Muscular Responses to TRT Vary by Administration Route

[Michael Scally MD]

[OA] Muscular Responses to Testosterone Replacement Vary by Administration Route

BACKGROUND: Inconsistent fat-free mass (FFM) and muscle strength responses have been reported in randomized clinical trials (RCTs) administering testosterone replacement therapy (TRT) to middle-aged and older men. Our objective was to conduct a meta-analysis to determine whether TRT improves FFM and muscle strength in middle-aged and older men and whether the muscular responses vary by TRT administration route.

METHODS: Systematic literature searches of MEDLINE/PubMed and the Cochrane Library were conducted from inception through 31 March 2017 to identify double-blind RCTs that compared intramuscular or transdermal TRT vs. placebo and that reported assessments of FFM or upper-extremity or lower-extremity strength. Studies were identified, and data were extracted and validated by three investigators, with disagreement resolved by consensus.

Using a random effects model, individual effect sizes (ESs) were determined from 31 RCTs reporting FFM (sample size: n = 1213 TRT, n = 1168 placebo) and 17 reporting upper-extremity or lower-extremity strength (n = 2572 TRT, n = 2523 placebo). Heterogeneity was examined, and sensitivity analyses were performed.

RESULTS: When administration routes were collectively assessed, TRT was associated with increases in FFM [ES = 1.20 +/- 0.15 (95% CI: 0.91, 1.49)], total body strength [ES = 0.90 +/- 0.12 (0.67, 1.14)], lower-extremity strength [ES = 0.77 +/- 0.16 (0.45, 1.08)], and upper-extremity strength [ES = 1.13 +/- 0.18 (0.78, 1.47)] (P < 0.001 for all).

When administration routes were evaluated separately, the ES magnitudes were larger and the per cent changes were 3-5 times greater for intramuscular TRT than for transdermal formulations vs. respective placebos, for all outcomes evaluated. Specifically, intramuscular TRT was associated with a 5.7% increase in FFM [ES = 1.49 +/- 0.18 (1.13, 1.84)] and 10-13% increases in total body strength [ES = 1.39 +/- 0.12 (1.15, 1.63)], lower-extremity strength [ES = 1.39 +/- 0.17 (1.07, 1.72)], and upper-extremity strength [ES = 1.37 +/- 0.17 (1.03, 1.70)] (P < 0.001 for all).

In comparison, transdermal TRT was associated with only a 1.7% increase in FFM [ES = 0.98 +/- 0.21 (0.58, 1.39)] and only 2-5% increases in total body [ES = 0.55 +/- 0.17 (0.22, 0.88)] and upper-extremity strength [ES = 0.97 +/- 0.24 (0.50, 1.45)] (P < 0.001). Interestingly, transdermal TRT produced no change in lower-extremity strength vs. placebo [ES = 0.26 +/- 0.23 (-0.19, 0.70), P = 0.26]. Subanalyses of RCTs limiting enrolment to men >/=60 years of age produced similar results.

CONCLUSIONS: Intramuscular TRT is more effective than transdermal formulations at increasing LBM and improving muscle strength in middle-aged and older men, particularly in the lower extremities.

Skinner JW, Otzel DM, Bowser A, et al. Muscular responses to testosterone replacement vary by administration route: a systematic review and meta-analysis. Journal of cachexia, sarcopenia and muscle 2018. Muscular responses to testosterone replacement vary by administration route: a systematic review and meta‐analysis

 

[Dr JIM]

Wo knowing the dosages and serum TT levels it’s difficult to say if the changes noted in LBM are the result of bioavailability.

Jim

 

[Old]

[OA] Muscular Responses to Testosterone Replacement Vary by Administration Route

BACKGROUND: Inconsistent fat-free mass (FFM) and muscle strength responses have been reported in randomized clinical trials (RCTs) administering testosterone replacement therapy (TRT) to middle-aged and older men. Our objective was to conduct a meta-analysis to determine whether TRT improves FFM and muscle strength in middle-aged and older men and whether the muscular responses vary by TRT administration route.

