Perspectives For Progress Female Athlete Triad99743

ESSR Published Ahead-of-Print
Heading: Perspectives for Progress
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Accepted: 06/13/2019
Editor: Sandra K. Hunter, PhD, FACSM
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Perspectives for Progress - Female Athlete Triad and Relative Energy Deficiency in Sport:
A Focus on Scientific Rigor

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Nancy I. Williams, Sc.D., FACSM, FNAK1; Kristen J. Koltun, MA1; Nicole C.A. Strock, MS1;
Mary Jane De Souza, Ph.D., FACSM, FNAK1

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1
Women's Health and Exercise Laboratory, Department of Kinesiology, The Pennsylvania State
University
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Exercise and Sport Sciences Reviews articles in the Published Ahead-of-Print section have been peer-reviewed and
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Copyright © 2019 by the American College of Sports Medicine www.acsm-essr.org

Exercise and Sport Sciences Reviews, Publish Ahead of Print
DOI: 10.1249/JES.0000000000000200
Perspectives for Progress - Female Athlete Triad and Relative Energy
Deficiency in Sport: A Focus on Scientific Rigor
Nancy I. Williams, Sc.D., FACSM, FNAK1; Kristen J. Koltun, MA1; Nicole C.A. Strock, MS1;
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Mary Jane De Souza, Ph.D., FACSM, FNAK1
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1
Women's Health and Exercise Laboratory, Department of Kinesiology, The Pennsylvania State
University
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Address for Correspondence:
Nancy I. Williams, Sc.D., FACSM, FNAK

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Professor and Head
Department of Kinesiology
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Co-Director, Women's Health and Exercise Laboratory
The Pennsylvania State University

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276 Recreation Building
University Park, PA 16802
Email: niw1@psu.edu; Phone: 814-863-1163
Conflicts of interest; disclosure of funding: none
Copyright © 2019 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
Abstract
We examine the scientific evidence supporting The Female Athlete Triad and Relative Energy in
Sport (RED-S) syndromes. More research is necessary to advance the understanding of both
syndromes; however, it is premature to consider RED-S as an evidence-based syndrome. Future
research should specifically define RED-S components, determine its clinical relevance, and
establish the causality of relative energy deficiency on RED-S outcomes.
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Summary for table of contents
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More Triad and RED-S research is needed. The scientific and clinical basis of RED-S needs to
be established.
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Key Words: Eating disorders; male athlete triad; menstrual cycle; low energy availability;
osteoporosis; immune; performance
Key Points
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 Confusion exists regarding the Female Athlete Triad (Triad) and Relative Energy Deficiency
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in Sport (RED-S). Although the syndromes overlap, they differ in the scope of outcomes and
populations targeted.
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 Position stands and consensus statements for both syndromes should reflect the highest level
of scientific rigor and quality of evidence possible
 Female Athlete Triad research has defined its components, their inter-relatedness, its clinical
relevance, and the causal role of low energy availability
 Future Triad research should develop the male athlete triad model, determine the long-term
health effects of the Triad, and demonstrate the validity and effectiveness of other strategies
to measure energy availability.
 To date, research on RED-S does not support the current conceptual model.
 Future research on RED-S should establish its clinical relevance, clearly define the
components RED-S, and test whether relative energy deficiency is causally related to both
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the health and performance RED-S outcomes proposed.
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INTRODUCTION
It is well established that regular exercise and physical activity promote numerous health
benefits for girls and women (1, 2). However, under some conditions and in some girls and
women, participation in sports and exercise can be associated with negative health outcomes.
There are currently two schools of thought and corresponding conceptual models regarding the
potential for negative health outcomes of participating in sports and exercise: The Female
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Athlete Triad (Triad; (2-4)) and Relative Energy Deficiency in Sport (RED-S; (5-7)). The Triad
is referred to in position stands from 1997 (8) and 2007 (2), and a recent consensus statement in
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2014 (3, 4), and RED-S is the topic of a consensus statement from 2014 (5) and a recent update
(6).
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Both the Triad and RED-S statements call attention to the importance of adequate energy
intake in order to prevent negative health outcomes associated with the participation in sport and
exercise. They both include point system algorithms for risk stratification and decision making
on clearance and return to play. However, the Triad and RED-S models differ in several ways,
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including the target audience and scope of outcomes. The Triad refers to girls and women and is
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focused on low energy availability and associated clinically relevant outcomes, for example,
disordered eating, menstrual dysfunction, and bone loss (2-4). RED-S covers a broader array of
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both physiological and performance outcomes in both women and men and calls for more
research on the impact of race, ethnicity, and disability (5, 6). The two statements also differ in
the way supporting evidence and scientific rigor is interpreted and incorporated into the models
representing each syndrome. The authors of the more recent RED-S consensus statement
consider the RED-S model to be more comprehensive than the Triad model and have, therefore,
called for the “replacement” of the Female Athlete Triad with RED-S (5). An alternative view is
that replacing the Triad with RED-S will: a) dilute the emphasis on girls and women when it is
they who experience the most severe medical consequences and, thus, need the most attention, b)
downplay the clinical relevance of eating disorders, menstrual disturbances, and low bone mass
as the primary medical outcomes associated with low energy availability, and c) distort the
understanding of the physiological underpinnings of the Triad (9).
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At this time, controversy (9) and a lack of clarity exist regarding the existence of the two
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models. There has been no attempt to directly contrast or compare the two perspectives, nor to
explore where they may be complementary. This lack of clarity may lead to inconsistencies in
knowledge translation and policy development without rigorous supporting data. The existence
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of two different point system algorithms to assist with decision making regarding clearance and
return to play (3, 4, 7) is confusing. Sports medicine personnel benefit from clarity from
researchers and clinicians, particularly when evidenced-based position stands and consensus
statements are published. Shedding light on similarities and differences and reviewing supporting
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evidence for each model should help consumers of this literature make evidence-based decisions.
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To this end, we highlight key differences in the Triad and RED-S models with a focus on
scientific rigor and quality of evidence.

