Dehydroepiandrosterone (DHEA) as a tool for conservation

Abstract

Dehydroepiandrosterone (DHEA) is a widespread vertebrate steroid that functions both as a precursor to sex steroids and as a regulator of stress, immunity, and reproductive physiology. Across taxa, DHEA frequently responds to environmental conditions in ways that complement or counterbalance glucocorticoids, providing insight into physiological resilience rather than stress exposure alone. This review evaluates the potential for dehydroepiandrosterone (DHEA) as an emerging endocrine tool for wildlife conservation. By synthesizing evidence across taxa to assess how DHEA has been measured, interpreted, and applied in ecological contexts, we seek to highlight methodological challenges, taxonomic gaps, and priority research directions needed to integrate DHEA monitoring into conservation physiology. Collectively, existing evidence suggests that DHEA represents an understudied and underutilized, yet promising biomarker for understanding adaptive capacity and for informing conservation management decisions.

Introduction

Wildlife conservation faces unprecedented challenges amid accelerating habitat loss, climate shifts, pollution, and exploitation (Ceballos et al., 2015). Traditional conservation approaches rely on censusing populations, monitoring genetic diversity, and assessing habitats, but such methods may not detect sublethal physiological effects that impact immunity, challenge reproduction and can precede population declines (Wikelski & Cooke, 2006). Applying physiological concepts, tools, and knowledge to wildlife preservation efforts offers mechanistic insights into how animals respond to environmental changes and can provide early warning signals before demographic shifts manifest (Cooke et al., 2013). The formal emergence of this “conservation physiology” framework in the early 2000 s represented a shift from primarily descriptive conservation approaches toward hypothesis-driven, mechanistic assessments of organisms functioning under natural and anthropogenic stressors, with early syntheses emphasizing the potential to link environmental change to fitness-relevant processes (Wikelski & Cooke, 2006). The field has expanded rapidly, integrating advances in endocrine monitoring, non-invasive sampling, and comparative physiology across taxa and ecological contexts. Within this framework, endocrine biomarkers have emerged as particularly valuable indicators of wildlife health and population viability for conservation applications.

Glucocorticoid (GC) hormones (e.g., cortisol in most mammals and fishes, and corticosterone in birds, reptiles, and most amphibians) have been extensively studied as primary mediators of the hormonal stress response (see Romero & Wingfield, 2015). These steroids coordinate critical processes during challenging conditions by mobilizing intrinsic reserves, enhancing energy availability, and temporarily redirecting resources away from non-essential functions, like digestion, growth, and reproduction (Sapolsky et al., 2000). This response is adaptive in the short term, but chronic GC elevation may signify a sustained environmental pressure that can precede population vulnerability (Dantzer et al., 2014). Though GCs are valuable biomarkers for conservation monitoring, study after study has shown that assessing them alone provides an incomplete picture of stress physiology (MacDougall-Shackleton et al., 2019).

The making of DHEA

Dehydroepiandrosterone (DHEA) represents a particularly promising yet understudied complementary indicator of stress and health that may have conservation application. This ubiquitous and abundant circulating androgen is primarily synthesized by adrenocortical and gonadal tissues with the relative contributions of each varying by species or even life history (Abbott & Bird, 2009). Conceptualized as a steroid precursor, DHEA is a C19 steroid that serves as a pivotal intermediary in the Δ⁵ steroidogenic pathway where the metabolism of cholesterol to pregnenolone is followed by conversion by 17α-hydroxylases to yield DHEA (Fig. 1). This DHEA can then be further hydrogenated by the enzyme 3β-hydroxysteroid dehydrogenase (3β-HSD) to a downstream androgen (e.g., androstenedione, testosterone) and/or then aromatized into an estrogen (Miller, 2002; Miller & Auchus, 2011; Fig. 1). In humans, this Δ⁵ pathway predominates over the Δ⁴ pathway that bypasses DHEA production entirely (Flück et al., 2011; Schiffer et al., 2019). Additionally, the sulfotransferase enzyme converts DHEA to DHEAS (Fig. 1), which circulates 300–500 times higher than DHEA in humans (Labrie et al., 2005). This has led to consideration of DHEA as the more bioactive form, whereas DHEAS is thought to be less bioactive but can be used after reconversion by steroid sulfatase (Labrie, 2019; Labrie et al., 2005; Mueller et al., 2015; Fig. 1). Thus, the relationship between DHEA and DHEAS is that of a bidirectional reservoir system and a sulfatase-mediated hydrolysis reaction that can recover bioactive DHEA in peripheral tissues (Mueller et al., 2015). For the purposes of this review, the convention “DHEA(S)” will hereafter be used when the two forms are not differentiated.

Fig. 1.

Simplified diagram indicating the synthesis and metabolism of the steroids DHEA and DHEAS via the Δ⁵ steroidogenic pathways (red arrows). Steroids and intermediate metabolites are shown in bold, and enzymes are shown in italics. Blue arrows indicate the Δ⁴ pathway for androgen synthesis and black arrows indicate conversions between the dominant steroid metabolic pathways. The reversible conversions of DHEA and DHEAS are shown with green arrows and pathways to glucocorticoid synthesis are shown with purple arrows. Note only the enzymes discussed in this review are shown

A resilience hormone?

Rather than serving only as a steroid precursor, DHEA(S) also demonstrates independent physiological activity, although a specific DHEA receptor has yet to be identified (Labrie et al., 2005). Among the functions of DHEA(S) is its ability to seemingly mitigate the catabolic, immunosuppressive, and neurotoxic consequences of sustained high GC levels, thus its reference as an “anti-GC” (Dutheil et al., 2021; Kalimi et al., 1994; Maninger et al., 2009; Fig. 2). As a result, some studies employ the GC-to-DHEA(S) ratio to assess the capacity to mitigate chronic stress effects, with lower ratios interpreted as a greater resilience (Hechter et al., 1997; Morgan et al., 2004).

Fig. 2.

Conceptual framework for understanding acute (short-term) and chronic (prolonged) stress responses in individuals with low versus high DHEA(S) concentrations. During acute stress, individuals with low DHEA(S) levels exhibit partial coping, but are still vulnerable to some effects of stress, whereas high DHEA(S) individuals show adaptive coping with high resilience and rapid recovery. Under chronic stress, individuals with low DHEA(S) levels progress toward allostatic overload resulting in higher risk of physiological dysfunction. In contrast, those with high DHEA(S) levels exhibit a greater persistence, as they can (at least partially) compensate for a reduced physiological performance. Arrows indicate the divergent trajectories from acute to chronic stress, highlighting how the ratio of GCs to DHEA(S) can serve as an integrative indicator of resilience and vulnerability

Both GCs and DHEA(S) respond differently to acute and chronic stress, with DHEA(S) showing a blunted profile under prolonged stress while GCs remain elevated (Lennartsson et al., 2022). Individuals with low versus high DHEA(S) may follow divergent trajectories, with low levels limiting coping capacity and increasing vulnerability to prolonged stress (Fig. 2). In contrast, higher DHEA levels may support resilience, enhance short-term responses and partially compensate for sustained exposure to stress (Fig. 2). The balance between GCs and DHEA(S) could thus serve as an integrative indicator of stress vulnerability. Hormonal imbalances may reveal stressed phenotypes and predict declines in fitness and reproductive success under anthropogenic pressures (Gabai et al., 2020). Given its roles in immunity, metabolism, reproduction, and stress responses, and its evolutionary conservation, DHEA(S) may be an ideal candidate for integrative assessments of wildlife health and conservation applications. As taxonomic and demographic influences on DHEA(S) remain poorly understood, the need for further study to determine whether it can reliably identify individuals with reduced resilience is paramount.

