Strung out on Ipamorelin, does it lower cortisol or worsen adrenal fatigue?

[Keepfit1]

I did a 5 day trial of Ipamorelin 100mcg before bed, at the end of 5 days I felt pretty wound up and a bit strung out as if my adrenals were having a hard time, after I stopt it it took about a week or two to settle down. I have hypogonadism and am on 15mg Hydrocortisone for Adrenal fatigue and 3.5 Grains ERFA thyroid and 10mg Pregnenolone, I am also on Testosterone . Dr Hertoghe reckons taking GH lowers cortisol and thats why some people like me dont feel good on GH, he reckons taking half GH and half IGF-1 is better as IGF-1 raises cortisol. I was planning to take Ipamorelin+CJC no DAC but thought best introduce one at a time to check if sensitive. Its possible I felt stung out for some other reason but wondered if anyone else knew about this. I read Ipamorelin doesnt raise cortisol but I wonder if it lowers it which might be why I felt strung out. I also wonder if Ipamorelin or other GH secreting peptides will raise GH or IGF-1 if I have hypogonadism?. All views welcome

 

[Deleted member 43589]

Abstract​

The development and pharmacology of a new potent growth hormone (GH) secretagogue, ipamorelin, is described. Ipamorelin is a pentapeptide (Aib-His-D-2-Nal-D-Phe-Lys-NH2), which displays high GH releasing potency and efficacy in vitro and in vivo. As an outcome of a major chemistry programme, ipamorelin was identified within a series of compounds lacking the central dipeptide Ala-Trp of growth hormone-releasing peptide (GHRP)-1. In vitro, ipamorelin released GH from primary rat pituitary cells with a potency and efficacy similar to GHRP-6 (ECs) = 1.3+/-0.4nmol/l and Emax = 85+/-5% vs 2.2+/-0.3nmol/l and 100%). A pharmacological profiling using GHRP and growth hormone-releasing hormone (GHRH) antagonists clearly demonstrated that ipamorelin, like GHRP-6, stimulates GH release via a GHRP-like receptor. In pentobarbital anaesthetised rats, ipamorelin released GH with a potency and efficacy comparable to GHRP-6 (ED50 = 80+/-42nmol/kg and Emax = 1545+/-250ng GH/ml vs 115+/-36nmol/kg and 1167+/-120ng GH/ml). In conscious swine, ipamorelin released GH with an ED50 = 2.3+/-0.03 nmol/kg and an Emax = 65+/-0.2 ng GH/ml plasma. Again, this was very similar to GHRP-6 (ED50 = 3.9+/-1.4 nmol/kg and Emax = 74+/-7ng GH/ml plasma). GHRP-2 displayed higher potency but lower efficacy (ED50 = 0.6 nmol/kg and Emax = 56+/-6 ng GH/ml plasma). The specificity for GH release was studied in swine. None of the GH secretagogues tested affected FSH, LH, PRL or TSH plasma levels. Administration of both GHRP-6 and GHRP-2 resulted in increased plasma levels of ACTH and cortisol. Very surprisingly, ipamorelin did not release ACTH or cortisol in levels significantly different from those observed following GHRH stimulation. This lack of effect on ACTH and cortisol plasma levels was evident even at doses more than 200-fold higher than the ED50 for GH release. In conclusion, ipamorelin is the first GHRP-receptor agonist with a selectivity for GH release similar to that displayed by GHRH. The specificity of ipamorelin makes this compound a very interesting candidate for future clinical development.

Ipamorelin, the first selective growth hormone secretagogue - PubMed

The development and pharmacology of a new potent growth hormone (GH) secretagogue, ipamorelin, is described. Ipamorelin is a pentapeptide (Aib-His-D-2-Nal-D-Phe-Lys-NH2), which displays high GH releasing potency and efficacy in vitro and in vivo. As an outcome of a major chemistry programme...

pubmed.ncbi.nlm.nih.gov

This is why Ipamorelin has been so popular, It can be used at much higher than normal saturation levels of peptides and not increase ACTH/cortisol. Adrenocorticotropic hormone (ACTH) is a hormone your pituitary gland releases that triggers your adrenal glands to release cortisol, the “stress hormone.” With GHR-6 and 2 is is very possible at dose larger than saturation levels (or 1mcg/kg) to increase cortisol and prolactin levels. So it is important to stick close to the saturation level as possible.

