Hormones in European Health Policies: How endocrinologists can contribute towards a healthier Europe
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Hormones in European Health Policies: How endocrinologists can contribute towards a healthier Europe
All rights reserved © 2021 European Society of Endocrinology.
Reuse is authorised provided the source is acknowledged.
The European Society of Endocrinology does not own the copyright
related to the following elements:
Page 6 © Andrea Giustina
Page 16 © Liesbeth van Rossum
Page 12 © Uberto Pagotto
Page 20 © Johan de Graaf
Page 22 © Michael Rosenberg
Page 24 © David Crews
Page 25 © Josef Köhrle
For any use or reproduction of photos or tables that is not under
European Society of Endocrinology copyright, permission must be
sought from the copyright holder.
Date of publication: May 2021.
For more information about this White Paper, please contact European
Society of Endocrinology by emailing info@euro-endo.org. The latest
version is available here
2 Hormones in European Health Policies: How endocrinologists can contribute towards a healthier Europe
Hormones in European
Health Policies:
How endocrinologists can contribute
towards a healthier Europe
European Society of Endocrinology White Paper
May 2021
Hormones in European Health Policies: How endocrinologists can contribute towards a healthier Europe 3
Contents
Methodology and Acknowledgements 5
Introduction 6
Executive summary 7
Endocrine health and disorders 10
Hormones in European Health Policies: four key policy areas 15
• Obesity 15
• Rare endocrine diseases 18
• Cancer and endocrinology 21
• Endocrine Disrupting Chemicals (EDCs) 24
Conclusions and policy recommendations 27
About European Endocrinology and the European Society of Endocrinology 29
Endorsements 30
References 35
4 Hormones in European Health Policies: How endocrinologists can contribute towards a healthier Europe
Methodology
This paper is based on an extensive consultation with endocrinologists across
Europe, combined with expert engagement and desk research.
A large survey carried out in 2018, and in which more than 3,000 endocrine healthcare providers participated,
provided the first ever mapping of endocrinology in Europe. The survey included an assessment of future trends and
areas where improved efforts – clinical, research and policy – are needed. A second survey was conducted among the
National Endocrine Societies that are members of the ESE Council of Affiliated Societies. Forty-three societies provided
their views on the importance and needs of endocrine health and diseases in European and national health policies.
These surveys were followed up with a careful assessment of European health policies, initially in the summer of 2019,
with revisions in 2020 taking the effects of the coronavirus pandemic into consideration.
In-depth interviews with endocrinology experts across various fields contributed to the development of responses to
several consultations issued by the European Commission and formed the basis of the policy content of this White
Paper. All persons listed under ‘Acknowledgements’ contributed to a certain phase in this process and provided
input into the manuscript of the White Paper. In a final phase the White Paper was submitted for final comments and
endorsements to experts, the National Endocrine Societies and Specialist Endocrine Societies affiliated with ESE, as
well as selected other stakeholders. The White Paper editing process ended on 30 March 2021. Any developments
after this date have therefore not been taken into account.
Acknowledgements
The European Society of Endocrinology would like to thank the following experts and patients for their valuable time
and input towards the development of this paper. This contribution relates to input provided during the process of
developing the ESE policy and advocacy strategy, the development of inputs to consultation processes and position
papers, and input and review of this White Paper publication.
In alphabetical order:
Faisal Ahmed, Glasgow, UK Robin Peeters, Rotterdam, The Netherlands
Anna Maria Andersson, Copenhagen, Denmark Alberto Pereira, Leiden, The Netherlands
Salvatore Benvenga, Messina, Italy Manel Puig Domingo, Barcelona, Spain
Felix Beuschlein, Zurich, Switzerland Ewa Rajpert–De Meyts, Copenhagen, Denmark
Jacqueline Bowman-Busato, Brussels, Belgium Martin Reincke, Munich, Germany
Davide Carvalho, Porto, Portugal Patrice Rodien, Angers, France
Luca Chiovato, Pavia, Italy Michael Rosenberg, Mikhmanim, Israel
Mirjam Christ-Crain, Basel, Switzerland Camilla Schalin-Jäntti, Helsinki, Finland
Sherwin Criseno, Birmingham, UK Jorma Toppari, Turku, Finland
Barbara Demeneix, Paris, France Mark Turner, Coventry, UK
Eva Diamantaki-Kandarakis, Athens, Greece Majorie van Duursen, Amsterdam, The Netherlands
Stefano Frara, Milan, Italy Aart-Jan van der Lelij, Rotterdam, The Netherlands
Francesco Giorgino, Bari, Italy Liesbeth van Rossum, Rotterdam, The Netherlands
Andrea Giustina, Milan, Italy Bulent Yildiz, Ankara, Turkey
Simona Glasberg, Jerusalem, Israel Ayse Zengin, Melbourne, Australia
Johan de Graaf, Almere, The Netherlands
Riccarda Granata, Turin, Italy We would also like to thank ESE’s Affiliated Specialist
Anita Hokken-Koelega, Rotterdam, The Netherlands Societies and the National Endocrine Societies of ECAS
Josef Köhrle, Berlin, Germany for their additions and insights to and endorsement
Beata Kos-Kudła, Katowice, Poland of this paper. We thank Hill + Knowlton Strategies
Márta Korbonits, London, UK and specifically Phoebe Blossom, Eva Bille and Maria
Csilla Krausz, Florence, Italy Maseda for writing and editorial assistance. We owe
Anton Luger, Vienna, Austria special thanks to Mischa van Eimeren, policy affairs
Djuro Macut, Belgrade, Serbia consultant to ESE, for his continued support, professional
Monica Marazuela, Madrid, Spain policy advice and input into the various stages of the
Uberto Pagotto, Bologna, Italy development of this White Paper.
Hormones in European Health Policies: How endocrinologists can contribute towards a healthier Europe 5Introduction
This White Paper will introduce the reader to the importance of hormones in
everyday life, and the contributions that the hormone specialist, the endocrinologist,
may offer to major European health policies developed or under development by
European and national institutions.
