erythropoiesis:
  • Increased Erythropoiesis: Androgens stimulate red blood cell production. Caution is advised, especially in patients with conditions affecting blood viscosity.
• Bone Maturation:
  • Prepubescent Males: Excessive androgens may accelerate bone maturation and compromise adult stature. Monitor bone growth carefully.

• Effects: Mastalgia, gynecomastia.
• Incidence: Gynecomastia (Testim: 1%, Androgel: 1-3%), Mastalgia (Androgel: 1-3%), Axiron (<1%).

• Effects: Libido increase or decrease, priapism.
• Incidence: Libido decrease (Androgel: 1-3%), priapism and impotence (Fortesta), spontaneous penile erection (1%).

• Effects: Prostatic hypertrophy, benign prostatic hyperplasia (BPH), increased PSA levels.
• Incidence: BPH (Testim: 1%), prostate abnormalities (Androderm: 5%), elevated PSA (Axiron: 1-4%, Fortesta: 1.3%).

• Effects: Application site reactions, acne, hirsutism.
• Incidence: Erythema, pruritus, blisters, acne (Axiron: >1%, Androgel: 1-8%), hirsutism (<1%).

• Effects: Hypertension, increased risk of severe cardiovascular events.
• Incidence: Hypertension (Androgel: 2.1-3%, Testim: 1%, Axiron: >1%), increased risk of MI (older males: 2-fold increase).

• Effects: Elevated liver enzymes, rare cases of jaundice, peliosis hepatis.
• Incidence: Rare liver dysfunctions, more likely with 17-alpha-alkylated androgens.

• Effects: Increased erythropoiesis, polycythemia, bleeding complications.
• Incidence: Increased hematocrit/hemoglobin, anemia (Androgel: 2.5%).

• Effects: Headache, mood alterations, gastrointestinal issues, bone density changes.
• Incidence: Headache (1-6%), mood changes (various <3%), GI issues (diarrhea: 3-4%, vomiting: 3-4%).

• Effects: Injection site reactions, anaphylactoid reactions.
• Incidence: POME reactions (Testosterone undecanoate: 9 events in 3556 patients), anaphylaxis (rare).

• Effects: Nasal irritation, dryness, bleeding.
• Incidence: Nasopharyngitis (3.8-8.7%), epistaxis (3.8-6.5%).

• Effects: Sleep apnea risk increase, acne vulgaris, alopecia.
• Incidence: Acne vulgaris (>1%), alopecia in long-term use.

• Contraindicated: Testosterone is not recommended for use during pregnancy due to potential adverse effects on the fetus. It is classified as FDA pregnancy risk category X.
• Contraception: Women of childbearing potential should use effective contraception while receiving testosterone treatment.
• Labor and Delivery: Testosterone should not be used during labor or delivery, as its safety and efficacy in these settings are not established.

• Contraindicated: Testosterone topical solutions, transdermal patches, and gels are not recommended for use in lactating women.
• Alternative Methods: Other testosterone formulations should also be avoided during breastfeeding.
• Concerns: The distribution of testosterone into breast milk is not well-documented, but significant exposure to the infant could lead to adverse androgenic effects and may interfere with lactation.
• Historical Use: Testosterone/androgens have been used in the past to suppress lactation, but alternative methods to breastfeeding are recommended for lactating women receiving testosterone therapy.

Store this medication in its original container 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.