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A very thorough well controlled 4 year study published on
The Journal of Clinical Endocrinology & Metabolism Vol. 87, No.8 3573-3577
clearly shows every other day (EOD) hGH injections to be much more beneficial in
the long run to everyday injections. Everyday injections seems to drastically lower
your body's sensitivity to it's own GH secretion. The study included children with idiopathic
short stature, but can be ever casting on us, normal non-deficient hGH individuals who
may use hGH periodically for bodybuilding, sports and health purposes.
The 38 children were divided into 2 groups:
Group I received daily hGH injections.
Group II received alternate day hGH injections.
It is important to note that the total weekly dosage of hGH
was the same for both groups.
Both groups received the hGH therapy contiguously for 2 years.
Their natural growth was followed for an additional 2 years after hGH therapy ended.
They were all measured at 3-month intervals during the 4 years period (2 years
with hGH therapy and 2 years after). Their Serum GH was measured by double antibody RIA kit.
During hGH therapy, both groups accelerated their growth substantially.
Group I receiving the daily hGH injections first & second year velocity was 3.4 and 2.3 SD
Group II receiving the alternate hGH inj. had 3.0 and 2.0 SD for first and second year respectively.
Over the initial 6 months after withdrawal of therapy, growth velocity decelerated to a low nadir -3.9 SD score
for the daily therapy group, whereas it decelerated in the alternate day group to only -0.2 SD score.
During the 2 years off therapy, the later group (taking EOD injections)
maintained growth rates of -0.2 to -1.2 SD score, which is similar to their SD score prior to the hGH treatment.
The daily group also recovered but very slowly, on the fourth semiannual evaluation off therapy.
The cumulative 4-year growth velocity (2yrs on and 2 yrs off therapy) of the alternate day group was greater
than that of the daily therapy group (mean, 0.9 vs. 0.3 SD score).
At the end of the 4-yr therapy period, the adult height prediction of the alternate day group was greater
than that of the daily group by a mea of 6.5cm (that's over 2.5" in height, quite a lot of difference)
In even simpler English, to translate what it may mean to us is that using hGH everyday will only
negligibly give better short-term results. Yet using alternate day hGH will give radically better long-term
results and much better recovery. As the body may get back to homeostasis much faster.
Remember the two groups got the same weekly total hGH dosage,
so your every other day hGH injections would be twice as if you used
it every day.
The researchers said, the dose was of less impotency than the schedule of the injections.
Daily hGH therapy for 3 years caused subnormal growth persisting for 1.5 years (very bad)
It may be that the problem is not enough hGH or IGF-1 secretion but rather
the body's decreased sensitivity to it. The interesting part is that the serum GH levels
and serum IGF-I and IGF-binding protein remained unaffected or relatively mutely affected.
Even your body's endogenous pulsatile secretion of GH resumes within just days
even after long-term hGH therapy.
The researchers hypothesis is that the tolerance may be in the "GH signal transduction in
selective target organs in response to the disappearance of the unique pulsatile
pattern of serum GH during GH therapy". You see, hGH taken via sc injections
do not imitate the your body's own GH secretion.
"Indeed, daily sc administration of GH results in an unphysiological serum GH profile, with peak
levels at 4 h and a slow decline over the course of the following 12–24 h. This pattern can be
regarded as continuous administration, rather than the physiological GH pulses,
with a frequency of about eight per day."
"Assuming that the withdrawal syndrome is related to tolerance that might have developed toward
hGH or IGF-I, we tried to prevent it by alternate day treatment. Moreover, hGH doses used in
therapy often stimulate IGF-I to supraphysiological serum levels, suggesting that target
tissues IGF-I may also be higher than normal. The mechanism seems, therefore, to rest
with hGH and IGF-I action at their target tissues. We now show that alternate day therapy
with hGH in children with an intact GH-IGF-I axis prevents the withdrawal syndrome"
Researchers mark the analogy to another endocrine tolerance and withdrawal syndrome:
"alternate day therapy with glucocoricoids prevents tolerance to that hormone to a substantial degree,
"Interestingly, glucocoricoids withdrawal syndrome can also occur while the
hypothalamic-pituitary-adrenal axis is intact (, indicating that tolerance to glucocoricoids has developed
at the target organ level (9). "
An example of a good safe protocol to follow in my opinion could be
hGH taken for 4 months (16 weeks) or more at 8IU every other day,
split to 4IU three hours after waking up (say 11:00am)
and another 4IU taken 4 hours later (say 3:00pm).
This approach is quite conservative and may be optimal.
Obviously, you may extend past 4months, and take more IUs per day.
