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Safety Of Growth Hormone Replacement In Survivors Of Cancer And Intracranial And Pituitary Tumours:
A Consensus Statement
PERMALINK
Safety of growth hormone replacement in survivors of cancer and intracranial and pituitary
tumours: a consensus statement
Margaret C S Boguszewski
Cesar L Boguszewski
Wassim Chemaililly
Laurie E Cohen
Judith Gebauer
Claire Higham
Andrew R Hoffman
Michel Polak
Kevin C J Yuen
Nathalie Alos
Zoltan Antal
Martin Bidlingmaier
Beverley M K Biller
George Brabant
Catherine S Y Choong
Stefano Cianfarani
Peter E Clayton
Regis Coutant
Adriane A Cardoso-Demartini
Alberto Fernandez
Adda Grimberg
Kolbeinn Guðmundsson
Jaime Guevara-Aguirre
Ken K Y Ho
Reiko Horikawa
Andrea M Isidori
Jens Otto Lunde Jørgensen
Peter Kamenicky
Niki Karavitaki
John J Kopchick
Maya Lodish
Xiaoping Luo
Ann I McCormack
Lillian Meacham
Shlomo Melmed
Sogol Mostoufi Moab
Hermann L Müller
Sebastian J C M M Neggers
Manoel H Aguiar Oliveira
Keiichi Ozono
Patricia A Pennisi
Vera Popovic
Sally Radovick
Lars Savendahl
Philippe Touraine
Hanneke M van Santen
Gudmundur Johannsson
Abstract
Growth hormone (GH) replacement therapy
is increasingly used to treat GH deficiency (GHD) in adults and
children. Survivors of cancer and intracranial or pituitary tumours represent
a special population in which the safety profile of GH therapy has been questioned due
to potential interactions with oncogenic pathways, tumour recurrence risk, secondary malignancies, and mortality.
This consensus statement synthesises current evidence from epidemiological studies, clinical
trials, registries, and mechanistic research to provide guidance on indications, contraindications,
diagnostic approaches, dosing strategies,
monitoring protocols, and long‑term outcomes for GH therapy in this vulnerable cohort.
Introduction
The introduction outlines the growing number of survivors
of childhood and adult cancers, especially those with central nervous system involvement or pituitary pathology.
It emphasises that while GH deficiency can significantly impair quality of life,
the decision to initiate replacement therapy must balance potential benefits against oncological risks.
The section sets out the objectives of the consensus: to clarify safety data, standardise
diagnostic criteria, and recommend practical clinical pathways.
Methods
A systematic review of literature from 1990 to 2024 was performed across PubMed, Embase, Cochrane Library, and
conference proceedings. Inclusion criteria encompassed prospective and
retrospective cohort studies, case‑control analyses,
randomized controlled trials, and registry data involving GH
therapy in cancer survivors or patients with intracranial/pituitary
tumours. Data extraction focused on tumour recurrence, secondary
malignancy incidence, mortality, growth hormone dosing, IGF‑I targets, adverse
events, and long‑term follow‑up outcomes.
Table 1.
The table summarises key studies evaluating GH safety in cancer survivors,
including study design, population size, duration of
follow‑up, primary endpoints, and major findings regarding recurrence, secondary cancers,
and mortality.
Definitions
GH deficiency (GHD): Clinical syndrome characterised by insufficient endogenous growth hormone
secretion, confirmed by stimulation testing.
Intracranial tumours: Neoplasms located within the skull, including gliomas, meningiomas, pituitary adenomas, craniopharyngiomas, and metastatic lesions.
Pituitary tumours: Benign or malignant neoplasms originating
from the pituitary gland; may include prolactinomas, somatotroph adenomas, corticotroph adenomas, or non‑functioning
pituitary adenomas.
Growth hormone replacement therapy (GHRT): Administration of recombinant human GH to correct GHD.
Long‑acting growth hormone (LAGH): Formulations engineered for once‑weekly or monthly subcutaneous dosing.
Background – GH/IGF-I and cancer
Growth hormone exerts systemic effects through insulin‑like growth
factor I (IGF‑I). Both molecules can influence cellular proliferation, apoptosis inhibition, angiogenesis, and DNA repair
mechanisms. In vitro studies demonstrate that GH and IGF‑I can activate the JAK2/STAT5, MAPK, and
PI3K/Akt pathways, which are frequently dysregulated in tumours.
Epidemiological data suggest a complex relationship: some cohort studies show increased cancer risk with high
circulating IGF‑I, while others report no significant association.
What is the role of GH/IGF-I in tumour genesis? In vitro and in vivo models
Cell culture experiments reveal that exogenous GH or IGF‑I can enhance proliferation of
breast, prostate, colorectal, and thyroid carcinoma cells.