Hormones are vital to good human health. Every day In this document, the community of European endocrine
they determine our development and growth, how our specialists presents its views on how, based on the
metabolism handles the food we consume, our sexual science we develop, the clinical work we do and our
function and fertility, and our cognitive processes. Our health-related expectations towards the future, the
general well-being is determined by these regulatory endocrine discipline can contribute to better health in
substances from the moment of our conception until the Europe.
day we die. When the hormonal systems become out of
balance or fail, prevalent non-communicable diseases The European Society of Endocrinology is grateful to all
with enormous socioeconomic impact like obesity, members and non-members, experts and other societies
diabetes, cancer, osteoporosis and infertility develop. that worked together with ESE to enable us to present
Many patients affected by these common diseases this document. Statements relating to the opinions of
are frail and vulnerable as clearly demonstrated by the the European endocrine community are derived from a
current COVID-19 pandemic. The effective prevention large survey, done at the end of 2018, and to which more
and treatment of these diseases is the best way to than 3,000 endocrine professionals (doctors, nurses,
protect these high-risk patients. Many rare diseases can scientists, trainees and others) responded.
also be connected to failures in our hormone system. ESE is committed to supporting the European and
Among the many factors that can cause the hormone national institutions in developing better healthcare
system to fail, the external environment is more and policies, to the benefit of all European citizens.
more recognised as a key driver.
The European Society of Endocrinology (ESE), on behalf
of more than 20,000 endocrinologists in Europe as well
as the millions of patients with endocrine diseases whom
it represents, applauds the agenda of the European
Institutions for the period 2019–2024.
The Cancer Mission and Beating Cancer Plan, the Green
Deal, the Chemicals Strategy for Sustainability, the
EU4Health Strategy and the Healthy Ageing agenda,
to mention a few: these plans are highly relevant to
our community of endocrine specialists, the science
they develop and the patients they see. Our endocrine
‘hormone’ expertise provides relevant insights needed
to develop targeted action plans, and support the
implementation and impact of these plans, aiming
Andrea Giustina
ultimately for better health for citizens around Europe –
President of the European Society of Endocrinology
both inside and outside the EU.
(2019-2021)
Member of the Italian Superior Health Council
Prorector and Chairman of the Institute of
Endocrine and Metabolic Sciences
San Raffaele Vita-Salute University and
IRCCS San Raffaele Hospital, Milan, Italy
6 Hormones in European Health Policies: How endocrinologists can contribute towards a healthier EuropeExecutive summary
Endocrinology is the field of medicine that relates to human hormonal systems.
The endocrine system plays an important role in the body’s ability to maintain
fundamental processes for life including heartbeat regulation, bone/tissue structure
and growth, energy intake and expenditure, as well as the ability to conceive a
baby. Disorders of the endocrine system cause conditions such as diabetes, obesity,
atherosclerosis, thyroid disease, growth disorders, hypertension, osteoporosis,
infertility and sexual dysfunction, endocrine cancers and a host of other endocrine-
related illnesses.1 Recent research shows that endocrine-related conditions such
as obesity, diabetes mellitus and hypovitaminosis D also negatively impact patient
outcomes with regard to COVID-19.2
With this White Paper, we call on all policymakers in Obesity increases the risk of comorbidities like type
Europe, including the EU institutions and national 2 diabetes, hypertension, cardiovascular diseases,
governments across Europe, to recognise the depression, infertility and arthritis, and is a contributing
importance of endocrinology in all EU and national factor to a host of life-threatening and debilitating
health policies. Addressing this cross-cutting, and in diseases.6,7 Obesity is also a risk factor for a number of
many cases, underlying element is crucial if we want to cancers,8 and closely linked to adverse outcomes from
achieve the objectives set out in key programmes such COVID-19.9
as the plans to address COVID-19 and other pandemics,
national cancer plans, obesity action plans, rare disease The European Commission’s March 2021 dedicated
networks, chemicals legislation and much more. brief on obesity prevention acknowledges the scale of
the issue and defines obesity as a ‘chronic relapsing
The four chapters of this White Paper set out some of the disease’, which in turn acts as a gateway to a range of
key priority areas linked to endocrinology that are having other non-communicable diseases, such as diabetes,
some of the biggest effects on societal health today. cardiovascular diseases and cancer.10 To adequately
There are many more – the prevention, diagnosis and address this societal challenge, the EU and national
interdisciplinary care of diabetes, avoiding osteoporosis governments across Europe should immediately and
and ensuring general bone health, vitamin D and without further delay treat obesity as a disease and
iodine deficiencies as well as thyroid health, to name a recognise the central role of hormones in preventing,
few. While all endocrine diseases deserve heightened treating and living with overweight and obesity.
attention, the four areas below are among the most In terms of concrete policy opportunities, now is the
pressing at this point in time. time to reinforce the ‘fork’ side of the Farm to Fork
Strategy,11 to encourage healthy lifestyle habits and to
Obesity and the complex hormonal put appropriate resources behind prevention, treatment
relationship and living with obesity. On the ‘farm’ side, we should
Obesity is defined as having abnormal or excessive reduce exposure to the many plant protection products
fat accumulation that presents a risk to health.3 The that contain Endocrine Disrupting Chemicals (EDCs), a
traditional view of fat tissue (known as adipose tissue) contributing factor to obesity.12 Partnering with scientific
is that it is an inactive reserve for energy storage – societies such as ESE and multi-stakeholder initiatives
when in fact it is an endocrine organ, producing over such as OPEN-EU13 would help provide efficient and
600 different hormones.4 Adipose tissue is integrally comprehensive solutions to this massive societal issue.
involved in coordinating a variety of biological processes
including energy metabolism, neuroendocrine function Rare endocrine disease in Europe
and immune function.5 Rare diseases, which affect fewer than 1 in 2,000
people,14 are less well known and researched, but
cover a wide range of conditions. Despite their rarity,
these conditions collectively affect approximately 30
million people across Europe15 and come with particular
challenges related to time to diagnosis, innovative
treatment options, and investment into research.
