Testosterone Cream

• Testosterone: The primary androgen in the body, produced by the testis, ovary, and adrenal cortex.
• Uses: Employed for treating congenital or acquired hypogonadism and as palliative therapy for breast cancer in postmenopausal women.

• Early Use: Testosterone has been used since 1938, with FDA approval in 1939.
• Controlled Substances: Anabolic steroids, derivatives of testosterone, became controlled substances in 1991.

• Approval: FDA-approved in 2000 by Uniumed Pharmaceuticals for treating hypogonadism, which affects mood, energy, and sexual function.
• Variants: Also known by other names like Testogel (UK), Testim (US), and various generic forms.

• Delivery System: Testosterone cream uses a transdermal delivery system.
• Application Sites: Absorbs best when applied to heavily muscled areas, similar to testosterone injections, due to higher density of capillaries that enhance absorption into the bloodstream.

• Testosterone is synthesized from cholesterol.
• It plays a critical role in sexual development and maintenance throughout life.

• Essential for male development from fetal stages through adulthood.
• Important during puberty for sexual maturation.

• Small amounts are secreted by ovaries.
• The adrenal cortex’s androgens are insufficient to sustain male sexuality.

• Elevated testosterone levels inhibit the release of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) through a negative-feedback mechanism.
• Affects erythropoietin production, calcium balance, and blood sugar levels.

• Lipid Solubility: Androgens, including testosterone, are lipid-soluble and rapidly penetrate target cells.
• Conversion: Inside cells, testosterone is converted to 5-alpha-dihydrotestosterone (DHT).
• Receptor Binding: DHT binds to cytosolic receptors to form a complex that enters the nucleus.
• Transcription: The steroid-receptor complex alters cellular activity by initiating transcription, leading to androgen effects.

• Protein Synthesis: Endogenous androgens stimulate RNA polymerase, enhancing protein synthesis.
• Development: Regulates growth and maturation of the prostate, seminal vesicles, penis, and scrotum.
• Puberty: Promotes muscle growth, body fat redistribution, and deepening of the voice. Facilitates the development of facial and body hair.
• Growth and Spermatogenesis: Controls epiphyseal fusion, cessation of growth, and preservation of spermatogenesis.

• Necessary for normal male development and growth in the absence of endogenous androgens.

• Breast Cancer: Testosterone can promote malignant tissue formation.
• Prostate Conditions: Avoid use in prostate cancer or prostatic hypertrophy as it may exacerbate symptoms or increase cancer risk.
• Heart Disease: Use cautiously due to potential links with serious cardiovascular events.
• Liver Disease: Caution advised due to decreased drug clearance and increased risk of drug buildup.
• Kidney Disease: Use with caution, especially in conditions like nephritis and nephrosis.
• Lung Disease: Careful use recommended in individuals with respiratory issues.
• Diabetes: May affect diabetic control; monitor blood glucose levels closely.
• Sleep Apnea: Can worsen sleep apnea; use cautiously in those with risk factors.

• Elderly Patients: Testosterone replacement is not advised for age-related hypogonadism or andropause due to insufficient evidence of safety and efficacy. The Beers Criteria suggest avoiding it due to potential cardiac issues and prostate cancer risk.
• Children and Adolescents: Not established for those under 18; can hasten bone maturation without promoting linear growth. Monitor bone development with radiographic exams.

• Pregnancy: Contraindicated due to potential harm to the developing fetus (FDA Category X).
• Breastfeeding: Avoid use as testosterone may adversely affect milk production and the infant.

• Flammability: Topical gels and solutions are flammable; avoid exposure to fire, flame, or smoking.
• Unintended Exposure: Take measures to prevent contact with others, especially women and children. Wash hands and cover application sites. If contact occurs, clean the area immediately.

• Anaphylactoid Reactions: Linked to testosterone undecanoate; monitor for severe reactions and ensure appropriate medical care. Follow REMS Program guidelines for administration.
• Pulmonary Oil Microembolism (POME): Associated with testosterone undecanoate injections; symptoms may include coughing, chest pain, and dyspnea. Monitor and manage accordingly.

• Intranasal Formulations: Not recommended for those with nasal disorders or congestion. Delay treatment until symptoms resolve.
• Polycythemia: Risk of increased hemoglobin and hematocrit; monitor regularly.

• Sports Organizations: Most athletic organizations prohibit the use of testosterone due to its performance-enhancing effects.

• Warfarin: Testosterone can enhance warfarin’s anticoagulant effects, increasing bleeding risk. Regular monitoring of INR and prothrombin time is advised. The effect on other anticoagulants like heparin is unclear.

• CYP3A4: Testosterone is metabolized by CYP3A4. Inhibitors of CYP3A4 may increase testosterone levels.
• P-glycoprotein: Testosterone is both transported by and an inhibitor of P-glycoprotein. This interaction can affect the absorption and clearance of other drugs.

• Cyclosporine: Testosterone may increase cyclosporine levels, raising the risk of nephrotoxicity.

