hGH desensitization: Why you may not want to inject hGH everyday (heightmaxers GTFIH)

[axm]

Prevention of Growth Deceleration after Withdrawal of Growth Hormone Therapy in Idiopathic Short Stature​

Meir Lampit, Ze’ev Hochberg. The Journal of Clinical Endocrinology & Metabolism, Volume 87, Issue 8, 1 August 2002, Pages 3573–3577. Published 01 August 2002.

The treatment of children with idiopathic short stature by daily injections of human GH (hGH) is followed after its withdrawal by a growth deceleration with normal serum GH and IGF-I levels.

The present study was designed to understand and prevent growth deceleration. We hypothesized that this phenomenon is due to tolerance at the target organ level, that tolerance develops in response to the unphysiological pharmacokinetics of daily-injected hGH, and that alternate day hGH therapy will prevent it.

Thirty-eight prepubertal children with idiopathic short stature, aged 3.3–9.0 yr, were studied. Their heights were less than −2 SD score, growth rate was above the 10th percentile for age, bone age was less than 75% of chronological age, and the stimulated serum GH concentration was greater than 10 μg/liter.

The children were matched for sex, height, and growth velocity SD score to receive daily or alternate day hGH at the same weekly dose of 6 mg/m2 for a period of 2 yr. The 1st and 2nd year mean growth velocities were 3.4 and 2.3 SD score for the daily therapy group and 3.0 and 2.0 SD score for the alternate day group, respectively (P = NS).

Over the initial 6 months after withdrawal of therapy, and growth velocity decelerated to a nadir of −3.9 SD score in the daily therapy group, whereas it decelerated in the alternate day group to only −0.2 SD score (P < 0.01).

Over the entire 2 yr off therapy the latter group maintained mean growth rates of −0.2 to −1.2 SD score, similar to their pretreatment velocities. The daily group recovered slowly to resume their mean pretreatment rate only on the fourth semiannual evaluation off therapy.

The cumulative 4-yr growth velocity (2 yr on and 2 yr off therapy) of the alternate day group was greater than that of the daily therapy group (mean, 0.9 vs. 0.3 SD score; P < 0.002). 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 mean 6.5 cm (P = 0.06).

What does this mean?

Everyday injections of exogenous hGH seem to drastically lower your body's sensitivity to its own GH secretion.

In this study, 38 ISS children were given either everyday (ED) or every other day (EoD) injections of hGH for two years (doses equated). The treatment then ceased and their heights were tracked for an additional two years after the treatment.

During hGH therapy, both groups accelerated their growth substantially:

The ED group first and second year velocity was 3.4 and 2.3 SD.

The EoD group had 3.0 and 2.0 SD for first and second year, respectively.

Over the initial six 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 latter 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—2 yrs 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 EoD group was greater than that of the daily group by a mean of 6.5 cm.

Why is this?

Typically, endogenous growth hormone comes in pulses or spikes, as opposed to a sustained release over many hours as seen in exogenous administration. It seems that the issue stems from desensitization of target tissues due to the unnatural release of growth hormone when exogenously administered subcutaneously. This is despite the fact that sustained GH release is known to boost IGF-1 higher than pulsatile secretion, further proving that GH itself contributes to growth as seen in some rodent models.

What Can We Do?

Alternate day dosing, as seen in the study, seems to ameliorate this. This is at the cost of short term height velocity though. We still do not understand how the desensitization may differ in other tissues, so it everyday dosing could maybe be considered if you believe your plates are soon to close and you want to max out height velocity during this time. Please keep in mind that the doses were equated, meaning double the dose once every other day. (as an example, from 3 IU's everyday, to 6 IU's every other day).

Another (theoretical) way this problem could be solved is through the use of peptidyl (not MK-677) growth hormone secretagogues and GHRH analogs. These peptides (especially in combination) seem to produce a spike much more similar to endogenous production. This (again, in theory) could mitigate desensitization and lead to better height gains. This is also combining with the multiple molecular weights your pituitary releases in response to the peptides as opposed to the 22 kDa exogenous hGH but that might be for a different thread.

I am not a medical professional, nothing written here should be considered medical advice. Do your own research. Thanks for reading!

 

[axm]

https://pubmed.ncbi.nlm.nih.gov/11133160/
This was the rodent model I was referring to by the way

 

[letsdoit]

@Osie

 

[Osie]

@Osie

I'll dm you about this

 

[Osie]

Why is this?