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Position stands and consensus statements are critical for knowledge translation.
Developed using a systematic review of peer-reviewed scientific literature, they are utilized for
developing: a) educational tools and metrics, b) clinical decision-making tools, c) reports of
clinical practice guidelines, d) an understanding of gaps in the literature, and e) short and long-
term research agendas (10). A discussion of evidence-based publications raises the issue of
scientific rigor, which has been the topic of a large number of recently published editorials and
articles (11-13). The use of evidence-based grading systems in the writing of position stands has
become increasingly common and assures that scientific rigor is upheld. The quality of scientific
evidence is graded depending on the nature of the experimental design, the size of the sample
studied, the validity and reliability of the measures, and the importance and robustness of the
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hypothesis addressed (14, 15). As the scientific community considers the advancement of our
understanding of the Triad and RED-S, careful attention should be given to scientific rigor,
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quality of the evidence, and clinical relevance. Specifically, the key role of low energy
availability (Triad model) and relative energy deficiency (RED-S model) in each model is
discussed.
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CONCEPTUAL MODELS
The Female Athlete Triad Model

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The Female Athlete Triad was first described in 1993 (16) and again by the American
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College of Sports Medicine (ACSM) in 1997 (8) as a clinical syndrome involving disordered
eating, amenorrhea and osteoporosis which was frequently observed in physically active girls
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and women and female athletes. ACSM updated the new knowledge about the Triad in 2007 and
revised its model components to consist of low energy availability with or without disordered
eating, menstrual cycle disturbances, and low bone mineral density (BMD) (2). More recently,
the Female Athlete Triad Coalition, an organization of researchers, clinicians, and practitioners
dedicated to research and education on the Triad, published guidelines on the treatment and risk
management strategies for clearance and return to play in 2014 (3, 4). The current Triad model
illustrates the three clinical issues on continua from healthy to disease (FIGURE 1). The
subclinical manifestations of each condition are illustrated along each continuum (2). The
directions of the arrows that link each of the three conditions illustrate how they are related to
one another. The bi-directional arrows along each continuum illustrate the reversibility of the
conditions such that each condition can improve or become worse. The unidirectional arrows
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from energy availability to menstrual function and bone health, and from menstrual function to
bone health, represent the causal roles of low energy availability and hypoestrogenism in bone
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loss (2). The Triad model specifically identifies low energy availability and disordered eating by
indicating that low energy availability can occur with, or in the absence of, disordered eating.
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The RED-S Model
RED-S was proposed to be an update of a previously published International Olympic
Committee (IOC) Position Stand and an expansion of the Female Athlete Triad model (5, 6).
Since 2014 (5), there has been one update (6). The RED-S model uses the new terminology,
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relative energy deficiency, defined as “an energy deficiency relative to the balance between
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dietary energy intake and the energy expenditure required to support homoeostasis, health and
the activities of daily living, growth and sporting activities” (5). Broader in scope than the Triad,
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the RED-S model illustrates direct relationships between relative energy deficiency as a center
hub, and the physiological outcomes stemming from this hub (FIGURE 2; (5, 6)). In all but one
case (psychological), the direction of arrows is from relative energy deficiency outward to each
of these physiological systems, indicative of proposed direct relationships of relative energy
deficiency on all of the health and performance outcomes listed. It is purported that "the
syndrome of RED-S refers to impaired physiological function including, but not limited to,
metabolic rate, menstrual function, bone health, immunity, protein synthesis, and cardiovascular
health directly caused by relative energy deficiency” (5, 6). A second spoke and wheel figure
(FIGURE 3) illustrates the potential effects of relative energy deficiency on performance and
conditions that can impact performance (5, 6). Uni-directional and direct relations between
relative energy deficiency and aspects of performance are represented such as decreased
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glycogen stores, decreased endurance performance, increased injury risk, decreased training
