Note: Educational and scientific document. Does not constitute individualized medical or veterinary guidance. Consult a qualified healthcare professional.
EXOGENOUS GROWTH HORMONE: INHIBITION OF THE ENDOGENOUS AXIS BY NEGATIVE FEEDBACK AND RECOVERY STRATEGIES FOR THE GH/IGF-1 AXIS — A COMPARATIVE REVIEW BETWEEN HUMAN AND VETERINARY MEDICINE
A Literature Review on Suppression Mechanisms and Physiological Restoration Protocols
AUTHORS / AUTORES
- Dr. Cláudio Amichetti Júnior¹,² — Médico-veterinário Integrativo, com todas as credenciais (CRMV-SP, MAPA, CREA), especialista em Nutrição Felina e Canina, Medicina Canabinóide e Alimentação Natural, Petclube, com mais de 40 anos de experiência.
- Gabriel Amichetti³ — Médico-veterinário, especialização em Ortopedia e Cirurgia de Pequenos Animais, Clínica 3RD.
EXOGENOUS GROWTH HORMONE: INHIBITION OF THE ENDOGENOUS AXIS BY NEGATIVE FEEDBACK AND RECOVERY STRATEGIES FOR THE GH/IGF-1 AXIS — A COMPARATIVE REVIEW BETWEEN HUMAN AND VETERINARY MEDICINE
Academic review work presented as a requirement for updating in Endocrinology and Human and Veterinary Performance.
SAO PAULO BRASIL 2026
ABSTRACT
This article reviews the physiological mechanisms by which exogenous growth hormone (GH) administration promotes the inhibition of endogenous production through negative feedback systems. Scientific literature demonstrates that elevated circulating levels of GH and, consequently, insulin-like growth factor 1 (IGF-1), activate inhibitory pathways in the hypothalamus and anterior pituitary. The central mechanism involves increased somatostatin (SRIF) release and reduced GH-releasing hormone (GHRH). Experimental studies show a marked suppression in the amplitude of spontaneous GH pulses following exogenous administration, although this effect demonstrates reversibility after stimulus cessation. Additionally, the review addresses veterinary clinical applications in species such as dogs, cats, and horses, highlighting physiological similarities and therapeutic particularities in the management of hyposomatotropism and within the context of equestrian sports. GH/IGF-1 axis recovery strategies are based on optimizing physiological factors such as deep sleep and high-intensity exercise, in addition to the potential use of GHRH secretagogues to stimulate the pituitary function. It is concluded that while suppression is a robust biological phenomenon, clinical recovery lacks standardized protocols in healthy humans and animals, requiring rigorous laboratory monitoring and therapeutic individualization.
Keywords: Growth Hormone; Negative Feedback; Somatostatin; IGF-1; GH/IGF-1 Axis; Veterinary Medicine; Secretagogues.
TABLE OF CONTENTS
1 INTRODUCTION 5 2 OBJECTIVES 7 3 METHODOLOGY 8 4 THEORETICAL FRAMEWORK 9 4.1 PHYSIOLOGY OF THE GH/IGF-1 AXIS 9 4.2 NEGATIVE FEEDBACK MECHANISM 11 4.3 EVIDENCE ON GH USE IN HEALTHY ADULTS............................... 13 4.4 ADVERSE EVENTS OF GH USE 14 4.5 VETERINARY CLINICAL APPLICATION OF GH 16 5 DISCUSSION 18 6 FINAL CONSIDERATIONS 21 REFERENCES 23
1 INTRODUCTION
Growth hormone (GH), or somatotropin, is a globular protein of
191 amino acids191 amino acids
produced by the somatotropic cells of the anterior pituitary. The historical trajectory of GH in medicine is marked by remarkable scientific advances and profound ethical challenges. The discovery of its clinical efficacy dates back to 1958, when endocrinologist Maurice Raben first used GH extracted from human cadaver pituitaries to treat a child with dwarfism. For nearly three decades, this was the only available source, which severely limited access to treatment. However, in 1985, the use of cadaver-derived GH was abruptly banned in several countries after the discovery that the biological material was contaminated by prions, causing Creutzfeldt-Jakob Disease in hundreds of patients. This catastrophic event accelerated the development of recombinant DNA technology, culminating in the launch of rhGH(recombinant human growth hormone) between 1985 and 1987, allowing for large-scale, safe, and biological contaminant-free production.