Hormones in European Health Policies: How endocrinologists can contribute towards a healthier Europe 7European Reference Networks (ERNs) have been sufficient attention needs to be directed to the impact
instrumental in creating clearly defined structures for of Endocrine Disrupting Chemicals and prevention,
sharing knowledge and care coordination for specific treatment and long-term management of obesity, all
rare diseases across the EU. These knowledge-based important and actionable factors in the prevention of
networks have been critical in shaping the rare disease cancer.
policy space. However, greater support from the EU is
needed to improve their functionality and to improve Through the Horizon Europe Mission Board for
health outcomes in rare disease patient populations. Cancer and other funding mechanisms, the EU and
national governments should direct future cancer
To reap the benefits of the ERNs and further improve funding towards academic consortia to study evolving
outcomes for those suffering from rare endocrine epidemiological trends of (endocrine) cancers and
diseases, the EU and Member States should continue improve current diagnostic processes (for example to
evolving and expanding funding for ERNs. Horizon improve the current late diagnosis of neuroendocrine
Europe funding would allow ERNs to expand their tumours).
activities and create a pan-EU data acquisition strategy
to improve current rare disease registries in a common Endocrine Disrupting Chemicals: exposure
and uniform data space, better coordinate the projects and health risks
and their infrastructure, and compensate patients and Endocrine Disrupting Chemicals (EDCs) are substances
the medical/academic communities for giving their that mimic, block or interfere with hormones in the
valuable time to the study of these diseases. body’s endocrine system. EDCs are found in everyday
consumer items including detergents, flame retardants,
National governments should increase funding for food additives, children’s toys, sunscreen, textiles,
Orphan Medicinal Products to provide better incentives anti-bacterial soaps, cosmetics, plastic bottles, metal
for the development of medicines for patients with rare food cans and pesticides.19 Recent studies estimate
(endocrine) diseases and reform their pricing structures that EDCs contribute substantially to disease and
to provide incentives to invest in the use of ‘old’ disability across a person’s lifetime, costing hundreds
medicines for new purposes. of billions of Euros per year.20
At the EU level there is an urgent need to move forward To safeguard human health and the environment, the
on European-level Health Technology Assessment European Commission and the European Chemicals
(HTA)16 legislation and joint funding to make medicines Agency (ECHA) should strictly apply the precautionary
for rare diseases available and accessible in all EU principle, to avoid production, distribution and exposure
countries. to pesticides, biocides or consumer products containing
suspected EDCs. The European Commission has taken
Cancer and the endocrine system
great steps towards phasing out EDCs with its recently
Cancer is the second leading cause of death and published Chemicals Strategy for Sustainability.21
morbidity in Europe, with more than 3.7 million new
cases and 1.9 million deaths each year.17 The interaction The European institutions should implement without
between the endocrine system and cancer is complex, delay the many actionable proposals in the Chemicals
and new research has highlighted the intricate nature Strategy for Sustainability and establish a legally
of this interaction in terms of prevention, treatment binding hazard identification of EDCs, improving
and post-treatment care. This manifests itself through the existing criteria for plant protection and
endocrine cancers, as well as patient vulnerability biocides to lower the burden of proof and allow more
to aggressive anti-cancer treatments that result in harmful substances to be restricted, boost funding
endocrine comorbidities in cancer survivors. This for alternatives and create a citizen portal to raise
interaction also relates to obesity as a gateway disease awareness about the prevalence and harmful effects
for cancer and other cancer risk factors such as exposure of EDCs. Other welcome steps include the proposals to
to EDCs. provide better public information, to develop a generic
approach to assessing chemicals, to register polymers
To address this challenge, the EU and Member States of concern, and to introduce risk assessment factors
should appropriately focus on and include the for mixtures under REACH and assess combination
endocrine perspective when implementing the effects in other legislation.
recently published Beating Cancer Plan18 and other
cancer-related policies, including through making
prevention measures a focus area, ensuring that ERNs
have a key role in improving early detection, diagnosis
and treatment, encouraging National Action Plans to
address gateway diseases and comorbidities in cancer
survivors and creating pan-European databases for
major and rarer endocrine-related cancers. Specific and
8 Hormones in European Health Policies: How endocrinologists can contribute towards a healthier EuropeHormones in European Health Policies: How endocrinologists can contribute towards a healthier Europe 9
Endocrine health and disorders
Introduction
Endocrinology is the field of medicine that relates to the human endocrine system,
a network of cells, tissues and organs that produces and releases hormones into the
bloodstream, regulating important bodily functions.
The endocrine system plays an important role in the which have an important role in the regulation and
body’s ability to maintain fundamental processes for life function of the human body.6,23,24,25
including heartbeat regulation, bone/tissue structure
and growth, energy intake and expenditure, as well as Hormones are critical to health and well-being
the ability to conceive a baby. The more well-known throughout life. They have a central role in regulating
hormone-producing glands in the human body include foetal growth and development, maturation of an
the hypothalamus, the pineal gland, the pituitary gland, adolescent into adult life, and other important life-
the brain, the thyroid and the parathyroid glands, the course changes resulting in a fertile and healthy ageing
adrenal gland, the pancreas, the ovaries and the testes.22 individual.26,27
However, hormones are also secreted by almost any
other tissue in the body such as adipose cells (fat cells),
gut, heart, kidney, lung, muscle, skin and bone – all of
10 Hormones in European Health Policies: How endocrinologists can contribute towards a healthier EuropeINTRODUCTION
Figure 1: How hormones work TO THE ENDOCRINE SYSTEM
Hormones are chemical messengers that travel throughout the body, There are hundreds of different types of
telling our cells and organs what to do. hormones, each with its own essen�al job.
Endocrinology is the study of hormones.
Hormones are essen�al for our everyday survival.
TESTOSTERONE
INSULIN
LEPTIN
ADRENALINE
OESTROGEN
MELATONIN
CORTISOL
THYROXINE
GROWTH HORMONE PROLACTINE
Form rela�onships
HORMONES HORMONES
When to When to Cope with other
stop ea�ng go to bed with stress people
TELL YOU HELP YOU
How to balance
How to grow blood pressure Stay fit Have children
HORMONES COME FROM HYPOTHALAMUS
THE GLANDS AND TISSUES THAT PITUITARY GLAND
PINEAL GLAND
FORM THE ENDOCRINE SYSTEM BRAIN
The glands secrete hormones to produce
specific responses from cells and organs THYROID GLAND
that tell them what to do
ADRENAL GLAND
PANCREAS
OVARY
ADIPOSE
TESTIS (FAT) TISSUE
MALE FEMALE
Once released, they bind themselves to target
receptors that fit the hormone perfectly
Hormones in European Health Policies: How endocrinologists can contribute towards a healthier Europe 11Endocrine disorders are amongst the Today, both the developed and developing world face
biggest diseases to impact society. serious public health challenges caused by the most
Disorders of the endocrine system cause conditions such common endocrine disorders. Diabetes, obesity and
as diabetes, obesity, thyroid disease, growth disorders, thyroid-related diseases are amongst the most prevalent
hypertension, osteoporosis, infertility and sexual and well-known. On the other hand, endocrine diseases
dysfunction, and a host of other endocrine-related which are uncommon and unfamiliar, like rare disorders
illnesses.28 of adrenal, pituitary, sexual differentiation, or related to
the bone and calcium metabolism, lipid disorders and
inborn disorders of metabolism, collectively account for
“More than three quarters of the population will a large proportion of endocrine patients.
