on October 28, 2026
The environment enters the biology of growth
Growth is not the result of the action of a single hormone.
It is a complex biological process in which genetics, nutrition, metabolism, hormones, immune status, sleep quality, environmental conditions, and numerous signals from tissues interact.
The environment in which a person lives can therefore become part of their biology.
Chemicals present in the air, water, food, consumer products, and everyday objects can come into contact with the body through different routes of exposure. Some of these substances are able to interfere with endocrine regulation and are defined as endocrine disruptors.
Among the most studied categories are bisphenols, phthalates, per- and polyfluoroalkyl substances (PFAS), certain pesticides, and other environmental contaminants.
Research is trying to understand whether and to what extent these exposures can alter particularly sensitive processes during critical windows of development: pregnancy, the fetal period, the first months of life, and childhood.
The topic is particularly important because development does not simply represent a succession of anatomical changes, but a phase in which numerous biological systems are defining their organization.
Endocrine disruptors: when a substance interacts with hormonal regulation
The endocrine system uses hormones and receptors to coordinate fundamental functions such as growth, metabolism, reproduction, neurological development, and organ maturation.
An endocrine disruptor is a substance or mixture capable of altering one or more functions of the endocrine system, with consequences for the organism or its offspring.
Interference can occur through different mechanisms: mimicking or antagonizing the action of a hormone, modifying its synthesis or metabolism, altering receptors, or interfering with intracellular signaling pathways.
This means that it is not enough to ask whether a substance is simply “toxic”.
The most important question is also how, when, and at what level of exposure it interacts with biological systems.
The most sensitive windows: pregnancy and early childhood
Pregnancy represents one of the phases in which the exposome takes on particular relevance.
The placenta constitutes a fundamental barrier, but it is not an absolute barrier. Various chemicals can cross it and reach the fetal compartment.
The fetus also has metabolic and detoxification systems that are still developing, while organs and systems are going through rapid phases of differentiation.
For this reason, exposure during pregnancy cannot be interpreted simply as a reduced version of exposure in adults.
The same amount of a substance can have different biological meanings at different times of development.
The postnatal period also represents a delicate phase. Height growth, brain development, immune maturation, metabolism, and body composition continue to change rapidly.
It is precisely in these windows that epidemiological research is focusing an increasing amount of attention.
The GH-IGF1 axis: one of the systems that regulate growth
Among the main endocrine systems involved in growth is the GH-IGF1 axis.
Growth hormone, or GH, is produced by the pituitary gland under the control of the hypothalamus through a regulation that mainly involves GHRH and somatostatin.
GH acts on various tissues and stimulates, among other effects, the production of IGF1.
IGF1 is produced mainly by the liver, but also by numerous peripheral tissues. It is involved in cell proliferation and differentiation and plays an important role in the development of the skeleton and tissues.
The system is regulated through feedback mechanisms.
But the GH-IGF1 axis does not operate in isolation.
Thyroid hormones, insulin, sex steroids, glucocorticoids, leptin, ghrelin, nutritional status, and numerous local signals participate in the regulation of growth.
Height growth must therefore be considered the result of an integrated endocrine and metabolic network, not a single parameter.
From the GH-IGF1 axis to the metabolic network
One of the most important achievements of modern endocrinology is precisely the move away from a linear view of growth.
GH and IGF1 are important, but they must be placed in a broader system that includes energy metabolism, nutrition, the thyroid, insulin, adipose tissue, and bone regulation.
Leptin and ghrelin, for example, provide information about the body's energy status and can influence the regulation of the growth axis.
Adipose tissue must no longer be considered exclusively an energy store. It is an endocrine organ capable of producing mediators that participate in metabolic and neuroendocrine regulation.
This leads to an important consideration: an altered biological environment can potentially interfere with growth through multiple pathways simultaneously.
Not necessarily by directly modifying GH secretion, but by intervening in metabolism, the thyroid, inflammation, energy availability, placental function, or other systems involved in development.
PFAS: one of the most studied categories
PFAS are a vast family of substances characterized by very stable carbon-fluorine bonds.
This characteristic has favored their use in numerous products and industrial applications, but also contributes to their environmental persistence.
Some PFAS have been studied for their possible interference with various biological systems, including metabolism, immune function, the thyroid, and development.