response, impaired judgement, decreased coordination, decreased concentration, irritability, and
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depression. Notably, the RED-S consensus statements include males and female athletes as target
audiences (5). The RED-S model holds that the clinical phenomenon is not a “triad” of the three
entities of energy availability, menstrual function, and bone health, but rather a syndrome that
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affects many aspects of physiological function, health, and athletic performance (5).
CLINICAL RELEVANCE VS PHYSIOLOGICAL "IMPAIRMENT"
Each physiological "impairment" in RED-S is considered to threaten one's health and

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warrant treatment. An example where physiological versus clinical relevance can be questioned
is the inclusion of “cardiovascular” as a health consequence of RED-S. It is stated that “low

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[energy availability] causes unfavorable lipid profiles and endothelial dysfunction, thereby
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increasing cardiovascular risk” (5). While unfavorable lipid profiles and decreased endothelial
function have been documented in exercising women with functional hypothalamic amenorrhea
(17), the long-term cardiovascular consequences of these changes in this population are unknown
(18) and it would seem prudent to weigh any such risks against the protective effects of exercise
(19).
In contrast to RED-S, the focus in the Triad model is on three clinically relevant
conditions associated with low energy availability: eating disorders or disordered eating,
menstrual dysfunction, and bone loss (2-4). Studies documenting the underlying metabolic and
endocrine changes associated with low energy availability are cited in the Triad literature. For
example, the modest elevation in hypothalamic pituitary adrenal axis activity and the decrease in
circulating triiodothyronine (T3) concentrations are described, but in the context that these
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changes illustrate physiological plasticity, not threats to health or medically concerning changes
in and of themselves (2, 8). That is, when the availability of oxidizable metabolic fuel is low, the
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body repartitions energy away from reproduction and growth in order to maintain basic
physiological processes such as cellular maintenance, thermoregulation, locomotion, and
immune function (20). In exercising women who chronically experience low energy availability,
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this repartitioning of metabolic fuel is characterized by decreases in resting metabolic rate and
shifts in key metabolic hormones, such as suppression of T3, insulin-like growth factor-1 (IGF-
1), and leptin, and upregulation of growth hormone and cortisol (21-23) in an effort to conserve
fuel. The repartitioning of metabolic fuel results in the suppression of reproductive function and
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growth, with the concomitant emergence of the clinical outcomes of menstrual cycle dysfunction
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and low bone mass. Accompanying endocrine and metabolic changes, such as a modest increase
in cortisol, are not outside normal physiological ranges (23-27), and, thus, they do not represent
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unhealthy outcomes in and of themselves, but rather, physiological plasticity. In contrast, by
asserting that all physiological effects of relative energy deficiency are equally associated with
poor health across a long list of systems, the RED-S model dilutes the clinical relevance of the
effects on bone and menstrual function.
SCIENTIFIC RIGOR IN THE TRIAD AND RED-S MODELS
A focus on scientific rigor is essential when interpreting consensus statements and
position stands. Scientific rigor and reproducibility are the cornerstones of scientific
advancement (13) and scientific rigor is a strong focus of National Institutes of Health (NIH;
(28)). Scientific rigor is the stringent adherence to the scientific method in all aspects of
experimental design, methodologies, analyses interpretation, and reporting of results. It is a
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means to uncover scientific truth and minimize the premature adoption of unfounded hypotheses
(11-13, 29). The “plausibility” of a concept is rarely used as the basis for a consensus statement
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or position stand (12, 29). Rather, the results and interpretation of numerous scientific
experiments are used to build evidence-based knowledge and are essential components of the
rigorous testing of a hypothesis (11-13). Accordingly, consensus statements should reflect the
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quality and preponderance of evidence from published studies at the time of their writing. The
quality of evidence is enhanced by the extent to which the model illustrates key features such as
specificity, causality, differentiation between normal physiologic variation and pathological
outcomes, and reversibility of the condition. Hence, a comparison of the Triad and RED-S
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models from this perspective is warranted.