need an endocrinologist at some point in their life.” As well as direct effects on the regulation of bodily
Prof. Dr Uberto Pagotto, functions, disorders of the endocrine system can lead
Unit of Endocrinology and Prevention to cardiovascular comorbidities, cancer and mental
and Care of Diabetes, Policlinic health conditions. Hormones also modulate other body
S.Orsola, University of Bologna, Italy systems such as the immune system. The sensitivity
ESE Focus Area Lead Diabetes Obesity and complexity of the endocrine system means that it is
Metabolism and Nutrition also very susceptible to medication, such as aggressive
anti-cancer treatments, as well as EDCs present in
our environment, which can in turn influence human
A 2018 mapping of more than 3,000 endocrinologists development as well as both obesity and cancer.30
showed the following distribution of workload and
disease areas:29 The link between COVID-19 and endocrine
disorders
Research shows that endocrine related conditions
6%
3% impact the outcomes of patients with COVID-19.2
There is recent evidence that people suffering from
hormone conditions, such as diabetes and obesity,
8%
have more severe symptoms and health outcomes
including death.31,32
36%
Complex socioeconomic factors also play a role in
9% Most common increasing the risk for diabetes, as well as for the
areas of work for epidemic of obesity coexisting with the COVID-19
endocrinologists pandemic. Further research is needed to understand the
complex interplay of gender, ethnicity and economic
10% status on increasing the susceptibility of people living
with endocrine conditions to more severe illness.
Vaccines are still recommended. A statement published
in January 2021 from endocrine experts stresses that the
recommendation for COVID-19 vaccination in patients
28% with stable endocrine disorders should not be different
from the one for the general population.33
Multi-disciplinary nature of preventing,
36% Diabetes, Obesity and Metabolism managing and treating endocrine disorders
28% Thyroid The field of endocrinology has been revolutionised
by advances in molecular biology, clinical chemistry,
10% Pituitary and Neuroendocrinology
imaging, information technology and therapies, and
9% Calcium and Bone has significantly advanced the modern concept of
8% Adrenal and Neuroendocrine Tumours life sciences and biomedicine. The close connection
between research and clinical output is central to
6% Reproductive Endocrinology the discipline of endocrinology and has contributed to
3% Other advancing the medical field. It may not be coincidental
that, in the past, the impact of endocrinology in
medicine was recognised by several Nobel Prizes
Figure 2: Representation of the most common areas of work for endocrinologist
Data from the Mapping Endocrinology in Europe (MEnEU) survey carried out by having been awarded to scientists for discoveries
ESE in 2018. related to hormones.34 Endocrinologists apply their
knowledge in the clinic as well as in the laboratory,
and as a result science merges with patient needs.
12 Hormones in European Health Policies: How endocrinologists can contribute towards a healthier EuropeFor instance, by regulating food intake and energy is critical for the future goals to prevent a range of
expenditure, hormones and their analogues represent endocrine related chronic, non-communicable diseases,
the cornerstone of the pharmacotherapy of obesity. This for example, type 1 diabetes and obesity, and improve
process is helped by the fact that endocrinology is often treatment and management of the cases we fail to
tertiary centre based, and engaged with multidisciplinary prevent. In all priority areas we advocate for rigorous
and pan-European research projects such as ERCUSYN,35 sex-specific research, which is particularly important for
ENS�T36 and ENETS.37 This results in tailored therapies endocrinology.39
addressing endocrine needs and maintaining individual
quality of life. How endocrinologists see the future
The Mapping Endocrinology in Europe (MEnEU) survey
Endocrinology plays an important role in a conducted by ESE in 201840 showed that:
multidisciplinary approach to develop better tools to
identify chemicals with endocrine disrupting abilities • Nearly 80% of respondents expect patient numbers to
essential for action on the reduction and prevention of increase, and for their issues to become more complex;
further production, distribution and human exposure to
• Diabetes, obesity, metabolism and thyroid disorders
major EDCs, thereby preventing their potential adverse
command the highest workload in the clinic;
effects on brain development, impaired fertility and
major diseases such as obesity and cancer. For instance, • In rare endocrine disease, an emphasis on improving
the collaboration between endocrinology and toxicology diagnosis, developing guidelines and equal access to
is important to improve methods to identify chemicals care and treatment is needed.
as EDCs. Moreover, other disciplines like developmental
medicine, biology or human epidemiology are needed to Endocrinologists who took the survey highlighted some
identify links, associations and exposures to chemicals. of the most important priorities as:
Notably, advances within the field of endocrinology are • Protecting and further developing endocrinology as an
not only important for the prevention, treatment and attractive discipline to cover the increasing demand for
management of endocrine diseases. Endocrinology endocrine expertise;
often plays a fundamental role in the diagnosis and
• Providing uniform quality education in institutions and
monitoring of prevalent non-endocrine diseases in
European accreditation standards;
which hormones are used as biomarkers of disease (e.g.,
nt-proBNP, a type of protein produced by the heart, in • Ensuring equality of care; ensuring equal access to
heart failure) and treatment of non-endocrine diseases diagnosis and medical care;
(e.g., erythropoietin for renal and other causes of
anaemia). Improved cancer treatment outcomes come • Ensuring that research funding budgets are sufficiently
with long-term management of the consequences of allocated to the disciplines that need them most.
the disease and its treatment by endocrinologists.38
Novel immunotherapies against many different cancers
often display severe side effects related to endocrine
organs such as pituitary and thyroid permanent
dysfunction and fulminant diabetes (a subtype of type
1 diabetes), that without a strong multidisciplinary
approach may lead to anti-cancer drug discontinuation.
The complexity of the endocrine system means that
there is a need for multi-disciplinary integration of
endocrinology in clinical practice. Endocrinologists
combine their practice with acute internal medicine and
so are frequently caring for the most severe patients.
