Table 3.

Summary of Testosterone Therapies

Route of Administration	Pharmacokinetics	Key Clinical Findings
		Efficacy	Safety
Buccal tablets3,25,76,77	● Short-acting  ● After application, testosterone is absorbed directly into systemic circulation via the mucosa, bypassing first-pass metabolism76  ● Testosterone reaches maximal levels within the normal physiologic range in 10 to 12 hours, with return to baseline in 2 to 4 hours76	Normal serum testosterone range in 87% to 97% of patients	● Generally well tolerated  ● Most common AEs unique to buccal tablets are gum and mouth irritation and taste perversion; 4.3% of patients discontinued due to these side effects25
IM injections30,35	● Long-acting (enanthate, cypionate, or undecanoate)	Average concentrations of testosterone and its metabolites (DHT and E2) in the eugonadal range	● Generally well tolerated  ● May be associated with higher risk of polycythemia
Transdermal gels23,24,78–80	● Steady-state  ● Patients with high BMI may require higher doses of transdermal testosterone formulations13	Normal serum testosterone in 75% to 86% of patients	● Generally well tolerated  ● Carries risk of transference  ● Has low risk of supraphysiological testosterone levels
Intranasal gel28	● Short-acting	Normal serum testosterone in approximately 90% of patients	● Generally well tolerated  ● In the Phase 3 trial, the highest number of drug-related treatment-emergent AEs (22.2%) belonged to the respiratory, thoracic, and mediastinal categories
SC injections3,26,81	● Long-acting (enanthate)  ● Administered weekly by SC injection or prefilled autoinjector26  ● No patients had a maximum testosterone level >1800 ng/dL in the phase 3 trial26	Normal serum testosterone range in 92% of patients	● Generally well tolerated  ● Small increases in systolic blood pressure (3.4 mm Hg) observed  ● Labeling includes a boxed warning for an increase in blood pressure that raises the risk of CV events41
Oral capsules3,29,40,82–84	● Short-acting  ● Dosed twice daily with food29,40  ● Some studies suggest absorption varies with lipid content of meals40  ● Peak levels roughly 4 hours after initial administration3	Normal serum testosterone range in 87% of patients	● Generally well tolerated  ● Small increases in ambulatory blood pressure occurred following 120 days of therapy  ● Labeling includes a boxed warning for an increase in blood pressure that raises the risk of CV events40
Subdermal pellets3,37,85–87	● Long-acting  ● Recommended starting dosage is 150 to 450 mg, but clinical experience has demonstrated that more pellets are needed to achieve satisfactory results3,87	Normal testosterone and LH levels and improvement of symptoms	● Generally well tolerated  ● Most common AEs unique to testosterone pellets are extrusion (8.5%), bleeding (2.3%), and infection (0.6%)86

Abbreviations: AE, adverse event; BMI, body mass index; CV, cardiovascular; E₂, estradiol; IM, intramuscular; LH, luteinizing hormone; SC subcutaneous.