Typically, endogenous growth hormone comes in pulses or spikes, as opposed to a sustained release over many hours as seen in exogenous administration. It seems that the issue stems from desensitization of target tissues due to the unnatural release of growth hormone when exogenously administered subcutaneously. This is despite the fact that sustained GH release is known to boost IGF-1 higher than pulsatile secretion, further proving that GH itself contributes to growth as seen in some rodent models.

What Can We Do?

Alternate day dosing, as seen in the study, seems to ameliorate this. This is at the cost of short term height velocity though. We still do not understand how the desensitization may differ in other tissues, so it everyday dosing could maybe be considered if you believe your plates are soon to close and you want to max out height velocity during this time. Please keep in mind that the doses were equated, meaning double the dose once every other day. (as an example, from 3 IU's everyday, to 6 IU's every other day).

View attachment 3026171

Another (theoretical) way this problem could be solved is through the use of peptidyl (not MK-677) growth hormone secretagogues and GHRH analogs. These peptides (especially in combination) seem to produce a spike much more similar to endogenous production. This (again, in theory) could mitigate desensitization and lead to better height gains. This is also combining with the multiple molecular weights your pituitary releases in response to the peptides as opposed to the 22 kDa exogenous hGH but that might be for a different thread.

I am not a medical professional, nothing written here should be considered medical advice. Do your own research. Thanks for reading!

Great post, I always love seeing analysis of interesting studies on the forum. The best way to handle this is by injecting peptides once in the morning and once in the afternoon, so twice a day, and then injecting HGH at night. This essentially allows for constant spiking of both endogenous production and exogenous production. However, when you are taking both of them, they have different break times, so you'd have to take breaks from the peptides and then potentially decide to continue using the HGH or stop until your body is resensitized and ready to use the peptides.

You can never inject peptides and HGH at the same time, they need like at least a 5-8 hour distance in terms of use time of administration. This is because exogenous HGH creates a feedback loop that directly signals the pituitary gland to not produce as much endogenous HGH in it's presence. Now, this means that if you were to inject peptides in a similar time frame, it's effects would be completely halted, as it increases endogenous production.

Another way is to simply take a break after every 3-4 months when your body is just beginning to desensitize, then hop back on after 2 weeks. This seems like a simple way to circumvent it, but may feel odd to the traditional heightmaxxer as a majority of studies keep blasting the same dosage regardless of the decrease in growth velocity.

 

[axm]

You can never inject peptides and HGH at the same time, they need like at least a 5-8 hour distance in terms of use time of administration. This is because exogenous HGH creates a feedback loop that directly signals the pituitary gland to not produce as much endogenous HGH in it's presence. Now, this means that if you were to inject peptides in a similar time frame, it's effects would be completely halted, as it increases endogenous production.

I've heard on some forums (namely DatBTrue) that you could potentiate a huge spike in GH by pinning some peptides, letting them reach their peak in say 15 min or so, and then dosing exogenous hGH. Besides, isn't the negative feedback loop exerted by IGF-1? So the suppression would be chronic instead of acute

 

[elemanzelvadre]

then im fucked up

 

[letsdoit]

Great post, I always love seeing analysis of interesting studies on the forum. The best way to handle this is by injecting peptides once in the morning and once in the afternoon, so twice a day, and then injecting HGH at night. This essentially allows for constant spiking of both endogenous production and exogenous production. However, when you are taking both of them, they have different break times, so you'd have to take breaks from the peptides and then potentially decide to continue using the HGH or stop until your body is resensitized and ready to use the peptides.

You can never inject peptides and HGH at the same time, they need like at least a 5-8 hour distance in terms of use time of administration. This is because exogenous HGH creates a feedback loop that directly signals the pituitary gland to not produce as much endogenous HGH in it's presence. Now, this means that if you were to inject peptides in a similar time frame, it's effects would be completely halted, as it increases endogenous production.

Another way is to simply take a break after every 3-4 months when your body is just beginning to desensitize, then hop back on after 2 weeks. This seems like a simple way to circumvent it, but may feel odd to the traditional heightmaxxer as a majority of studies keep blasting the same dosage regardless of the decrease in growth velocity.

Can you check Whatsapp Osie

 

[Deleted member 33409]

Bunp

 

[heightmaxxer1133]

Prevention of Growth Deceleration after Withdrawal of Growth Hormone Therapy in Idiopathic Short Stature​

Meir Lampit, Ze’ev Hochberg. The Journal of Clinical Endocrinology & Metabolism, Volume 87, Issue 8, 1 August 2002, Pages 3573–3577. Published 01 August 2002.








What does this mean?

Everyday injections of exogenous hGH seem to drastically lower your body's sensitivity to its own GH secretion.