Case in point: the COVID-19 pandemic has seen
endocrinologists at the frontline treating patients
with the most critical symptoms but also disclosing
the clinical relevance of emerging endocrine features
of COVID-19 such as calcium, vitamin D and fractures.
For example, the improved treatment of hyperglycaemia
has demonstrated that patients under good glycaemic
control have a substantial decrease in mortality.
Moreover, the management of nutritional support is
crucial for preventing undernutrition and sarcopenia in
these patients. An increased level of funding for basic as
well as clinical research within the field of endocrinology
Hormones in European Health Policies: How endocrinologists can contribute towards a healthier Europe 1314 Hormones in European Health Policies: How endocrinologists can contribute towards a healthier Europe
Hormones in European Health
Policies: four key policy areas
Disruption of the normal functioning of the endocrine system can be caused by
inherited genetic conditions, but also through the direct impact of external factors
such as lifestyle, aggressive forms of medical treatments, and the environment we live
in. The following chapters – obesity, rare disease, cancer and Endocrine Disrupting
Chemicals – set out some of the key priority areas linked to endocrinology that are
having some of the biggest effects on societal health and healthcare spending today
and that are most relevant to the ambitions of European policymakers. While these
areas deserve priority attention in European health policies, ESE remains engaged in
securing better European and national health policies for all endocrine disorders.
Obesity The simplest way to diagnose obesity is by measuring
Body Mass Index (BMI), an index that is defined as a
person’s weight in kilograms divided by the square of
Obesity and the complex hormonal their height in metres (kg/m2). For adults, the World
relationship Health Organisation (WHO) defines obesity as a BMI
greater than or equal to 30, and generally speaking the
Obesity is defined as having abnormal or excessive
higher the BMI the more body fat.43
fat accumulation that presents a risk to health.4 The
traditional view of fat tissue (known as adipose tissue) Although BMI provides a useful population-based
is that it is an inactive reserve for energy storage – but measurement, it should be considered alongside other
in fact fat is an endocrine organ, producing over factors such as genetic predisposition, lifestyle (such as
600 different hormones.5 Adipose tissue is integrally stress and lack of sleep), medication and environmental
involved in coordinating a variety of biological processes considerations such as EDCs, which are all contributing
including energy metabolism, neuroendocrine function, to the rise in obesity.42 Other methods in addition to BMI,
and immune function.6 such as skinfold measurement, are used to determine
excess fat accumulation.
Obesity, a condition that is characterised by a
disturbance in normal metabolic homeostasis, should The two-way relationship between obesity and
therefore be defined as an endocrine condition, and is hormones is complex. Having an endocrine condition
a direct result of a chronic imbalance between energy can be an underlying risk factor for obesity, and
intake and energy expenditure with the excess energy increased body fat can lead to a number of hormonal
stored in adipose tissue.41 Once obesity is present, changes, such as insulin resistance,44 low vitamin D
weight reduction is difficult to accomplish, partly due and low testosterone levels. Indeed, several other
to disturbances of appetite regulating hormones. endocrine disorders, including insulinoma (tumour of
Often extra therapies are necessary in addition to a the pancreas), Cushing’s syndrome, hypothyroidism,
healthy lifestyle and addressing negative social factors polycystic ovarian syndrome and growth hormone
(e.g. poverty, stress). Treatments such as surgical deficiency are all associated with obesity.45
or pharmacological interventions and cognitive-
behavioural therapy may be required. People affected One example from the more than 600 hormones
by obesity face major discriminatory attitudes in relation produced by fat tissue is the hormone leptin which,
to employment, education and healthcare, as well when it works as intended, suppresses appetite.
as psychiatric comorbidities,42 when in fact they are However, people with obesity often develop excess
suffering from a disease and should be receiving leptin, leading to leptin resistance in the body – the
medical care. leptin simply does not work as it should anymore.
Obesity can also result from missing leptin or missing
function of the leptin receptor, underscoring that this
Hormones in European Health Policies: How endocrinologists can contribute towards a healthier Europe 15is not a simple issue but a complex endocrine problem attention in recent years, but it will be important not to
requiring endocrine solutions.46 Moreover, several neglect the policies required to address adult obesity as
lipophylic EDCs accumulate in the adipose tissue. Thus, well, such as reimbursement for lifestyle and treatment
the adipose tissue serves as a reservoir of EDCs that can options, and to include both prevention and treatment
be released into the system in response to hormonal options over the entire course of life.
stimulation.
Obesity and COVID-19
A global epidemic with associated
comorbidities There is growing evidence that people living with hormone
conditions such as diabetes, obesity, adrenal insufficiency
Obesity is fast becoming the most prevalent health
and Cushing’s syndrome face an increased risk of severe
issue globally, with estimations that more than half
infection with COVID-19. Studies show that 26% of
of all European adults are living with overweight or
COVID-19 patients with a symptomatic disease had
obesity.47 It is estimated that the global prevalence of
obesity, 15% had diabetes and more than 30% had already
obesity has increased almost threefold since 1975,
suffered from bone fractures. These individuals had worse
affecting 650 million adults in 2016.48
outcomes and poorer survival rates compared to people not
Obesity increases the risk of comorbidities, and suffering from obesity, diabetes or bone fractures.9,52,53,54,
is responsible for about 80% of cases of type 2
Policy efforts in relation to COVID-19 are currently
diabetes, 35% of ischaemic heart disease and 55% of
focusing on crisis management, vaccine research
hypertensive disease among adults in Europe.5 Obesity
and development, and potential treatments. It will be
is also a gateway disease for certain cancers, with nearly
important not to neglect the underlying conditions
40% of all cancers attributed to overweight and obesity.6
and factors that make populations vulnerable and
The economic and psychosocial costs of obesity are exacerbate the COVID-19 pandemic. Prevention
striking. Coupled with the economic costs of the and research around the connection of COVID-19 to
associated comorbidities, the impact on countries’ underlying health conditions such as obesity are critical
healthcare systems and workforces is vast. In 2014, in order to increase resilience and avoid overburdening
healthcare costs in Europe associated with healthcare systems.