The objectives of this review are threefold. First, I provide a comparative synthesis of DHEA(S) research across major taxonomic groups, highlighting both conserved and divergent physiological roles. Second, I critically evaluate methodological approaches, sampling matrices, and interpretive challenges relevant to conservation practitioners. Third, I will outline how DHEA monitoring can be integrated into conservation biology to address some contemporary threats such as climate change, habitat degradation, and endocrine disruption. Collectively, this review explores the potential for DHEA(S) to serve as an integrative biomarker of physiological state, with possible applications for conservation decision-making under increasing environmental pressures.

Mammals: mechanisms to monitoring

In mammals, DHEA(S) roles have received very little study in wildlife, compared to humans and laboratory primates and rodents. Mammals synthesize DHEA(S) predominantly in the adrenal cortex, unlike the largely gonadal origin in other taxa (Conley et al., 2004). Furthermore, most mammals maintain high circulating DHEA(S) levels while other vertebrates may have minimal, even undetectable amounts (Rege et al., 2019; Table 1). This shift toward increased adrenal DHEA(S) secretion may be an evolutionary adaptation linked to higher metabolism associated with endothermy or to aspects of stress physiology unique to mammals (Miller, 2002). Due to the substantial research in this group, discussion will proceed by outlining DHEA(S) studies across key mammalian taxa.

Table 1.

Overview of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) across taxonomic groups, highlighting circulating detectability, dominant physiological roles, and relevance for conservation applications

Taxonomic group	Detectability in circulation	Sites of synthesis and metabolism	Documented roles	Conservation relevance
Mammals	High (especially DHEAS)	Adrenal cortex, gonads, brain	Stress modulation, reproduction, immune buffering, aging	Welfare assessments, reproductive monitoring, resilience indices
Birds	Moderate (DHEA dominant; DHEAS minimal)	Adrenal, brain	Non-breeding aggression, social behavior, neuroprotection	Behavioral ecology, urban stress, non-invasive feather sampling
Reptiles	Moderate–Low (species-specific)	Adrenal and interrenal tissue, gonads	Energy balance, stress responses, reproductive cycling	Assessing energetic stress, breeding readiness
Amphibians	Low–Undetectable	Brain, gonads, fat bodies	Neurosteroid activity, reproduction	Emerging opportunity via non-invasive sampling of skin
Bony fish	Low–Undetectable	Gonads, brain, detectable in scales	Intermediate steroidogenesis, stress response	Retrospective stress assessment using scales
Elasmobranchs	Poorly characterized	Gonads, adrenal-like tissues	Reproductive steroid precursor	Baseline endocrine data for threatened species
Agnathans	Detectable (DHEA and DHEAS)	Brain, gonads	Steroid intermediate	Evolutionary context, non-lethal sampling potential
Invertebrates	Variable, often environmental	Limited endogenous synthesis	Possible Developmental or reproductive effects	Environmental contamination indicators

Primates

Expectedly, human-based biomedical studies have extended to primates (Urbanski et al., 2004), where research has revealed crucial roles for DHEA(S), establishing a foundation for possible conservation application. Circulating levels range from μg/mL for DHEAS to ng/mL for DHEA depending on the species, but despite these high circulating levels, DHEA(S) detection from other sources (e.g., urine, excreta) can be very difficult (Dittami et al., 2008; Möhle et al., 2002). Direct relationships between excreta and serum DHEAS levels have been shown in Japanese macaques (Macaca fuscata), and excreta levels are associated with stress in multiple species of the family Hylobatidae, highlighting the potential value of such sources for primate studies (Takeshita et al., 2018; 2022; Mouri & Shimizu, 2023).

Comparative studies have also revealed broad trends such as the consistently higher circulating DHEA(S) concentrations in New World platyrrhine monkeys compared to Old World catarrhine monkeys, which may underscore an evolutionary divergence of these lineages (de Silva et al., 2021). An even more robust trend is the age-related decline in circulating DHEA(S) concentrations. Age-related declines in plasma DHEAS profiles, particularly in males, have been noted for several catarrhine species including rhesus macaques (M. mulatta; Kemnitz et al., 2000; Muehlenbein et al., 2003; Downs et al., 2008), pig-tailed macaques (M. nemestrina; Muehlenbein et al., 2002); Japanese macaques (M. fuscata; Takeshita et al., 2013); and olive baboons (Papio anubis; Sapolsky et al., 1993; Willis et al., 2014). Similarly, in the prosimian gray mouse lemur (Microcebus murinus), DHEAS levels also decline with age, but this involves a seasonal component where the depreciating breeding levels eventually match those of non-breeding lows (Perret & Aujard, 2005). Data from great apes also shows DHEAS declines with age in chimpanzees (Pan troglodytes), bonobos (Pan paniscus), and orangutans (Pongo pygmaeus), but interestingly not in gorillas (Gorilla gorilla) (Seraphim et al., 2008a, b; Behringer et al., 2012; Takeshita et al., 2019; Edes et al., 2022). In male common marmosets (Callithrix jacchus), the DHEAS age declines are accompanied by decreased expression of steroid-synthesizing enzymes and a reduced volume of the adrenal zona reticularis, where DHEA(S) is produced (Pattison et al., 2005, 2007). The term “adrenopause” describes this age-related DHEAS decline, which parallels reproductive senescence (Blevins et al., 2013; Nguyen & Conley, 2008) but not cognitive impairment (Herndon et al., 1999). In captive primates, this adrenopause can be mitigated with caloric restriction (Lane et al., 1997; Mattison et al., 2003). Functionally, in young primates, higher DHEA levels have been linked to enhanced ovarian activity (Abbott et al., 2009), improved spermatogenesis and sperm quality (Conley et al., 2004), increased masculinization of female offspring (Drea, 2011), maternal experience (Bardi et al., 2014), and greater affiliative interactions between young males (Bardi et al., 2017). An emerging interest is the “adrenarche,” a shift in adrenal steroid production in primates marked by a puberty-like phase that includes increased DHEA(S) output (Bernstein et al., 2012; Nguyen et al., 2008), but the ecological and conservation implications of adrenarche are currently unstudied. Understanding age-related DHEA(S) shifts provides important insights into reproductive readiness and senescence, thus informing captive breeding and management strategies for imperiled primates.

Regarding DHEA(S) as protection against the effects of chronic GC concentrations, there has been an increasing push to examine DHEA(S) for conservation welfare assessments. A study of captive gorillas incorporated DHEAS in an index of allostatic load, defined as the cumulative impacts of repeated stress exposure, during welfare assessments across multiple zoos (Edes et al., 2018). Similar primate studies have used the GC-to-DHEA(S) ratio as an index of resilience and recovery (Parker et al., 2006). Interestingly, both acute and chronic stress increase DHEAS levels in rhesus macaques, but unlike cortisol, which declined with repeated stress, the DHEAS response was sustained and thus may act as a more reliable bioindicator of prolonged stress than even cortisol, which attenuates due to negative feedback (Maninger et al., 2010). Examples of social and environmental stressors that can significantly alter DHEA(S) in primates include dominance hierarchies (Sapolsky, 2005) and environmental enrichment (Behringer et al., 2012). Furthermore, DHEAS also counteracts the negative effects of sustained testosterone secretion (e.g., immunosuppression) in both rhesus macaques (Sorwell et al., 2014) and orangutans (Prall et al., 2015). Together, these data support using DHEA(S) to assess the ability of individuals to resist the negative impacts of chronic stress in conservation contexts.

Cetaceans and pinnipeds

Marine mammal studies have tested the reliability of circulating DHEA(S) measurements in cetaceans including bottlenose dolphins (Tursiops truncatus; Bechshoft et al., 2020); narwhals (Monodon monoceros; Béland et al., 2023); pilot whales (Globicephala melas; Hoydal et al., 2017); and killer whales (Orcinus orca; O’Brien et al., 2017; Ross et al., 2023). Furthermore, Bechshoft et al. (2020) validated DHEA detection in dolphin skin, providing a less invasive and logistically easier physiological evaluation than blood sampling for conservation applications. Recent isolation of DHEA from the blubber of short-finned pilot whales (Globicephala macrorhynchus) shows great promise for field studies (Wisse et al., 2025), and although not explicitly isolated from respiratory vapor (i.e., blow), validating such a method for DHEA(S), as has been done for other steroids (Burgess et al., 2016; Hogg et al., 2009), would permit the study of larger cetacean species.

