Safety Aspects and Rational Use of Testosterone Undecanoate in the Treatment of Testosterone Deficiency: Clinical Insights

Figures & data

Table 1 Comparison of Modalities of Exogenous Testosterone

Method	Formulation Details	Brand Names	Max T Concentration (ng/dL)	Time to Tmax	Effect Duration	Benefits	Adverse Effects	Special Considerations
Subcutaneous	Pellets placed subcutaneously	Testopel	780	3 weeks	20 weeks	Infrequent dosing	Infection, pellet extrusion, Fibrosis	Insertion requires physician
Transdermal	Patch or gel applied to skin	Androgel, Androderm	765	8 hours	Few (2–5) days	Non-invasive, simple application	Pruritus	Can be transmitted through person–person contact
Mucosal	Intranasal spray or tablet placed in mouth	Striant, Natesto	467	1 hour	~12 hours	High bioavailability, simple administration	Gum irritation, gingivitis, headache, runny nose	Buccal discontinued due to adverse effects
Injectable	Intramuscular injections	Depo-Testosterone, Delatestryl	~1200	1–5 days	50–60 days	Cost-effective	Acne, breast enlargement, mood swings	Must be able to tolerate self-injection
Oral	Pill or capsule	Andriol, Jatenzo, Tlando, Kyzatrex	1008	2 hours	9 hours	Improved compliance	Hepatic dysfunction; GI discomfort	Cost-prohibitive

Table 2 Pharmacokinetic Properties of Oral TU Formulations

	FDA Approval	PharmacoKinetics	Time to Tmax	Bioavailability in AUC0-tlast in nmolh/L	Metabolism	Starting Dose	Titration	Special Precautions	Significant Adverse Effects
Jatenzo	Yes; April 2019		5 hours	1034	Beta oxidation	237 mg taken as one 158 mg capsule BID	Up or down titrate to maintain T concentration within normal range	None	Small increased incidence of elevated systolic blood pressure
Andriol	No	Ester bond is cleaved to release testosterone + inactive undecanoate; testosterone is then broken down to biologically active dihydrotestosterone (DHT) by 5a reductase	4–5 hours	41.7–1050		120–160 mg taken as 1–2 40 mg capsules BID for 2–3 weeks for initial dosing	Up or down titrate for maintenance dose of 40–120 mg daily	Must take with food as bioavailability is highly dependent on fat intake	Minor GI upset and headache
Tlando	Yes; March 2022		4–6 hours	29581		225 mg taken as one 112.5 mg capsule twice daily	No titration; if serum T is outside of normal range (300–1080 ng/dL), discontinue	Must take with food for optimal absorption	Small increased incidence of elevated systolic blood pressure
Kyzatrex	Yes; August 2022		4–5 hours	10425±5521		200 mg twice daily	Up or down titrate based on serum testosterone for a maintenance dose between 100 mg once daily–400 mg twice daily	Must take with food for optimal absorption	Small increased incidence of elevated systolic blood pressure

Table 3 Pharmacokinetic Properties of Injectable TU Formulations

	FDA Approval	PharmacoKinetics	Time to Tmax	Bioavailability in AUC0-tlast (ng/h/L)	Metabolism	Starting Dose	Titration	Special Precautions	Significant Adverse Effects
Aveed	Yes; March 2014	Ester bond is cleaved to release testosterone + inactive undecanoate; testosterone is then broken down to biologically active dihydrotestosterone (DHT) by 5a reductase	4 days	21,385	Beta oxidation	3 mL (750 mg) injected IM; then 4 weeks; then every 10 weeks	No titration	None	Acne, injection site reaction, pulmonary microembolism
Nebido	No		7 days	4051		4 mL (1000 mg) injected IM	No titration	None