master.on
New Member
Was that sermorelin prescribed by a doctor or just UGL/RC?
There's a big difference
MESO-Rx
Anabolic Steroids
My generic hgh vs sermoralin from my dr... which to choose!?
- Thread starter erick r
- Start date
There's a big difference
Your results and those of others speak for themselves; NEITHER!
If your going to run GH use Ph grade anything else (and I don't care what you have been told or heard) is a crap shoot.
If you're drinking ETOH AT ALL, certain LFTs will increase.
POST ONE non-rodent human study, I'd love to critique it.
It's shocking IMO how those who "can't afford" Ph GH are willing to use unproven methods as a substitute expecting similar "results".
The PROBLEM with essentially all secretagogues is what's called NEGATIVE FEEDBACK.
Thus when the pituitary is stimulated to produce GH by these substances SOMATOSTATIN is also released which INHIBITS GH secretion.
It should be no surprise then secretagogues are not used medically for growth retardation in CHILDREN. Primarily bc the GH levels acheived are simply not sufficient.
They maybe useful in ADULTS with GH deficiency or PERHAPS as a "leaning" agent.
In addition physicians are more apt to prescribe them, bc they KNOW or should, supra-physiologic GH levels are not possible AND bc "off label" prescribing of Sermor is NOT prohibited (or is less well defined) by federal law!
Thus when the pituitary is stimulated to produce GH by these substances SOMATOSTATIN is also released which INHIBITS GH secretion.
It should be no surprise then secretagogues are not used medically for growth retardation in CHILDREN. Primarily bc the GH levels acheived are simply not sufficient.
They maybe useful in ADULTS with GH deficiency or PERHAPS as a "leaning" agent.
In addition physicians are more apt to prescribe them, bc they KNOW or should, supra-physiologic GH levels are not possible AND bc "off label" prescribing of Sermor is NOT prohibited (or is less well defined) by federal law!
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A physician prescribing PEPs, that's a first IME, and is highly suspect someone has a vested interest in the products they are prescribing!
Yea I was perplexed too, i think it's because they can't sell HGH and everyone wants it so they sell it as an HGH alternative. Now that I found some pharm grade hgh I think I'll cut out the peptides.. thanks for your advice
What do you mean by "selling non-Gh
meds"?
Your doc is selling the products he's prescribing?
Physicians CAN prescribe any number of meds, based on the limits of their license, but DISPENSING (exclusive of samples) them in connection with a SALE is an entirely different ball game, as it creates a conflict of interest.
You know that's would be like asking an UGL if they sell only quality products, or does this med really enhance SKM anabolism?
Would anyone expect them to say NO, lol.
It seems ironic BB don't hold the UGL they are purchasing their PEDS from to the same standard as their DOC!
meds"?
Your doc is selling the products he's prescribing?
Physicians CAN prescribe any number of meds, based on the limits of their license, but DISPENSING (exclusive of samples) them in connection with a SALE is an entirely different ball game, as it creates a conflict of interest.
You know that's would be like asking an UGL if they sell only quality products, or does this med really enhance SKM anabolism?
Would anyone expect them to say NO, lol.
It seems ironic BB don't hold the UGL they are purchasing their PEDS from to the same standard as their DOC!
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Sustained Elevation of Pulsatile Growth Hormone (GH) Secretion and Insulin-Like Growth Factor I (IGF-I), IGF-Binding Protein-3 (IGFBP-3), and IGFBP-5 Concentrations during 30-Day Continuous Subcutaneous Infusion of GH-Releasing Peptide-2 in Older Men and Women,
Cyril Y. Bowers, Ramona Granda, Subburaman Mohan, Jonathan Kuipers, David Baylink, and Johannes D. Veldhuis, JCEM vol 89 issue 5
Abstract
We test the interlinked hypotheses that in healthy older adults: 1) iv injection of GH-releasing peptide-2 (GHRP-2) and GHRH synergizes more in aging women than men; 2) sc infusion of both GHRP-2 (1 μg/kg·h = 1) and GHRH (1, 3, or 10) for 24 h augments GH secretion more than either agonist alone; and 3) continuous sc delivery of GHRP-2 (1) for 30 d stimulates daily GH secretion and IGF-I, IGF-binding protein-3 (IGFBP-3), and IGFBP-5.