This approach goes with 8IU EOD, so it is equivalent to folks that would
otherwise go with 4IU ED, which is what most do.
There is some controversy as to how many of these IUs the body
can utilize at once
Obviously, there are lot of studies, some better conducted, some less.
Lots of opinions and doctrines in endocrinology, bodybuilding etc..
So you should make your own decision, I guess old individuals on
hGH for life would not mind, as no rebound would affect them. Professional
bodybuilders probably wouldn't mind as well.
I would rather follow a protocol like this. For most part due to the
nasty rebound that I could get after withdrawing from long-term ED hGH treatment.
Nothing worse then look awesome, stop hGH then after several months having:
Low body sensitivity to your own body's GH.
Slow recovery
Decline in resting cardiac output
Increase fat mass
Decrease in metabolic rate
Negative nitrogen balance, phosphorus, sodium and potassium.
Again, I said "could" not "would", because this study cannot absolutely manifest
our use of hGH. Moreso, we are not children, we are not idiopathic hGH deficient
and not aGHD. But since the weekly dosages do remain the same as well as the
duration of the hGH usage. Just changing to the EOD protocol from the well
hyped everyday inj protocol is worth in my honest opinion. It seems statistically
a better bet, with more chance to win, than loose as opposed to the ED protocol.
I just tried to summarize the findings of the study, which was by the way,
a pleasure to read as the study is well written and was prepared by
Dr Hochberg, MD, a renowned well respected figure in endocrinology.
You can read the full article with all the graphs and details here:
http://jcem.endojournals.org/cgi/content/full/87/8/3573
With references to 23 studies.
Here are some interesting graphs:
http://jcem.endojournals.org/conten...g0828721002.gif
This graph shows the difference growth velocity difference pre GH treatment, and at the
end of the trial, 4 years after (2 years after withdrawal from GH treatment)
The dark bar marks the alternate day injections. The light bar marks the every day injections,
note that the every day injections group saw worse long-term (4 yrs) results as opposed
to the alternate day group.
http://jcem.endojournals.org/conten...g0828721003.gif
This graph shows the annual bone age advancement in children treated with
alternate GH injections and daily injections.
The light bar marks the every day injections, the dark bar the alternate day injections.
In first two years (the years they were taking hGH), take a look at the relatively
small advantage ED injections gave over the EOD inj, as opposed to the 2 years
after withdrawal of the treatment.
The Journal of Clinical Endocrinology & Metabolism Vol. 87, No.8 3573-3577
clearly shows every other day (EOD) hGH injections to be much more beneficial in
the long run to everyday injections. Everyday injections seems to drastically lower
your body's sensitivity to it's own GH secretion. The study included children with idiopathic
short stature, but can be ever casting on us, normal non-deficient hGH individuals who
may use hGH periodically for bodybuilding, sports and health purposes.
The 38 children were divided into 2 groups:
Group I received daily hGH injections.
Group II received alternate day hGH injections.
It is important to note that the total weekly dosage of hGH
was the same for both groups.
Both groups received the hGH therapy contiguously for 2 years.
Their natural growth was followed for an additional 2 years after hGH therapy ended.
They were all measured at 3-month intervals during the 4 years period (2 years
with hGH therapy and 2 years after). Their Serum GH was measured by double antibody RIA kit.
During hGH therapy, both groups accelerated their growth substantially.
Group I receiving the daily hGH injections first & second year velocity was 3.4 and 2.3 SD
Group II receiving the alternate hGH inj. had 3.0 and 2.0 SD for first and second year respectively.
Over the initial 6 months after withdrawal of therapy, growth velocity decelerated to a low nadir -3.9 SD score
for the daily therapy group, whereas it decelerated in the alternate day group to only -0.2 SD score.
During the 2 years off therapy, the later group (taking EOD injections)
maintained growth rates of -0.2 to -1.2 SD score, which is similar to their SD score prior to the hGH treatment.
The daily group also recovered but very slowly, on the fourth semiannual evaluation off therapy.
The cumulative 4-year growth velocity (2yrs on and 2 yrs off therapy) of the alternate day group was greater
than that of the daily therapy group (mean, 0.9 vs. 0.3 SD score).
At the end of the 4-yr therapy period, the adult height prediction of the alternate day group was greater
than that of the daily group by a mea of 6.5cm (that's over 2.5" in height, quite a lot of difference)
In even simpler English, to translate what it may mean to us is that using hGH everyday will only
negligibly give better short-term results. Yet using alternate day hGH will give radically better long-term
results and much better recovery. As the body may get back to homeostasis much faster.
Remember the two groups got the same weekly total hGH dosage,
so your every other day hGH injections would be twice as if you used
it every day.