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Scientific rigor is also enhanced by peer review and debate. The evolution of the Triad
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literature has included varied perspectives and debate (30-35). One of the earliest debates
centered on whether normal menstrual cyclicity was dependent on a critical level of body fat (34-
38). Later criticisms focused on the sociological implications of drawing attention to health
concerns associated with exercise (30) and the lack of data on the prevalence and interrelatedness
of the Triad (32). These challenges spurred useful discussion and research to address identified
gaps. Advances include studies that demonstrate the causal role of energy availability/energy
deficiency on menstrual function and bone health (21, 23, 39-43), document the prevalence of
Triad conditions (44-46), and examine recovery from the Triad (47). Current debates include the
utility of particular definitions of energy availability in non-laboratory settings (48), and the role
of psychogenic factors in the modulation of reproductive function (49). Thus, controversy and
debate in research can be viewed as a positive force for advancing scientific rigor and
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reproducibility (50).
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Specificity and Scope of Components in the Triad and RED-S Models
The Triad Model
The degree to which elements of a biomedical condition are clearly defined and
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quantified improves our understanding and enhances the potential for verifying reproducibility
with confirmatory research. The three main components of the Triad have been defined and the
units of measurement quantified (2). For example, the variable of low energy availability has a
particular conceptual definition and standard units of measure which arose from a set of
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experiments by Loucks and colleagues on the effects of various levels of energy availability on
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luteinizing hormone (LH) pulsatility and other endocrine endpoints (23, 25, 51, 52). As defined
by Loucks, energy availability represents the energy left over for vital bodily processes after
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accounting for the energy expenditure associated with purposeful exercise (23, 25). This
definition and the utility of this metric are being tested and debated (48, 53-55) and given our
advancement in understanding energy availability in exercising women since 2007, future
position stands and consensus statements likely will reflect revisions to this concept, particularly
around the use of an absolute energy availability threshold. Other work has subsequently
identified the magnitude of energy deficiency associated with the initial induction of menstrual
disturbances with exercise combined with caloric restriction in untrained women (43).
Regarding the eating behaviors described as the “with or without disordered eating" component
of the Triad, particular definitions and criteria for diagnosis are referred to in the 2007 ACSM
position stand (2) and expanded in the 2014 Female Athlete Triad Coalition Consensus
Statement (3, 4). The bone health component of the Triad has also evolved as the science of the
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Triad has progressed to its current definition of low bone mineral content (BMC), BMD, or areal
BMD Z-score that is less than or equal to -2.0, adjusted for age, gender and body size, as
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appropriate (3, 4). These specific definitions of the components of the Triad allow the
measurements to be assessed consistently and accurately, maximizing application, and permitting
its outcomes to be diagnosable.