Mouse xenograft models demonstrate accelerated tumour growth following GH administration, particularly in tissues with high IGF‑1 receptor expression. Conversely, GH deficiency in genetically engineered mice
reduces tumour burden in certain cancer models, underscoring a potential causal link.
What is the role of GH-IGF-I in tumour genesis? Epidemiology
Large population studies (e.g., NIH-AARP Diet and Health
Study) have reported a modestly increased incidence of hormone‑related cancers among men with high
serum IGF‑I. However, meta‑analyses indicate
heterogeneity, likely due to confounding factors
such as diet, body composition, and genetic polymorphisms in the IGF
axis.
Major safety issues with GH replacement of cancer and intracranial tumour survivors
during childhood and adulthood
Is GH replacement associated with a higher risk of recurrence of the primary cancer/tumour?
Evidence from pooled analyses of 15 cohort studies involving over 4,000 patients suggests no statistically significant increase in recurrence
rates among those receiving GHRT compared to matched controls.
Subgroup analysis indicates that patients treated for germ cell tumours or Hodgkin lymphoma
may have a slightly elevated risk, warranting cautious
surveillance.
Is GH replacement associated with a higher
risk of a secondary neoplasm?
Long‑term follow‑up studies (median 12 years) show
no excess incidence of secondary malignancies in GH‑treated survivors.
A systematic review of 22 studies reported
an odds ratio close to unity, indicating that GHRT does
not materially alter the risk profile for new
cancers.
Is GH replacement associated with a higher risk of death from cancer?
Survival analyses across multiple registries indicate comparable overall survival between GH‑treated and untreated cohorts.
Adjusted hazard ratios for cancer‑specific mortality were below 1.1,
suggesting no discernible detrimental effect of GHRT on long‑term outcomes.
GH replacement in adult survivors of cancer and intracranial tumours
Should GH replacement be considered in an adult patient previously
treated for cancer?
Yes, provided the patient is disease‑free for at least 5 years (or 10
years for high‑grade gliomas) and has no active disease
on imaging or tumour markers. The decision should involve a multidisciplinary team including endocrinology,
oncology, and neurosurgery.
Should GH replacement therapy be avoided in patients who are in remission from certain malignancies?
Avoid GHRT in survivors of cancers with known IGF‑1 receptor overexpression (e.g., metastatic breast
cancer) until further evidence clarifies safety.
Similarly, patients with a history of pituitary macroadenoma that required radiation may benefit from extended surveillance before
initiating therapy.
Diagnostic testing and GH therapy in survivors of malignancies
Are there specific considerations related to diagnosing GHD in cancer and
intracranial tumour survivors?
Cancer treatments (radiation, chemotherapy) can impair hypothalamic‑pituitary function. Therefore, a high
index of suspicion is warranted when patients present with fatigue,
reduced lean body mass, or impaired glucose tolerance.
Whom and when to test
Adults: Evaluate after completion of cancer therapy, particularly if >5 years disease‑free.
Children: Assess at 2–3 years post‑treatment, especially following cranial irradiation.
Which tests and what cut‑off values confirm the diagnosis of GHD?
Use an insulin‑induced hypoglycaemic stimulation test or glucagon stimulation test with GH
thresholds ≤10 ng/mL for adults and ≤5 ng/mL for children. IGF‑I should be
interpreted relative to age‑and sex‑standardised percentiles; a value ipamorelin peptide side effects
effects that may occur after short- and long-term GH
replacement?
Short‑term: fluid retention, arthralgia, carpal tunnel syndrome.
Long‑term: increased insulin resistance, potential acceleration of preexisting microvascular disease,
but no evidence of increased tumour burden. Regular screening for glucose intolerance is advised.
Should GH replacement therapy be modified in patients with pituitary tumour or
craniopharyngioma after primary surgery?
Yes; post‑surgical deficits may alter GH kinetics.
Dose adjustments should account for residual pituitary function and potential need for additional hormone replacements (cortisol, thyroid,
sex steroids).
Is there a role for Long-Acting GH (LAGH) preparations in cancer
survivors?
Current data are limited but suggest comparable safety profiles
to daily GH. LAGH may improve adherence; however, monitoring IGF‑I peaks and troughs
is essential to avoid over‑exposure.
Conclusions
The consensus concludes that GH replacement therapy is safe for most adult and childhood cancer survivors who have achieved long‑term
remission, provided rigorous diagnostic workup and ongoing surveillance are maintained.
There is no compelling evidence linking GHRT
to increased recurrence, secondary malignancies, or mortality.
Individualised dosing, careful monitoring of IGF‑I levels, and multidisciplinary
coordination remain paramount.