In this study, 38 ISS children were given either everyday (ED) or every other day (EoD) injections of hGH for two years (doses equated). The treatment then ceased and their heights were tracked for an additional two years after the treatment.

During hGH therapy, both groups accelerated their growth substantially:

The ED group first and second year velocity was 3.4 and 2.3 SD.

The EoD group had 3.0 and 2.0 SD for first and second year, respectively.

Over the initial six 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 latter 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—2 yrs 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 EoD group was greater than that of the daily group by a mean of 6.5 cm.

Why is this?

Typically, endogenous growth hormone comes in pulses or spikes, as opposed to a sustained release over many hours as seen in exogenous administration. It seems that the issue stems from desensitization of target tissues due to the unnatural release of growth hormone when exogenously administered subcutaneously. This is despite the fact that sustained GH release is known to boost IGF-1 higher than pulsatile secretion, further proving that GH itself contributes to growth as seen in some rodent models.

What Can We Do?

Alternate day dosing, as seen in the study, seems to ameliorate this. This is at the cost of short term height velocity though. We still do not understand how the desensitization may differ in other tissues, so it everyday dosing could maybe be considered if you believe your plates are soon to close and you want to max out height velocity during this time. Please keep in mind that the doses were equated, meaning double the dose once every other day. (as an example, from 3 IU's everyday, to 6 IU's every other day).

View attachment 3026171

Another (theoretical) way this problem could be solved is through the use of peptidyl (not MK-677) growth hormone secretagogues and GHRH analogs. These peptides (especially in combination) seem to produce a spike much more similar to endogenous production. This (again, in theory) could mitigate desensitization and lead to better height gains. This is also combining with the multiple molecular weights your pituitary releases in response to the peptides as opposed to the 22 kDa exogenous hGH but that might be for a different thread.

I am not a medical professional, nothing written here should be considered medical advice. Do your own research. Thanks for reading!

i have some questions come in private please

 

[DR. NICKGA]

Hgh injections are usseles

 

[moggr2009]

growth hormone secretagogues and GHRH analogs. These peptides

which ones would u reccomend
and also good thread

 

[moggr2009]

and what do you think about this article as a solution to ed dosing's affects on desensitization?

https://journals.physiology.org/doi/full/10.1152/ajpendo.00414.2009

 

[axm]

which ones would u reccomend
and also good thread

the drugs that are well known to the forum, and have some human trials. GHRP-6,-2, Ipamorelin, Hexeralin, mod-GRF/CJC-1295 no DAC etc.

and what do you think about this article as a solution to ed dosing's affects on desensitization?

https://journals.physiology.org/doi/full/10.1152/ajpendo.00414.2009

This is about the growth hormone secretagogue receptor (ghrelin), not the growth hormone receptor itself.

Treatment of humans with lipid infusions suppresses the GH secretagogue effect of ghrelin (11). This modulation of the GH secretagogue response in vivo may well be complicated by additional effects of lipids in the pituitary, for example, on GH-releasing hormone receptor function (15). We have used an in vitro approach to directly examine the modulatory effects of OFAs (oleic and linoleic acids) and cholesterol on GHSR function.

This study referenced in your paper says that:

In humans, ghrelin exerts a strong stimulatory effect on GH secretion which is partially refractory to the inhibitory effect of both glucose and FFA load and is not enhanced by ARG. These factors almost abolish and potentiate, respectively, the GH response to GHRH

The fact that fatty acids and glucose in the bloodstream inhibits the release of GH from secretagouges is well known info.

Initial experiments showed that oleic and linoleic acid had no acute effects on the response of the GHSR to ghrelin, as assessed using the aequorin assay (120 μM OFA; Fig. 1A). In this case, GHSR/aequorin cells were exposed to OFAs only during the 20-s integration period required to measure aequorin's fluorescence response to ghrelin. A range of OFA concentrations ≤1 mM were tested, none of which had acute effects on the sensitivity of the receptor to ghrelin (data not shown). However, prolonged 96-h treatment of the GHSR/aequorin cells with OFA caused a significant increase in sensitivity of the cells to ghrelin relative to untreated controls. At 60 μM OFA the EC50 was significantly decreased, 2.4- (P < 0.001) and 2.9-fold (P < 0.001) for oleic and linoleic acid, respectively, relative to controls (Fig. 1B). At 120 μM OFA the EC50 was decreased 3.7-fold (P < 0.001) for both oleic and linoleic acid relative to controls (Fig. 1C). A possible mechanism for the improved response to ghrelin in OFA-treated cells is that receptor affinity for its ligand has been increased. Therefore, we next measured the ability of unlabeled ghrelin to displace radiolabeled ghrelin from GHSR/aequorin-expressing cells. We found that treatment for 96 h with either 60 or 120 μM oleic acid had a slight but nonsignificant effect on binding (P > 0.05, t-test; Fig. 2, A and B).

