Does everyone develop antibodies to HGH?

[shadow1]

Does does everyone develop antibodies to growth? Does it happen to some or is it inevitable? Some have said they cycle 6 months then come of for 6 weeks. Seems tough since things start getting really good around 6 months.

Ive ran growth at low does for long stretches, then kicked it up to 6iu months.. dont think ive ever developed antibodies.

Any input?

 

[dale338]

From what the experts say on here most seem to with like generics, especially the Chinese made ones. From what I gather you can run your I GF-1 and see a decline that starts in at 3-6 months on the same dose. I'm nearing the six month mark and definitely am noticing the accelerated results. So coming off for 8 weeks right now would SUCK. My plan is once I hit the six month mark, I'm going to run the numbers again and if they're declining I'll definitely take a break.

 

[johnjuanb1]

There should be no antibodies produced ic using pharmaceutical HGH.
The provider grey tops and scioxx HGH are low in dimers and very pure so they should be fine long term as well.

 

[musclemoose]

This is right from US Pharma HGH site...

"10 to 20% of people who get GH therapy will develop GH antibodies in reaction to it. This often happens soon after GH treatment starts—usually after a 3- to 6-month growth period. The antibodies can cause the treatment to not work."

They recommend you get antibody test by physician to see if treatment is still working. Some people just don't respond well. I dont think it matters whether generic or not.

 

[powerof2]

I have been on for about a year. Generic. Still working great. I have switch between 3 different brands.


Sent from my iPhone using Tapatalk

 

[shadow1]

If I switch to a brand im on now to the greytops from tp, would that be good. Maybe switching brands after 6 months??

What do you think? Again, who wants to break when things start to get really good.

 

[musclemoose]

If I switch to a brand im on now to the greytops from tp, would that be good. Maybe switching brands after 6 months??

What do you think? Again, who wants to break when things start to get really good.

If you read my reply two posts up you'll see that it probably doesn't matter what brand you take. Quality probably has a little to do with it but i think the main point is that if your body is susceptible to building antibodies then it will (if you fall between the 10-20% of people that it happens to). Now remember this is based on giving it to kids with growth deficiencies. I dont know what the data would be in adults using it for the purposes we are using it for. If i had to guess it could be higher for adults since we really dont need it at this point. It would be an interesting clinical study to have someone run. What i do since im on trt with my doc is i run an igf-1 test with my normal labs every 5-6 months when my doctor has me come in. If my igf-1 isnt in the 400-500 range then id worry that my generics arent doing the job. Ive been constantly over 400 running 5-6iu per day of the meditropes. so i think if i would have built up antibodies then i think it would have happened by now (since it states it happens within the first 6 months).

 

[shadow1]

If you read my reply two posts up you'll see that it probably doesn't matter what brand you take. Quality probably has a little to do with it but i think the main point is that if your body is susceptible to building antibodies then it will (if you fall between the 10-20% of people that it happens to). Now remember this is based on giving it to kids with growth deficiencies. I dont know what the data would be in adults using it for the purposes we are using it for. If i had to guess it could be higher for adults since we really dont need it at this point. It would be an interesting clinical study to have someone run. What i do since im on trt with my doc is i run an igf-1 test with my normal labs every 5-6 months when my doctor has me come in. If my igf-1 isnt in the 400-500 range then id worry that my generics arent doing the job. Ive been constantly over 400 running 5-6iu per day of the meditropes. so i think if i would have built up antibodies then i think it would have happened by now (since it states it happens within the first 6 months).

Great input. How long have you run the Meditrope without a break? If you took a break, how long was the break?

 

[dale338]

If you read my reply two posts up you'll see that it probably doesn't matter what brand you take. Quality probably has a little to do with it but i think the main point is that if your body is susceptible to building antibodies then it will (if you fall between the 10-20% of people that it happens to). Now remember this is based on giving it to kids with growth deficiencies. I dont know what the data would be in adults using it for the purposes we are using it for. If i had to guess it could be higher for adults since we really dont need it at this point. It would be an interesting clinical study to have someone run. What i do since im on trt with my doc is i run an igf-1 test with my normal labs every 5-6 months when my doctor has me come in. If my igf-1 isnt in the 400-500 range then id worry that my generics arent doing the job. Ive been constantly over 400 running 5-6iu per day of the meditropes. so i think if i would have built up antibodies then i think it would have happened by now (since it states it happens within the first 6 months).