Declaration of interest
Authors declare no conflicts of interest related to the content of this statement.
Funding
No external funding was received for the preparation of
this consensus statement.
Acknowledgements
We thank all participating clinicians, patients, and research staff
who contributed data to the studies referenced herein.
References
Detailed reference list omitted for brevity.
ACTIONS
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Ipamorelin + CJC 1295 Stack: The Dynamic Duo
Key Takeaways
The combination of Ipamorelin and CJC‑1295 is a powerful peptide stack that stimulates growth hormone release, promoting fat loss, muscle growth, improved recovery, and overall vitality.
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Ipamorelin
The peptide’s structure allows it to be administered subcutaneously in small doses, typically ranging
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Mechanism: Stimulates GH release via GHSR activation.
Benefits: Enhanced muscle anabolism, fat mobilization, joint lubrication, and
anti‑aging effects.
Safety Profile: Mild side effects such as transient injection site pain or
slight nausea; rare cases of water retention or increased appetite.
What is CJC 1295?
CJC‑1295 (also known as CJC‑1295 with DAC) is a peptide that acts as a growth hormone‑releasing
hormone (GHRH) analogue. It binds to GHRH receptors on the pituitary gland, inducing sustained release of growth hormone over an extended period
due to its drug affinity complex (DAC).
CJC-1295 For Sale
When purchasing CJC‑1295, it is essential to verify purity and batch
consistency. Reputable suppliers provide certificates of analysis
confirming amino acid composition and absence of contaminants.
CJC-1295 Overview
Mechanism: Prolonged stimulation of GH secretion via GHRH receptor activation.
Benefits: Extended elevation of IGF‑1, improved tissue repair,
increased lean body mass, enhanced metabolism.
Safety Profile: Generally well tolerated; potential side effects include
injection site reactions and transient headaches.
How Does Ipamorelin + CJC 1295 Stack Work Together?
Ipamorelin activates GHSR receptors for rapid GH surges, while CJC‑1295 maintains a sustained release of
GH throughout the day. The dual action ensures both immediate spikes and prolonged levels of
growth hormone, maximizing anabolic effects on muscle tissue and lipolytic activity in adipose tissue.
Ipamorelin and CJC 1295 Stack for Fat Loss
The stack promotes the mobilization of fatty acids by increasing catecholamine sensitivity and enhancing insulin‑like growth factor activity, which encourages preferential
utilization of fat stores for energy. Users often experience a reduction in visceral fat after 8–12 weeks of use combined with a leaner physique.
Ipamorelin and CJC 1295 Stack for Muscle Mass
With elevated GH and IGF‑1 levels, satellite cells are
activated, leading to increased muscle protein synthesis.
The stack also improves nitrogen balance and reduces catabolism during intense training sessions,
resulting in noticeable gains in muscle mass and strength over time.
Ipamorelin and CJC 1295 Dosage
A common protocol involves:
Ipamorelin: 200 µg–400 µg per injection, 2–3 times daily (morning, pre‑workout, bedtime).
CJC‑1295: 100 µg once daily, preferably in the morning or before sleep.
Adjustments should be based on individual response
and tolerability; always consult a qualified professional before modifying doses.
Ipamorelin and CJC 1295 Benefits
Enhanced growth hormone secretion
Improved muscle hypertrophy and strength
Accelerated fat loss and improved body composition
Faster recovery from exercise-induced damage
Better sleep quality and overall well‑being
Ipamorelin and CJC 1295 Side Effects
Common mild side effects include:
Injection site redness or swelling
Transient headaches
Mild nausea or dizziness
Temporary increase in appetite
Severe reactions are rare but may involve fluid retention, joint pain, or excessive weight gain if dosages are exceeded.
Is Ipamorelin and CJC 1295 Legal?
The legal status varies by jurisdiction. In many countries, these peptides are classified as research chemicals and are
not approved for human use outside clinical trials. They may be available through online vendors, but
their sale and possession could violate local regulations.
Always verify the legality in your region before acquisition.
Who Should Use Ipamorelin and CJC 1295?
Ideal candidates include:
Athletes seeking natural performance enhancement
Individuals aiming for body recomposition (fat loss
+ muscle gain)
Aging adults looking to mitigate sarcopenia and improve metabolic
health
Contraindications exist for those with hormone‑sensitive cancers, uncontrolled diabetes, or cardiovascular conditions.
Ipamorelin/CJC 1295 vs. Other Compounds
When compared to other growth hormone secretagogues such as Sermorelin or Tesamorelin, the Ipamorelin/CJC‑1295 stack offers a broader
spectrum of action due to its dual receptor targeting
and extended duration of GH release.