Physiologically, the GH/IGF-1 axis plays a central and ubiquitous role in mammalian metabolism. GH exerts both direct and indirect effects; direct effects include the stimulation of lipolysis in adipocytes and the modulation of insulin resistance, while indirect effects are mediated by insulin-like growth factor 1 (IGF-1), synthesized mostly in the liver under GH stimulation. IGF-1 is primarily responsible for anabolic actions, promoting protein synthesis, longitudinal bone growth, and cellular proliferation in various tissues. This system is finely regulated to maintain energetic and structural homeostasis, responding to stimuli such as hypoglycemia, physical stress, fasting, and, crucially, the circadian cycle, with secretion peaks concentrated during deep sleep phases.
Despite its precise clinical indications for treating severe hormonal deficiencies, GH has become one of the most coveted agents in the ergogenic and anti-aging landscape. In humans, the quest for the "fountain of youth" or aesthetic and athletic enhancement has driven the use of supraphysiological doses by healthy individuals. A similar phenomenon is observed in Veterinary Medicine, where somatotropin is explored both for treating growth disorders in companion animals and for increasing productivity in livestock or performance in elite equines. This indiscriminate use, however, often ignores the complexity of endocrine regulation systems, exposing the organism to significant metabolic and structural risks resulting from the deregulation of the natural axis.
The central issue motivating this review is the negative feedback phenomenon. The organism operates under a principle of economy and balance; when elevated levels of GH or IGF-1 are detected in circulation, the hypothalamus and pituitary respond by reducing endogenous production to avoid hormonal toxicity. This inhibition, while a defense mechanism, can lead to functional atrophy of somatotropic cells and dependence on exogenous sources. The clinical relevance of this suppression is critical: the abrupt cessation of exogenous GH use can leave the individual (or animal) in a state of temporary hyposomatotropism, with impairments to body composition, lipid metabolism, and general vitality until the axis is restored.
Therefore, a comparative review between human and veterinary medicine is justified. Although species-specific particularities exist, the architecture of the somatotropic axis is highly conserved among mammals. Understanding how negative feedback operates in different biological models allows for a more holistic view of endocrinology. By analyzing scientific evidence from both areas, this work seeks to provide support for the safe management of the GH/IGF-1 axis, discussing recovery strategies based on physiology and contemporary clinical evidence, under the aegis of the One Healthconcept.
2 OBJECTIVES
The general objective of this work is to analyze, in a profound and systematic way, the impact of exogenous GHadministration on endogenous hormonal production, focusing on inhibition mechanisms and the possibilities of physiological restoration. To achieve this purpose, the study is based on a comparative perspective between human and veterinary physiology, seeking to integrate knowledge from both fields.
As specific objectives, this review proposes to:
- Describe in detail the short-loop and long-loop negative feedback mechanisms that regulate the GH/IGF-1 axis, elucidating the role of hypothalamic and peripheral hormones;
- Compare the biological effects and safety profiles of exogenous GH relative to GH secretagogues, evaluating the impact of each on endogenous pulsatility;
- Identify and categorize the main adverse events associated with the supraphysiological use of GH, with emphasis on metabolic, cardiovascular, and osteoarticular risks;
- Analyze the legitimate clinical applications and risks of GH use in Veterinary Medicine, addressing everything from the treatment of pituitary dwarfism to the ethical implications in equestrian sports;
- Propose and discuss therapeutic and lifestyle strategies based on scientific literature for the recovery of somatotropic axis functionality after periods of suppression.
3 METHODOLOGY
This research is configured as a qualitative, descriptive, and exploratory bibliographic review, adopting an integrative approach to synthesize current knowledge on the somatotropic axis. The data collection process was structured to ensure scientific robustness, using high-impact databases, including PubMed/MEDLINE, ScienceDirect, Google Scholar, Scielo, and specialized repositories in veterinary medicine and comparative endocrinology.