I've been on for six months, only 2iu per day and seeing decent results. I run Kefie. My IGF-1 has been in the 290 range, so it's legit and I get all the sides. Since running it, I have had some weird rashes and such crop up, so I'll be curious to see if I'm developing antibodies. A light rash on my back and one suddenly appeared under my arm once. Could just be a coincidence. I'd be really fucked if I developed antibodies as I plan to run this for life with maybe just a few breaks here and there.

 

[musclemoose]

Great input. How long have you run the Meditrope without a break? If you took a break, how long was the break?

Ive been running the meditropes since January 6th with no break.

 

[IronLion2]

Even with pharma grade 191aa GH we see antibodies develop at high doses, the dose cause more antibodies in a linear fashion. Ive always imagined the quality, timing, and total dosages all play roles in the creation of antibodies.

No data to prove this; but ive always hypothesized when running high dosages of GH its important to take 1-2 days off a week, if running only smaller dosages multiple times a day you can run it ED with less problems.

 

[homonunculus]

**broken link removed**

Because of the high incidence of antibodies after HGH therapy in our hypopituitary patients, we have studied the plasma of all HGH-treated children with a sensitive radioimmunological method. We found antibodies to HGH in 12 out of 21 children who were initially treated with a cloudy preparation of HGH Raben, and in only 2 out of 14 children treated with HGH Roos. Growth was not inhibited in 4 children with low and in 2 out of 4 children with medium-high antibody titers. In one patient, antibodies in medium-high concentrations inhibited the growth response to administered HGH and seemed to suppress also the effect of endogenous GH. Replacement of the cloudy preparation by a clear solution of HGH Raben or by HGH Roos led to a decrease or the disappearance of antibodies, and, in the absence of antibodies, growth response to therapy returned. Thus, the quality of the HGH preparation might account for the appearance of antibodies in low and medium-high titers. In 6 children with isolated GH deficiency, antibodies developed in high concentrations independent of the quality of the HGH preparation used. Antibodies were still present 2–5 yr after discontinuation of HGH therapy, and their titers rose immediately to very high levels after resuming therapy with HGH Roos. Four of these children are related to each other. These patients can be distinguished from others with isolated growth hormone deficiency by their typical appearance, shortness at birth, early onset of growth retardation resulting in extreme dwarfism, and by a strong anabolic action of HGH before antibodies appear. These observations suggest that these 6 patients suffer from a hereditary prenatal GH deficiency, and that the antibody formation is due to a lack of immunotolerance to homologous human GH.

-------

**broken link removed**

By measuring [125I]hGH binding in the plasma of human GH (hGH)-deficient children at 3- to 4-month intervals during hGH therapy with hGH prepared by Raben's method, we have defined three patterns of antibody formation. One group of patients developed antibodies by 3 months of therapy that persisted despite the length or type of hGH therapy. Their antibodies were characterized by a low affinity (1.49 × 109 M−1) and a high capacity (29 nmol/liter plasma). The development or presence of antibodies adversely affected the growth rate in only one patient in this group. This patient's antibodies were characterized by the highest capacity (1235 nmol/liter plasma) and lowest affinity (0.044 × 109 M−1). The capacity decreased to 134 nmol/liter plasma upon switching to a hGH preparation without aggregated hGH.

The second group developed antibodies to hGH by 6–9 months of therapy, but [125I]hGH binding by the plasma returned to control levels by 20 months of therapy. The antibodies of this group were characterized by a higher affinity (12.7 × 109 M−1) and a lower capacity (0.9 nmol/liter plasma) than the group with antibodies. This group had received hGH with less than 5% aggregated hGH.

The third group did not develop significant [125I]hGH binding in the plasma despite prolonged therapy with multiple hGH preparations.

Several patients have been treated solely with recent hGH preparations from the National Pituitary Agency which contain less than 10% aggregated hGH compared to earlier preparations containing more than 20%. The incidence (44%) of significant [125I]hGH binding by these patients' plasmas was similar to that of patients receiving hGH with aggregated hGH; however, hGH binding by the plasma of most of these patients was characteristic of that of patients with transient antibodies.

