GH - (ed verses eod)
posted by BMF2 on Qualitymuscle
GH - (ed verses eod)
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.
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:
With references to 23 studies.
Here are some interesting graphs:
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.
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.
liftsiron is a fictional character and should be taken as such.
I was doing 4iu ed and had to back off to 2 iu ed because of joint and water problems. His suggestion in my case would be 4iu eod. hmm, will have to see if there is any other supporting data.
I seen a similiar read awhile back based on a shorter study, I'll see if I can locate it.
liftsiron is a fictional character and should be taken as such.
Professional sprinters use 2.5iu EOD.
mathematitian bastard mode /on:
used at least untill 2000 when someone gave uo the program.
now its most likely different with igf and ngf and stuff...
and they used it synergisticaly with insulin after morning weights to be able to pull off speed at the evening
"tiss a visitor i muttered
knokcing on my chamber door
only this and nothing more"
I swear by this method now, I remember when the study was first posted hear so I changed from 3iu's ED to 6iu's EOD and after a few weeks I dropped all the excess water and no longer got any of limb numbness.
Interesting. Anyone else experiment with this protocol, and what were the results - mainly in terms of body composition?
I wonder if a lower dosage eod would be just as efficient, though - such as 6IUs eod instead of 4IUs ed.
I found these studies supporting the eod dosing:
J Endocrinol Invest. 2003 May;26(5):420-8.
Three weekly injections (TWI) of low-dose growth hormone (GH) restore low normal circulating IGF-I concentrations and reverse cardiac abnormalities associated with adult onset GH deficiency (GHD).
Pincelli AI, Bragato R, Scacchi M, Branzi G, Osculati G, Viarengo R, Leonetti G, Cavagnini F.
University of Milan, IRCCS San Luca Hospital, Italian Auxologic Institute, Milan, Italy.
GH replacement therapy given 3 times weekly (TWI) and adjusted to allow serum IGF-I concentrations in the mid-normal range for sex and age has been shown to be as effective as the daily regimen in improving lipid profile, body composition, bone mass and turnover in adult GH deficient (GHD) patients. Only one study has investigated so far the short-term (6 months) effect of a fixed weight-based TWI dosing schedule on heart structure and function in childhood onset (CO) GHD patients, whereas such a schedule in adult onset (AO) GHD patients has not been studied as yet. Aim of this study was to investigate whether a 1-yr low-dose titrated TWI GH-replacement regimen aimed at achieving and maintaining IGF-I levels within the low normal limits for age and sex is able to affect cardiovascular and heart parameters in a group of AO GHD patients. Eight adult patients (4 women and 4 men, age 35.8 +/- 3.37 yr, body mass index, BMI, 28.7 +/- 2.62 kg/m2) with AO GHD were included in the study, along with 10 healthy subjects, matched for age, sex, BMI and physical activity (6 women and 4 men, age 35.2 +/- 4.05 yr, BMI 28.4 +/- 2.34 kg/m2). M- and B- mode ecocardiography and pulsed doppler examination of transmitral flow were performed in GHD patients at baseline and after 3 and 12 months of GH therapy (mean GH dose 6.7 +/- 0.8 microg/kg/day given thrice a week), while normal subjects were studied once. Treatment with GH for 1 yr induced a significant increase in left ventricular (LV) diastolic and systolic volumes (+11.1 and +16.5%, respectively). Systolic LV posterior wall thickness and LV mass were increased (+10.2 and +7.7%, respectively) by GH administration. Systemic vascular resistance was significantly decreased by 1-yr GH therapy (-13.8% after 1 yr), while stroke volume, cardiac output and cardiac index were increased (+9.4, +11.6 and + 11.9%, respectively). LV end-systolic stress was decreased at the end of GH therapy (-11.2%). E and A wave, significantly reduced at baseline, were increased by 1 yr of GH therapy (+23.3% and +28.1%, respectively); likewise, the abnormally high E peak deceleration time was partially reversed by GH administration (-10.7%). Our study, though conducted in a small sample size, demonstrates that a TWI GH treatment schedule is able to reverse the cardiovascular abnormalities in AO GHD patients and to improve body composition and lipid profile. The maintenance of circulating IGF-I concentrations within the low normal range allows to avoid most of the side-effects reported with higher GH doses while being cost-effective and improving the patient's compliance.
J Clin Endocrinol Metab. 2000 Oct;85(10):3720-5.
Recombinant growth hormone (GH) therapy in GH-deficient adults: a long-term controlled study on daily versus thrice weekly injections.
Amato G, Mazziotti G, Di Somma C, Lalli E, De Felice G, Conte M, Rotondi M, Pietrosante M, Lombardi G, Bellastella A, Carella C, Colao A.