overweight and obesity were estimated at €120.6
Experts are warning that vaccines may not work as
billion, and this is projected to rise by 63% to €197
effectively in people who are obese and are calling for more
billion by 2025.49
of this population to be included in COVID-19 vaccine
Paediatric obesity trials. Other existing vaccines are known to be relatively less
effective in people who are obese. Although the definitive
Levels of paediatric obesity are also rising across Europe
reason for this is not known, it could be due to factors such
and despite policy efforts aimed at obesity prevention,
as inflammation caused by obesity changing the behaviour
many countries in the European Region as designated by
of cells that fight infection, fat tissue making it harder to
the World Health Organisation (WHO) are continuing to
reach the muscle with the vaccine needle, or the body
struggle with increasing rates of childhood obesity.50 It is
requiring a higher vaccine dose.55
estimated that severe obesity affects some 400,000 of
the estimated 13.7 million children aged between six
and nine across 21 European countries.51
Even in childhood, obesity is associated with
socioeconomic costs and increases in healthcare
expenditures. The first six months of life are a
critical window for adiposity programming. A high
concentration of EDCs during this vulnerable period via
breastfeeding and/or the water in formula feeding has
great input on adiposity programming, via disruption of
appetite regulating hormones and hormones involved
in metabolism. Children who are obese are more likely to
remain so into adulthood, and obesity is associated with
adolescent cancer prevalence, impacting healthcare
systems and expenditure throughout their lifetime.43
The heterogeneous nature of obesity means that it
requires specialist knowledge by endocrinologists,
working within a multidisciplinary team, to determine
the cause and recommended treatment. The rise of
childhood obesity has gained much well-deserved
16 Hormones in European Health Policies: How endocrinologists can contribute towards a healthier EuropeThe European Commission has drafted a number
of initiatives and guidelines to support EU Member
“Body fat is not just a passive tissue for storage States, guided since 2007 by the Strategy on nutrition,
and isolation. More than 600 hormones and other overweight and obesity-related health issues.61 The
substances are produced in body fat, which is an strategy focuses on action that can be taken at local,
regional, national and European levels to reduce the
active organ. Some of the substances which are
risks associated with poor nutrition and limited physical
produced in fat have pro- or anti-inflammatory exercise, while addressing the issue of inequalities across
and immune functions, others affect appetite Member States. Science has evolved rapidly over the
and metabolism and yet others affect the body’s past 14 years, and it is therefore high time to update
sensitivity to insulin. So, fat is a conductor giving this strategy to complement scientific advances and,
and receiving instructions to and from the brain importantly respond to the prevalence of obesity in
Europe which has increased during this time.
and other parts of the body through the release of
hormones. When the amount of fat becomes too Relevant regulation also exists in other interlinked areas
large imbalances of the fat hormones occur, and where the EU does have legislative powers, such as the
these contribute to a state of chronic inflammation, Food Labelling Regulation,62 which makes it mandatory
to provide nutritional information. The Farm to Fork
with many adverse consequences. It seems also
Strategy, a key element of the 2019-2024 Commission’s
an important factor in the current COVID-19 Green Deal, promises to take this further, through
pandemic in which obesity is a clear risk factor for focusing on ensuring food security, nutrition and public
a more serious course of the disease.” health. In fact, one of the targets of the Strategy is to
reduce obesity by introducing healthy lifestyle habits
Prof. Elisabeth van Rossum MD PhD, among the population and trying to promote better
Obesity Center CGG, Erasmus MC nutrition. However, there is still room to reinforce both
Rotterdam, The Netherlands the ‘farm’ and the ‘fork’ side of the Farm to Fork Strategy
ESE Focus Area Lead Diabetes Obesity to phase out endocrine disrupting crop protection
Metabolism and Nutrition products and use the momentum to encourage healthy
lifestyle habits as well as environments and price
incentives that stimulate healthy behavior with respect
Obesity must urgently be treated as a to nutrition and exercise. Encouragingly, the Horizon
chronic relapsing endocrine disease Europe Work Programme for 2021-2022 will allocate
Acknowledging the growing proportion of people part of its funding to obesity.
suffering from obesity in Europe, the EU has created
various initiatives and campaigns in recent years to Within the research funding provided to address the
help fight the disease. How obesity is regulated and consequences of COVID-19, obesity has not yet been
prevented, and whether or not it is treated a disease, given sufficient attention.63 Partnering with scientific
varies among European countries. societies such as ESE and EASO, and multi-stakeholder
initiatives such as OPEN-EU, would help policymakers
On the occasion of World Obesity Day 2021, the find efficient and comprehensive solutions for emerging
European Commission published a new dedicated brief issues, from the obesity epidemic itself to how it overlays
on primary prevention of obesity in which obesity was with the global COVID-19 pandemic.
categorised as a major non-communicable disease.56
However, the European Commission has not yet taken
measures to have obesity uniformly treated as a chronic
endocrine disorder at European level, as recommended
by many other members of the medical community.57
Obesity is currently only classified as a disease in three
European countries – Italy,58 The Netherlands,59 and
Portugal.60 Around the world, the United States, Canada
and Israel also do recognise obesity as a disease. Given
the scientific evidence that it is an endocrine disease
requiring endocrine solutions, ESE believes that all
European countries should urgently and without
delay classify obesity as a disease. As an extension
of this, the EU and governments across Europe should
recognise the central role of hormones in preventing,
treating and living with overweight and obesity.
Hormones in European Health Policies: How endocrinologists can contribute towards a healthier Europe 17Rare endocrine diseases It is estimated that it takes an average of four years
to receive a rare disease diagnosis.67 Rare endocrine
diseases are often chronic and life-threatening68 and
Rare endocrine disease in Europe accurate estimations of their genuine economic cost and
Rare diseases, which affect fewer than 1 in 2,000 people,13 societal burden have not been properly quantified in the
are less well known and researched than more prevalent EU. Many rare diseases involve paediatric populations,
diseases, but cover a wide range of conditions. Despite which brings severe societal and healthcare costs, and
their rarity, these conditions collectively affect limited future opportunities in life for the individuals
approximately 30 million people across Europe13 affected by these diseases and their families.
and come with particular challenges related to time to
Advances in the management and treatment for rare
diagnosis, the need for innovative treatment options,
endocrine conditions are being made, including for
and investment into research. Due to the limited amount
pituitary disease, hypoparathyroidism, some rare
of strong epidemiological data, the real prevalence and
bone and lipid disorders, and rare diseases affecting
incidence of many of these rare diseases is not known.