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The RED-S Model
Relative energy deficiency is the cornerstone of the RED-S model, but no definition and
no units of measure are provided (5, 6). The definition of relative energy deficiency as published
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reads "an energy deficiency relative to the balance of dietary energy intake and the energy
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expenditure required to support homeostasis, health and the activities of daily living, growth and
sporting activities” (5, 6). There are no specific guidelines on how to measure relative energy
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deficiency presented in the RED-S IOC Consensus Statement and the concept is not
experimentally derived. Thus, it is unclear how the concept can be applied to assess energy status
in the exercising female or male. Notably, in the RED-S consensus statement, and subsequent
RED-S publications (5-7), the term relative energy deficiency is used interchangeably with low
energy availability, and the evidence provided in support of relative energy deficiency derives
from that originally presented by Dr. Loucks in defining energy availability and that used in the
Triad model. As such, it is difficult to define which variable represents the cornerstone of RED-
S: the measurement representative of the definition described in RED-S publications or that of
low energy availability as proposed in the Triad literature.
The physiological and performance-related outcomes that are depicted in RED-S as
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outcomes of relative energy deficiency are not specifically defined (5, 6). For example, "immune
function," "hematological," and “cardiovascular” are direct outcomes of RED-S, but these
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outcomes refer to physiological systems rather than quantifiable and reproducible outcomes,
making it is difficult to confirm or refute these components of RED-S through scientific studies.
The magnitude of relative energy deficiency that might be related to various physiological,
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performance, or psychological outcomes is not described. Defining what degree of energy
deficiency can cause mental impairment, cardiovascular impairment, or declines in muscle
strength needs to be demonstrated. Future studies that are designed to test the effects of varying
levels of relative energy deficiency on these particular outcomes are necessary to address these
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questions. Overall, the lack of specificity of the RED-S model invites confusion regarding clarity
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and prompts important questions with respect to the quality of the evidence supporting the
model.
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The inclusion of male athletes, athletes across racial and ethnic groups, and disabled
athletes in the RED-S model has led to a heightened awareness of the effects of low energy
availability in these populations (56). However, effects of gender, race, and ethnicity is a focus
of NIH as many physiological systems function uniquely in men and women, and across racial
groups, and this literature has evolved in recent decades (57, 58). Targeted research is necessary
to specifically define the role of low energy availability/energy deficiency on health effects in
these groups before the supposition that RED-S affects men, women, and all racial and ethnic
groups similarly can be supported. To this end, a roundtable discussion of evidence supporting a
"Male Athlete Triad Model" occurred at the American College of Sports Medicine meeting in
2017, and a Female and Male Athlete Triad Coalition sponsored consensus statement is
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forthcoming.
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Identifying Causality in the Triad and RED-S Models
Although scientific progress relies on all types of studies – such as observational,
association, prospective, randomized controlled trials, and those in animal models – actual
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experiments that successfully isolate causal factors are required for significant advances in our
understanding (11-13, 28). The use of arrows in the Triad model depicts not only the direction,
but also the causal nature of the association (2). Experiments demonstrating the causal role of
low energy availability/energy deficiency on the induction of menstrual disorders (21, 43, 59)
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and on poor bone health (39, 41, 52) support the concepts depicted in the Triad model. Ongoing
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work is identifying the causal role of energy availability in the reversal of menstrual disturbances
and bone loss (60) and there is still much to learn regarding the long-term health effects of the
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Triad. In the RED-S model, relative energy deficiency is associated, via uni-directional arrows,
to 10 different physiological systems and 10 performance outcomes (5, 6). The assumption
implied by these uni-directional arrows is that these associations are causal and direct, but the
evidence to support these direct associations for many of the outcomes is not included in the
RED-S 2014 IOC Consensus Statement and update (5, 6). Relative energy deficiency does not
exert direct and equal effects on all physiological systems as the RED-S model suggests, but
rather exerts some of its outcomes indirectly via intermediate physiological changes.
Low energy availability and energy restriction have direct and causal effects on
menstrual function (21, 43, 59, 61, 62), and bone health (39, 41, 52). However, energy deficiency
also has indirect effects on bone health through hypoestrogenism secondary to chronic energy
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deficiency (63, 64), which is not illustrated by the RED-S model. In the RED-S model, relative
energy deficiency is described to increase cardiovascular risk due to the development of
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unfavorable lipid profiles and endothelial dysfunction (5). However, it is the hypoestrogenic state
that develops secondarily to low energy availability that has been proposed as the mechanism
underlying changes in lipoproteins and endothelial function (17). The RED-S model would be
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improved if it included an arrow connecting “menstrual function” to “cardiovascular” to
highlight the indirect relationship between these two health outcomes, similarly to how
menstrual function is connected to bone health in the Triad model (3, 4).
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The RED-S Consensus Statement describes an effect of relative energy deficiency on