Institute of Endocrinology, Seconda Universita of Naples, Italy. firstname.lastname@example.org
Currently, replacement recombinant GH (rGH) therapy in GH-deficient (GHD) adults is performed in daily injections. This modality of treatment is not complied with by the totality of GHD patients, who are supposed to receive life-long replacement. The aim of our study was to compare daily vs. thrice weekly (TIW) rGH injection effects on lipid profile, body composition, bone metabolism, and bone density in 34 GHD patients (13 women and 21 men; median age, 39 yr; range, 30-55 yr) randomly assigned to different therapeutic regimens. Group A included 18 patients receiving daily rGH injections, and group B included 16 patients receiving TIW injections of rGH. The starting dose of rGH was 10 microg/kg x day in both groups. Subsequently, the dose was adjusted to maintain serum insulin-like growth factor I (IGF-I) concentrations in the normal age-adjusted range. IGF-I levels were assessed before and after 1, 3, 6, and 12 months of rGH treatment, and lipid profile, body composition, bone metabolism, and bone density were evaluated before and after 6 and 12 months of treatment. Thirty-four healthy subjects served as controls. In the basal condition, lipid profile, body composition, bone metabolism, and bone density were significantly different in patients compared to controls. Conversely, patients included in groups A and B had similar serum IGF-I levels, lipid profile, body composition, bone metabolism, and bone density. After 3 months of rGH treatment, IGF-I levels were normalized in 15 of 18 patients (83.3%) in group A and in 7 of 16 patients (43.7%) in group B (chi2 = 4.21; P = 0.04). At this time point, serum IGF-I levels in patients in group A (202+/-57.5 microg/L) were significantly higher than those in patients in group B (155+/-45.1 microg/L; P = 0.001). After 6 months of therapy, serum IGF-I levels were normalized in all patients and were similar in both groups (223+/-35.2 vs. 212+/-41.4 microg/L, A vs. B, respectively). IGF-I levels remained normal until the 12-month follow-up. After 6 months of rGH replacement, total cholesterol, low density lipoprotein cholesterol, triglycerides, bioelectrical impedance, and body fat mass were significantly reduced, whereas high density lipoprotein cholesterol levels and lean body mass were significantly increased in both groups of patients, without any difference between them. No further change in lipid profile and body composition was observed after 12 months of treatment. Serum bone GLA protein and procollagen III levels were significantly increased after 6 months, and a downward trend was observed after 12 months of rGH replacement. However, a slight, but significant, increase in bone mineral density was observed in both groups only after 12 months (P = 0.0001). All patients in group B had good compliance to the TIW treatment, whereas 5 patients in group A had poor compliance to the treatment (chi2 = 3.2; P = 0.07). In conclusion, our randomized, prospective, and controlled study confirmed that rGH therapy with TIW injection regimen is effective in normalizing IGF-I levels and improving lipid profile, body composition, bone metabolism, and bone density. It also demonstrated that this efficacy is comparable to that observed in patients treated with daily rhGH therapy, with few side-effects and good compliance.
There's also these, where many studies use eod injections of GH: http://www.ncbi.nlm.nih.gov/entrez/...=ExternalSearch
Oh, and this article, if you scroll down to the chapter on lipodystrophia, it refers to a study (couldn't access the abstract) where the treatment group starting off with ed injections then switching to eod injections had better results than all the other groups: http://www.thebody.com/sfaf/winter03/hgh.html
I know I've been in and out lately, so I've may have missed something, but it's nice to see you back around posting, Blade!
"In any contest between power and patience, bet on patience."
"Only two things are infinite, the universe and human stupidity, and I'm not sure about the former."
i posted this one, some time ago:
Clin Endocrinol (Oxf). 1995 Aug;43(2):143-9.
Which adults develop side-effects of growth hormone replacement?
Holmes SJ, Shalet SM.
Department of Endocrinology, Christie Hospital NHS Trust, Manchester, UK.
OBJECTIVE: Although the nature of the side-effects of GH replacement in adults are well described, the factors influencing their development are ill understood. The aim of this study was to determine whether there were any characteristics of adults with GH deficiency that predicted whether or not they developed side-effects of GH replacement. DESIGN: A 12-month study (double blind placebo controlled for the first 6 months and open for the second 6 months) of GH replacement (0.125 IU/kg/week for the first month and 0.25 IU/kg/week thereafter) in adults. PATIENTS: Sixty-three adults (27 men, 36 women, aged 34.9 +/- 1.4 (mean +/- SE, range 20.1-59.5 years)) with GH deficiency (peak serum GH response to provocative testing of less than 10 mU/l) who took part in a 12-month study of GH replacement. Twenty-five patients (40%) did not develop side-effects, 19 patients (30%) developed side-effects which did not necessitate a reduction in dose of GH, and 19 patients (30%) required a reduction in dose of GH because of side-effects. MEASUREMENTS: The three groups of patients were compared according to age, height, weight and body mass index (BMI) at entry into the study and to pretreatment peak serum GH response to provocative testing. They were also compared according to serum concentration of insulin-like growth factor (IGF)-I and IGF binding protein-3, and age-adjusted serum IGF-I standard deviation score (SDS), at entry into the study and by change in these measurements after 6 months of GH replacement. The patient's sex, whether GH deficiency was of childhood or adult onset, estimated duration of GH deficiency, presence or absence of additional pituitary hormone deficiencies, underlying pathological disorder and previous therapeutic interventions were also compared in the three groups of patients. RESULTS:Those patients who required a reduction in dose of GH because of side-effects were more likely to have a peak serum GH response of greater than 1 mU/l (P = 0.005) and to have adult onset GH deficiency (P = 0.04) than those who did not develop side-effects or who did not require a reduction in dose of GH because of side-effects. In addition, those who needed a reduction in GH dose were older (P = 0.002), heavier (P = 0.04) and had a greater BMI (P = 0.003) than those who did not develop side-effects. Those who developed side-effects but did not require a reduction in dose of GH had a greater increment in IGF-I SDS after 6 months of GH replacement than those who did not develop side-effects (P = 0.03). CONCLUSION: Side-effects of GH replacement are more likely to occur in older patients, in those with a peak serum GH response to provocative testing of greater then 1 mU/l, in those with a greater increment in serum IGF-I SDS whilst receiving GH replacement, in those with greater weight and BMI, and those with adult onset GH deficiency.
