I'm wondering about the validity on a clinical and perceived basis of cycling on and off TRT. I wouldn't eve pursue the question except for some research that was done on it, believe from University of Texas (Huston?). And I can't find the link now, ncbi, I thought. Study involved Test Propionate, cycling 4 weeks on 4 weeks off then a break period. Again, apologizes, I can't locate the exact study. Madman's extensive knowledge may already have it foremost.
Reason for consideration: I got on TRT thinking to boost libido when my levels were 671 TT at its lowest but relatively high SHBG and low FreeT. Got it all optimal for awhile but did nothing for libido except briefly. Went from test cyp, quite for about 1-1/2 year, tried clomiphene for 9 months, quite several months, then test cream. Each time observed "honeymoon" phases with libido. Now off cream for about two weeks and feeling better then ever.
So, what's the point? Perhaps there can be some positive physical benefit from being on TRT short term cycling. Not for libido-too many factors and unpredictable, but for maintaining bone mass, muscle and other organ benefits controlled by the hormone. In the study I mentioned, their conclusion was it had some validity.
Sure.....if you can handle going from hypogonadal--->eugonadal let alone running supra-physiological (high/in many cases absurdly high) T levels only to end up being hypogonadal again!
Although steady-state would be reached much sooner when using TP.....pulling the plug 4 weeks in would result in crashing T levels.
Even when using the medium-acting esters (TE/TC) it will take 4-6 weeks for blood levels to stabilize.....pulling the plug 4 weeks in would still result in crashing T levels.
The body would have no clue whether it is coming or going.
To what degree one will experience negative effects during the 4 weeks off would come down to the dose used/individual.
The goal of trt is to achieve healthy hormones which will result in relief/improvement of low-t symptoms (energy/mood/libido/erectile function/recovery/body composition)/ overall well-being let alone prevent/minimize any possible side-effects and keeping blood markers healthy long-term.
Keep in mind that the study was for 20 weeks and the 24 patients were older men 70 ± 2 yr of age with 8 men following the
monthly cycled testosterone (MO, n=8; alternating months of 100 mg testosterone-enanthate/week and placebo).
*Twenty-four healthy, community-dwelling older men (60 – 85 yr) with endogenous levels of serum total testosterone in the lower half of the normal range (between 280 and 500 ng/dl)
A Randomized Pilot Study of Monthly Cycled Testosterone Replacement or Continuous Testosterone Replacement Versus Placebo in Older Men (2011)
Context: Cycling androgens have been reported by athletes to improve physical performance by enhancing muscle mass and strength, a paradigm that has not been studied, and may have clinical value in older men being treated with testosterone.
Objective: We investigated the efficacy of a monthly cycled testosterone regimen that uses half the testosterone dose as the current standard of care continuous therapy on body composition and muscle strength in older men.
Design, Setting, and Patients: Twenty-four community-dwelling older men 70 ± 2 yr of age with total testosterone levels below 500 ng/dl were randomized at the Institute for Translational Sciences-Clinical Research Center into a 5-month double-blind placebo-controlled trial.
Intervention: Subjects were dosed weekly for 5 months, receiving continuous testosterone (TE, n=8; 100 mg testosterone enanthate, IM injection), monthly cycled testosterone (MO, n=8; alternating months of testosterone and placebo), or placebo (PL, n=8).
Main Outcome Measures: Main outcomes included body composition by dual-energy x-ray absorptiometry and upper and lower body muscle strength. Secondary outcomes included body weight, serum hormones, and mixed-muscle protein fractional synthesis rate (FSR).
Results: Total lean body mass was increased and percent fat was reduced after 5 months in TE and MO (P <0.05). Upper body muscle strength increased in TE, and lower body muscle strength increased in TE and MO (P<0.05). FSR increased in TE and MO (P< 0.05) but not in PL.
Conclusions: Cycled testosterone improved body composition and increased muscle strength compared with placebo and increased FSR similarly to continuous testosterone.
The use of testosterone is increasing in middle-aged and older men in the United States (1). Testosterone is used to enhance athletic performance, with cycled dosing being a common practice among athletes (2, 3). However, the mechanisms through which cycled testosterone exert its action on skeletal muscle are poorly understood. In previous studies, the short-term (1 month) anabolic effect of testosterone is consistently associated with an increase in basal (fasting) rates of muscle protein synthesis (4 –7). However, as the duration of testosterone administration increases, the potential contributions of fasting rates of muscle protein synthesis and breakdown to the overall anabolic response is less clear (5, 8) and may involve a shift from an initial promotion of muscle protein synthesis to a later slowing of protein degradation (5). Because cycling androgens is highly successful among athletes at enhancing muscle mass and strength, we sought to determine whether a cycled testosterone administration (i.e. using half the dose) would be similarly efficacious in healthy older men, because they represent the most clinically treated age group and suffer the greatest risk of testosterone side effects.
*Therefore, we conducted a randomized, double-blinded trial in older men to test the efficacy of testosterone, administered for 5 months in a monthly cycled on-off fashion. We hypothesized that monthly cycled testosterone administration would enhance body composition and muscle strength via a preferential stimulation of muscle protein synthesis.