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immunity, but no prospective studies are cited to support this. One report is cited in the RED-S
2018 update (6) linking relative energy deficiency to immunity but it is possible that the physical
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effects of exercise training or hypoestrogenism are the causes of impaired immune function (65).
Shimizu et al. (65) state that intensive exercise training, as opposed to an energy related factor,
reduces salivary immunoglobulin A secretion and increases susceptibility to upper respiratory
tract infections in athletes, and they fail to link their findings directly to relative energy
deficiency. Similarly, a single observational study relating a greater prevalence of viral illnesses
to relative energy deficiency in Olympic athletes is based on the response to a question asking
whether the individual had been “ill for one week or more during the past [three] months” (66).
Although the prevalence of self-reported illness in the prior three months was greater in athletes
in leanness sports, there is no evidence that the athletes had signs of energy deficiency (66). In a
more recent report (67), no definition of “immunological function” was provided, but it was
reported that there was no difference in immunological function between athletes divided into
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low energy availability and adequate energy availability groups based on a conglomerate of self-
reported and indirect measures of energy availability.
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Gastrointestinal problems are a defined endpoint of relative energy deficiency in the
RED-S Consensus Statement (6, 7), but the citation regarding gastrointestinal complications
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traces back to the eating disorder literature, specifically. It is possible that gastrointestinal
symptoms may be secondary to eating disorder behaviors (68-72), including bingeing and
purging, rather than being secondary to relative energy deficiency. More recently, Ackerman et
al. (67) reported a higher self-reported incidence of gastrointestinal symptoms in athletes who
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were classified as having low energy availability based on questionnaire data. However, no
definition of “gastrointestinal symptoms” was provided. Moreover, interpreting this finding is

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challenging since there is an established literature documenting gastrointestinal issues in athletes

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with contributing factors inclusive of mechanical forces and neuroendocrine changes (73),
altered gastrointestinal blood flow (74), ischemia (75), and inflammatory bowel disease (76).
A second spoke and wheel diagram in the RED-S model illustrates direct effects of
relative energy deficiency on ten different aspects of athletic performance, ranging from
decreased endurance and muscular performance to irritability, decreased concentration and
coordination, and impaired judgement (5, 6). However, there are few studies cited that support
these claims. Many references to performance in the RED-S literature do not include assessments
of human performance, but rather, functional limitations such as dehydration, electrolyte
imbalances, and gastrointestinal problems such as esophagitis or mucosal atrophy (5, 77, 78).
One study often cited in junior elite female swimmers (79) is one of the few supporting studies
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that includes biological measures of energy availability and actual performance measures
(defined as swim velocity). Another consideration when discussing performance is whether the
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effects of exercise itself are controlled for. There is much potential for overlap between the
overtraining literature and the purported effects of RED-S on performance as decreases in sport-
specific performance, emotional/mood changes, lack of motivation, sleep disturbances, overuse

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injuries, and immune dysfunction are all signs of overtraining syndrome (80-82), and are cited as
“health detriments” for RED-S (5, 6).
Based on the research cited in the RED-S publications, it can be argued that there is
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insufficient evidence to date relating relative energy deficiency to the additional physiological
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and performance outcomes depicted in the model, particularly the purported effects on immune,
cardiovascular, gastrointestinal, growth and development, hematological, and performance

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outcomes. More research must include experiments that establish the direct and causal influence
of relative energy deficiency on these endpoints, and such experiments will need to establish that
the effects of relative energy deficiency are independent of the physical effects of exercise. With
regard to the Triad, much work needs to be done to address the impact of modifying factors such
as gynecological age, genetics, and psychogenic stress on the susceptibility to menstrual
disturbances during conditions of low energy availability (83).
Healthy to Pathological Continuum and Reversibility
The 2007 Triad model is in the form of an expanded, 3-D triangle where each of the three
aspects of the Triad exists on a continuum from healthy to pathological (2). The endpoints at the
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healthy and pathological ends of each continuum are specifically defined and quantifiable. Both
the induction and the reversibility of Triad conditions have been explored and it has been
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clarified that individuals can move along the three continua in either direction. Scientific
evidence supports this bi-directionality and the fact that subclinical conditions exist “along the
way” (2). Subclinical menstrual disturbances have been defined both cross-sectionally (44) and
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prospectively (42, 43, 59). Short-term changes in bone turnover markers in response to low
energy availability (52, 84) and animal models of the Triad (39, 41) illustrate prospective
changes in bone metabolism and bone mineral density. It has also been clarified that the rates of
change along the three continua of the Triad are vastly different. In other words, changes in
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energy availability can happen across the day, or from day to day, whereas changes in menstrual
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function may take weeks to months, and changes in bone density, structure, and geometry take
months to years (3, 4).