Acute two-peptide synergy was 3-fold greater in young (n = 16) than older volunteers (n = 17; P < 0.025) and was 2.3-fold higher in elderly women than men (P < 0.025). The 24-h infusion of GHRP-2 (1) combined with GHRH (3 or 10) in men and with GHRH (10) in women drove GH secretion more than GHRH alone (P ≤ 0.024). In the entire cohort (n = 11), GHRP-2/GHRH (1/10) stimulated GH secretion more than either GHRP-2 (1; P = 0.021) or GHRH (10; P = 0.012).
The 30-d delivery of GHRP-2 (1; n = 17 subjects): 1) stimulated pulsatile, rhythmic, and entropic GH secretion by more than 3-fold on d 1 and more than 1.8-fold on d 14 and 30 (each P < 0.001 vs. saline); 2) elevated IGF-I to a stable plateau on d 1, 14, and 30 (P < 0.025 vs. baseline); and 3) increased IGFBP-3 (P < 0.01) and IGFBP-5 (P < 0.025) on d 14 and/or 30.
Safety screening tests remained normal. In summary, in healthy elderly women and men: 1) acute synergy of GHRP-2 and GHRH is greater in the female; 2) 24-h combined GHRP-2 and GHRH drive is more effective than either agonist alone; and 3) 30-d stimulation with GHRP-2 sustains a physiologically activated somatotropic axis. We conclude that age, gender, stimulus duration, and secretagogue combination determine acute, intermediate, and extended responses of the somatotropic axis in the older adult.
GH-RELEASING PEPTIDES (GHRP) were synthesized more than 2 decades ago as derivatives of metenkephalin that stimulate GH secretion directly in vitro and more markedly in vivo (1, 2). The cognate G protein-coupled receptor and natural GHRP, ghrelin, were cloned in 1996 and 1999, respectively (3, 4). Clinical studies using peptidyl agonists (e.g. GHRP-6, GHRP-1, hexarelin, and GHRP-2), nonpeptidyl mimetics of GHRP, and native ghrelin establish that joint hypothalamo-pituitary actions mediate maximal stimulation of GH release by this class of secretagogues (5, 6, 7, 8, 9). From a mechanistic vantage, GHRP synergizes acutely with GHRH in humans and experimental animals (5, 9, 10, 11, 12, 13), releases hypothalamic GHRH into portal blood in the sheep (14, 15), and opposes certain central inhibitory effects of somatostatin in rodents (16, 17, 18). A functional role for the murine GHRP receptor-effector pathway was inferred recently by partial molecular silencing of the central nervous system ghrelin receptor; this intervention reduced GH and IGF-I concentrations and GH pulse height in the adult female, but not the male, animal (19).
Acute administration of a high dose of GHRP downregulates homologous responsiveness of the somatotropic axis in all mammalian species studied (20, 21, 22, 23, 24). However, limited indirect data suggest that continuous delivery of or repeated exposure to a low dose of GHRP can maintain elevated GH secretion and IGF-I concentrations for 12 h to 4 d (25, 26, 27, 28, 29, 30, 31). We hypothesized that constant exposure to a submaximal concentration of GHRP may mimic the physiological pattern of relatively stable systemic ghrelin concentrations (32, 33).
GH secretion and IGF-I concentrations decline significantly in healthy aging individuals. Postulated mechanisms include impaired stimulation by endogenous peptidyl secretagogues, such as GHRH and possibly ghrelin, and accentuated inhibition by hypothalamic somatostatin (34, 35, 36). We hypothesized that if relative hyposomatotropism in elderly adults arises at least in part from reduced peptidyl drive, then combined stimulation with GHRP-2 and GHRH acutely by bolus injection and over 24 h by continuous infusion should augment GH secretion more effectively than either agonist alone. In corollary, prolonged unvarying stimulation with a synthetic ghrelin analog that putatively synergizes with hypothalamic GHRH should amplify pulsatile GH secretion and elevate IGF-I concentrations. The present studies examine these interlinked postulates in healthy aging women and men.
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...