Serum total testosterone
All subjects entered the study with similar concentrations of circulating total testosterone in the lower half of the normal range (348 88 ng/dl). Total testosterone remained at baseline concentrations after each month of placebo treatment and increased after each month of testosterone treatment regardless of group (Fig. 1A). Among all groups, testosterone concentrations never went out of the normal upper physiological range in response to testosterone treatment (range between months 0 and 5, 157– 1303 ng/dl).
Fractional synthetic rate
Postabsorptive mixed-muscle FSR at baseline were similar between groups and remained unchanged in PL (Fig. 1B). FSR increased in both TE and MO at months 1 and remained elevated above baseline for the remainder of the study.
Lean body mass (LBM) and fat mass
LBM increased in both TE and MO after the first month of testosterone, which was sustained in TE across the 5 months (Fig. 1C).
Although LBM returned back to near baseline levels in MO around month 2 (i.e. between the first cycle of placebo and the second cycle of testosterone), the subsequent months showed a sustained increase in LBM.
*The decline in fat mass was significant only in TE (Fig. 1D).
Muscle strength
Muscle strength for arm curl (Fig. 1E), arm extension (Fig. 1F), leg curl (Fig. 1G), and leg extension (Fig. 1H) increased in TE.
Leg curl strength increased in MO, and there was a trend for increased leg extension (P 0.076). There were no changes in one-repetition maximal voluntary strength tests in PL.
Discussion
Cycling of androgens has long been employed by athletes to build muscle strength and mass and improve performance without careful scientific study (2, 3).
This study determined 1) the efficacy of cycled testosterone to increase muscle mass and strength in older men and 2) whether cycled testosterone promotes skeletal muscle anabolism by preferential stimulation of muscle protein synthesis. We found that monthly cycles of testosterone preferentially stimulated muscle protein synthesis, likely due to the repeated removal and reintroduction of the anabolic stimulus testosterone. The rationale for conducting this study came from our previous work in older men where we showed that skeletal muscle protein synthesis accounted for the anabolic effects of testosterone at 1 month, but at 6 months, net anabolism resulted from an inhibition of skeletal muscle breakdown (5, 15).
Our healthy older men provided a unique model to study cycling testosterone because their total testosterone concentrations were in the lower half of the normal range and increased to the upper half of the normal range with cycled testosterone administration, therefore enabling us to assess the mechanism by which testosterone promotes muscle anabolism by increasing testosterone while still maintaining serum values within the normal range for men.
Interestingly, Fig. 1A shows that older men in the MO group returned to baseline testosterone serum concentrations during the off months without testosterone. Although LBM declined somewhat during the initial month without testosterone, it recovered with the subsequent month of replacement and did not decline during the subsequent month without testosterone, staying nearly identical to the TE group at month 5 (Fig. 1C). More importantly, skeletal muscle protein synthesis remained elevated during the cycled withdrawing of testosterone (Fig. 1B). The change in total fat mass followed a similar inverse pattern to LBM (Fig. 1D) and contributed to the significant decline in percent fat mass in both groups receiving testosterone. Although changes in muscle strength in MO reached significance only in a single muscle group, strong positive trends were seen in all other muscle groups (Fig. 1, E–H).
Our findings of decreased high-density lipoprotein (HDL) cholesterol in TE and MO are consistent with the observed decreases in HDL cholesterol after testosterone treatment in healthy older men by others (16). It is not clear why triglycerides decreased only in the TE group, but it is possible that, although not significant, the lower triglyceride concentrations in this group at baseline indicate some predisposition in this group for a further decline in circulating lipids. Because previous studies have shown that testosterone side effects increase with increasing doses, it is possible to infer that a therapeutic approach using half the testosterone dose would result in reduced side effects (17, 18).
With respect to efficacy and mechanism, the major difference in the two treatment paradigms appears to be a slowing of the gains in lean mass and strength in MO relative to TE during the initial months of treatment. Importantly, however, by 5 months, gains in lean mass were similar in MO and TE, and gains in strength in MO approached or equaled those of TE. Notably, the month-to-month variation in LBM in the MO group was much greater than that of FSR, which remained relatively constant once treatment was initiated during month 1. This suggests that testosterone’s anabolic effects are not entirely explained by changes in fasting muscle protein synthesis but may also involve changes in fasting rates of muscle protein breakdown or fed-state muscle protein metabolism and, furthermore, that changes in these variables are responsible for the relatively slower rate of adaptation to the MO dosing regimen.
Finally, our data show that by raising testosterone concentrations from the lower half to the upper half of the normal range in a monthly cycled paradigm, skeletal muscle FSR remains consistently elevated in healthy older men. Thus, if monthly on/off cycles of testosterone can consistently increase muscle protein synthesis and LBM without an increase in side effects, then this paradigm offers significant treatment for preventing sarcopenia in older men. However, larger and longer-term studies are needed to assess the cumulative effects of this dosing paradigm on efficacy, safety, and functions of daily living such as sexual function, vitality, and overall quality of life.
