Where does this quote come from – it’s not in either article you cite in the post. In fact the cited article fails to support your point, and somewhat goes against it, as it provides evidence for the idea that GH signalling exerts most of its lifespan effect from exposure in late development, rather than maturity. This idea is well enough established by now that we can perhaps take it as proven, in mice at least. IIRC there is some mouse evidence that GH in adulthood has a nonzero, though much smaller effect. You don’t cite this, and skimming your sources down-thread all of them speak to the effects of early exposure.
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Here is a new study confirming that very high levels of growth hormone (as is the definition when a person is diagnosed with acromegaly), result in higher cancer risks.
But, the definition of acromegaly is IGF-1 levels that are 1.3 Times higher than the upper limit of normal IGF-1 levels. Hopefully people dosing HGH don’t reach this level (and even if they did, it would only be for a small fraction of their life, very late in life, so the impact on cancer risk should be significantly less.
From Medscape:
Patients With Acromegaly Have Higher Risk for Cancer
Patients with acromegaly had a higher risk for overall and several specific cancers than control individuals from the general population, with the increased risk being evident even 5 years before acromegaly diagnosis. The risk for cancer-related mortality was higher among those aged 40-60 years.
https://www.medscape.com/viewarticle/patients-acromegaly-have-higher-risk-cancer-2026a1000a65
Original Paper: https://academic.oup.com/jcem/advance-article/doi/10.1210/clinem/dgag137/8565929
Diagnosis of Acromegaly
The diagnosis of acromegaly hinges on the biochemical evaluation of two interdependent hormones: Growth Hormone (GH) and Insulin-like Growth Factor 1 (IGF-1). Because GH secretion is highly pulsatile, measuring its downstream effector, IGF-1, provides a stable, integrated assessment of disease activity.
The current clinical consensus for diagnosis relies on the following measures and thresholds:
1. Insulin-like Growth Factor 1 (IGF-1): The Primary Screen
IGF-1 is the most reliable initial screening biomarker for acromegaly. Because normal levels vary significantly throughout the human lifespan, results must always be age-adjusted.
- Diagnostic Range (Positive Screen): An IGF-1 level > 1.3 times the upper limit of normal (ULN) for the patient’s age and sex, combined with characteristic physical manifestations, is highly specific and effectively confirms the diagnosis.
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The current treatment consensus from the European Society of Endocrinology and the Endocrine Society is that growth hormone supplementation, which raises IGF-1 levels into the age- and sex-matched normal range, theoretically does not add additional cancer risk—this is based on studies in patients with growth hormone deficiency.
What confuses me the most is that all the expert consensus statements cite papers on acromegaly patients or patients with growth hormone receptor gene mutations causing GH resistance, and all the anti-aging papers widely cite various mouse lifespan studies. No one attacks those expert consensuses, yet when I do the same, I get a flood of criticism. Who wouldn’t want to cite perfect studies? The conditions simply don’t allow it. For example, I cite the fact that acromegaly patients have larger thymuses, but their lifespan is far shorter than normal—and someone comments, “But these are acromegaly patients, not normal people.”
My god, shouldn’t these people take a look at how current medical consensus assesses cancer risk—do they not cite clinical studies on exactly these kinds of “not normal” individuals? Such comments are completely meaningless. We always have to make conclusions in the absence of complete data. Medicine is all about constantly updating prior probabilities with new evidence to arrive at posterior probabilities that are closer to the truth. That’s why we need to study the effects of compounds on lifespan in in vitro cell models, nematodes, fruit flies, and mice, and then try to translate that to humans. I’m really fed up with those overly “correct” comments.
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A very clear example is this: if a compound has no studies in normal people, but studies in “abnormal” people conclude that it increases the risk of death or cancer, then when extrapolating to the general population, we should of course take such studies into account and would recommend against its use. We would not say, “These are abnormal people, so it’s safe for normal people.” It’s just like many drugs are recommended against for use in pregnant women based on animal or cell evidence—and at that point, people become very rational. But when I point out that growth hormone shortens the lifespan of certain mice, and that human studies have not shown a reduction in cancer risk, cancer mortality, or all-cause mortality—and may even show an increase—suddenly those same people become quite irrational.
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It improves heart failure in humans. There are roughly five studies showing this. Why are we just acting like there are zero studies showing benefits? Let’s be fair here.
