By the end of a 12-week period, total testosterone C-trough, C-avg (0 to 168 hours), and C-max were inversely related to BMI.

Body mass index (BMI) is an important factor when selecting dosage of subcutaneous testosterone enanthate (TE; Xysoted), investigators report.1

By the end of a 12-week period, total testosterone C-trough, C-avg (0 to 168 hours), and C-max were inversely related to BMI, according to findings presented at the 2021 Sexual Medicine Society of North America Fall Scientific Meeting.

“[This is] an intuitive assumption that never has been found to be the case before,” said co-author Martin M. Miner, MD, in an interview with Urology Times®.

Because there is little knowledge about how BMI affects the pharmacokinetic (PK) profile or dosing of testosterone therapies in men with testosterone deficiency, even though obesity or high BMI (≥30 kg/m2) is typically associated with low levels of testosterone, Miner and co-authors sought to understand the potential relationship.

“My question was: in men with a larger BMI, would they have data to support the use of a larger dose of their weekly testosterone injection? This is part of men receiving testosterone therapy for hypogonadism, or low testosterone levels associated with clinical signs and symptoms of testosterone deficiency,” Miner said.

In this post-hoc analysis, a single-arm phase 3 trial of subcutaneous TE was examined to determine PK parameters of weekly subcutaneous TE treatment among men with testosterone deficiency and varying BMIs. The primary end point was the percentage of patients who received at least 1 dose of subcutaneous TE and achieved an average serum total testosterone concentration of 300 ng/dL to 1100 ng/dL over a 7-day dosing of TE (C-avg [0 to 168 hours]) at week 12.

The PK population consisted of 142 patients, all of whom were patients in the safety population (received 1 or more doses of subcutaneous TE) with at least 1 blood sample drawn after the dose was administered. Of this population, 137 patients finished the study to completion (12 weeks) and were categorized into tertiles based on baseline BMI. Tertile 1 had a BMI ≤29 kg/m2 (n=45). Tertile 2 had a BMI > 29-32 kg/m2 (n=33). Tertile 3 had a BMI > 32 kg/m2 (n=59).

PK parameters included total testosterone trough concentration (C-trough), AUC-(0 to 168 hours), C-avg (0 to 168 hours), and C-max. At weeks 6 and 12, BMI tertiles were used to assess C-trough and C-avg (0 to 168 hours). At week 12, C-trough and C-avg (0 to 168 hours) were calculated according to their treatment doses and an overall dose-normalized linear regression model was utilized.

At baseline, the mean (SD) serum total testosterone levels for patients in tertiles 1-3 were 250.7 (101.3) ng/dL, 235.3 (91.2) ng/dL, and 226.4 (81.1) ng/dL, respectively. Prior to dosing adjustments at week 6, tertiles 2 and 3 mean (SD) C-trough (459.2 [157.0] ng/dL and 453.2 [133.0] ng/dL) were lower than tertile 1 (616.9 [181.6] ng/dL). At week 6, 21.2% of the total variance in C-trough levels could be predicted from BMI (P < .001).

At the completion of this study, results showed that tertiles 2 and 3 had lower serum total testosterone C-trough compared with tertile 1 (494.8 [137.6] ng/dL and 469.0 [146.2] ng/dL, respectively, vs 517.7 (153.5) ng/dL). For tertiles 1-3, the mean (SD) C-avg (0 to 168 hours) values were 585.2 (148.1) ng/dL, 554.2 (104.5) ng/dL, and 528.5 (118.0) ng/dL, respectively. And at week 12, the mean doses were 65.0 (13.48) ng/dL, 78.0 (12.12) ng/dL, and 78.4 (12.68) mg, respectively. So, patients in Tertiles 2 and 3 required higher final doses of subcutaneous TE vs those in tertile 1, demonstrating an inverse relationship related to BMI.

In addition, the regression model found that 9.36% (P < .001) and 16.96% (P < .001) of the total variance in C-trough and C-avg (0 to 168 hours) could be predicted from independent BMI and dose variables at the completion of this study (12 weeks), respectively.

Overall, 98.5% of men with testosterone deficiency who made it to the end of this study (12 weeks) achieved a C-avg (0 to 168 hours) of 300 ng/dL to 1100 ng/dL.

Reflecting on these findings, Miner explained, “The initial levels were inversely related to body mass index, so…men who are the largest…or had the largest BMI have the lowest testosterone levels. And that's what you would expect with obese men, that the greater the amount of obesity, the lower their endogenous levels would be, and that men would require the largest dose adjustment if they had a larger BMI.”

1. Miner M, Amy T, Gollen R, et al. Subcutaneous testosterone enanthate and the effect of body mass index on serum testosterone in men with testosterone deficiency. Paper presented at 2021 Sexual Medicine Society of North America Fall Scientific Meeting; October 21-24, 2021. Abstract 002.

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