We conclude that 1) the development of antibodies to hGH during therapy is dependent on individual susceptibility and the presence of aggregated hGH in the hGH preparation, 2) the antibody response is more likely to be transient if the content of aggregated hGH is low, and 3) the eventual incidence of significant hGH binding in plasma of patients who receive hGH prepared by Raben's method without aggregated hGH will be the same as that observed in patients receiving hGH prepared by other methods.

-S

 

[musclemoose]

**broken link removed**

Because of the high incidence of antibodies after HGH therapy in our hypopituitary patients, we have studied the plasma of all HGH-treated children with a sensitive radioimmunological method. We found antibodies to HGH in 12 out of 21 children who were initially treated with a cloudy preparation of HGH Raben, and in only 2 out of 14 children treated with HGH Roos. Growth was not inhibited in 4 children with low and in 2 out of 4 children with medium-high antibody titers. In one patient, antibodies in medium-high concentrations inhibited the growth response to administered HGH and seemed to suppress also the effect of endogenous GH. Replacement of the cloudy preparation by a clear solution of HGH Raben or by HGH Roos led to a decrease or the disappearance of antibodies, and, in the absence of antibodies, growth response to therapy returned. Thus, the quality of the HGH preparation might account for the appearance of antibodies in low and medium-high titers. In 6 children with isolated GH deficiency, antibodies developed in high concentrations independent of the quality of the HGH preparation used. Antibodies were still present 2–5 yr after discontinuation of HGH therapy, and their titers rose immediately to very high levels after resuming therapy with HGH Roos. Four of these children are related to each other. These patients can be distinguished from others with isolated growth hormone deficiency by their typical appearance, shortness at birth, early onset of growth retardation resulting in extreme dwarfism, and by a strong anabolic action of HGH before antibodies appear. These observations suggest that these 6 patients suffer from a hereditary prenatal GH deficiency, and that the antibody formation is due to a lack of immunotolerance to homologous human GH.

-------

**broken link removed**

By measuring [125I]hGH binding in the plasma of human GH (hGH)-deficient children at 3- to 4-month intervals during hGH therapy with hGH prepared by Raben's method, we have defined three patterns of antibody formation. One group of patients developed antibodies by 3 months of therapy that persisted despite the length or type of hGH therapy. Their antibodies were characterized by a low affinity (1.49 × 109 M−1) and a high capacity (29 nmol/liter plasma). The development or presence of antibodies adversely affected the growth rate in only one patient in this group. This patient's antibodies were characterized by the highest capacity (1235 nmol/liter plasma) and lowest affinity (0.044 × 109 M−1). The capacity decreased to 134 nmol/liter plasma upon switching to a hGH preparation without aggregated hGH.

The second group developed antibodies to hGH by 6–9 months of therapy, but [125I]hGH binding by the plasma returned to control levels by 20 months of therapy. The antibodies of this group were characterized by a higher affinity (12.7 × 109 M−1) and a lower capacity (0.9 nmol/liter plasma) than the group with antibodies. This group had received hGH with less than 5% aggregated hGH.

The third group did not develop significant [125I]hGH binding in the plasma despite prolonged therapy with multiple hGH preparations.

Several patients have been treated solely with recent hGH preparations from the National Pituitary Agency which contain less than 10% aggregated hGH compared to earlier preparations containing more than 20%. The incidence (44%) of significant [125I]hGH binding by these patients' plasmas was similar to that of patients receiving hGH with aggregated hGH; however, hGH binding by the plasma of most of these patients was characteristic of that of patients with transient antibodies.

We conclude that 1) the development of antibodies to hGH during therapy is dependent on individual susceptibility and the presence of aggregated hGH in the hGH preparation, 2) the antibody response is more likely to be transient if the content of aggregated hGH is low, and 3) the eventual incidence of significant hGH binding in plasma of patients who receive hGH prepared by Raben's method without aggregated hGH will be the same as that observed in patients receiving hGH prepared by other methods.

-S

If you research this more it has to do with this... By 1985, pituitary GH was in use for nearly 30 years in the United States and Canada, either for research purpose or therapeutically. In 1985, US Food and Drug Administration (US FDA) received reports of four young adults in the United States with the fatal, slow viral (prion-mediated) Creuzfeldt Jacob Disease (CJD), who had been treated with GH from the NPA in the 1960s. VARIOUS methods have been used for the purification of human growth hormone (HGH). The method described by Roos et al.1 uses especially mild conditions with extraction of homogenized frozen pituitary glands at pH 6.2,

You cant use those studies you posted since its for HGH that is no longer produced anymore. The HGH that is produced now has way less incidences of antibodies but again in 10-20% of some people they will be the unlucky ones.