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Currently, there is a lack of any prospective study using cardiovascular events as an endpoint to confirm the cardiovascular benefits of growth hormone therapy. Growth hormone is not mentioned in any expert guidelines on heart failure. In contrast, metformin reduces all-cause mortality and heart failure hospitalization rates in patients with heart failure. For example, such clear endpoint studies on metformin are cited in heart failure guidelines across countries. Brother, trust me—if you are injecting growth hormone to prevent heart failure, it is completely unnecessary. The quality of evidence supporting the use of growth hormone for treating or preventing heart failure is, at best, a D; if there were a Z, I would give it a Z.
Conversely, elevated fasting growth hormone levels are associated with an increased risk of coronary artery disease, stroke, congestive heart failure, and all-cause mortality (a reminder here that those injecting growth hormone for muscle gain should use it with caution). Moreover, there are clear large-scale studies showing that growth hormone injections increase cancer incidence and cancer mortality in certain populations.
You can scroll up to see the studies I have already shared. Furthermore, I have been quite fair—some people, afraid of being criticized for publicly sharing the downsides, can only send me private messages sharing their experiences with growth hormone. This only hinders the spread of information. Therefore, I am preparing to share another set of relevant studies without any personal information—the more people see them, the more valuable they become.
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https://academic.oup.com/jcem/article/110/4/e1252/7905809
Abstract
Context
Guideline-directed medical therapy of heart failure (HF) primarily targets neurohormonal activation. However, GH has emerged as a potential treatment for the multiple hormonal deficiency syndrome, which is associated with worse outcomes in HF.
Objective
This study evaluates the efficacy and safety of GH therapy in HF.
Data Sources
A systematic search was conducted in PubMed, Cochrane Library, and ClinicalTrials.gov, according to PRISMA guidelines
Study Selection
Randomized, placebo-controlled trials studying GH therapy in adult HF patients were included. Of the 1184 initially identified records, 17 studies (1.4%) met the inclusion criteria.
Data extraction
Two independent authors conducted the search, with any disagreements resolved by a third author. Study quality was assessed using predefined criteria, including randomization, blinding, and the presence of a placebo group.
Data Synthesis
A random-effects model was applied due to heterogeneity across studies. GH therapy significantly improved left ventricular ejection fraction (+3.34%; 95% CI, 1.09-5.59; P = .0037), peak oxygen consumption (+2.84 mL/kg/min; 95% CI, 1.32-4.36; P = .0002), and New York Heart Association class (−0.44; 95% CI, −0.08 to −0.81; P = .023). GH therapy also reduced the composite of death, worsening HF or ventricular tachycardia by 41% (RR = .59; 95% CI, 0.39-0.90; P = .013). Subgroup analyses indicated that patients with ischemic cardiomyopathy, baseline ejection fraction ≥30%, and longer treatment duration experienced greater benefits.
Conclusion
GH therapy demonstrated improvements in cardiac function, exercise capacity, and HF symptoms, along with a statistically significant trend toward improvements in hard endpoints. Event-driven trials are needed to validate these findings.
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If this is true and you guys are reading this, post it here. Why would there be a fear? That’s silly. No one is emotionally attached to anything.
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The mortality rate in the GH group was 5.1% (9/176), compared to 7.3% (13/178) in the placebo group. The risk ratio (RR) was 0.70, with a 95% confidence interval of 0.31 to 1.59, which crossed 1, indicating no statistical significance. The risk of worsening heart failure was indeed significantly reduced, but worsening heart failure was not a primary endpoint in any of the 17 original trials. That is, the definition and recording criteria for worsening heart failure varied across these small trials. The authors used the Q statistic and I² statistic and found significant heterogeneity for all outcomes across all trials. In plain English, the conclusions contradict each other.
Trust me, the overall quality grade is Z. That’s why no national heart failure guideline has ever mentioned growth hormone.
@DrFraser @KarlT Doctors can assess whether there are any issues with my interpretation of the paper.
The lack of more research has more to do with stigmatization of it and the fact we have other effective heart failure drugs now.
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Shouldn’t we refer to this study involving tens of thousands of people? Because your so-called growth hormone treatment for heart failure is completely unnecessary, just as you said—it doesn’t even rank among the therapies for heart failure.
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I think our disconnect is because my point is different than how you are interpreting it. I’m not saying people should rush to inject growth hormone for heart failure (although it would probably improve their condition). I am just demonstrating that there is a clear positive signal that growth hormone has health benefits as you can see from the heart failure studies.