The descriptors used in the search were selected based on MeSH (Medical Subject Headings) terms and included: "Growth Hormone", "Negative Feedback", "IGF-1 Axis", "Veterinary Endocrinology", "Somatostatin", "GHRH", and "GH Secretagogues". The search strategy combined these terms using Boolean operators (AND, OR) to refine the results. The period delimited for the selection of sources comprises publications between 1992 and 2026, allowing for the inclusion of classic experimental studies that defined feedback mechanisms, as well as the most recent evidence on new peptides and recombinant technologies.
The established inclusion criteria were: (a) original experimental research articles in humans or animal models; (b) systematic reviews and meta-analyses; (c) guidelines from endocrinology societies; and (d) case studies with proven clinical relevance. Articles without clear methodological foundation, unreferenced opinion pieces, and studies that did not directly address the feedback mechanism or axis recovery were excluded.
The methodological limitations of this review include the heterogeneity of GH administration protocols in the analyzed studies (varying in dose, frequency, and duration) and the scarcity of long-term randomized clinical trials in recreational GH users, which requires caution in extrapolating some results. However, the comparative analysis between species seeks to mitigate these gaps by identifying universal physiological patterns.
4 THEORETICAL FRAMEWORK
4.1 PHYSIOLOGY OF THE GH/IGF-1 AXIS
The secretion of GH does not occur continuously, but rather through a highly organized pulsatile and circadian pattern. In humans, most of the daily secretion occurs during deep sleep (stages 3 and 4 of NREM sleep), mediated by coordination between the hypothalamus and the pituitary. This orchestration depends on the dynamic balance between two main hypothalamic neuropeptides: GHRH (GH-Releasing Hormone), which stimulates the synthesis and release of GH by somatotropic cells, and somatostatin (SRIF), which exerts a potent and tonic inhibitory effect. Recently, ghrelin, a predominantly gastric hormone, was identified as an essential third regulator, acting through the GH secretagogue receptor (GHS-R) to potentiate pulsatile release.
Once secreted into the bloodstream, GH travels to the liver, where it binds to specific receptors to stimulate the production of IGF-1. Unlike GH, which has a short half-life (approximately
20 minutes20 minutes
), IGF-1 circulates bound to transport proteins, mainly IGFBP-3, which gives it a much longer half-life and more stable plasma levels throughout the day. IGF-1 acts as the peripheral effector for most of GH's growth actions, promoting chondrocyte proliferation in epiphyseal plates and muscle anabolism. Furthermore, IGFBPs (Insulin-like Growth Factor Binding Proteins) not only transport IGF-1 but also regulate its bioavailability and interaction with tissue receptors, adding an extra layer of complexity to axis regulation.
Throughout life, the somatotropic axis undergoes predictable changes. GH levels reach their zenith during puberty, coinciding with the growth spurt, and begin a progressive decline starting from the third decade of life, a phenomenon known as somatopause. This decline is associated with changes in body composition, such as increased visceral fat and reduced lean mass. In animals, similar patterns are observed, although with significant variations between species. Large breed dogs, for example, present IGF-1 profiles distinct from small breeds, which directly influences their longevity and predisposition to diseases. Equines, in turn, demonstrate a marked sensitivity of the axis to intense physical exercise, which acts as a potent physiological stimulus for GH secretion.
The introduction of exogenous GH into a functional physiological system drastically alters this balance. While secretagogues attempt to mimic natural pulsatility by stimulating the pituitary to release its own stock, recombinant GHprovides a constant hormonal load or supraphysiological peaks that the organism interprets as a signal to cease its own production, as detailed in Table 1.
Table 1 – Comparison between exogenous GH and secretagogues
| Characteristic | Exogenous GH (rhGH) | Secretagogues (GHRH/Ghrelin) |
|---|---|---|
| Mechanism | Direct supply of the hormone | Stimulation of endogenous production |
| Effect on Pituitary | Direct suppression/inhibition | Stimulation and cellular preservation |
| Indication | Severe GHD, catabolic states | Axis restoration, anti-aging |
| Cost | High | Moderate to High |
| Endogenous Suppression | High (Robust negative feedback) | Minimal (Maintains pulsatility) |
Source: Prepared by the author (2026).