Titrating, can make a difference.
J Clin Endocrinol Metab. 2007 Mar 13;
IGF-based Dosing of GH Therapy in Children:A Randomized Controlled Study.
Cohen P, Rogol AD, Howard CP, Bright GM, Kappelgaard AM, Rosenfeld RG.
Context: Weight-based dosing of GH is the standard-of-care for short-children, although IGF-I is thought to be the main mediator of GH-actions on growth. Objective: To test whether IGF-I levels achieved during GH therapy are determinants of the growth-responses to GH-treatment. Design: Two-year, open-label, randomized, IGF-I concentration-controlled-trial. Prepubertal short-children (n=172, mean age=7.53 yrs, mean height-SDS [HT-SDS]=-2.64) with low IGF-I levels (mean IGF-I SDS=-3.56) were randomized to receive one of two GH dose-titration arms in which GH-dosage was titrated to achieve an IGF-I SDS at the mean (IGF(low) group, n=70), or the upper-limit of the normal-range (+2 SDS, IGF(high) group, n=68) or to a comparison-group of conventional-GH-dose of 40 microg/kg/d (n=34). Setting: Multi-center, outpatient. Primary-Outcome-Measure: Change in HT-SDS over 2-years. Results: 147 patients completed the trial. Target IGF-I levels were achieved in the dose-titration arms within 6-9 months. The changes in HT-SDS were +1.0, +1.1 and +1.6 for conventional, IGF(low), and IGF(high), respectively, with IGF(high) showing significantly greater linear-growth response (P<0.001 compared to the other two groups). The IGF(high) arm required higher doses (>2.5 times) than the IGF(low) arm and these GH doses were highly variable (20-346 mcg/kg/day). Multivariate-analyses suggested that the rise in the IGF-I SDS significantly impacted height-outcome along with the GH-dose and the pretreatment peak stimulated-GH level. Conclusion: IGF-I-based GH-dosing is clinically-feasible and allows maintaining serum-IGF-I concentrations within the desired target-range. Titrating the GH-dose to achieve higher IGF-I targets results in improved growth-responses, although at higher average GH doses.
Endocr J. 2006 Dec;53(6):853-8.
Growth hormone (GH) effects on central fat accumulation in adult Japanese GH deficient patients: 6-month fixed-dose effects persist during second 6-month individualized-dose phase.
Chihara K, Shimatsu A, Kato Y, Kohno H, Tanaka T, Takano K, Irie M.
Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Japan.
Both Japanese and Caucasian adults with GH deficiency (GHD) have pronounced abdominal obesity, which is associated with increased risk of cardiovascular complications. We investigated the effects of GH treatment in 27 adult Japanese GHD patients, 15 with adult onset (AO) and 12 with childhood onset (CO) GHD. Patients initially received GH titrated to 0.012 mg/kg/day for 24 weeks in a double-blind design and the dose was then individualized for each patient according to IGF-I for a further 24 weeks. Dual-energy x-ray absorptiometry (DXA) data were evaluated for percentages of trunk fat, total body fat and lean body mass. Serum IGF-I and lipid concentrations were determined at a central laboratory. There were 25 patients who completed 48 weeks of treatment, with 7, 6 and 12 patients then receiving GH at 0.003, 0.006 and 0.012 mg/kg/day, respectively. With the reductions in dose when individualized between weeks 24 and 48, mean serum IGF-I level was reduced and excessively high values, observed in AO patients on the fixed GH dose, were no longer seen. The decrease from baseline in trunk fat was similar at week 24 (-3.8 +/- 3.3%, p<0.001) and week 48 (-3.1 +/- 3.7%, p<0.001), and the difference between changes was not significant. Total cholesterol was decreased from baseline by -24 +/- 28 mg/dl (p<0.001) at week 24 and -17 +/- 28 mg/dl (p = 0.007) at week 48. Two patients had elevated HbA1c levels: one continued GH treatment after a dose reduction and the other discontinued due to persistent impaired glucose tolerance. Therefore, excessively high IGF-I levels can be avoided by individualized dosing during long-term GH treatment. Individualized dosing maintains the decrease in abdominal fat in adult Japanese GHD patients and should reduce the cardiovascular risk.