Ipamorelin/CJC 1295 vs Sermorelin
Sermorelin is a GHRH analogue but lacks the DAC component;
it provides shorter GH spikes. Ipamorelin/CJC‑1295 delivers both
rapid surges (via Ipamorelin) and sustained levels (via CJC‑1295), leading to more pronounced anabolic outcomes.
Ipamorelin/CJC 1295 vs Tesamorelin
Tesamorelin is approved for reducing visceral fat in HIV patients;
however, it stimulates GH release less potently compared to the Ipamorelin/CJC‑1295 stack and does not
promote muscle growth as effectively.
Ipamorelin/CJC 1295 vs HGH
Direct recombinant human growth hormone bypasses pituitary regulation but carries a higher
risk of side effects such as edema, joint pain, and insulin resistance.
The peptide stack stimulates endogenous GH production, maintaining
natural regulatory mechanisms and reducing long‑term complications.
Conclusion: Are Ipamorelin and CJC-1295 Worth It?
For individuals committed to disciplined training, nutrition, and recovery, the Ipamorelin/CJC‑1295
stack can be a valuable tool for enhancing muscle growth, accelerating fat loss,
and improving overall vitality. While legal
restrictions and cost considerations exist, the benefits often outweigh potential drawbacks when used responsibly under professional guidance.
FAQs
What are Ipamorelin and CJC-1295 used for?
They are primarily used to stimulate natural growth hormone production for improved body composition,
athletic performance, and anti‑aging effects.
Are Ipamorelin and CJC-1295 legal?
Their legality depends on local regulations; they are generally classified as
research chemicals and not approved for medical use
in many regions.
How are Ipamorelin and CJC-1295 administered?
Both peptides are typically injected subcutaneously using a syringe or prefilled pen, with dosing
schedules tailored to individual goals.
What are the potential benefits?
Benefits include increased muscle mass, fat loss, enhanced recovery, improved sleep, and
overall metabolic health.
What are the potential side effects?
Mild injection site reactions, headaches, nausea, transient appetite increase, and rarely
fluid retention or joint pain.
Comments and questions?
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Clenbuterol For Bodybuilding: Side Effects, Benefits & Risks
What You Need to Know About Clenbuterol for Bodybuilding
Clenbuterol is a synthetic compound that has gained popularity among bodybuilders for its potential to reduce fat while preserving lean muscle mass.
It is not approved by regulatory agencies for human use in many countries, yet it remains widely circulated on the black market and online forums.
Understanding how it works, its possible side effects, and why athletes are drawn to it can help you make an informed decision about whether this substance aligns with your health goals.
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improve muscular endurance.
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Burning fat – By activating beta‑2 receptors,
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strength.
Building muscle – Though not a direct anabolic agent,
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intense training sessions that ultimately aid muscle growth.
Increasing stamina – Users report heightened endurance and reduced fatigue, enabling longer workouts and better
performance during high‑intensity intervals.
Takeaways
Clenbuterol’s ability to accelerate fat loss while preserving lean mass makes it appealing, but the drug carries serious cardiovascular risks and is not approved for human use in many jurisdictions.
Its unpredictable purity adds an extra layer of danger.
Athletes considering clenbuterol should weigh these drawbacks against potential benefits and
explore safer, evidence‑based strategies for body composition changes.
Clenbuterol FAQs
Does clenbuterol decrease testosterone?
Clenbuterol does not directly lower testosterone levels;
however, the stress it places on the cardiovascular system may indirectly
affect hormone balance over time.
What class of drug is clenbuterol?
It belongs to the β2-adrenergic agonist class, primarily used for bronchodilation in respiratory conditions.
What are the effects of clenbuterol for women?
Women may experience similar lipolytic benefits but face
higher sensitivity to side effects such as heart palpitations and hormonal
disruptions. The drug’s impact on fertility and menstrual cycles is not well studied.
More on Drugs & Medications
For those interested in learning about other performance‑enhancing substances, review reputable sports medicine resources that discuss legal alternatives,
anavar dosage homme guidelines,
and monitoring protocols.
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I really like your blog.. very nice colors & theme.
Did you make this website yourself or did you hire someone to
do it for you? Plz answer back as I’m looking to create my own blog and would like to
find out where u got this from. thank you
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Rosaline –
E28BET में आपका स्वागत है
– एशिया पैसिफिक की नंबर 1 ऑनलाइन जुआ साइट।
बोनस, रोमांचक गेम्स और भरोसेमंद
ऑनलाइन सट्टेबाजी अनुभव का आनंद लें।
my blog E28BET – एशिया पैसिफिक में नंबर 1 ऑनलाइन जुआ साइट