Male killer whales appear to exhibit an adrenarche with adrenal DHEA serving as the precursor for testosterone at the onset of sexual maturity (O’Brien et al., 2017). In females, DHEA levels vary across the stages of pregnancy in a manner consistent with having a direct role in reproduction (Robeck et al., 2017). Thus, consideration of DHEA in routine conservation monitoring of cetacean reproduction is warranted. In captive dolphins, higher DHEA levels relative to cortisol were associated with better behavioral outcomes during mental welfare assessments (Miller et al., 2021a). Similar usage of the GC-to-DHEA(S) ratio for Pacific white-sided dolphins (Lagenorhynchus obliquidens); killer whales; and belugas (Delphinapterus leucas) suggests they have utility as an indicator of adrenal activity and thus may be used to inform conservation intervention decisions, such as incorporating enrichment (Miller et al., 2021b).

Though less studied, pinnipeds also demonstrate links between DHEA and reproduction and/or stress responses in free-living northern fur seals (Callorhinus ursinus; Browne et al., 2006), 006 and in harbor seals (Phoca vitulina) and gray seals (Halichoerus grypus) living under human care and rehabilitation (Gundlach et al., 2018). In northern elephant seals (Mirounga angustirostris), adrenocorticotropic hormone (ACTH), the primary regulator of GC secretion, failed to increase DHEAS levels, suggesting its secretion is either already at a maximum or is regulated independently (McCormley et al., 2018). Taken together, incorporating DHEA(S) into standardized conservation monitoring of health in marine mammals will doubtlessly advance our understanding of its actions.

Carnivores

Initial studies in the domestic dog (Canis lupus familiaris) serve as the starting point for understanding DHEA in an ecological context in wild carnivores. In dogs, DHEA is a modulator of stress responses alongside cortisol (Gabai et al., 2020) and has been used to detect early-life stress in newborn puppies and even to predict survival outcomes (Fusi et al., 2021, 2022). Other dog studies have observed DHEAS increases during a natural infection with bacterial ehrlichiosis, perhaps suggestive of its involvement in immunity, likely by restraining the effects of cortisol (Rondelli et al., 2015). Immunology research in cats (Felis catus) infected with feline immunodeficiency virus suggests DHEA also exhibits moderate antiviral properties in chronically infected feline cells (Bradley et al., 1995; Pedersen et al., 2003; Tejerizo et al., 2012). Behaviorally, circulating DHEA is positively correlated with dog aggression (Rosado et al., 2010). Such laboratory-based studies set a precedent and a framework for applying DHEA(S) to wild carnivore biology.

Research on polar bears (Ursus maritimus) reveals that DHEA concentrations far exceed those of other adrenal steroids (Gustavson et al., 2015a), and in captive bears, DHEA levels are much higher in breeding animals of both sexes, but especially in non-parturient females (Brandhuber et al., 2023), suggesting DHEA(S) may be necessary for optimal success during parturition, which is relevant for breeding programs. Indeed, urinary DHEA has been used to successfully detect timing of fertility in giant pandas (Ailuropoda melanoleuca; Wilson et al., 2022). Seasonal variation in DHEA is also documented in members of the Mustelidae. Mink (Mustela vison) have higher serum DHEA concentrations during the winter hair growth cycle compared to the summer, suggesting DHEA may help regulate the seasonal fur growth rate (Rose et al., 1998). In contrast, American martens (Martes americana) also have higher winter DHEA levels, but this was instead interpreted as a mechanism for sustaining territoriality during the non-breeding season when testosterone concentrations would be very low (Boonstra et al., 2018). In hair samples from the Iberian lynx (Lynx pardinus), DHEA was the most abundant steroid, and the cortisol-to-DHEA ratio was higher in wild-caught animals compared to captive-bred individuals (Azevedo et al., 2020). Some caution in interpretation is needed, as in dogs, hair follicular cells are known to metabolize DHEA (Bamberg et al., 2004). Only a single study has documented disruptions to DHEA synthesis by environmental pollutants. In polar bears, DHEA levels were negatively correlated with several organic pollutants, including polychlorinated biphenyls (PCBs) and polyfluoroalkyl substances (PFASs), indicating these contaminants may disrupt DHEA production or metabolism (Gustavson et al., 2015b; Pedersen et al., 2016; Ciesielski et al., 2017). However, such single opportunistic studies in one species are common in DHEA literature, with the lack of any follow-up research hindering general conclusions relevant to conservation management.

Rodents and lagomorphs

In rodents and lagomorphs, DHEA promotes territoriality, which may ultimately influence population distribution. As in martens above, adrenal DHEA can support social and physiological functions normally relying on testosterone outside the breeding season by serving as an alternative androgen source (Boonstra et al., 2008). Experimental studies of Siberian hamsters (Phodopus sungorus) demonstrate precursor DHEA regulates non-breeding aggression through neural conversion into bioactive androgens, a process seemingly mediated by melatonin in both males and females (Munley et al., 2018; Rendon et al., 2015, 2020; Scotti et al., 2009). Some additional support comes from the natural seasonal variation in DHEA observed in Arctic ground squirrels (Urocitellus parryii), with highest levels in late summer in males during a time when both resource caching and aggression are observed (Richter et al., 2017). Further support for this hypothesis comes from the observation of very low DHEA levels in snowshoe hares (Lepus americanus) and eastern cottontail rabbits (Sylvilagus floridanus), which do not exhibit non-breeding territoriality (Boonstra et al., 2022). Interestingly, in deer mice (Peromyscus maniculatus), DHEA, although measurable, was unresponsive to shifts in photoperiod (Kriegsfeld & Nelson, 1998). In contrast, both red squirrels (Tamiasciurus hudsonicus) and American pikas (Ochotona princeps) have higher plasma DHEA levels as they maintain year-round territoriality, with greater population densities of the former having the highest DHEA levels (Boonstra et al., 2008, 2014, 2022).

In laboratory rodents (i.e., mice and rats), DHEA is primarily found in the brain and gonads, with minimal or undetectable levels in both circulation and the adrenal glands (Labrie et al., 2005). However, in other murine rodents, DHEA may play multifaceted roles including: the timing of hibernation (Richter et al., 2017); immune function (Rasmussen & Healey, 1992); reproductive suppression (Cherry et al., 2002); energy balance regulation (Navar et al., 2006); parental care (Bardi et al., 2011); and longevity (Sahm et al., 2021). One especially intriguing species is the Cairo (Egyptian) spiny mouse (Acomys cahirinus), where adrenal DHEA appears to regulate the cyclic uterine reorganization, making it the only rodent known to naturally menstruate and giving it emerging importance as a research surrogate model for studies that would normally be conducted on primates (Bellofiore & Evans, 2019; Bellofiore et al., 2021). However, to date no ecological explanation for such a unique phenomenon in this species has been provided.