Regarding fetal growth, epidemiological evidence has become progressively more consistent, although it remains heterogeneous.
A meta-analysis of 21 studies found inverse associations between maternal exposure to PFOA and PFOS and birth weight, with a particularly evident association for PFOS. However, the authors highlighted the presence of heterogeneity and limited evidence of a dose-response relationship.
Prospective studies have also observed associations between specific maternal PFAS and anthropometric parameters at birth.
The biological significance of these results is important, but it does not allow us to state that every exposure to PFAS necessarily determines a growth disorder.
From birth to growth in the early years
One of the most interesting aspects of recent research is the shift from simply assessing birth weight to studying growth trajectories.
Growth is not, in fact, a static value.
Two children can be born with a similar weight and subsequently follow completely different trajectories.
A recent prospective study conducted on over 23,000 children analyzed the association between maternal exposure to different PFAS and different trajectories of weight, height, and body mass index in the early years of life.
Associations emerged between specific PFAS and trajectories characterized by more limited height growth, while for some compounds, associations with different weight trajectories were observed.
These results reinforce the idea that prenatal exposure may be associated not only with a single parameter at birth, but also with the dynamics of subsequent growth.
However, it is important to emphasize that these are observational studies: identifying an association does not automatically prove a causal relationship.
Phthalates and the GH-IGF1 system
Phthalates constitute another category of substances of particular interest.
They were used for many years as plasticizers and can be present in numerous consumer products.
Epidemiological research has studied their possible relationship with the thyroid and the GH-IGF1 system.
In a study conducted on children, some phthalate metabolites were found to be associated with lower concentrations of IGF1 and IGFBP3 and with changes in certain thyroid parameters.
Another longitudinal cohort found associations between specific phthalate metabolites and variations in T3, T4, FT4, IGF1, and IGFBP3.
These data are particularly interesting because they show a possible link between environmental exposure and endocrine biomarkers directly involved in growth.
However, they do not prove that exposure necessarily causes a clinically significant height deficit.
There is, in fact, a biological distance between an altered biomarker and disease that must be assessed through longitudinal and clinical studies.
The role of the thyroid
Growth is also closely linked to thyroid function.
Thyroid hormones participate in skeletal and neurological development and interact with the GH-IGF1 axis.
For this reason, a substance capable of modifying thyroid function could potentially indirectly influence growth processes as well.
Some studies on children have observed associations between phthalate metabolites and thyroid hormones.
Once again, however, the interpretation must be cautious.
A statistical association between exposure and a hormonal parameter does not automatically equate to a pathological endocrine condition.
Clinical relevance must be assessed by considering exposure concentration, duration, age, sex, nutritional status, genetics, and numerous other factors.
There is no single endocrine disruptor
One of the most complex aspects is that in real life we are generally not exposed to a single substance.
The exposome includes a multitude of chemical and non-chemical exposures that occur simultaneously.
PFAS, phthalates, pesticides, metals, atmospheric contaminants, bisphenols, and other compounds can be present together.
To these are added non-chemical factors: diet, physical activity, socioeconomic conditions, stress, air quality, sleep, and the home environment.
For this reason, research is progressively shifting from the concept of “one substance-one effect” to the study of mixtures.
This is a fundamental shift because the actual biological response may depend on the combination of exposures and individual vulnerability.
Microbiota, gut, and growth
The gut microbiota is also entering growth research.
The relationship between microbiota, metabolism, immunity, and skeletal development represents a relatively recent field of study.
The microbiota can influence nutrient metabolism, metabolite production, immune regulation, and numerous communication pathways between the gut and other organs.
The so-called gut-bone axis is now a subject of increasing interest, as are the possible interactions between the gut, brain, and endocrine system.
Some observational studies have found differences in microbiota composition between children with idiopathic short stature and comparison populations.
These results are interesting but do not yet allow us to establish whether the modification of the microbiota represents a cause, a consequence, or simply a correlate of the condition.
The field is promising, but requires longitudinal and interventional studies.
Epigenetics: when the environment meets the genes
Another level of complexity concerns epigenetics.
Environmental exposure can influence certain mechanisms that regulate gene expression without directly modifying the DNA sequence.
DNA methylation, histone modifications, and microRNA are some of the systems through which the environment can interact with cellular regulation.