METHODS: Systematic literature searches of MEDLINE/PubMed and the Cochrane Library were conducted from inception through 31 March 2017 to identify double-blind RCTs that compared intramuscular or transdermal TRT vs. placebo and that reported assessments of FFM or upper-extremity or lower-extremity strength. Studies were identified, and data were extracted and validated by three investigators, with disagreement resolved by consensus.

Using a random effects model, individual effect sizes (ESs) were determined from 31 RCTs reporting FFM (sample size: n = 1213 TRT, n = 1168 placebo) and 17 reporting upper-extremity or lower-extremity strength (n = 2572 TRT, n = 2523 placebo). Heterogeneity was examined, and sensitivity analyses were performed.

RESULTS: When administration routes were collectively assessed, TRT was associated with increases in FFM [ES = 1.20 +/- 0.15 (95% CI: 0.91, 1.49)], total body strength [ES = 0.90 +/- 0.12 (0.67, 1.14)], lower-extremity strength [ES = 0.77 +/- 0.16 (0.45, 1.08)], and upper-extremity strength [ES = 1.13 +/- 0.18 (0.78, 1.47)] (P < 0.001 for all).

When administration routes were evaluated separately, the ES magnitudes were larger and the per cent changes were 3-5 times greater for intramuscular TRT than for transdermal formulations vs. respective placebos, for all outcomes evaluated. Specifically, intramuscular TRT was associated with a 5.7% increase in FFM [ES = 1.49 +/- 0.18 (1.13, 1.84)] and 10-13% increases in total body strength [ES = 1.39 +/- 0.12 (1.15, 1.63)], lower-extremity strength [ES = 1.39 +/- 0.17 (1.07, 1.72)], and upper-extremity strength [ES = 1.37 +/- 0.17 (1.03, 1.70)] (P < 0.001 for all).

In comparison, transdermal TRT was associated with only a 1.7% increase in FFM [ES = 0.98 +/- 0.21 (0.58, 1.39)] and only 2-5% increases in total body [ES = 0.55 +/- 0.17 (0.22, 0.88)] and upper-extremity strength [ES = 0.97 +/- 0.24 (0.50, 1.45)] (P < 0.001). Interestingly, transdermal TRT produced no change in lower-extremity strength vs. placebo [ES = 0.26 +/- 0.23 (-0.19, 0.70), P = 0.26]. Subanalyses of RCTs limiting enrolment to men >/=60 years of age produced similar results.

CONCLUSIONS: Intramuscular TRT is more effective than transdermal formulations at increasing LBM and improving muscle strength in middle-aged and older men, particularly in the lower extremities.

Skinner JW, Otzel DM, Bowser A, et al. Muscular responses to testosterone replacement vary by administration route: a systematic review and meta-analysis. Journal of cachexia, sarcopenia and muscle 2018. Muscular responses to testosterone replacement vary by administration route: a systematic review and meta‐analysis

Interesting report with the possible suggestion that brief supraphysiological levels followed by drops to low-normal (typical IM 'cycle' due to time between injection) may be more effective than topicals which produce a more steady state (and more DHT which one might expect should increase growth)

Because it is a Meta-Analyses, the data is all over the place. Fortunately the authors detail the studies they used. Most of the IM have the typical long time between injections. But data is muddled between using TE and TU ... and even more so the varying duration times between studies. Compare the two Svartberg studies: TE 6 months vs TU 12 months. Also, Page [17] and Snyder [11] stand out but were 36 months. [ Please correct me docs but isn't the Snyder dosage rather low compared to what Page used? ] The Storer [14] study is not remarkable although it was also 36 months.

Perhaps for BB the implication is that short esters applied frequently aren't the way to go? Or perhaps the data is nullified when looking at the use of supraphysiological dosing?