4.2 NEGATIVE FEEDBACK MECHANISM
The negative feedback system of the somatotropic axis is one of the most robust homeostatic mechanisms in the human and animal body. It operates through two main loops: the short loop and the long loop. In the short loop, circulating GHitself exerts a direct inhibitory effect on the pituitary and hypothalamus. GH receptors located in hypothalamic neurons, when activated, stimulate the release of somatostatin, which in turn blocks GH secretion by somatotropic cells. This is a rapid response mechanism that prevents excessive oscillations in hormonal levels.
The long loop is primarily mediated by IGF-1. When IGF-1 levels increase in response to GH, it signals the central nervous system to reduce GHRH tone and increase somatostatin release. Additionally, IGF-1 exerts direct inhibition on the somatotropic cells of the anterior pituitary, reducing GH gene expression. This system ensures that once the desired peripheral effect (anabolism) is achieved, the central stimulus is mitigated. In contexts of exogenous use, this loop is kept permanently activated, leading to a state of silencing of the endogenous axis that can persist for variable periods after cessation of use.
Experimental evidence for these mechanisms is solid. The classic study by Lanzi and Tannenbaum (1992) used animal models to demonstrate the precision of this control. Upon administering doses of GH, they observed that the amplitude of spontaneous endogenous GH pulses dropped drastically from basal levels of approximately
208 ng/ml208 ng/ml
to a mere
46 ng/ml46 ng/ml
. This suppression occurred within a time window of about
4 hours4 hours
after administration, highlighting how quickly the organism detects and reacts to hormonal excess. Another relevant study, conducted by Rosenthal et al. (2008), used in vitro cell cultures to demonstrate that this inhibition occurs directly in the pituitary tissue, independent of hypothalamic mediation under certain conditions, reinforcing the multifaceted nature of the suppression.
The clinical implications of this suppression are profound. Chronic use of exogenous GH can result in pituitary "laziness," where the gland loses the ability to respond promptly to natural physiological stimuli. In humans, this translates into a hormonal "crash" period after the cycle, characterized by fatigue, muscle mass loss, and fat accumulation. In animals, especially in competition equines, axis suppression can compromise post-exercise recovery capacity and long-term metabolic health. Reversibility of this process is possible but depends on the integrity of somatotropic cells and the normalization of somatostatin levels, as summarized in Table 2.
Table 2 – Key studies on GH negative feedback
| Author/Year | Study Design | Main Finding | Reference |
|---|---|---|---|
| Lanzi & Tannenbaum (1992) | Animal Experimental | Drop in pulses from |
208 ng/ml208 ng/ml
46 ng/ml46 ng/ml
Source: Prepared by the author (2026).
4.3 EVIDENCE ON GH USE IN HEALTHY ADULTS
The use of GH by healthy adults, without a diagnosed hormonal deficiency, is a subject of intense debate. A comprehensive meta-analysis published in 2017 in ScienceDirect reviewed several controlled clinical trials and brought conclusions that challenge common sense regarding the hormone's ergogenic efficacy. The data indicate that while GHadministration results in a measurable increase in lean body mass, this gain does not necessarily translate into improved functional performance. Histological and metabolic analysis suggests that weight gain is mostly due to extracellular water retention and increased connective tissue volume, rather than actual hypertrophy of contractile muscle fibers (myofibrillar protein synthesis).
This finding contrasts sharply with the effects of GH in patients with severe GHD (Growth Hormone Deficiency). In these individuals, hormonal replacement promotes dramatic improvements in bone density, lipid profile, and exercise capacity, as it is restoring a physiological level that was absent. In healthy individuals, however, the system already operates at an optimal level; the addition of exogenous hormone exceeds the physiological ceiling, activating resistance mechanisms and side effects without providing proportional gains in muscle strength or power.
Furthermore, ergogenic use of GH often occurs in combination with other agents, such as anabolic steroids and insulin, which masks the isolated effects of the hormone and potentiates risks. For the clinician, it is essential to understand that GH in healthy adults acts more as a nutrient partitioning agent and water modulator than as a primary muscle builder. The illusion of mass gain can lead to prolonged use, exacerbating endogenous axis suppression and increasing the likelihood of chronic adverse events.