This is an in vitro cell culture experiment, where "Oleic and linoleic acids [oligounsaturated fatty acids (OFAs)] have no acute effect on responsiveness of GHSR to ghrelin, whereas long-term (96 h) treatment with OFAs increases the sensitivity of GHSR to ghrelin". I'm honestly not educated enough to draw many conclusions from this, but the fact that this was done in a Petri dish over 96 hours, and that this is with exogenous ghrelin (not its selective counterparts like the drugs I listed above) which is not commonly used for GH secreting properties, and that fatty acids are otherwise known to inhibit GH secreting properties from ghrelin/GHS' leads me to believe that this probably won't apply to humans. From what I've read, desensitization from GH releasing peptides only occurs with excessively high doses above saturation dose and can be easily ameliorated by switching drugs or taking a break for a few days.

Interesting read though.

 

[moggr2009]

This is an in vitro cell culture experiment, where "Oleic and linoleic acids [oligounsaturated fatty acids (OFAs)] have no acute effect on responsiveness of GHSR to ghrelin, whereas long-term (96 h) treatment with OFAs increases the sensitivity of GHSR to ghrelin". I'm honestly not educated enough to draw many conclusions from this, but the fact that this was done in a Petri dish over 96 hours, and that this is with exogenous ghrelin (not its selective counterparts like the drugs I listed above) which is not commonly used for GH secreting properties, and that fatty acids are otherwise known to inhibit GH secreting properties from ghrelin/GHS' leads me to believe that this probably won't apply to humans. From what I've read, desensitization from GH releasing peptides only occurs with excessively high doses above saturation dose and can be easily ameliorated by switching drugs or taking a break for a few days.

Thanks for the response, high iq response and your def better at these things then me.
Yeah, after reading I agree with everything you said.

Great response

 

[Deleted member 90503]

Hgh injections are usseles

hgh increases igf1 if you take it with aromasin it will increase your height (correct me if im wrong)

 

[MyDreamIsToBe183CM]

Prevention of Growth Deceleration after Withdrawal of Growth Hormone Therapy in Idiopathic Short Stature​

Meir Lampit, Ze’ev Hochberg. The Journal of Clinical Endocrinology & Metabolism, Volume 87, Issue 8, 1 August 2002, Pages 3573–3577. Published 01 August 2002.








What does this mean?

Everyday injections of exogenous hGH seem to drastically lower your body's sensitivity to its own GH secretion.

In this study, 38 ISS children were given either everyday (ED) or every other day (EoD) injections of hGH for two years (doses equated). The treatment then ceased and their heights were tracked for an additional two years after the treatment.

During hGH therapy, both groups accelerated their growth substantially:

The ED group first and second year velocity was 3.4 and 2.3 SD.

The EoD group had 3.0 and 2.0 SD for first and second year, respectively.

Over the initial six 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 latter 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—2 yrs 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 EoD group was greater than that of the daily group by a mean of 6.5 cm.

Why is this?

Typically, endogenous growth hormone comes in pulses or spikes, as opposed to a sustained release over many hours as seen in exogenous administration. It seems that the issue stems from desensitization of target tissues due to the unnatural release of growth hormone when exogenously administered subcutaneously. This is despite the fact that sustained GH release is known to boost IGF-1 higher than pulsatile secretion, further proving that GH itself contributes to growth as seen in some rodent models.

What Can We Do?

Alternate day dosing, as seen in the study, seems to ameliorate this. This is at the cost of short term height velocity though. We still do not understand how the desensitization may differ in other tissues, so it everyday dosing could maybe be considered if you believe your plates are soon to close and you want to max out height velocity during this time. Please keep in mind that the doses were equated, meaning double the dose once every other day. (as an example, from 3 IU's everyday, to 6 IU's every other day).

View attachment 3026171

Another (theoretical) way this problem could be solved is through the use of peptidyl (not MK-677) growth hormone secretagogues and GHRH analogs. These peptides (especially in combination) seem to produce a spike much more similar to endogenous production. This (again, in theory) could mitigate desensitization and lead to better height gains. This is also combining with the multiple molecular weights your pituitary releases in response to the peptides as opposed to the 22 kDa exogenous hGH but that might be for a different thread.

I am not a medical professional, nothing written here should be considered medical advice. Do your own research. Thanks for reading!

great thread