Ungulates and elephants

Here, DHEA(S) shows promising utility as a stress and reproduction biomarker under both managed and natural conditions for ungulates. In captive giraffes (Giraffa camelopardalis), lower DHEAS levels were linked to an allostatic load index comprising both biochemical indicators and body condition (Beer et al., 2023). Similarly, in bulls (Bos taurus), salivary DHEA levels responded to the stress of heat and humidity even exceeding the cortisol response (Giaretta et al., 2023). Regarding reproduction, testicular DHEA in roe deer (Capreolus capreolus) was expectedly elevated before the rut and then declined post-rut, where it presumably served as the precursor to testosterone (Elmi et al., 2021), and plasma DHEA was highest during early antler growth in red deer stags (Cervus elaphus; Suttie et al., 1995). Similarly, circulating DHEA levels were elevated in male Asian elephants (Elephus maximus) during the cyclic hormonal state in males known as musth, which was characterized by an increase in aggressiveness, and levels were also responsive to stimulation with ACTH during this time (Yon et al., 2007a, b). Interestingly, Veronesi et al. (2025) in a rare study that measured both DHEA and DHEAS found fluctuations in their levels during pregnancy consistent with each hormone having slightly different roles in regulating gestation in mares (Equus caballus), and similar seasonality has been reported for DHEAS in stallions (Olvera-Maneu et al., 2021). In pigs (Sus scrofa domesticus), both circulating and hair DHEA and DHEAS were higher in males than females (Bergamin et al., 2019), yet these two hormones showed opposing correlations to serum triglyceride concentrations in both sexes, which again suggest potentially divergent roles in energy regulation (Tagliaferro & Ronan, 2001). This may have immune implications in pigs as tapeworm infections elevate both serum DHEA and DHEAS levels to different degrees (Trevisan et al., 2017). These studies underscore the need to quantify both hormones since which is measured may lead to different interpretations.

Birds: brain and behavior

In birds, unlike mammals, DHEA is the predominant circulating form, with DHEAS levels essentially undetectable in blood (Schlinger et al., 2008; Table 1). Avian studies reveal notable seasonal variation in DHEA, with levels fluctuating relative to life-history stage and behavioral requirements (Heimovics et al., 2016; Newman et al., 2008, 2013; Wacker et al., 2016). Indeed, bird studies have revealed intriguing links between DHEA and behavior more than in other taxa, based on experimental research addressing how local DHEA conversion into neuroactive sex steroids, which has been well validated for birds (Pradhan & Soma, 2012; Pradhan et al., 2008; Schlinger et al., 2008; Vanson et al., 1996) can occur within the avian brain regions involved in regulating social behavior (Soma et al., 2015a, b; Tsutsui et al., 2006, 2013).

The above “neurosteroid pathway” (Baulieu, 1998) may permit year-round male territorial aggression when gonadal testosterone levels are extremely low in winter, and thus DHEA could maintain aggressive behavior independent of circulating gonadal sex steroids (Soma, 2006; Soma & Wingfield, 2001; Soma et al., 2008, 2015a, b). Here, the song sparrows (Melospiza melodia) of the Pacific coast of North America have emerged as models in exploring non-breeding territoriality (Soma, 2006; Soma & Wingfield, 2001; Soma et al., 2008, 2015a, b). Circulating DHEA levels do not differ between seasons in this species (Maddison et al., 2012; Soma & Wingfield, 2001) and non-breeding male aggression is unaffected by castration yet remains an estrogen-dependent behavior (Soma et al., 2000). Administration of DHEA to non-breeding males increases aggression, territorial singing and volume of neural song control nuclei (Soma et al., 2002; Wacker et al., 2008), and simulating a territorial infringement rapidly increases DHEA in circulation (Heimovics et al., 2016; Newman & Soma, 2011). As the necessary enzymes to convert DHEA to estrogen are present within social brain areas in birds (Heimovics et al., 2023; Pradhan et al., 2010; Soma et al., 2003, 2004), this pathway provides sparrows with a means to maintain territoriality outside the breeding season while bypassing the metabolic and immune costs associated with elevated testosterone (Newman & Soma, 2011; Newman et al., 2010a; Pradhan et al., 2010). This neural conversion of DHEA into bioactive steroids may manifest in DHEA concentrations differing between jugular and systemic circulation in some birds (Chin et al., 2008; Fokidis et al., 2013; Newman et al., 2008). Furthermore, DHEA may serve neuroprotective functions to avoid potential damaging effects of stress during territoriality (Newman et al., 2010b). Note that recent studies using liquid chromatography—tandem mass spectrometry failed to detect DHEA within both sparrow plasma and brain regardless of age or season (Gray et al., 2024; Jalabert et al., 2021; however, derivatization improved the detection of DHEA (Jalabert et al., 2024). Potential explanations for their lack of detection include the rapid conversion of DHEA within the brain to more bioactive steroids, and possibly cross-reactivities of antibodies to DHEA metabolites fatty acid conjugates (Jalabert et al., 2024).

Beyond song sparrows, similar mechanisms may function in spotted antbirds (Hylophylax naevioides; Hau et al., 2004; Hau & Beebe, 2011), golden-collared manakins (Manacus vitellinus; Eaton et al., 2018), Northern cardinals (Cardinalis cardinalis; Fokidis, 2016); buff-breasted wren (Thryothorus leucotis; Gill et al., 2008); brant geese (Branta bernicla; Poisbleau et al., 2009), and even in various mammals (Boonstra et al., 2008, 2014, 2018). Subtle differences in behavior between color-morphs of white-throated sparrows (Zonotrichia albicollis) may also involve DHEA regardless of sex (Spinney et al., 2006). Studies have also identified the enzymes for DHEA metabolism in social brain networks of several species including in zebra finches (Taeniopygia guttata; Eaton et al., 2018), golden-collared manakins (Eaton et al., 2018), Furthermore, in captive zebra finches, experimental food restriction simultaneously elevated social instability and DHEA levels, illustrating how this hormone can respond to changes in resource availability with consequences for aggression (Fokidis et al., 2013). Interestingly, water restriction did not impact plasma nor neural levels of DHEA in zebra finches (Prior et al., 2012) and no differences between sexes and reproductive state have been observed (Prior et al., 2016, 2017). Interestingly, female song wrens (Cyphorhinus phaeocephalus) with active brood patches had higher DHEA levels than those without suggesting a dependence on reproductive state (Busch et al., 2008). Nonetheless, studies of DHEA in birds can also produce mixed results. Nonbreeding territoriality in the European nuthatch (Sitta europaea) does not appear to be regulated by DHEA (Landys et al., 2013). Food supplementation did not influence DHEA levels in cardinals (Wright & Fokidis, 2016), unlike in zebra finches. Furthermore, no relationship between favorable morphological traits and DHEA was observed in barnacle geese (Branta leucopsis; Doyle et al., 2021) and relationships between sibling aggression and DHEA were not observed in Nazca booby chicks (Sula granti; Ferree et al., 2004).

Behavioral effects of DHEA in birds extend beyond aggression to include social cohesion, with DHEA administration in European starlings (Sturnus vulgaris) increasing undirected singing, a behavior which helps maintain flock cohesion during winter movements (Heimovics et al., 2023). Another study in starlings suggested DHEA may promote pair formation during early breeding (Pinter et al., 2011). Birds inhabiting urban areas are thought to often suppress GC responses as a presumed adaptation to novel urban stimuli, but no such difference in DHEA levels was reported between urban and forest-living cardinals (Wright & Fokidis, 2016). Interestingly, in cardinals, handling stress decreased DHEA, but paradoxically injection with ACTH did not affect circulating DHEA levels (Fokidis, 2016). Similarly, a decrease in DHEA levels with restraint stress was reported in only one of two subspecies of white-crowned sparrows (Zonotrichia leucophrys; Krause et al., 2014). Predation can also influence DHEA levels in song sparrows, with high predation pressure associated with decreased concentrations (Newman et al., 2013). Most avian DHEA studies involve blood; however, less invasive methodologies for isolating and quantifying feather DHEA are being developed, as recently done in both red kites (Milvus milvus) and griffon vultures (Gyps fulvus) to investigate impacts of pollutants and allostatic load, respectively (Monclus et al., 2018; Frongia et al., 2020). These avian studies, perhaps more than in mammals, provide new opportunities to investigate ecological sources of variation in this hormone while also establishing DHEA as an intermediary between the seasonal environment and behavior.