Discussion
This is the first study to demonstrate that in healthy older adults combined bolus iv injection of GHRP-2 and GHRH evokes 2.3-fold greater synergy in postmenopausal women than men of similar age, combined continuous sc infusion of GHRP-2 and GHRH for 24 h stimulates pulsatile and total daily GH secretion approximately 2.5-fold more effectively than either secretagogue alone, and constant sc delivery of a potent synthetic GHRP receptor agonist for 30 d amplifies (and sustains) pulsatile, total, 24-h rhythmic, and entropic (feedback-sensitive) modes of GH secretion and elevates concentrations of IGF-I, IGFBP-3, and IGFBP-5.
A key mechanistic insight of this investigation is that administration of GHRP-2 as an unvarying and submaximal stimulus will sustain physiological features of somatotropic axis activation for at least 1 month. In contrast,intermittent stimulation with a high dose of GHRP rapidly down-regulates GH secretion(see introduction). The present concept is adumbrated in short-term studies (0.5–4 d), wherein repeated or continuous submaximal GHRP administration appears to maintain elevated GH concentrations and drive pulsatile GH secretion (25, 26, 27, 28, 29, 62, 63, 64). The exact basis for the apparent resistance to down-regulation of secretagogue effects under uninterrupted and submaximal feedforward is not known. Laboratory data indicate that prolonged constant sc delivery of GHRP induces expression of the pituitary GH gene in the GHRH-depleted infantile rat (65). In addition,intragastric administration of a high dose of a nonpeptidyl mimetic of GHRP down-regulates GH and IGF-I production within 24 h, whereas daily stimulation with a minimally effective dose of the same agonist progressively increases pulsatile and entropic modes of GH secretion and IGF-I concentrations (26).
In short-term clinical studies in postmenopausal women, continuous iv infusion of GHRP-2 separately or combined with GHRH for 24 h amplifies pulsatile and total GH secretion by 30- to 120-fold and elevates fasting IGF-I concentrations (27, 28, 29). The present outcomes extend such inferences in older men and women by demonstrating thatunvarying sc infusion of GHRP-2 for 1 month augments pulsatile, total, 24-h rhythmic, and entropic measures of GH secretion and IGF-I, IGFBP-3, and IGFBP-5 concentrations. From a qualitative viewpoint, the foregoing specific ensemble of neuroendocrine and systemic responses is identical to that observed at the time of maximal linear growth in healthy pubertal girls and boys (66). From a quantitative vantage, continuous GHRP-2 administration for 2 and 4 wk increased the 24-h GH secretion rate in elderly adults to approximately 0.5 mg (assuming a 7% distribution volume). The latter value is approximately 50% of that attained in adolescents at peak growth velocity (66, 67, 68).
In earlier pilot studies we administered GHRP-2 and/or GHRH by bolus injection in doses ranging from 0.1–3 μg/kg, sc, and at frequencies varying from once every other day to twice daily for 1–2 wk in elderly volunteers (30, 33, 69, 70, 71). In these short-term protocols, a high dose of GHRP-2 blunted the subsequent effect of the same peptide as well as that of GHRH. On the other hand, twice (but not single) daily iv pulses of GHRH for 7 d amplified the effects of later bolus injection of either GHRP-2 or GHRH. Once daily iv pulses of GHRP-2 and GHRH together for 1 wk also maintained the responsiveness of the GH/IGF-I axis in healthy older individuals. The present analyses extend the last finding by demonstrating that continuous combined sc infusion of GHRP-2 (1 μg/kg·h) and GHRH (3 and 10 μg/kg·h in women and 10 μg/kg·h in men) for 24 h stimulates GH secretion and elevates IGF-I concentrations significantly more than either agonist alone.
The precise mechanisms that mediate the facilitative interaction between GHRP-2 and GHRH over 24 h are not established. However, GHRP impacts GHRH stimulation and somatostatin inhibition via several pathways in the experimental animal. Specifically, members of the GHRP secretagogue family stimulate pituitary GH secretion directly by 2- to 3-fold (2, 33, 72), oppose central nervous system and pituitary inhibition by somatostatin (2, 17, 73), elicit arcuate nucleus release of GHRH into portal blood (14, 15), synergize with GHRH in the hypothalamo-pituitary-intact individual (21), and induce pituitary GH gene expression during prolonged administration in vivo and possibly in vitro (65, 74). Other outcomes suggest possible modulation of synergy by currently unknown hypothalamo-pituitary factors (2, 5).
