Comparative Efficacy of Testosterone Replacement Therapy Formulations

Efficacy Comparison by Formulation

Transdermal testosterone preparations, such as gels and patches, are generally recommended over intramuscular injections for most patients due to their ability to provide more stable day-to-day testosterone levels and better cardiovascular safety profile, according to the American Gastroenterological Association 1, 2
Gels and patches provide more stable serum testosterone concentrations day-to-day compared to injections, with gels having better skin tolerability, although absorption can be variable 1, 2
Testosterone injections offer the benefit of avoiding daily administration and can be advantageous in patients with reduced personal disease-management skills or resources, but safety concerns exist due to increased time spent in both supratherapeutic and subtherapeutic ranges between doses 1, 2
Some evidence suggests testosterone injections are associated with a greater risk of cardiovascular events, hospitalizations, and deaths compared to gels, as reported by the American Gastroenterological Association 1

Transdermal testosterone preparations generally cost more than injectable options, with an annual cost in 2016 per Medicare beneficiary of $2,135.32 for transdermal formulations versus $156.24 for intramuscular formulations, according to the American College of Physicians 5

53% of patients receiving testosterone treatment chose injectable testosterone over gel-based or pellet regimens, mostly due to lower cost, while 71% of patients preferred topical gel over injection or patch after using a TRT product for more than one month, citing convenience, ease of use, and non-staining of clothes, as reported by the American College of Physicians 5

For patients receiving testosterone injections, levels should be measured midway between injections, targeting a mid-normal value, and for patients receiving transdermal preparations, levels can be measured at any time, with the understanding that peak values occur 6-8 hours after application of the patch, according to the American Gastroenterological Association 1
Testosterone levels should be tested 2-3 months after treatment initiation and/or after any dose change, and once stable levels are confirmed, monitoring every 6-12 months is typically sufficient, as recommended by the American Gastroenterological Association 1

Gel preparations can be inadvertently transferable to other individuals via prolonged skin contact, and testosterone injections can cause local pain, soreness, bruising, erythema, swelling, nodules, or furuncles, as reported by the New England Journal of Medicine 1, 2, 3, 4
Oral testosterone formulations available in the US should be strongly discouraged due to associated hepatotoxicity, and testosterone therapy may be associated with exacerbation or development of sleep apnea, particularly with higher doses of parenteral testosterone, according to the New England Journal of Medicine 3, 4