Here is something on the GH effect on cortisol

Abstract​

The adrenocortical responses to the daily administration of 10 mg human GH (hGH) for 4-6 days were compared in 12 patients with Cushing's disease, 2 patients with cortisol-secreting adrenal cortical adenoma, and 4 healthy subjects. The administration of hGH resulted in a significant mean percent decrease in urinary 17-hydroxycorticosteroids [17OHCS; 30 +/- 7.8 (SE)], cortisol secretion rate (32 +/- 5.5), plasma 17OHCS (31 +/- 5.1), and urinary 17-ketosteroids (46 +/- 6.0) in the patients with Cushing's disease. In contrast, it did not significantly decrease urinary or plasma 17OHCS or the cortisol secretion rate in the other groups of subjects similarly studied. Treatment with hGH did not impair the adrenocortical response to exogenous ACTH, but it decreased the response to metyrapone in all subjects tested. In one of the healthy subjects who had exhibited diminished response to metyrapone on hGH, measurement of plasma ACTH levels demonstrated a lower rise after the administration of the drug. Treatment with hGH did not alter the peripheral metabolism of cortisol, as measured by cortisol turnover rates. We conclude that hGH inhibits ACTH release and that this effect is maximally demonstrated in patients with increased hypothalamic-pituitary-adrenal function.

Suppression of cortisol secretion by human growth hormone - PubMed

The adrenocortical responses to the daily administration of 10 mg human GH (hGH) for 4-6 days were compared in 12 patients with Cushing's disease, 2 patients with cortisol-secreting adrenal cortical adenoma, and 4 healthy subjects. The administration of hGH resulted in a significant mean percent...

pubmed.ncbi.nlm.nih.gov

question - "I also wonder if Ipamorelin or other GH secreting peptides will raise GH or IGF-1" Absolutely it does both

 

[Keepfit1]

Abstract​

The development and pharmacology of a new potent growth hormone (GH) secretagogue, ipamorelin, is described. Ipamorelin is a pentapeptide (Aib-His-D-2-Nal-D-Phe-Lys-NH2), which displays high GH releasing potency and efficacy in vitro and in vivo. As an outcome of a major chemistry programme, ipamorelin was identified within a series of compounds lacking the central dipeptide Ala-Trp of growth hormone-releasing peptide (GHRP)-1. In vitro, ipamorelin released GH from primary rat pituitary cells with a potency and efficacy similar to GHRP-6 (ECs) = 1.3+/-0.4nmol/l and Emax = 85+/-5% vs 2.2+/-0.3nmol/l and 100%). A pharmacological profiling using GHRP and growth hormone-releasing hormone (GHRH) antagonists clearly demonstrated that ipamorelin, like GHRP-6, stimulates GH release via a GHRP-like receptor. In pentobarbital anaesthetised rats, ipamorelin released GH with a potency and efficacy comparable to GHRP-6 (ED50 = 80+/-42nmol/kg and Emax = 1545+/-250ng GH/ml vs 115+/-36nmol/kg and 1167+/-120ng GH/ml). In conscious swine, ipamorelin released GH with an ED50 = 2.3+/-0.03 nmol/kg and an Emax = 65+/-0.2 ng GH/ml plasma. Again, this was very similar to GHRP-6 (ED50 = 3.9+/-1.4 nmol/kg and Emax = 74+/-7ng GH/ml plasma). GHRP-2 displayed higher potency but lower efficacy (ED50 = 0.6 nmol/kg and Emax = 56+/-6 ng GH/ml plasma). The specificity for GH release was studied in swine. None of the GH secretagogues tested affected FSH, LH, PRL or TSH plasma levels. Administration of both GHRP-6 and GHRP-2 resulted in increased plasma levels of ACTH and cortisol. Very surprisingly, ipamorelin did not release ACTH or cortisol in levels significantly different from those observed following GHRH stimulation. This lack of effect on ACTH and cortisol plasma levels was evident even at doses more than 200-fold higher than the ED50 for GH release. In conclusion, ipamorelin is the first GHRP-receptor agonist with a selectivity for GH release similar to that displayed by GHRH. The specificity of ipamorelin makes this compound a very interesting candidate for future clinical development.