This perspective is particularly interesting during fetal development, when numerous biological programs are activated and stabilized.
However, even in this case, the presence of an epigenetic change must not automatically be interpreted as evidence of disease.
Research still needs to establish which modifications are transient, which persist over time, and which have real clinical relevance.
Growth and health: why prevention must start with the environment
Growing attention to endocrine disruptors brings with it an important consequence: prevention cannot focus solely on the individual.
There is an environmental dimension to health.
Reducing unnecessary exposure to contaminants, improving air and water quality, promoting safer materials, and making information about the substances used in products more transparent are public health interventions.
At the individual level, especially during pregnancy and early childhood, it may be reasonable to adopt strategies to reduce avoidable exposures without turning daily life into an obsessive search for the absence of contaminants.
Effective prevention must be proportionate.
It is not realistic to think of an environment completely free of chemicals.
It is, however, possible to work on reducing unnecessary exposures, especially during the biologically most sensitive stages.
An integrated reading of the exposome
Growth represents a particularly striking example of how contemporary medicine must deal with complex systems.
Genetics, hormones, metabolism, nutrition, microbiota, the environment, and psychosocial conditions can interact.
This does not mean that everything is connected in an indistinct way.
It means that medicine must learn to distinguish biologically plausible relationships from those that have been clinically demonstrated.
For this reason, the study of endocrine disruptors can become particularly interesting also within the framework of integrated medicine: not to replace pediatric endocrinology or environmental medicine, but to expand the ability to observe the context in which the person grows and develops.
Personalization starts with the individual history
The same exposure does not necessarily produce the same effect in every person.
Age, sex, genetics, nutrition, metabolic status, liver and kidney function, microbiota, pregnancy conditions, and exposure characteristics can alter the biological response.
This is also why medicine of the future will probably be increasingly oriented toward individual risk assessment.
This does not mean subjecting every person to a long list of tests for environmental pollutants.
Rather, it means learning to identify situations in which further investigation is truly indicated and interpreting data in their clinical context.
From awareness to prevention
Research on endocrine disruptors must not generate fear.
It must generate awareness.
Pregnancy, early childhood, and adolescence represent periods in which development is particularly dynamic. Protecting these stages means acting not only on individual risk factors, but on the overall environment.
At the same time, simplifications must be avoided.
Not every chemical substance is an endocrine disruptor. Not every exposure produces a disease. Not every epidemiological association implies causality.
The quality of evidence must remain the criterion for interpreting results.
The challenge is to build prevention capable of integrating biology, environment, lifestyle, and individual vulnerability.
Growth as an expression of biological complexity
A child's growth is one of the most visible manifestations of the interaction between the organism and the environment.
Behind centimeters and kilograms lies an extremely sophisticated network of endocrine, metabolic, immune, genetic, and environmental signals.
The GH-IGF1 axis represents one of the fundamental nodes of this network, but it is not the only one.
Available evidence suggests that some endocrine disruptors, in particular PFAS and phthalates, may be associated with changes in growth parameters, birth weight, and certain endocrine biomarkers. The most recent studies on growth trajectories make the picture even more interesting, but also confirm the need for caution in interpretation.
The future of research will have to clarify which exposures have clinically relevant effects, which are the most vulnerable time windows, what biological mechanisms are involved, and above all, which prevention strategies are truly effective.
Understanding these relationships means going beyond a fragmented view of health.
It means recognizing that growth is a biological process in which the organism and the environment are in continuous dialogue.
And it is precisely in this dialogue that prevention can find one of its most important spaces.
PLEASE NOTE
The contents of this page are for informational and educational purposes only and do not constitute medical advice, a diagnosis, or a prescription. They do not replace the assessment of a pediatrician, endocrinologist, or other qualified healthcare professional.
The associations described between environmental exposures, endocrine disruptors, and growth parameters derive largely from observational studies and do not necessarily demonstrate a cause-and-effect relationship. The possible presence of a contaminant in the body does not automatically equate to the presence of a disease or clinical harm.
During pregnancy, childhood, and adolescence, it is not recommended to independently undertake “detoxification” protocols, dietary eliminations, supplementation, or other treatments based solely on presumed exposure to contaminants. Prevention should prioritize the reasonable reduction of avoidable exposures and, when necessary, an appropriate healthcare assessment.
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