The researchers said, the dose was of less impotency than the schedule of the injections.
Daily hGH therapy for 3 years caused subnormal growth persisting for 1.5 years (very bad)
It may be that the problem is not enough hGH or IGF-1 secretion but rather
the body's decreased sensitivity to it. The interesting part is that the serum GH levels
and serum IGF-I and IGF-binding protein remained unaffected or relatively mutely affected.
Even your body's endogenous pulsatile secretion of GH resumes within just days
even after long-term hGH therapy.
The researchers hypothesis is that the tolerance may be in the "GH signal transduction in
selective target organs in response to the disappearance of the unique pulsatile
pattern of serum GH during GH therapy". You see, hGH taken via sc injections
do not imitate the your body's own GH secretion.
"Indeed, daily sc administration of GH results in an unphysiological serum GH profile, with peak
levels at 4 h and a slow decline over the course of the following 12–24 h. This pattern can be
regarded as continuous administration, rather than the physiological GH pulses,
with a frequency of about eight per day."
"Assuming that the withdrawal syndrome is related to tolerance that might have developed toward
hGH or IGF-I, we tried to prevent it by alternate day treatment. Moreover, hGH doses used in
therapy often stimulate IGF-I to supraphysiological serum levels, suggesting that target
tissues IGF-I may also be higher than normal. The mechanism seems, therefore, to rest
with hGH and IGF-I action at their target tissues. We now show that alternate day therapy
with hGH in children with an intact GH-IGF-I axis prevents the withdrawal syndrome"
Researchers mark the analogy to another endocrine tolerance and withdrawal syndrome:
"alternate day therapy with glucocoricoids prevents tolerance to that hormone to a substantial degree,
"Interestingly, glucocoricoids withdrawal syndrome can also occur while the
hypothalamic-pituitary-adrenal axis is intact (, indicating that tolerance to glucocoricoids has developed
at the target organ level (9). "
An example of a good safe protocol to follow in my opinion could be
hGH taken for 4 months (16 weeks) or more at 8IU every other day,
split to 4IU three hours after waking up (say 11:00am)
and another 4IU taken 4 hours later (say 3:00pm).
This approach is quite conservative and may be optimal.
Obviously, you may extend past 4months, and take more IUs per day.
This approach goes with 8IU EOD, so it is equivalent to folks that would
otherwise go with 4IU ED, which is what most do.
There is some controversy as to how many of these IUs the body
can utilize at once
Obviously, there are lot of studies, some better conducted, some less.
Lots of opinions and doctrines in endocrinology, bodybuilding etc..
So you should make your own decision, I guess old individuals on
hGH for life would not mind, as no rebound would affect them. Professional
bodybuilders probably wouldn't mind as well.
I would rather follow a protocol like this. For most part due to the
nasty rebound that I could get after withdrawing from long-term ED hGH treatment.
Nothing worse then look awesome, stop hGH then after several months having:
Low body sensitivity to your own body's GH.
Slow recovery
Decline in resting cardiac output
Increase fat mass
Decrease in metabolic rate
Negative nitrogen balance, phosphorus, sodium and potassium.
Again, I said "could" not "would", because this study cannot absolutely manifest
our use of hGH. Moreso, we are not children, we are not idiopathic hGH deficient
and not aGHD. But since the weekly dosages do remain the same as well as the
duration of the hGH usage. Just changing to the EOD protocol from the well
hyped everyday inj protocol is worth in my honest opinion. It seems statistically
a better bet, with more chance to win, than loose as opposed to the ED protocol.
I just tried to summarize the findings of the study, which was by the way,
a pleasure to read as the study is well written and was prepared by
Dr Hochberg, MD, a renowned well respected figure in endocrinology.
You can read the full article with all the graphs and details here:
http://jcem.endojournals.org/cgi/content/full/87/8/3573
With references to 23 studies.
Here are some interesting graphs:
http://jcem.endojournals.org/conten...g0828721002.gif
This graph shows the difference growth velocity difference pre GH treatment, and at the
end of the trial, 4 years after (2 years after withdrawal from GH treatment)
The dark bar marks the alternate day injections. The light bar marks the every day injections,
note that the every day injections group saw worse long-term (4 yrs) results as opposed
to the alternate day group.
http://jcem.endojournals.org/conten...g0828721003.gif
This graph shows the annual bone age advancement in children treated with
alternate GH injections and daily injections.
The light bar marks the every day injections, the dark bar the alternate day injections.
In first two years (the years they were taking hGH), take a look at the relatively
small advantage ED injections gave over the EOD inj, as opposed to the 2 years
after withdrawal of the treatment.