4.4 ADVERSE EVENTS OF GH USE
The administration of supraphysiological doses of GH is not without significant risks, which manifest in various organ systems. One of the most concerning effects is the diabetogenic mechanism. GH is an insulin counter-regulatory hormone; it stimulates hepatic gluconeogenesis and reduces glucose uptake in peripheral tissues. Chronic use invariably leads to insulin resistance, compensatory hyperinsulinemia, and, in predisposed individuals, the development of Type 2 Diabetes Mellitus. This risk is exacerbated by GH's ability to elevate free fatty acids in circulation, which directly interferes with insulin receptor signaling.
Another common and early-reported adverse event is peripheral edema, resulting from sodium and water retention mediated by the renin-angiotensin-aldosterone system and direct effects of GH on renal tubules. This fluid accumulation is primarily responsible for Carpal Tunnel Syndrome, a painful condition caused by compression of the median nerve in the wrist due to swelling of surrounding soft tissues. In more severe cases, water retention can overload the cardiovascular system, contributing to arterial hypertension.
In the long term, concerns turn toward left ventricular hypertrophy and other cardiac alterations. GH and IGF-1 exert direct anabolic effects on cardiomyocytes; while this may seem beneficial, hypertrophy induced by hormonal excess is often pathological, leading to fibrosis and diastolic dysfunction. There are also discussions regarding oncogenic potential, given that IGF-1 is a potent mitogen that inhibits apoptosis; although a direct causal relationship with the emergence of new cancers is still debated, there is consensus that elevated IGF-1 levels can accelerate the growth of pre-existing neoplasms. In animals, side effects include lameness, metabolic disorders, and behavioral changes, as summarized in Table 3.
Table 3 – Adverse events of GH use
| Effect | Mechanism | Evidence |
|---|---|---|
| Peripheral Edema | Sodium and water retention | Discover Medicine (2025) |
| Carpal Tunnel Syndrome | Nerve compression by fluids | Discover Medicine (2025) |
| Insulin Resistance | Diabetogenic effect (anti-insulin) | BMC Nephrology (2019) |
| Ventricular Hypertrophy | Chronic cardiac anabolic stimulus | BMC Nephrology (2019) |
Source: Prepared by the author (2026).
4.5 VETERINARY CLINICAL APPLICATION OF GH
In Veterinary Medicine, the use of GH is an area of growing interest but faces unique challenges in diagnosis and availability. The primary legitimate clinical indication is the treatment of canine hyposomatotropism, also known as pituitary dwarfism. This condition is most frequently observed in breeds such as the German Shepherd and results from a failure in the development of the anterior pituitary. Affected animals present severe growth retardation, persistence of puppy coat (lanugo), and symmetrical bilateral alopecia. Treatment with GH (preferably of porcine origin or specific recombinant) can restore growth and improve quality of life, although the prognosis depends on early diagnosis and the presence of other concomitant hormonal deficiencies.
In equines, somatotropin use has been explored to accelerate the healing of extensive skin wounds and the repair of tendon and ligament injuries, which are common causes of early retirement in athlete horses. GH stimulates fibroblast proliferation and collagen synthesis, accelerating the regenerative phase of tissues. However, the use of GH in competition horses is strictly prohibited by most equestrian federations (such as the FEI), being classified as doping. Abuse aims at increasing muscle mass and reducing body fat but brings ethical and animal welfare risks, including the development of osteoarthritis and metabolic disorders.
An interesting phenomenon in feline endocrinology is spontaneous acromegaly, usually caused by a GH-secreting pituitary adenoma. Unlike exogenous use, this condition provides a natural model to study the effects of chronic GHexcess in animals. Acromegalic cats often present insulin-resistant diabetes mellitus, enlargement of extremities, and mandibular prognathism. Management of these cases is complex and illustrates GH's potency in deregulating glycemic homeostasis.
Finally, GH use in veterinary medicine raises important ethical and regulatory questions. Pressure for results in sports competitions or animal production can lead to the indiscriminate use of substances that compromise the long-term health of animals. The need for rigorous monitoring and ethical conduct by veterinarians is fundamental to ensure that hormone use is restricted to proven therapeutic purposes, respecting the physiology of each species, as demonstrated in Table 6.