Reptiles: energy and resilience

Within the reptile clade, adrenal gland structure varies markedly, particularly in the degree of integration between steroidogenic interrenal cells and renal tissue (reviewed in Capaldo, 2023). This variation reflects phylogenetic relationships, with turtles retaining an amphibian-like interrenal gland, squamates exhibiting more dispersed steroidogenic tissues, and crocodilians possessing compact, bird-like adrenals (Capaldo, 2023). As steroid biosynthesis is influenced by adrenal tissue organization (e.g., enzyme localization and pituitary responsiveness), lineage-specific architectures may constrain steroidogenic pathways differently. As a result, the capacity for DHEA synthesis and its regulation relative to glucocorticoid production may differ substantially among reptilian lineages.

Early studies showed the Δ⁴ pathway of androgen biosynthesis predominates in the gonads (Lupo Chan & Callard, 1974; di Prisco et al., 1968), whereas the Δ⁵ pathway is important in the reptilian adrenals (Phillips et al., 1962). Research on adrenal steroidogenesis in eastern fence lizards (Sceloporus undulatus), Yarrow’s spiny lizards (S. jarrovii), and the Yucatan banded gecko (Coleonyx elegans) demonstrates that stress alters adrenal steroid production in reptiles in a flexible species-specific manner (Carsia et al., 2012, 2023). Importantly, these studies may suggest that DHEA synthesis can be integrated into a broader endocrine feedback loop, interacting with gonadal steroids to shape sex-specific stress responses (Carsia et al., 2023). Such work highlights reptilian adrenal plasticity and its responsiveness to hormonal and environmental changes that doubtlessly also impact DHEA, though this has not been specifically investigated in a conservation context.

Research on DHEA in lizards is very limited, but one study noted how fasting in male Cuban brown anole lizards (Anolis sagrei) triggered increases in plasma DHEA concentrations that were not seen in fed controls (Himmelstein et al., 2021). Interestingly, elevated DHEA levels in adrenal and heart tissue above those found in plasma were also reported, which suggests local DHEA synthesis and/or metabolism may be occurring in these organs (Himmelstein et al., 2021). Thus, as previously reported in birds (Fokidis et al., 2013), elevated DHEA secretion may have an adaptive function during energy scarcity, such as supporting immunity and metabolism by possibly counteracting GC actions (Table 1).

The interaction of DHEA and GC stress responses has received some study in farmed Nile crocodiles (Crocodylus niloticus), where DHEA levels rapidly increased in response to capture/immobilization stress but also quickly recovered to baseline (Swanepoel et al., 2024). Furthermore, a moderate correlation between DHEA and corticosterone supports the former as an active component of the stress response (Swanepoel et al., 2024). Seasonal analysis of American alligators (Alligator mississippiensis) found relatively high DHEA concentrations that coincide with stages of the reproductive cycle; in females during oviposition and in males during the start of the mating season (Hamlin et al., 2011, 2014). Interestingly, male alligators maintain blood DHEA levels in concert with testosterone, but only exceed it in the non-breeding season, when it may maintain territorial behavior as in some birds and mammals (Hamlin et al., 2011). Finally, circulating DHEA levels significantly modulated the relationship between testosterone and microbial killing capacity in alligators (LaVere et al., 2021), suggesting that DHEA can act as a buffer of steroid–immune interactions.

In male yellow-bellied slider turtles (Trachemys scripta scripta), DHEA is the most common steroid in serum, testis, and liver and circulating levels are lower in turtles with significant shell melanism (Garstka et al., 1991). In congener sliders, DHEA levels were higher in Haitian sliders (T. decorata) than in Dominican sliders (T. stejnegeri vicina), but levels were higher in males than females in the latter (Feliz et al., 2026). Furthermore, measurable DHEA was reported in claw samples in both species, which likely have accumulated over the duration of claw growth, but these levels did not differ between species (Feliz et al., 2026). Injection with DHEA failed to elicit courtship behavior in male yellow-bellied sliders, unlike testosterone injections, suggesting DHEA functions primarily as a precursor rather than having independent activity (Garstka et al., 1991). In the red-eared slider (T. scripta elegans), ACTH injection did not impact DHEA levels, despite elevating corticosterone (Tassent & Fokidis, 2025). However, DHEA secretion did increase in response to neuropeptide Y (NPY), an appetite stimulator, further suggesting DHEA may be modulated by energy demands (Tassent & Fokidis, 2025) in a manner that aligns with previous research in lizards (Himmelstein et al., 2021) and finches (Fokidis et al., 2013). Earlier studies have also identified the presence of hydroxysteroid enzymes in the liver of turtles (Hamel-Jonsson et al., 1987) suggesting DHEA metabolism can occur outside traditional steroid-producing tissues (Table 1). Though disparate, research in reptiles highlights how DHEA may play critical roles in the management of stress, particularly during energy deficits, and thus can offer conservation programs a means to assess population health, breeding readiness, and adaptive capacity to environmental or anthropogenic stressors.

Amphibians: opportunity with urgency

The global amphibian decline was first recognized in the late 1980 s (Wake, 1991) and has since been attributed to a combination of threats including: (1) habitat destruction and degradation; (2) the introduction of non-native species like predatory fish or invasive amphibians like bullfrogs (Lithobates catesbeianus), cane toads (Rhinella marina), and Cuban tree frogs (Osteopilus septentrionalis) that have disrupted ecosystems; (3) water pollution, particularly pesticides and endocrine disruptors; (4) infectious disease agents such as the chytrid fungus (Batrachochytrium dendrobatidis) and ranaviruses, which are responsible for regular outbreaks across multiple continents; and (5) climate shifts in temperatures and precipitation patterns that impact both amphibian survival and breeding cycles (reviewed in Luedtke et al., 2023). Despite the massive interest in amphibian conservation, the state of endocrine research and especially on DHEA, in this group, is largely confined to a handful of physiological studies investigating the broader mechanisms of steroidogenesis.

Steroid synthesis within the amphibian brain has long been recognized, as the necessary enzymes are present and the brain contains high DHEAS concentrations (Beaujean et al., 1999; Takase et al., 1999, 2011; Mensah-Nyagan et al., 2000; Cevasco et al., 2009; Vaudry et al., 2011). This neurosteroid DHEA(S) production has been documented in several species such as marsh frogs (Pelophylax ridibundus; Mensah-Nyagan et al., 2000; Beaujean et al., 2002; Burel et al., 2013), edible frogs (Rana esculenta; Do Rego et al., 2007), black-spotted frogs (Pelophylax nigromaculatus; Takase et al., 1999), African clawed frogs (Xenopus laevis; Takase et al., 1999), and Japanese red-bellied newts (Cynops pyrrhogaster; Inai et al., 2003, Takase et al., 2011). This capacity for neurosteroid synthesis may also be sexually dimorphic and seasonally modulated (Santillo et al., 2017) and possibly influenced by current nutritional state (Beaujean et al., 2002). Enzymatic studies in edible frogs, Japanese wrinkled frogs (Rana rugosa), and South American toads (Rhinella arenarum) all confirm the necessary enzymes to produce DHEA(S) are present in the testes (Canosa & Ceballos, 2001; Sakurai et al., 2008; Scaia et al., 2015; Chianese et al., 2014). Furthermore, studies have shown testicular DHEA(S) secretion can be inhibited by GCs (Scaia et al., 2015; Czuchlej et al., 2019) potentially adding a stress-dimension to DHEA secretion. Amphibian adipose tissue (i.e., fat bodies) can also synthesize steroids, including DHEA (Table 1), and likely serves as a reservoir for such sex steroid precursors to support gonadal production (Lupo di Prisco et al., 1971). Together these findings establish a range of amphibians as possible models for understanding DHEA biosynthesis both within the brain and in peripheral tissues. Incredibly little research has explored circulating DHEA levels in amphibians, likely due to the difficulty of obtaining sufficient blood volume from most species (Narayan, 2013). Another possibility is that levels are very low to undetectable, as for instance in the hellbender (Cryptobranchus alleganiensis), where plasma DHEA was “rarely or never detected” in the pre-breeding season (Galligan et al., 2021). Amphibian conservation endocrinology is in its infancy with a typical focus on GCs and sex steroids, but with the continued validation of non-invasive tools (e.g., dermal secretions, urine or water sampling) for hormone assessment, studies of DHEA represent an opportunity to provide urgent additional conservation insights on stress, immunity, and reproduction in this fascinating but imperiled group.