 

[musclemoose]

Study #1

According to a recent report “Development of antibodies against growth hormone (GH) during rhGH therapy in a girl with idiopathic GH deficiency: a case report.” Studied an 11 year old Italian girl who was suffering from a growth hormone deficiency, which was treated. However, the girl developed antibodies and the treatment stopped working resulting in stunted grown. You can find the entire publication at http://www.ncbi.nlm.nih.gov/pubmed/23612536. The point here is that even with medical grade HGH like Saizen, Protropin and Humatrope there is a risk of developing antibodies to HGH.

Study #2

HGH in two patients reported by Trafford et al or in three patients reported by Roth et al. The growth-promoting effect appeared to be neutralized in the three patients of Prader et a and in the patient described by Parker et al. The short-term metabolic effects of HGH were inhibited in two of Prader's patients as measured by nitrogen balance studies. These findings suggest that antigenicity of HGH preparations in man may limit their therapeutic usefulness.

We have observed the development of antibodies to HGH in one of three patients receiving long-term therapy with Li HGH. This patient failed to show a growth response to HGH therapy. Immunological and biological studies of this anti-HGH

Study #3

Adherence to Growth Hormone Therapy: A Practical Approach. http://www.researchgate.net/publica...o_Growth_Hormone_Therapy_A_Practical_Approach

ABSTRACT Background: Early detection of suspected poor adherence to growth hormone (GH) therapy is crucial to achieve normal final height in GH-deficient (GHD) patients. Patients: 106 children (73 M, 33 F) with a median age of 10.47 ± 3.48 years (mean ± standard deviation score (SDS)) exhibited short stature (-1.76 ± 0.64 SDS) and a delayed bone age (8.68 ± 3.42 years). These patients admitted incomplete adherence to GH injections and clinical and anthropometric measurements revealed their poor response to therapy. © 2014 S. Karger AG, Basel.

The study went on to conclude that antibodies to the HGH occurred and as a result, those children being administered HGH injections would have been monitored more closely.

Study #4

According to Saizen, as with all protein pharmaceuticals, a small percentage of patients may develop antibodies to the protein. Anti-growth hormone (GH) antibody capacities below 2 mg/L have not been associated with growth attenuation. In some cases when binding capacity exceeds 2 mg/L, growth attenuation has been described.

 

[musclemoose]

https://www.ncbi.nlm.nih.gov/pubmed/15000864

Forty-seven children were treated for up to 6 months with recombinant human growth hormone (rhGH-Novo), 0.1 IU/Kg body weight, subcutaneously, three times weekly. The magnitude of growth response was similar to those expected from clinical experience with pituitary growth hormone. We examined sera for specific antibodies against rhGH by ELISA methods. Four patients developed serum antibodies against growth hormone.

 

[homonunculus]

If you research this more it has to do with this... By 1985, pituitary GH was in use for nearly 30 years in the United States and Canada, either for research purpose or therapeutically. In 1985, US Food and Drug Administration (US FDA) received reports of four young adults in the United States with the fatal, slow viral (prion-mediated) Creuzfeldt Jacob Disease (CJD), who had been treated with GH from the NPA in the 1960s. VARIOUS methods have been used for the purification of human growth hormone (HGH). The method described by Roos et al.1 uses especially mild conditions with extraction of homogenized frozen pituitary glands at pH 6.2,

You cant use those studies you posted since its for HGH that is no longer produced anymore. The HGH that is produced now has way less incidences of antibodies but again in 10-20% of some people they will be the unlucky ones.

Musclemoose,

(Thanks for the response, BTW...)

Yeah, I just threw those out there. I think there is some value in those studies in that they suggest the effect of GH aggregation on the development of antibodies, i.e., they can give us some idea of how the extent of this aggregation in (oxidized) non pharm-grade GH could lead to antibody formation.

(1. Mulinacci F, Poirier E, Capelle MA, Gurny R, Arvinte T. Influence of methionine oxidation on the aggregation of recombinant human growth hormone. European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik eV. 2013;85(1):42-52.)