children.14 However, new strategies to fund research and
Rare endocrine diseases include inherited disorders (e.g., clinical trials for conditions that affect a small number
congenital adrenal hyperplasia), cancer (e.g., multiple of patients – and therefore do not represent attractive
endocrine neoplasia syndromes), and conditions commercial value for innovative medicines – need to be
associated with metabolic disorders such as diabetes, developed.
calcium and bone metabolism, lipid metabolism,
hypogonadism, and adrenal, pituitary and thyroid
European Reference Networks (ERNs)
dysfunction.64 For paediatric and adult endocrinologists ERNs have been instrumental in creating clearly defined
care for patients with rare diseases constitutes a key structures for sharing knowledge and care coordination
focus for their activities, due to the multitude of diseases for specific rare diseases across the EU.69 Certain ERNs
with an endocrine component or origin. incorporate rare endocrine diseases into their health
remit including Endo-ERN,70 BOND-ERN,71 MetabERN,72
According to the European Registries for and EURACAN.73
Rare Endocrine Conditions65 there are over
440 distinct rare diseases that affect the
endocrine system.66
18 Hormones in European Health Policies: How endocrinologists can contribute towards a healthier EuropeName of network Geographical reach Thematic groups
Endo-ERN 71 reference centres • Adrenal disorders
& 15 affiliated • Disorders of calcium and phosphate homeostasis
The European partners in 27
Reference Network • Disorders of sex development and maturation
countries
on Rare Endocrine • Genetic disorders of glucose and insulin homeostasis
Conditions • Genetic endocrine tumour syndromes
• Disorders of growth and genetic obesity syndromes
• Pituitary disorders
• Thyroid disorders
ERN-BOND 17 expert centres • Osteogenesis imperfecta
from 10 EU Member • Achondroplasia
The European States
Reference Network • Hypophosphatasia
on Rare Bone • Multiple osteochondromas
Diseases • Fibrous dysplasia / McCune-Albright syndrome
• Pseudopseudohypoparathyroidism
• Other rare bone diseases (hypophosphataemia, fibrodysplasia
ossificans progressiva, others)
MetabERN 78 healthcare • Amino acid and organic acid diseases
providers in 23 EU • Disorders of pyruvate metabolism, mitochondrial oxidative
The European Member States disorders, thiamine transport and metabolism
Reference Network
for Hereditary • Carbohydrate, fatty acid oxidation and ketone bodies diseases
Metabolic Diseases • Lysosomal storage diseases
• Peroxisomal diseases and lipid related disorders
• Congenital disorders of glycosylation
• Neurotransmitter and small molecule disorders
EURACAN 66 healthcare • Sarcoma of the soft tissue, bone and viscerae (Sarcoma)
providers in 17 • Rare neoplasm of the female genital organs and placentas
The European European countries,
Reference Network • Rare neoplasm of the male genital organs, and of the urinary tract
and 22 Associate
for Rare Adult Solid Partners including • Neuroendocrine tumours
Cancers European Patient • Rare neoplasm of the digestive tract
Advocacy Groups • Rare neoplasm of endocrine organs
and rare disease • Rare neoplasm of the head and neck
stakeholders
• Rare neoplasm of the thorax
• Rare neoplasm of the skin and eye melanoma
• Rare neoplasm of the brain and spinal cord
Table 1 – Examples of ERNs and their activities. This table was developed in November 2020
These knowledge-based networks have been critical in as currently endocrinologists focused in this area have
shaping the rare disease policy space. However, greater limited capacity to be involved with these programmes.
support from the EU is needed to improve their
functionality and to improve health outcomes in rare Experts advise that many countries in Europe are not
disease patient populations. aware of the existence of these reference networks, so
increased promotion within the medical community and
Although Europe is ahead of other regions with regard to towards European and national institutions is needed.
reference networks, the level of funding is not sufficient Moreover, interaction between European and national
to allow for lead research projects to be undertaken institutions should also be fostered.
within these networks. Funding and resources to
manage projects and ERN infrastructure and to be able The EU should continue evolving and expanding funding
to collect good quality data in these registries is required, for ERNs so that they can expand their activities, for
example through the research programme Horizon
Hormones in European Health Policies: How endocrinologists can contribute towards a healthier Europe 19Europe, which should play a more prominent role the EU to obtain a better understanding of the links
in supporting the ERNs due to their significance for between rare (endocrine) diseases and COVID-19. On a
European research in the area of rare cancers and more positive note, COVID-19 has fostered the uptake
other rare diseases. Increased funding would also of digital tools for patients, including for example virtual
help the ERNs better coordinate the projects and consultations. These digital tools may help improve care
their infrastructure and compensate patients and the and patient outcomes in the future.
medical/academic communities for giving their valuable
time to the study of these diseases. A unique European opportunity to improve
livelihoods for rare disease patients
In addition to the ERNs, the EU institutions have
“As a patient, I really appreciate the founding developed a number of programmes focused on
of ERNs because for the first time, patients are financing research and innovation in the area of rare
really part of a network in which they have the diseases. The main tool through which the European
opportunity to work side by side with healthcare Commission has been contributing to this is the EU
professionals and give their opinion on important Framework Programmes for Research and Innovation.
Altogether more than €1 billion has been committed in
matters concerning them. For example, endocrine collaborative research through the Seventh Framework
patients all over Europe were recently asked for Programme (FP7)78 and Horizon 202079 in more than 200
their opinion on patient information materials projects related to rare diseases. Many of these projects
and their unmet needs in medical research. The link with the ERNs.
outcomes of these surveys will be used to shape The EU4HealthProgram,80 drafted by the European
the research agenda and will give insight into how Commission in the wake of COVID-19, makes reference
to reach out to even more patients in the future. to the specific burden of rare diseases on the challenges
Patient representatives are involved on a voluntary faced in the areas of health security and health systems.
basis and though Endo-ERN does its utmost to Concretely, the EU4Health package promises a welcome
make their involvement possible, improved funding scale-up of networking and extending the ERNs to
non-communicable diseases. Furthermore, the EU also
mechanisms would enable the ERNs to compensate pursues efforts to increase visibility in the public domain
patients better for their time.” on the topic of rare diseases and supports the national
Johan de Graaf, plans for rare diseases in EU countries. The EU should
Dutch Pituitary Foundation ensure comprehensive implementation of National Rare
ERN patient representative, Disease plans, as these plans help give rare diseases high
living with pituitary adenoma/ relevance among national health policies.