Bony fish: blood and scale

As in other vertebrates, DHEA is naturally present in bony fish as an intermediate in steroidogenesis and has been extracted from the testes of many species (Ozon, 1972; Sundaray et al., 2003; Table 1). Furthermore, the necessary enzymes for synthesis and active DHEA(S) metabolism within the brain of zebrafish (Danio rerio) has been reported (Diotel et al., 2011a, b; Pasmanik & Callard, 1985; Sakamoto et al., 2001). Additionally, the structural properties of the sulfotransferase enzymes (i.e., that metabolize DHEA to DHEAS have been characterized in both channel catfish (Ictalurus punctatus) and zebrafish (James, 2011; Kurogi et al., 2019)). Note that few studies have attempted to quantify circulating DHEA(S) and in both rainbow trout (Oncorhynchus mykiss) and goldfish (Carassius auratus), it was undetectable in serum (Kennedy & Janz, 2022, 2023). However, scale DHEA was measurable in both trout and goldfish with levels increasing in response to stress in the former (Kennedy & Janz, 2022, 2023). In contrast, other studies failed to report detectable DHEA(S) in the scales or skin mucus of Mediterranean killifish (Aphanius fasciatus; Mazzi et al., 2023) or the plasma and brain tissue of the weakly electric fish, Gymnotus omarorum (Zubizarreta et al., 2023). Low circulating DHEA(S) levels may represent a low synthesis rate or its rapid clearance from the blood (Rege et al., 2019). Aquaculture research has shown administering DHEA can increase both weight gain and even skew sex ratios towards males in tilapia (Oreochromis hybrids; Mohamed et al., 2012). As with amphibians there are opportunities for research, such as exploring whether DHEA uptake in the integument could deplete plasma levels. The paucity of DHEA(S) research in fish should be addressed with studies that focus on functional aspects which can benefit fish conservation practice and commercial aquaculture alike.

Elasmobranchs: diversity meets scarcity

Cartilaginous fish also possess the enzymes for DHEA synthesis via the Δ⁵ steroidogenic pathway, based on a recombinant study in the spiny dogfish shark (Squalus acanthias) (Trant, 1996). Comparative research has also characterized the kinetics of the 3β-HSD enzyme in multiple elasmobranch species including: the southern stingray (Dasyatis americana), the blacktip shark (Carcharhinus limbatus), finetooth shark (Carcharhinus isodon), Atlantic sharpnose shark (Rhizoprionodon terraenovae), and the bonnethead (Sphyrna tiburo), with variation attributed to species-specific differences in steroidogenic demand or regulation (Bailey, 2017; Cuevas et al., 1992; Nunez & Trant, 1998). Despite such apparent functional differences, molecular analysis revealed the DHEA-binding regions of the 3β-HSD enzyme are relatively conserved between species (Nunez & Trant, 1998), and functional studies confirm the conversion of DHEA is necessary for proper spermatogenesis (Cuevas et al., 1993). Direct measurements of DHEA in elasmobranchs are scarce (Table 1), likely from a combination of logistical field issues with sampling, and this group often utilizes unique steroids not found in other vertebrates, thus limiting the availability of validated assays (Manire et al., 1999; Ruiz-Jarabo et al., 2019). Understanding these fundamental aspects of elasmobranch reproductive physiology is increasingly critical given that many shark and ray species face population declines from overfishing and habitat degradation, making baseline endocrine data essential for effective conservation management.

Agnathans: origins and enzymes

The jawless fish or Agnathans are basal vertebrates whose endocrine systems illuminate early vertebrate evolution. Although the scant endocrine research on the hagfish (order Myxiniformes) has not exclusively identified DHEA(S) (Nozaki, 2013), analytical studies in sea lamprey (Petromyzon marinus) and European river lamprey (Lampetra fluviatilis) have identified both DHEA and DHEAS in plasma, urine, and the brain (Adams et al., 1987; Bussy et al., 2016; Close et al., 2010; Kime & Larsen, 1987; Wang et al., 2016). Among the most abundant steroids in the lamprey brain, it occurs at a much-reduced concentration in plasma (Bussy et al., 2016), where DHEAS exceeds DHEA concentrations (Close et al., 2010; Table 1). In contrast, earlier work on larval lampreys (i.e., ammocoetes) found low or undetectable steroid levels and DHEA was not reported (Dashow et al., 1984).

Lampreys utilize the Δ⁵ steroidogenic pathway and as usual, genomic studies reveal they possess all the ancestral and highly conserved enzymes necessary for synthesis (Baker et al., 2015; Bryan et al., 2008). Although analytical limitations in lamprey ovarian follicles and testis fragments, specifically overlapping retention times between DHEA and 15α-hydroxyandrostenedione, prevented clear differentiation of these steroids (Lowartz et al., 2003), the detection of upstream precursors supports DHEA’s role as a steroid intermediate in agnathans (Didier, 2019). Furthermore, the metabolism of DHEA into androstenedione, the direct testosterone precursor and the bioactive androgen in lampreys has been confirmed in both sea lamprey and Pacific lamprey (Entosphenus tridentalus) in blood and other tissues (Bryan et al., 2007; Didier, 2019). Early studies in the brook lamprey (Lampetra planeri), further support DHEA metabolism in both gonadal and “adrenal” tissue, where 3β-HSD activity was reported (Seiler et al., 1983). Furthermore, the sulfation of DHEA to DHEAS is also reported to be inhibited by the lamprey stress steroid, 11-deoxycortisol (Close et al., 2010). These data, combined with the lamprey’s basal position within the vertebrate phylogeny, suggest that lampreys utilize DHEA(S) as a metabolic intermediate rather than as a terminal bioactive hormone, although functional studies remain scant. The presence of DHEA in both basal agnathans and elasmobranchs underscores its evolutionary antiquity, and future studies are necessary to determine whether functional insights that are relevant for conservation can be ascribed.

Invertebrates: knowns and unknowns

There is a complex evolutionary distribution of DHEA(S) across invertebrates including the basal chordates. In most invertebrates, DHEA appears primarily through environmental uptake rather than endogenous synthesis (Table 1), as they lack key vertebrate steroidogenic enzymes (Scott, 2012). For instance, while the ciliate Tetrahymena pyriformis may contain measurable DHEA and DHEAS alongside trace sex hormones (Csaba et al., 1985), mollusks overwhelmingly absorb DHEA from their environment, as they lack the enzymes needed for its synthesis (Janer et al., 2004). Indeed, measurable quantities of DHEA have even been reported in plants infected by fungi (Oktay et al., 2025). Experimental DHEA administration has been linked to reproduction in juvenile sea scallops (Placopecten magellanicus) where it can accelerate gonadal development and skew sex ratios toward males (Wang & Croll, 2004). At the biochemical level, oysters (Crassostrea virginica) possess an acyltransferase that conjugates DHEA to fatty acids within digestive glands and gonads (Janer et al., 2004), supporting a conserved steroid-inactivation and/or storage mechanism. In arthropods, in the tiger shrimp (Penaeus monodon), a crustacean, a dramatic increase in ovarian DHEA was observed during vitellogenesis (Fairs et al., 1990). The presence of a sulfotransferase-like enzyme within the fruit fly (Drosophila melanogaster) brain capable of sulfating DHEA suggests a neuronal role (Liu et al., 2008). Similarly, one study found DHEA was one of seven vertebrate-type steroids identified in whole adult red palm weevils (Rhynchophorus ferrugineus), suggesting this insect is capable of natural DHEA production (Cangialosi et al., 2012). In echinoderms, in vitro DHEA metabolism has been reported in tissues from the sea star (Asterias rubens) and the process may even respond to photoperiodism (Voogt et al., 1991). Despite these observations, clear evidence of an endogenous DHEA biosynthetic pathway in any non-chordate invertebrate remains largely lacking, and mere presence of such hormones cannot be taken as evidence of an endocrine role (Fodor et al., 2022; Scott, 2012).