• Prednisone/Cortisone: Co-administration may increase the risk of edema, especially in patients with liver or heart conditions. Caution is advised.

• 5-alpha Reductase Inhibitors: Drugs like dutasteride and finasteride, which inhibit 5-alpha reductase, may counteract the effects of testosterone.

• General: Use with caution due to the risk of enhanced hepatotoxicity, particularly in patients with liver disease.

• Human Growth Hormone: Testosterone may affect growth hormone responses, but high doses can accelerate epiphyseal maturation in prepubescent males.

• Epoetin Alfa: Testosterone may enhance the response to epoetin alfa, potentially reducing the dose required for anemia treatment. Monitor for increased blood viscosity.

• Saw Palmetto: May have antiandrogenic effects that could oppose testosterone therapy.

• Fluconazole: Can increase testosterone levels. This effect is more pronounced at higher doses. Similar effects might occur with voriconazole.

• Ranolazine: Increased absorption due to testosterone’s P-glycoprotein inhibition.
• Ambrisentan: Monitor for increased absorption and adverse effects when coadministered with P-glycoprotein inhibitors like testosterone.

• Oxyphenbutazone: May increase oxyphenbutazone levels. Monitor for adverse effects.
• Propranolol: Testosterone can increase propranolol clearance, potentially reducing its effectiveness.
• Dabigatran: Co-administration with testosterone may raise dabigatran levels, increasing the risk of side effects, especially in patients with renal impairment.
• Afatinib: Testosterone may increase afatinib exposure. Consider dose adjustments if necessary.
• Intranasal Drugs: Avoid concurrent use with other intranasal drugs due to unknown interactions.

• Monitoring: Regularly monitor for adverse effects and interactions, especially when starting or changing doses of testosterone or other interacting medications.
• Inform Healthcare Providers: Always provide a complete list of all medications, supplements, and health conditions to your healthcare provider to avoid potential interactions.

• Symptoms: Mastalgia (breast tenderness) and gynecomastia (breast enlargement).
• Prevalence:
  • Testim: 1%
  • Androgel: 1-3%
  • Axiron: <1%
• Cause: Suppression of gonadotropins and conversion of androgens to estrogens.

• Libido: Can increase or decrease; decrease reported in 1-3% of Androgel users.
• Priapism and Excessive Excitement: Notable in older males; Testim reported 1% incidence.
• Erectile Dysfunction: Reported with Fortesta and Androgel.

• Enlargement: Benign prostatic hyperplasia (BPH) reported in 1% of Testim users.
• PSA Levels: Increased in clinical trials
  • Axiron: 1-4%
  • Fortesta: 1.3%
  • Natesto: 5.1-5.8%
• Cancer Risk: <1% incidence in Axiron users; increased PSA levels linked to prostate cancer in some studies.

• Common Reactions: Erythema, pruritus, acne, xerosis.
• Serious Reactions: Bullous rash, skin necrosis, severe allergic contact dermatitis.
• Patch Specific: 28% incidence of application site reactions; 5% stopped due to chronic discomfort.

• Hypertension: Reported in 1-3% of testosterone gel users.
• Cardiovascular Events: Increased risk of MI, stroke, and death in some observational studies.
• FDA Review: Under review for potential associations with serious cardiovascular events.

• Liver Dysfunction: Increased hepatic enzymes more common; serious liver dysfunction is rare.
• Monitoring: Regular liver function tests advised, particularly for 17-alpha-alkylating hormones.

• Polycythemia: Increased red blood cell count, hematocrit, and hemoglobin in some users.
• Thrombosis Risks: Increased risk of DVT and pulmonary embolism; periodic hemoglobin and hematocrit checks recommended.

• Headache, Mood Changes: Reported in 1-6% of users.
• Gastrointestinal: Diarrhea and vomiting in some.
• Nasal Effects: For intranasal testosterone, issues like rhinorrhea, epistaxis, and nasal irritation reported.

• Sleep Apnea: Risk may increase in patients with pre-existing conditions.
• Anaphylaxis and POME: Reported with testosterone undecanoate; managed under REMS program.

Immediate Actions: Contact healthcare provider if experiencing severe symptoms like signs of an allergic reaction, significant changes in prostate health, or severe cardiovascular symptoms.

• Not Recommended: Testosterone is classified as a Category X drug by the FDA, meaning it is not recommended for use during pregnancy due to potential harm to the developing fetus.
• Contraception: Women of childbearing age should use reliable contraception while undergoing testosterone therapy.
• Labor and Delivery: Testosterone is not used during labor or obstetric delivery, and there is no data supporting its safety and efficacy in these contexts.

• Topical Solutions and Gels: The use of testosterone topical solutions, transdermal patches, and gels is not advised for nursing mothers.
• Unknown Effects: There is uncertainty about the levels of testosterone in breast milk and its potential effects on the infant. Significant exposure could have adverse androgenic effects on the baby and might interfere with the mother’s milk supply.
• Alternative Methods: Women who are breastfeeding and receiving testosterone therapy should consider alternative methods to breastfeeding.

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.
down a sink or drain.