It's interesting that the same group found that oxidation doesn't change the conformation of the GH, which would mean oxidized GH would still have powerful biological actions, but also tend to cause antibody formation.

1. Mulinacci F, Bell SE, Capelle MA, Gurny R, Arvinte T. Oxidized recombinant human growth hormone that maintains conformational integrity. J Pharm Sci. 2011;100(1):110-122.

---------------------

Also, the presence of anti-bodies 2-5 years after GH use was worthy of note. It's possible of course that that duration of antibody production was specific to the use of these forms of GH.

-------------------

So, yes, I agree that those studies aren't representative of the incidence of GH antibody formation when using pharm / research grade GH (in children).

On the other hand ... many folks here aren't using charm-grade GH, which may fall prey to production issues such as oxidation and aggregation.

I wouldn't say we "can use those studies" to inform us, as long as we're cognizant of what they are telling us.

-S

P.S. Thanks for the well thought out response. I just blasted those last night before bed. TBH, very often in threads like this my posts don't get a response, so I was admittedly being a bit lazy in just dropping in those studies. I'm glad you took a look.

 

[saffire]

so that means when you build antibodies then no break will help ( if 2-5 years after GH its still there) , otherwise all people that doesn't build antibodies could use hgh without breaks ?

 

[homonunculus]

so that means when you build antibodies then no break will help ( if 2-5 years after GH its still there) , otherwise all people that doesn't build antibodies could use hgh without breaks ?

This not a black or white situation in the least, IMO.

Those antibodies, if formed, might be specific to the antigen that brought about their formation (aggregated GH) and not bind be (as) immunoreactive to the GH from another source. Not all antibodies are created the same, which is this nature of antibodies.

Someone might start forming antibodies who didn't previously, just like allergies can come and good, as well as food intolerances.

To what extent the antibodies interfere with GH's binding to it's receptor (as they would effectively be comping with the GHR and endogenous GH binding proteins in the blood) could also vary.

-S

 

[musclemoose]

Musclemoose,

(Thanks for the response, BTW...)

Yeah, I just threw those out there. I think there is some value in those studies in that they suggest the effect of GH aggregation on the development of antibodies, i.e., they can give us some idea of how the extent of this aggregation in (oxidized) non pharm-grade GH could lead to antibody formation.

(1. Mulinacci F, Poirier E, Capelle MA, Gurny R, Arvinte T. Influence of methionine oxidation on the aggregation of recombinant human growth hormone. European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik eV. 2013;85(1):42-52.)

It's interesting that the same group found that oxidation doesn't change the conformation of the GH, which would mean oxidized GH would still have powerful biological actions, but also tend to cause antibody formation.

1. Mulinacci F, Bell SE, Capelle MA, Gurny R, Arvinte T. Oxidized recombinant human growth hormone that maintains conformational integrity. J Pharm Sci. 2011;100(1):110-122.

---------------------

Also, the presence of anti-bodies 2-5 years after GH use was worthy of note. It's possible of course that that duration of antibody production was specific to the use of these forms of GH.

-------------------

So, yes, I agree that those studies aren't representative of the incidence of GH antibody formation when using pharm / research grade GH (in children).

On the other hand ... many folks here aren't using charm-grade GH, which may fall prey to production issues such as oxidation and aggregation.

I wouldn't say we "can use those studies" to inform us, as long as we're cognizant of what they are telling us.

-S

P.S. Thanks for the well thought out response. I just blasted those last night before bed. TBH, very often in threads like this my posts don't get a response, so I was admittedly being a bit lazy in just dropping in those studies. I'm glad you took a look.

What i really want to know, since its clear you can develop antibodies, is if you are one of the unlucky ones does that mean when you discontinue HGH injections that your body wont ever produce HGH ever again. Does anyone know anything about what happens after you've developed the antibodies? That's a study id like to see cause that's even more concerning to me.

 

[nickels]

What i really want to know, since its clear you can develop antibodies, is if you are one of the unlucky ones does that mean when you discontinue HGH injections that your body wont ever produce HGH ever again. Does anyone know anything about what happens after you've developed the antibodies? That's a study id like to see cause that's even more concerning to me.

And also related to your thought, would it then not be more effective to instead use mk-677?