Interventional trials in children with idiopathic short stature indicate that once or repeated daily administration of a GHRP receptor agonist by intranasal, sc, or oral routes for 6 months can accelerate linear growth over the baseline rate (75, 76, 77, 78, 79). In these reports, fasting morning GH concentrations increased by 2- to 4-fold initially and then declined by about 50% to a plateau value that exceeded baseline by approximately 2-fold. In contradistinction, IGF-I concentrations rose promptly and remained equivalently elevated for at least 6 months of secretagogue delivery.We report comparable temporal dissociation between GH secretion and IGF-I concentrations during 30-d continuous GHRP-2 delivery in healthy elderly adults. The mechanistic basis for the time-dependent disparity in GH and IGF-I responses in children and adults is not known. Plausible (nonexclusive) postulates could include 1) the prominent immediate rise in mean GH concentrations, which may equal or exceed maximal stimulation of hepatic IGF-I synthesis; 2) the emergence of more effectual GH secretory patterns, which maintain systemic IGF-I production at lower GH output; 3) partial down-regulation of hypothalamo-pituitary responsiveness to unvarying GHRP drive; and/or 4) changes in concentrations of one or more IGFBPs that influence negative feedback by free and/or bound IGF-I (80, 81, 82).
Gender comparisons disclosed that acute bolus iv injection and 30-d continuous sc infusion of GHRP-2 stimulate about 2-fold greater GH secretion in hormonally replaced postmenopausal women than in elderly men. In other studies, untreated healthy pre- and postmenopausal women manifest higher amplitudes of GH concentration peaks and commensurately more pulsatile GH secretion than men of comparable age (83, 84, 85). Moreover, short-term supplementation of estradiol potentiates acute responses to synthetic GHRPs in prepubertal girls and postmenopausal women (46, 47, 86). An inferred molecular mechanism is the ability of estradiol to enhance transcriptional activity of the human GHRP receptor gene promoter in vitro (87). However, whether the latter mechanism operates in vivo or whether chronic vis-à-vis short-term estrogen replacement enhances hypothalamopituitary responsiveness to GHRP receptor agonists has not been elucidated.
The primary cause of aging-associated waning of GH and IGF-I production has not been clarified definitively (20, 21, 88). Current hypotheses include attenuation of stimulation by GHRH and possibly ghrelin and/or augmentation of inhibition by somatostatin (89). One clinical study is consistent with the idea that all three mechanisms apply, inasmuch as only combined injection of GHRH, GHRP, and l-arginine (assumed to withdraw somatostatin restraint) evoked equivalent GH release in healthy older and young adults (90). Significant two-peptide facilitation of acute and 24-h GH secretion in the current investigation would support (but not prove) the postulated diminution of GHRH and ghrelin drive, and reduced acute synergy would be consistent with excessive somatostatinergic restraint.
Constant sc delivery of GHRP-2 for 30 d increased fasting concentrations of IGF-I, IGFBP-3, and IGFBP-5, but not those of non-GH-dependent proteins, IGFBP-4 and IGF-II (91). In relation to other hormonal and metabolic markers, biochemical indexes of hepatorenal function remained normal. No clinically significant adverse events occurred. Fasting plasma glucose concentrations rose by 12% within the euglycemic range in postmenopausal women. In earlier studies, oral administration of the nonpeptidyl GHRP mimetic, MK0677, elevated glucose concentrations in elderly volunteers at 1 month of study (62). On the other hand, sc injection of hexarelin for 3 d or 4 months did not (92, 93).
Whereas synthetic GHRP and ghrelin inhibit insulin secretion acutely (11, 94), continuous delivery of GHRP-2 for 1 month in the current analysis did not alter fasting insulin concentrations. Ghrelin, GHRP, and nonpeptidyl analogs evoke ACTH and cortisol secretion acutely (95). However, administration of GHRP-2 for 1 month (present study); ipamorelin for 0.5, 1, or 2 months; and hexarelin for 3 d did not increase cortisol concentrations (62, 64, 92). In one study, sc injection of hexarelin twice daily for 4 months lowered 3-h mean morning serum (but not urinary free) cortisol concentrations (93). Prolonged GHRP-2 stimulation did not change leptin or adiponectin concentrations. Leptin concentrations may decline as fat mass decreases during prolonged GH treatment in adults with organic hyposomatotropism (96). Lastly, extended GHRP-2 infusion elevated PRL concentrations in women and men by 25%. Once daily administration of ipamorelin orally for 1 month increased PRL concentrations to a similar degree, but twice daily injection of hexarelin for 3 d had no effect (62, 92). The clinical import of the foregoing increments in glucose and PRL within the normal range is not defined.
