Comparing Testosterone Suppression in Intramuscular and Subcutaneous Leuprolide Acetate Formulations

Introduction Androgen deprivation therapy (ADT) is commonly used to treat prostate cancer. Leuprolide acetate (LA) is a common ADT, manufactured as an intramuscular injection, Lupron® (LA-IM), and a subcutaneous injection, Eligard® (LA-SC) with the goal of testosterone < 50 ng/dL. We investigated for differences in testosterone suppression between the two formulations in patients with prostate cancer. Methods Clinical data was abstracted from our medical records system for patients with prostate cancer who started leuprolide acetate between January 2016 through March 2022 with a subsequent testosterone value checked. Primary endpoint was the proportion of subjects with testosterone levels < 50mg/dL, with secondary endpoints including the proportion of subject achieving testosterone levels < 20ng/dL and median testosterone levels. Results 525 subjects were included. The LA-IM and LA-SC groups were balanced for age and race but the doses of leuprolide differed across the two groups. 99.2% (373 of 376) of subjects on LA-IM achieved testosterone < 50ng/dL compared to 92.6% (138 of 149) on LA-SC (p = 0.0001). There was no difference in the ability to achieve testosterone < 20ng/dL (79.5% LA-IM and 79.2% LA-SC, p = 0.9335). Median testosterone for both groups was 14.0 ng/dL (p = 0.4305). Conclusions Our retrospective study suggests a pharmacodynamic difference in the ability of LA-IM and LA-SC to achieve medical castration in men with prostate cancer. LA-IM achieved goal testosterone (<50ng/dL) at a higher frequency compared to LA-SC. This finding warrants further prospective confirmation and if confirmed, could affect selection of therapy in this clinical setting.