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Among the offspring of centenarians, IGF-I bioactivity (p < 0.01), total IGF-I (p < 0.01), and the IGF-I/IGFBP-3 molar ratio (p < 0.001) were significantly lower than those in the control group of offspring whose parents both died prematurely.
It should be noted that growth hormone significantly elevates IGF-1.
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https://onlinelibrary.wiley.com/doi/10.1111/acel.12519
The median 24-hour total GH secretion in offspring of long-lived families was 172 mU/L, significantly lower than the 238 mU/L in the control group (P=0.04), and the basal GH secretion in offspring of long-lived families was 14.5 mU/L, significantly lower than the 26.9 mU/L in the control group (P=0.03).
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Pooling five independent experiments (covering rats/mice, males/females, and different starting ages), long-term low-dose GH treatment at a dose range comparable to that used in clinical trials for treating human GH deficiency and reversing age-related physiological decline had no effect on median or maximum lifespan.
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Pooling five independent experiments (covering rats/mice, males/females, and different starting ages), long-term low-dose GH treatment at a dose range comparable to that used in clinical trials for treating human GH deficiency and reversing age-related physiological decline had no effect on median or maximum lifespan.
Since you left out some details…
Studies were carried out to examine the effects of long-term recombinant human growth hormone (GH) therapy on longevity in rodents. In the first study, 150 18-month-old female F344 rats were divided into three groups of 50 rats per group: Group 1, solvent vehicle; Group 2, 10 microg GH/kg body weight three times per week; Group 3, 50 microg GH/kg body weight three times per week. GH and solvent vehicle therapies were started at 18 months of age and continued until all the animals died spontaneously. Serum insulin-like growth factor (IGF)-I was measured at 18 and 29 months of age and on 3-month-old rats. Serum IGF-I level decreased between 3 and 29 months of age. GH therapy reversed the decrease in a dose-dependent manner, with the 50 microg GH dose returning the serum IGF-I level to that of 3-month-old animals. However, statistical analysis revealed no significant effect of GH therapy on median life span, 10th percentile life span, or maximum life span. Similar observations on longevity were made on aged F344 male rats and on aged Balb/c mice, even when the dose of GH was increased to 1.0 mg/kg body weight two times per week. The main pathologic lesions in control animals were nephropathy, cardiomyopathy, leukemia, and testicular interstitial cell tumor; the prevalence of these lesions was not significantly altered by GH therapy.
…
We conclude that long-term low-dose GH therapy that includes doses in the range that is given to humans in clinical trials in GH deficiency and to revert age-related physiologic declines has no overt deleterious effects on longevity and pathology in aged rodents.
Also from the cohort study you posted at the beginning of the thread:
A cohort of 15 809 GH-treated patients were analyzed (mean follow-up of 5.3 years). AEs were reported in 51.2% of patients (treatment-related in 18.8%). Crude AE rate was higher in patients who were older, had GHD due to pituitary/hypothalamic tumors, or adult-onset GHD. AE rate analysis adjusted for age, gender, etiology, and follow-up time showed no correlation with GH dose(!)
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https://www.sciencedirect.com/science/article/abs/pii/004763749190026V?via%3Dihub
During a specific aging window of 17–21 months, twice-weekly low-dose growth hormone injections (30 µg/mouse) significantly reduced the natural mortality rate in this cohort of male Balb/c mice. During the first 13-week observation period, GH treatment reduced mortality by 54%. In the 4-week withdrawal period following the first phase (13 weeks), all remaining control mice died, whereas only one mouse died in the GH-treated group.
The Balb/c mice aged 17 to 21 months in this paper are roughly equivalent to humans around 55 to 65 years old.
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Correct my if I’m wrong but isn’t GH only helpful in HF if the patient is GH deficient?
I don’t think we know for sure if it’s helpful in non GH deficient people. Probably could make an anrgument either way. That’s assuming we are talking about physiologic doses and not supraphysiologic.
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some people, afraid of being criticized for publicly sharing the downsides, can only send me private messages sharing their experiences with growth hormone.
Cole,
I encourage you to ask these people to share their downside experiences with HGH. Actual experience speaks very loudly. I don’t recall anyone here ever being criticized for talking about their experiences. They should definitely not be afraid of that.
Thanks,
Jay
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