The sustained elevation of IGF-I, GH, and GH-inducible IGFBPs during 1 month of GHRP stimulation in elderly adults mimics some somatotropic axis responses to shorter-term secretagogue infusions reported in patients with protracted critical illness (97, 98, 99). A gender difference in secretagogue effectiveness is also evident in the latter context. Like aging, critical illness is marked by impaired anabolism, reduced availability of trophic hormones, and, in women, relative androgen predominance (99).
In summary, the present investigation in healthy older adults demonstrates that 1) acute (bolus) iv injection of GHRH and GHRP-2 together is more synergistic in postmenopausal women than in men of comparable age; 2) short-term (24-h) constant combined sc infusion of GHRP-2 and GHRH stimulates GH secretion and elevates IGF-I concentrations more than either peptide alone; and 3) prolonged (1-month) continuous sc delivery of GHRP-2 drives pulsatile, total, 24-h rhythmic, and entropic (feedback-adaptive) GH secretion and increases IGF-I, IGFBP-3, and IGFBP-5 concentrations. Further investigations will be required to elucidate the mechanisms that transduce the evidently sustained hypothalamo-pituitary responsiveness to unabated feedforward by GHRP.
•study done on humans•
There's also reference to synergistic effects of ghrp & ghrh combined
Respectfully
Just now found your response, thanks big man, i appreciate your time.
Prescribed by a doc, thought i said that but maybe i was t clear. And it was a complete waste of time and money. 4 months on 2iu ed GH and the results are night and day.
Fine job I'll give them a look see but at first glance I noted some were conducted using a continuous infusion which is quite different than the brief several minute, "square peg" peak and trough levels achieved thru intermittent SubQ injections.
A related difference was noted in early MK677 infusion GH studies which were NOT reproducible with pulse dosing.
Regs
Jim
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OP where were your prescribed PEPs filled?
Actually the study is well done but its unfortunate somatostatin levels were not obtained to determine what effect, if any, the use of combined (GHRP and GHRH) therapy had on HTPA feedback mechanisms.
Nonetheless this study once again reveals the superiority of "continuous SQ infusion" secretagogue therapy over that which is practiced by essentially all BB, "bolus" SQ administration of PEPs.
In addition, the rise in IGF-1, from either single or combined treatment with GHRP and/or GHRH, reaching a peak of somewhere between 165-210ug/L is much less than impressive as such values are the NORM for many young males, yet NOT for PMP females which is why I suspect the latter were selected as study subjects.
Finally and I quote; …… "GHRP/GHRH SQ infusion therapy increased the 24 hour GH secretion rate to approximately 0.5mg/day, which is 50% of that attained in adolescents at peak growth velocity".
For these reasons should one elect to use GH secretagogues I would FIRST recommend they obtain a BASELINE IGF-1 level, combine a GHRH and GHRP PEP, and administer them at LEAST three times a day, AND AT THE VERY BEST anticipate those changes reported in the literature from the daily use of roughly 1.5IU of pharm grade rHGH!
Thanks MGH-74
Regs
JIM
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dr Jim, could you help me answer some questions. If I go see an endocrinologists claiming to be gh deficient, she will schedule to perform a growth hormone stimulating test right. how many times do they perform the test ?
for example, if the test doesn't raise my gh levels, will they schedule another test ? also, does heath insurance cover hgh therapy for people diagnosed with adult gh deficiency ?
Heck no they will tell you your NOT GH defecient and that NO TESTING is required.
CdnGuy
New Member
Bump
My baseline igf-1 was below normal. I've considered stopping generic hgh and follow up with my primary care doc which will refer me to a specialist (endo, I believe). .......just to see if I could get HGH prescribed....paying for it is still impractical as my prescription benefits suck.
But I already know getting a script is very difficult because unlike low testosterone, I can still function fine because I bet my low igf-1 and testosterone level are results of 10+ yrs of abusing opiate pain killers and more
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