hypopituitarism There is an established legislative framework to
provide incentives for the development of drugs for
rare diseases (orphan medicines). The Regulation on
Rare endocrine diseases and COVID-19 Orphan Medicinal Products81 was first adopted in 2000
People living with certain rare diseases may have a to encourage pharmaceutical companies to develop
higher risk of serious illness from COVID-19.74 There medicines for rare diseases. A number of drugs in the
is uncertainty around the risks of serious disease in this pituitary, bone and calcium, and rare lipid disease
community due to the difficulties in prognosis and the areas have benefitted from coming to market with the
small number of people affected, who can often have orphan designation. An evaluation of this legislation was
very individualised symptoms and comorbidities.75 published in August 202082 – the next expected step is
Further research in this area and support for some of the an Impact Assessment of possible legislative options.
most vulnerable patients, whose feelings of isolation This evaluation is an opportunity to support an effective
may be exacerbated at this time, is needed. According instrument for channelling R&D into specific therapeutic
to a study by EURORDIS, COVID-19 caused severe areas and the development of pathways in national
disruptions to care for 83% of people living with a pricing and reimbursement schemes to better assess
rare disease.76 the value of these type of medicines. Regardless of how
the impact assessment progresses, rare disease patients
The ESE Rare Disease Committee, alongside ENDO- would benefit if governments increase funding for
ERN, has engaged in an initiative to collect essential Orphan Medicinal Products to provide better incentives
data concerning specific groups of patients with for the development of medicines.
rare endocrine conditions, who are also affected by
COVID-19. This project is designed to understand the Furthermore, one of the main problems faced by
occurrence of a wide range of conditions to allow the medicines for rare diseases is reimbursement. The bar
clinical networks to objectively map the conditions and for orphan medicines is very high; health technology
activity.77 Similar initiatives should be stimulated across assessment bodies and payers expect the same
20 Hormones in European Health Policies: How endocrinologists can contribute towards a healthier Europerobustness of evidence as compared to medicines for to provide EU-wide assessment of how new health
other more prevalent diseases. However, the scientific technologies compare with existing treatments. The EU
evidence is more difficult to gather due to the rarity of should urgently move forward on European-level HTA
the diseases they are meant to treat. legislation and joint funding to make medicines for rare
diseases available and affordable in all EU countries.
European Health Technology Assessment (HTA) Some progress has been made in the framework of the
legislation is therefore another avenue that could European Network for Health Technology Assessment
improve accessibility for patients with rare diseases. The (EUnetHTA) which aims at defining and implementing
HTA file has been underway for several years now, but it a sustainable model for the scientific and technical
had not progressed since Council discussions in 2019.83 cooperation on HTA in Europe. Nevertheless, this effort
In April 2021, the Council agreed on its negotiating is voluntary for Member States and its impact is yet to be
mandate which will hopefully unlock negotiations seen.84
with the European Parliament. The legislation aims
Cancer and endocrinology postmenopausal breast and colorectal cancer – all
related to the endocrine system – account for many of
the cancers attributed to obesity.
Cancer is the second leading cause of death and
morbidity in Europe, with more than 3.7 million new cases 5. T
he impact of environmental factors. Exposure
and 1.9 million deaths each year.16 It is estimated that to EDCs is known to have an effect on different
40% of all EU28 citizens will face cancer at some point in hormones, and is associated with reduced fertility,
their lives.85 Cancer care is rapidly evolving, with the costs impaired neurodevelopment, and the development of
of treatment frequently debated. Studies in 2018 show obesity and cancer. 92,93,94,95
that in Europe, the estimated costs of cancer to society
Endocrine cancers
were approximately, in the region of €199 billion.86
Endocrine cancers begin in the glands that secrete
The interaction between endocrinology hormones. Tumours can occur in any of the major
glands of the body, including the thyroid, pituitary and
and cancer is complex, and new research adrenal glands, and the pancreas.96 In addition, because
has highlighted the intricate nature of this endocrine tumour cells grow from cells that produce
interaction in terms of prevention, treatment hormones, the tumour itself can produce hormones that
can cause serious illness.97 As an example, endocrine
and post-treatment care. glands such as the testis or the ovary can be affected
There are five significant ways in which the endocrine by malignancies and have negative impacts on basic
system relates to cancer: functions like reproduction.
1. Classic endocrine cancers. Certain endocrine Endocrine cancers are considered rare, but despite this,
cancers are on the rise. Thyroid cancer has seen certain types are on the rise. The most common type of
increases of >50,000 new cases per year,87 and more endocrine cancer is thyroid, which has seen increases
than 60% of neuroendocrine tumours (NETs) are of more than 50,000 new cases per year83, and is now
diagnosed at a late stage, impacting the outcomes of the second most common cancer in young women
these cancers.88 The incidence of breast and testicular after breast cancer.98 Although some of the increase
cancers is also on the rise.89, 90 in incidence is likely to be due to improved detection
at the early stages of the disease, other factors such
2. Hormone-dependent cancers and their endocrine as obesity have been identified as contributing to the
treatments. For instance, prostate cancer or breast increase in incidence rates.99,100 Another example is
cancer antiandrogens/antiestrogens have endocrine neuroendocrine tumours (NETs). NETs originate from
side effects (muscle and bone loss, fractures, neuroendocrine cells that are the intersection between
cardiometabolic risk). the nervous and endocrine systems. Neuroendocrine
cells are found in organs throughout the body (pancreas,
3. Long-term effects of cancer treatments. The lung and breast, to name a few), and perform specific
endocrine system is vulnerable to aggressive functions such as regulating the air and blood flow in the
anti-cancer treatments that result in endocrine lungs and the speed at which food moves through the
comorbidities in cancer survivors.91 gut.93 Although NETs are also considered as rare, their
4. Obesity as a risk factor. Obesity has been identified incidence and prevalence has been steadily rising.101 As
as an independent risk factor for many cancers, they are frequently diagnosed late due to their body-
with nearly 40% of all cancers attributed to being wide presentation and variability, patients generally
overweight and obese.7 In particular endometrial, experience worse outcomes, with the median survival for
patients with advanced NETs at just 33 months.84
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