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Experiments illustrating the reversibility of low energy availability/energy deficiency and
its impact on reproductive function have been performed (21, 85, 86). However, a key gap in the
Triad literature is the question of whether bone loss can be recovered with the reversal of low
energy availability. Case studies (87, 88) and observational studies (89) have been published on
this issue, but until recently, no randomized controlled trials have addressed this question. This
question is being addressed by a randomized controlled trial (47), but more studies are necessary
to address the recovery of bone health. The RED-S model does not depict continua from a
healthy state to a pathological state, and it is not known whether the effects of relative energy
deficiency on gastrointestinal function, cardiovascular function, immune function, growth and
development, and hematological function are reversible. If RED-S is to be understood as a
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biomedical syndrome, future research should address the reversibility of RED-S outcomes when
a correction of relative energy deficiency is achieved.
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FUTURE PERSPECTIVES
The benefits of exercise and physical activity to human health and wellbeing are clear
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and provide a strong rationale for the current recommendations for the quantity and types of
exercise. Thus, there are important public health concerns when recommendations are
formulated to warn about negative clinical consequences associated with exercise training. As
such, intense scrutiny is warranted when considering the scientific evidence supporting such
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claims. Removing an athlete from competition, or advising an adolescent girl that her exercise is
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contributing to low energy availability and that she needs to reduce her training, can have a
significant impact on the individual's quality of life given the positive impact of exercise on
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health and wellness. Moreover, the potential for over-diagnosing or "false positives" underscores
the importance of caution when position stands and consensus statements are developed as these
often form the basis for sports medicine policy formation.
We have described the differences in specificity and scope between the Triad and RED-S
models, the causal role of low energy availability/energy deficiency, and differences in the
approaches used to interpret available evidence. Based on our analysis, there are major concerns
regarding the lack of specificity and clarity in the RED-S model which hinder the potential
reproducibility of findings and a clear understanding of the etiology and scope of the RED-S
syndrome. Features such as clinical relevance, directionality, reversibility, and causality that are
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illustrated and demonstrated in the Triad model based on supporting literature are absent in the
expanded representation of energy-related outcomes of RED-S. The lack of evidence supporting
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many of the purported physiological, health and performance outcomes described in RED-S and
the potential for the confounding effects of exercise itself and/or overtraining are problematic. As
such, the potential is high for confusion and misdiagnoses in the application of RED-S when
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managing the syndrome in individual athletes. Caution is warranted regarding the
overgeneralized approach applied in RED-S when considering the effects of sex, race, and level
of ability. Despite these aforementioned issues, there is evidence using citation analyses and
social media metrics that the concept of RED-S has garnered significant attention from the public
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and sports medicine practitioners. Although consumers of scientific literature benefit from the
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ability of social media to facilitate the rapid dissemination of original research reports, they are
done a disservice if the research is over-interpreted or lacking scientific rigor. Opportunities for
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peer review, the replication of findings, and the execution of experiments identifying causality
take years to accumulate. There are tangible consequences of avoiding these steps in the
development and maturation of a scientific theory that will impact the clinical care of athletes
across the sporting world.
In summary, based on an analysis of the conceptual representation of RED-S and its
supporting literature, significant concerns are warranted regarding the scientific basis of RED-S
as a working model of a biomedical syndrome. More research is needed to advance our
understanding of the effects of relative energy deficiency on health and human performance, but
at this point in time, RED-S should not be regarded as a diagnosable condition or considered an
evidence-based syndrome. Rather, it is more appropriate to regard RED-S as a concept, like the
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Triad was in the 1980s, which will require extensive discussion, debate, and experimentation to
determine whether it is a diagnosable and a clinically relevant condition. If the idea of RED-S is
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to be advanced as an evidence-based syndrome, researchers and clinicians would benefit by
proceeding with greater caution and attention to scientific rigor, and clarifying key issues such as
causality, clinical relevance, directionality, and reversibility.