Evolutionary advancements emerge in the cephalochordates like amphioxus (Branchiostoma spp.), which possess orthologs of key vertebrate steroidogenic enzymes, suggesting de novo DHEA synthesis capability (Mizuta & Kubokawa, 2007). Interestingly, DHEA can activate neurotrophic receptor signaling in amphioxus and in two mollusk species, suggesting a potential role as the ancestral ligand for this receptor class (Pediaditakis et al., 2015). Furthermore, Baker (2004) hypothesized that ancestral estrogen receptors were also activated by DHEA before the evolution of dedicated estrogen receptors. In contrast, the tunicates (or urochordates) present an intriguing case, as their genomes lack these steroidogenic enzymes, but Cangialosi et al. (2010) identified several steroids, including DHEA, in ascidian (Ciona intestinalis) ovaries using gas chromatography-mass spectrometry. This suggests either an alternative steroid synthesis pathway or efficient environmental absorption. Despite its presence across diverse taxonomic groups, the evolutionary significance and physiological roles of DHEA in these early chordates and invertebrates remain incompletely understood, warranting further investigation.

Taxonomic summary

This extensive taxonomic survey reveals DHEA(S) is an ancient steroid with diverse yet consistent functions in stress mediation and reproduction (Table 1). The responsiveness of DHEA to environmental stressors (pollutants, nutrition, habitat quality) makes it useful for conservation monitoring, despite variation in sites of synthesis, metabolism, and circulating levels, with levels generally highest in primates, progressively lower in birds, reptiles, amphibians, fish, and invertebrates (Table 1). Thus, DHEA(S) plays distinct roles beyond simply being a steroid precursor, and its widespread connections to both reproduction and stress support its inclusion as a tool for understanding physiological impacts of environmental change in conservation biology.

Integrating DHEA into conservation biology

As conservation biology increasingly incorporates biomarkers to understand how environmental changes affect wildlife, there is strong potential for DHEA(S) as an active player spanning multiple physiological processes (e.g., immunomodulation, neuroprotection, and metabolic regulation) to be valuable for assessing long-term physiological impacts, particularly alongside information from GC studies. Below are descriptions of how monitoring DHEA(S) may assist conservation efforts in understanding the consequences of three globally relevant environmental issues.

For field-based conservation, DHEA monitoring is most feasible when integrated into existing endocrine frameworks rather than used in isolation. Non-invasive matrices such as feathers, hair, skin, blubber, scales, and claws allow retrospective hormone assessment while minimizing animal handling (Table 2). Costs and feasibility vary by matrix, but several methods now align with routine glucocorticoid monitoring, enabling paired analyses that better capture physiological resilience. Ethical considerations are particularly important for endangered species, where minimizing disturbance and validating opportunistic samples (e.g., shed feathers, biopsies collected for other purposes) should be prioritized.

Table 2.

Characteristics and feasibility of biological matrices used to quantify DHEA(S) in wildlife with implications for conservation

Sampling matrix	Invasiveness	Temporal resolution	Validated taxa	Conservation advantages	Conservation limitations
Blood/plasma	High	Minutes – Hours	Most vertebrates	Physiological precision and validated methods	Stress from capture
Urine/feces	Low	Hours – Days	Mammals, esp. Primates	Non-invasive, repeated sampling	Interpretation of metabolites
Hair/fur	Low	Weeks – Months	Mammals	Retrospective endocrine record	Localized metabolism
Feathers	Low	Weeks – Months	Birds	Retrospective endocrine record	Timing of molt constraints
Skin/blubber	Moderate	Hours – Days	Marine mammals	Integrates stress and reproduction	Logistics of biopsy
Scales	Low	Weeks – Months	Bony fish	Minimal handling needed	Limited validation on few species
Claws/nails	Low	Weeks – Months	Reptiles, mammals	Retrospective endocrine record	Growth rate variability
Dermal secretions	Very low	Minutes – Hours	Amphibians	Rapid sampling	Method development and validation needed

Climate change

Climate change presents complex challenges for wildlife conservation, with physiological responses often preceding visible population effects. Measuring DHEA(S) could offer a window into multifaceted responses, particularly if it can be related to direct thermoregulatory challenges or altered resource availability (Jessop et al., 2013). Very few studies have related DHEA(S) to any climatic variables, although research on bulls showed that circulating DHEA(S) can respond to temperature increases (Giaretta et al., 2023), and lab research on mice shows adding DHEA can reduce core body temperature and heat stress (Antrobus et al., 2022; Catalina et al., 2002). Nonetheless direct associations between DHEA(S) and climate remain speculative, but greater opportunities lie in studying DHEA(S) in its counter-regulatory role to GCs, as ecosystem-level changes brought about by climate change can manifest GC roles in wildlife in varying forms (Crino et al., 2023; Mentesana & Hau, 2022). A decline in DHEA(S) or an imbalanced DHEA-to-GC ratio may indicate that an animal is experiencing allostatic overload and thus, conservation practitioners can leverage this knowledge to identify climate-vulnerable populations.

Beyond stress, DHEA(S) also supports immune function and influences longevity, both of which can shift with increasing environmental instability. Climate change is likely to amplify the spread of diseases and parasites, especially in ecosystems where temperature and precipitation patterns are shifting (Short et al., 2017; Thieltges et al., 2025). Detecting low DHEA(S) levels can inform conservation managers about possible increased susceptibility of wildlife to such threats due to potentially compromised immune responses (Hazeldine et al., 2010). As DHEA(S) is a sex steroid precursor, monitoring levels in circulation may help document reproductive timing, which is a key conservation concern as many species face mismatches between traditional breeding periods and new seasonal patterns caused by climate disruption (Walker II et al. 2019; Brandhuber et al., 2023). Thus, studying DHEA(S) in tandem with other stress and reproductive hormones could reveal how wildlife is adapting or failing to adapt to rapidly changing environmental cues.

Habitat degradation and urbanization

Habitat degradation and urbanization can compromise wildlife health through the novel stressors of habitat loss, altered predation pressure and competition from invasives, and resource scarcity which can all potentially disrupt adrenal function. Despite many ecophysiological studies employing GCs as a metric for such disturbances (reviewed in Bonier, 2012), very little research has sought to incorporate DHEA(S) as a conservation measure. There are many instances where expected differences in GCs between habitats, urban scales, or populations are not observed, and interpretations can be complicated. These interpretations can include: (1) the conditions are not stressful; (2) they are only temporarily or acutely stressful, but with GC levels returning to baseline with negative feedback processes; (3) both are chronically stressed to the same degree; (4) stressed but in a manner not captured by GCs, due to interference from the capture process, the timing of the sample, or other factors; and (5) the stress manifests with other mechanisms that do not involve GCs. Studies that only report GCs not changing can benefit from also assessing DHEA(S) levels as a ratio of these hormones may reveal stress effects that single hormones fail to capture.

Urban wildlife studies can exemplify this conservation utility. For example, city northern cardinals maintain a different DHEA-to-corticosterone ratio than forest-living counterparts (Wright & Fokidis, 2016). Meta-analyses have revealed conflicting evidence for urban effects on GC levels in wildlife (Injaian et al., 2020; Sinclair et al., 2022), but incorporating measures of a “resilience hormone” could possibly reveal new coping mechanisms in urban animals. By providing early warning of physiological stress before population declines, DHEA(S) monitoring can help inform timely conservation interventions. Future research should focus on standardizing DHEA(S) sampling protocols across species, establishing baseline values for conservation-priority taxa, and clarifying relationships between DHEA(S) profiles and population-level outcomes.