Table 6 – Comparison of the GH/IGF-1 axis between species
| Species | Secretion Pattern | Legitimate Clinical Use | Main Indication |
|---|---|---|---|
| Human | Pulsatile (Night peak) | GHD, Turner, Cachexia | Hormonal Deficiency |
| Dog | Episodic (Variable) | Hyposomatotropism | Pituitary Dwarfism |
| Cat | Low pulsatility | Rare (Research use) | Acromegaly (Spontaneous) |
| Equine | Pulsatile (Exercise influence) | Healing, Orthopedics | Musculoskeletal Injuries |
Source: Prepared by the author (2026).
5 DISCUSSION
The integrated analysis of the presented data reveals that the GH/IGF-1 axis is a high-precision system, whose integrity is fundamental for metabolic health in humans and animals. The negative feedback phenomenon should not be seen merely as an obstacle to exogenous hormone use, but as an essential biological protection mechanism. The synthesis of findings demonstrates that exogenous administration, by artificially elevating IGF-1 levels, silences natural GH pulses, leading to functional atrophy that can have systemic consequences. The comparison between human and veterinary medicine reinforces that, despite differences in pulsatility frequency and tissue sensitivity, the principles of suppression and hypothalamic regulation are virtually identical among mammals, validating the use of comparative models for the advancement of endocrinology.
From a clinical standpoint, medical and veterinary practice must be guided by caution. Evidence that lean mass gain in healthy individuals is predominantly water-based demystifies GH use as a "superior anabolic" and highlights the importance of educating patients and owners about the real limitations of therapy. Furthermore, the implications of GH-induced insulin resistance require that any hormonal intervention be accompanied by rigorous metabolic monitoring. The transition from exogenous use to endogenous axis recovery is the moment of greatest vulnerability, requiring strategies that do not merely "wait" for natural recovery but actively optimize the physiological environment for the resumption of pulsatility.
Recovery strategies for the deregulated axis are based on removing the inhibitory stimulus and reactivating natural stimuli. Cessation of exogenous GH is the mandatory first step, allowing IGF-1 levels to drop and feedback on the hypothalamus to be relieved. In parallel, lifestyle interventions play a crucial role. Sleep hygiene is fundamental, as GHsecretion is dependent on slow-wave sleep; without adequate rest, the recovery of circadian pulsatility is severely impaired. High-intensity exercise (HIIT) and strength training also act as potent acute stimuli for endogenous GHRHrelease, assisting in the "re-education" of the pituitary.
The use of GHRH secretagogues, such as CJC-1295 or Ipamorelin, emerges as a promising therapeutic frontier for axis restoration. Unlike direct GH, these peptides stimulate the gland to secrete its own hormone, preserving pulsatility and minimizing the risk of severe negative feedback. However, the use of these substances must be judicious and monitored by frequent laboratory tests. Monitoring should include not only IGF-1 but also safety parameters such as fasting glucose, insulin, glycated hemoglobin (A1C), cortisol, and thyroid function, since the somatotropic axis interacts dynamically with other endocrine axes.
Table 4 – Strategies for recovery of the GH/IGF-1 axis
| Strategy | Mechanism | Evidence/Indication |
|---|---|---|
| GH Cessation | Removal of direct negative feedback | Lanzi and Tannenbaum (1992) |
| Sleep Hygiene | Optimization of circadian pulse | Endocrine Physiology |
| Exercise (HIIT) | Acute stimulus of endogenous GHRH | Sports Literature |
| Secretagogues (CJC-1295) | Mimicry of hypothalamic GHRH | Open Journal of Clin. Diag. (2026) |
Source: Prepared by the author (2026).
The interpretation of IGF-1 levels is the clinician's compass in this process. Persistently low levels after cessation indicate profound suppression or an underlying deficiency, while levels in the upper third of normality suggest an optimal physiological state. Table 5 summarizes the recommended actions based on the laboratory profile, serving as a practical guide for recovery management.
Table 5 – IGF-1 ranges and recommendation
| IGF-1 Range | Profile | Action |
|---|---|---|
| Below Lower Limit | Deficiency or Severe Suppression | Clinical investigation and stimulus |
| Lower Third of Normal | Somatopause or Mild Suppression | Lifestyle optimization |
| Upper Third of Normal | Optimal Physiological Level | Maintenance |
| Above Upper Limit | Risk of Acromegaly or Abuse | Dose reduction or suspension |
Source: Prepared by the author (2026).