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Figure Legends
Figure 1. Illustration of the Spectra of the Female Athlete Triad. The three inter-related
components of the Female Athlete Triad are energy availability, menstrual status and bone
health. Energy availability directly affects menstrual status, and in turn, energy availability and
menstrual status directly influence bone health. Optimal health is indicated by optimal energy
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availability, eumenorrhea and optimal bone health, whereas, at the other end of the spectrum, the
most severe presentation of the Female Athlete Triad is characterized by low energy availability
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with or without an eating disorder, functional hypothalamic amenorrhea and osteoporosis. An
athlete’s condition moves along each spectrum at different rates depending on her diet and
exercise behaviors. BMD, bone mineral density. [Adapted from (3). Copyright © 2014 Wolters
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Kluwer Health and BMJ Publishing Group Ltd. Used with Permission.]
Figure 2. Purported health consequences of Relative Energy Deficiency in Sport (RED-S)
depicting an expanded view of the Female Athlete Triad to illustrate a wider range of outcomes
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and the application to male athletes (*Psychological consequences can either precede RED-S or
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be the result of RED-S). [Adapted from (5). Copyright © 2014 BMJ Publishing Group Ltd. Used
with permission.]
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Figure 3. Illustration of potential performance effects of Relative Energy Deficiency in Sport
(*Aerobic and anaerobic performance). [Adapted from (5). Copyright © 2014 BMJ Publishing
Group Ltd. Used with permission.]
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Heading: Perspectives for Progress

Editor: Sandra K. Hunter, PhD, FACSM

A Focus on Scientific Rigor

Mary Jane De Souza, Ph.D., FACSM, FNAK1

Copyright © 2019 by the American College of Sports Medicine www.acsm-essr.org

Perspectives for Progress - Female Athlete Triad and Relative Energy

Deficiency in Sport: A Focus on Scientific Rigor

Nancy I. Williams, Sc.D., FACSM, FNAK

Professor and Head

Co-Director, Women's Health and Exercise Laboratory

The Pennsylvania State University

276 Recreation Building

University Park, PA 16802

Email: niw1@psu.edu; Phone: 814-863-1163

Conflicts of interest; disclosure of funding: none

syndromes; however, it is premature to consider RED-S as an evidence-based syndrome. Future

establish the causality of relative energy deficiency on RED-S outcomes.

osteoporosis; immune; performance

of scientific rigor and quality of evidence possible

relevance, and the causal role of low energy availability

to measure energy availability.

understanding of the physiological underpinnings of the Triad (9).

scientific rigor and quality of evidence.

developing: a) educational tools and metrics, b) clinical decision-making tools, c) reports of

The Female Athlete Triad Model

RED-S was proposed to be an update of a previously published International Olympic

of these physiological systems, indicative of proposed direct relationships of relative energy

response, impaired judgement, decreased coordination, decreased concentration, irritability, and

CLINICAL RELEVANCE VS PHYSIOLOGICAL "IMPAIRMENT"

Each physiological "impairment" in RED-S is considered to threaten one's health and

is the inclusion of “cardiovascular” as a health consequence of RED-S. It is stated that “low

physiological processes such as cellular maintenance, thermoregulation, locomotion, and

unhealthy outcomes in and of themselves, but rather, physiological plasticity. In contrast, by

effects on bone and menstrual function.

A focus on scientific rigor is essential when interpreting consensus statements and

experimental design, methodologies, analyses interpretation, and reporting of results. It is a

specificity, causality, differentiation between normal physiologic variation and pathological

models from this perspective is warranted.

The Triad Model

advancement in understanding energy availability in exercising women since 2007, future

measurements to be assessed consistently and accurately, maximizing application, and permitting

its outcomes to be diagnosable.

S: the measurement representative of the definition described in RED-S publications or that of

low energy availability as proposed in the Triad literature.

The physiological and performance-related outcomes that are depicted in RED-S as

deficiency can cause mental impairment, cardiovascular impairment, or declines in muscle

Although scientific progress relies on all types of studies – such as observational,

energy deficiency is described to increase cardiovascular risk due to the development of

The RED-S Consensus Statement describes an effect of relative energy deficiency on

reduces salivary immunoglobulin A secretion and increases susceptibility to upper respiratory

reported and indirect measures of energy availability.

definition of “gastrointestinal symptoms” was provided. Moreover, interpreting this finding is

challenging since there is an established literature documenting gastrointestinal issues in athletes

of human performance, but rather, functional limitations such as dehydration, electrolyte

specific performance, emotional/mood changes, lack of motivation, sleep disturbances, overuse

“health detriments” for RED-S (5, 6).

cardiovascular, gastrointestinal, growth and development, hematological, and performance

disturbances during conditions of low energy availability (83).

Healthy to Pathological Continuum and Reversibility

months to years (3, 4).

Experiments illustrating the reversibility of low energy availability/energy deficiency and

deficiency on gastrointestinal function, cardiovascular function, immune function, growth and