Ipamorelin, the first selective growth hormone secretagogue - PubMed

The development and pharmacology of a new potent growth hormone (GH) secretagogue, ipamorelin, is described. Ipamorelin is a pentapeptide (Aib-His-D-2-Nal-D-Phe-Lys-NH2), which displays high GH releasing potency and efficacy in vitro and in vivo. As an outcome of a major chemistry programme...

pubmed.ncbi.nlm.nih.gov

This is why Ipamorelin has been so popular, It can be used at much higher than normal saturation levels of peptides and not increase ACTH/cortisol. Adrenocorticotropic hormone (ACTH) is a hormone your pituitary gland releases that triggers your adrenal glands to release cortisol, the “stress hormone.” With GHR-6 and 2 is is very possible at dose larger than saturation levels (or 1mcg/kg) to increase cortisol and prolactin levels. So it is important to stick close to the saturation level as possible.

Here is something on the GH effect on cortisol

Abstract​

The adrenocortical responses to the daily administration of 10 mg human GH (hGH) for 4-6 days were compared in 12 patients with Cushing's disease, 2 patients with cortisol-secreting adrenal cortical adenoma, and 4 healthy subjects. The administration of hGH resulted in a significant mean percent decrease in urinary 17-hydroxycorticosteroids [17OHCS; 30 +/- 7.8 (SE)], cortisol secretion rate (32 +/- 5.5), plasma 17OHCS (31 +/- 5.1), and urinary 17-ketosteroids (46 +/- 6.0) in the patients with Cushing's disease. In contrast, it did not significantly decrease urinary or plasma 17OHCS or the cortisol secretion rate in the other groups of subjects similarly studied. Treatment with hGH did not impair the adrenocortical response to exogenous ACTH, but it decreased the response to metyrapone in all subjects tested. In one of the healthy subjects who had exhibited diminished response to metyrapone on hGH, measurement of plasma ACTH levels demonstrated a lower rise after the administration of the drug. Treatment with hGH did not alter the peripheral metabolism of cortisol, as measured by cortisol turnover rates. We conclude that hGH inhibits ACTH release and that this effect is maximally demonstrated in patients with increased hypothalamic-pituitary-adrenal function.

Suppression of cortisol secretion by human growth hormone - PubMed

The adrenocortical responses to the daily administration of 10 mg human GH (hGH) for 4-6 days were compared in 12 patients with Cushing's disease, 2 patients with cortisol-secreting adrenal cortical adenoma, and 4 healthy subjects. The administration of hGH resulted in a significant mean percent...

pubmed.ncbi.nlm.nih.gov

question - "I also wonder if Ipamorelin or other GH secreting peptides will raise GH or IGF-1" Absolutely it does both

thanks fo rthis info, so Ipamorelin doesnt raise cortisol but does it lower it like GH?

My question a the end was " I wonder if Ipamorelin or other GH secreting peptides will raise GH or IGF-1 IF I HAVE HYPOGONADISM, the if I have hypogonadism is the question, thanks

 

[Deleted member 43589]

No, Ipamorelin does not cause the release of ACTH so it will not raise cortisol. hGH actually inhibits ACTH. All GRFs and GHRPs will raise GH levels which in turn rase IGF-1 levels even if you have hypogonadism.

 

[Deleted member 43589]

Here is a good artile you might like to read:

Health Alert: Adrenal Crisis Causes Death in Some People Who Were Treated with hGH​

Health Alert: Adrenal Crisis Causes Death in Some People Who Were Treated with hGH - NIDDK

Health Alert: Adrenal Crisis Causes Death in Some People Who Were Treated with hGH

www.niddk.nih.gov

 

[Keepfit1]

Here is a good artile you might like to read:

Health Alert: Adrenal Crisis Causes Death in Some People Who Were Treated with hGH​

Health Alert: Adrenal Crisis Causes Death in Some People Who Were Treated with hGH - NIDDK

Health Alert: Adrenal Crisis Causes Death in Some People Who Were Treated with hGH

www.niddk.nih.gov

thanks for that info , its a bit strange though because the Headline implies HGH is the culprit but on reading it , its a bit misleading because it says HGH isnt the cause Ie
"Treatment with hGH does not cause adrenal crisis, but because a number of people lacking growth hormone also lack ACTH, adrenal crisis has occurred in some people who were treated with hGH." so its more correlation as opposed to causation

 

[Deleted member 43589]

Dr Hertoghe reckons taking GH lowers cortisol and thats why some people like me dont feel good on GH, he reckons taking half GH and half IGF-1 is better as IGF-1 raises cortisol.

Seems you doctor has a good plan, I would go with it.

 

[Keepfit1]

Seems you doctor has a good plan, I would go with it.

he's not my doc currently and although he knows a lot I am not totally convinced about taking IGf-1 bit yet, or a few other things he likes to do, some other docs I spoke with were not keen on the safety of taking Igf-1 and they were not the most conservative type docs