6 FINAL CONSIDERATIONS
This review has unequivocally demonstrated that exogenous GH administration exerts a profound and predictable impact on the endogenous somatotropic axis. The negative feedback mechanism, mediated by increased somatostatin and direct IGF-1 inhibition on the pituitary, results in a robust suppression of natural pulsatility. Although the organism possesses an intrinsic capacity for reversibility, the restoration process is not immediate and can be accompanied by metabolic morbidities if not properly managed. The distinction between the real effects of GH (often water-based in healthy individuals) and desired effects (protein anabolism) is crucial for evidence-based clinical practice.
The limitations of this study lie in the qualitative nature of the review and the need for more clinical trials to standardize recovery protocols, especially in populations that have used supraphysiological doses recreationally. However, the integration of data from human and veterinary medicine offers a valuable perspective, reinforcing that endocrine challenges are universal among species. The One Health concept becomes imperative here: understanding hormonal mechanisms in animals not only improves veterinary practice but also sheds light on complex human physiological processes, promoting a more integrated science.
As future perspectives, there is a need to investigate more deeply the role of new GH secretagogues and ghrelin receptor modulators as tools to mitigate somatopause and accelerate axis recovery. Personalized medicine, supported by biomarkers more sensitive than IGF-1 alone, may in the future offer more precise and safer hormonal restoration protocols. It is concluded that preserving endogenous functionality must be the top priority, reserving the use of exogenous hormones for cases of proven deficiency and always under rigorous professional supervision.
REFERENCES
AL-SAMERRIA, S.; RADOVICK, S. The Role of Insulin-like Growth Factor-1 (IGF-1) in the Control of Neuroendocrine Regulation of Growth. Cells, v. 10, n. 10, p. 2664, 2021.
BMC NEPHROLOGY. The potential effects of anabolic-androgenic steroids and growth hormone as commonly used sport supplements on the kidney: a systematic review. BMC Nephrology, v. 20, p. 198, 2019.
DE GRAAF-ROELFSEMA, E. et al. The GH/IGF-1 axis in horses: influence of exercise, training and growth. Domestic Animal Endocrinology, 2007.
DISCOVER MEDICINE. Adverse events with usage of human growth hormone: a review. Discover Medicine, 2025.
ENDOCRINOLOGY REVIEW. Central and peripheral regulation of the GH/IGF-1 axis: GHRH and beyond. Endocrinology Review, 2024.
LANZI, R.; TANNENBAUM, G. S. Time course and mechanism of growth hormone's negative feedback effect on its own spontaneous release. Endocrinology, v. 130, n. 2, p. 780-788, 1992.
MEDICAL SCIENCE. Human growth hormone abuse in elite sports: physiological efficacy, adverse health effects, and anti-doping challenges: A narrative review. Medical Science, 2025.
MEIJ, B. P. et al. Somatotroph pituitary tumors in dogs: diagnosis and treatment. Journal of Veterinary Internal Medicine, 2002.
OPEN JOURNAL OF CLINICAL DIAGNOSTICS. Growth Hormone Secretagogues: Between Endocrine Physiology and the Therapeutic Frontier of GH-IGF-1 Axis-Modulating Peptides. Open Journal of Clinical Diagnostics, 2026.
REVIEWS IN ENDOCRINE AND METABOLIC DISORDERS. Hypothalamic GHRH. Reviews in Endocrine and Metabolic Disorders, v. 26, p. 297-303, 2025.
ROSENTHAL, S. M.; SILVERMAN, B. L.; WEHRENBERG, W. B. Exogenous Growth Hormone Inhibits Bovine but Not Murine Pituitary Growth Hormone Secretion in vitro. Neuroendocrinology, 2008.
SCIENCEDIRECT. Impact of GH administration on athletic performance in healthy young adults: A systematic review and meta-analysis of placebo-controlled trials. ScienceDirect, 2017.
SCOTT-MONCRIEFF, J. C. Hypopituitarism in dogs. Veterinary Clinics: Small Animal Practice, v. 45, n. 4, 2015.