Endocrine disruptors and xenobiotics

Contamination with exogenous chemicals released into ecosystems presents a pervasive threat to both wildlife and humans, which has helped emphasize a biomedical role in conservation, known as the “One Health” approach (Mackenzie & Jeggo, 2019; Jota Baptista et al., 2024). The effects of such natural or synthetic chemicals (i.e., xenobiotics) are often subtle yet biologically significant and as an intermediate metabolite in steroidogenesis, DHEA(S) appears particularly vulnerable to potential disruption by contaminants (Monneret, 2017). Chemical pollution can disrupt steroid metabolism and signaling (i.e., endocrine-disrupting chemicals or EDCs), and DHEA(S) can serve as an integrative indicator of such effects for conservation monitoring. Persistent pollutants (e.g., PFAS, PCBs, heavy metals) accumulate in food chains and alter endocrine function, including DHEA synthesis and conversion (Hayes et al., 2010; Hoydal et al., 2017). Positive associations between feather accumulation of these pollutants and feather levels of both corticosterone and DHEA deposition have already been documented in red kites suggesting they can be used for monitoring, although more research is needed (Monclus et al., 2018). In another example, common plasticizers (e.g., bisphenol A and phthalates) are known to inhibit the sulfotransferase enzyme that converts DHEA to DHEAS (Harris et al., 2007), which in turn can dysregulate the bioavailability of DHEA for subsequent conversion to bioactive steroids. Measuring DHEA(S) can help differentiate whether pollutants affect the Δ⁵ pathway and whether any compensatory alternate metabolic pathways are present and could help link pollutant exposure to population-level effects (e.g., reduced fertility or shifts in sex differentiation) in a species (Windsor et al., 2018). For example, pollutants like tributyltin (TBT) are known to inhibit DHEA esterification in oyster tissues (Janer et al., 2004) and can perturb overall steroid levels in Ciona ovaries (Cangialosi et al., 2010) leading to potential impacts on reproduction and survival. Furthermore, measuring both GCs and DHEA(S) may uncover sublethal pollutant-associated stress as a potential signal of immune compromise (Whitham et al., 2020). Given that environmental pollutants can alter DHEA levels, this steroid precursor holds promise as a biomarker for contamination exposure in conservation contexts, though toxicological research in this area remains critically needed.

Captive breeding programs

To maximize conservation impact, DHEA research must be effectively integrated with active management practices. Captive breeding represents a critical conservation tool for many endangered species, yet reproductive challenges often limit its effectiveness. Monitoring DHEA offers insights into reproductive endocrinology, especially healthy steroid synthesis, which is necessary for breeding success. Circulating DHEA levels fluctuate with reproductive cycles, and in some species, particularly mammals, peaks in DHEA(S) are associated with estrus, ovulation, and late gestation (Abbott et al., 2009; Brandhuber et al., 2023; Maninger et al., 2009). Thus, appropriate DHEA(S) dynamics during gestation may correlate with fetal development and pregnancy maintenance, while deviations may indicate reproductive failure (Hart et al., 2023). The potential implications for captive breeding of endangered species are obvious, with routine monitoring of DHEA improving the timing for assisted reproduction or the assessment of reproductive potential of specific animals in conservation programs.

Current gaps and limitations

Despite its promise, the application of DHEA(S) in conservation physiology is constrained by several substantive knowledge gaps and methodological limitations. First, there is a strong taxonomic bias toward mammals and birds, with amphibians, fishes, and invertebrates severely underrepresented. Second, most studies rely on cross-sectional sampling, providing only static snapshots of a hormone that functions as a dynamic intermediate precursor, thereby restricting interpretation of how longitudinal stress exposure imparts fitness consequences, or informs population-level trends. Such interpretation is further complicated by incomplete understanding of how DHEA(S) varies with demographics, environmental factors, across sites of synthesis, and its interactions with other endocrine axes such as GCs, thyroid, and reproductive systems, particularly outside well-studied laboratory models. Third, methodological inconsistency, including assay cross-reactivity, failure to distinguish DHEA from DHEAS, and variable extraction protocols further complicates any cross-study comparisons. These issues underscore the critical need for both analytical validation (i.e., assay accuracy, specificity, and parallelism within each matrix) and biological validation demonstrating that measured hormone variation meaningfully reflects known physiological or ecological processes. Finally, validation of non-invasive sampling matrices, such as skin, feathers, feces, or mucus remains incomplete for many taxa, and clear guidance on which biological samples best reflect biologically meaningful variation is sorely lacking. Without rigorous validation linking hormone concentrations in alternative matrices to circulating levels or experimentally induced endocrine change, cross‑taxonomic inference remains tenuous and may obscure rather than clarify endocrine function (Palme, 2019; Touma & Palme, 2005). Collectively, addressing these limitations is essential before DHEA(S) can be reliably incorporated into routine monitoring as a conservation biomarker.

Conservation value of DHEA(S)

The above limitations underscore why continued investigation into DHEA(S) is scientifically justified. Unlike terminal endocrine outputs, DHEA(S) occupies a central position as a metabolic precursor and modulatory hormone capable of influencing multiple physiological systems (e.g., stress responsiveness, energy allocation, immune function, and reproduction). This integrative position suggests DHEA(S) can offer further insight into physiological trade-offs, resilience, and compensatory mechanisms that are not readily captured by single biomarkers (i.e., GCs) alone. Furthermore, growing evidence for widespread DHEA synthesis and resulting effects highlights the importance of localized regulation (Himmelstein et al., 2021). This dimension of endocrine function is unexplored in conservation contexts but can be pertinent in situations where animals must cope with chronic or sublethal levels of environmental stress. More comparative investigation into DHEA across diverse taxonomic groups and environmental conditions may help clarify how endocrine systems evolve to buffer against environmental variability, beyond stress exposure.

Research into DHEA(S) can offer a mechanistic complement to established conservation tools which, while often more immediately predictive of population trajectories, frequently lack explanatory power regarding individual variation in susceptibility or resilience. By elucidating how physiological pathways mediate responses to change, DHEA(S) studies may strengthen causal inference and improve interpretation of observed ecological patterns. Indeed, even if DHEA(S) never becomes a routine monitoring metric, defining its limits, its context dependence, and its interactions with other hormonal systems can still represent a meaningful contribution to conservation physiology. In this sense, targeted research on DHEA(S) is warranted not as an applied shortcut, but as a foundational effort to refine understanding of endocrine diversity in an era of rapid environmental change.

We proposed future conservation research should prioritize (1) pilot studies validating DHEA in non-invasive matrices across understudied taxa, (2) longitudinal monitoring to link DHEA profiles with survival and reproductive success, and (3) cross-taxa comparisons to establish reference ranges and resilience thresholds. Integrating DHEA with GC monitoring will offer a more complete assessment of physiological state, particularly under stress and with standardized methods and targeted validation, DHEA has potential to become a routine component of conservation physiology and adaptive management.

Author contribution

The sole author, HBF conceived, wrote and edited the manuscript and takes full responsibility for the contents.

Funding

This work was supported by a National Science Foundation EAGER grant (IOS-2221192).

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics Approval

All authors have read, understood, and complied as applicable with the statement on “Ethical responsibilities of Authors” as found in the Instructions for Authors.

Conflict of interest

The authors declare no competing interests.

Declaration of generative AI and AI-assisted technologies in the writing process

During the preparation of this work, the author used ChatGPT 5.0 to improve readability of certain sections of the manuscript, particularly to improve conciseness and to cross-reference missing in-text citations with the literature cited. After using this tool, the author reviewed and edited the manuscript as needed and took full responsibility for the content of the publication.

Clinical trial number

Not applicable.