IngredientsEpiandrosterone — also spelled epi-androsterone and commonly abbreviated Epi-Andro — is a naturally occurring endogenous steroid hormone. It is known by several systematic and common names: isoandrosterone, 3β-androsterone, 3β-hydroxy-5α-androstan-17-one, and 5α-androstan-3β-ol-17-one, and it is characterized as a steroid hormone with weak androgenic activity. The compound is also listed in the NIST WebBook under additional synonyms including D-Epiandrosterone, iso-Androsterone, trans-Androsterone, and 3β-Hydroxyetioallocholan-17-one.
The molecular formula is C₁₉H₃₀O₂, with a molecular weight of 290.44 and seven defined stereocenters. In formal chemical classification, epiandrosterone is a 3β-hydroxy steroid that is (5α)-androstane substituted by a β-hydroxy group at position 3 and an oxo group at position 17. The PubChem CID for the compound is 441302.
Within the 5α-androstan-17-ones, the 3α-hydroxy orientation at C3 sets androsterone apart from its C3 epimer, epiandrosterone, which bears a 3β-hydroxy group. In plain terms, epiandrosterone and androsterone are stereoisomers — they share an identical molecular formula and ring system, differing only in the spatial orientation (alpha vs. beta) of the hydroxyl group at carbon-3. Androsterone is a 3-alpha isomer, and epiandrosterone is a 3-beta isomer of the compound.
The 17-ketosteroid epiandrosterone is a metabolite of the testosterone precursor dehydroepiandrosterone (DHEA). It is also a metabolite of testosterone and dihydrotestosterone (DHT). Epiandrosterone has been considered to be merely an inactive end product of DHEA, but it may in fact be a physiological effector in its own right; it is formed in peripheral tissues, from which it is released into the circulation and is ultimately excreted in the urine.
Epiandrosterone is a naturally occurring steroid hormone and a metabolite of dehydroepiandrosterone (DHEA) in the human body. It is produced in the adrenal glands, gonads, and brain, and plays a significant role in various physiological functions.
Epiandrosterone has been shown to naturally occur in most mammals, including pigs. Beyond mammalian endogenous production, it is also naturally found in pine pollen. Epiandrosterone is excreted in urine as a routine metabolic end product, which is the reason it can be measured in clinical and anti-doping laboratories. Epi-andro is naturally found in most mammals and is excreted as a normal part of metabolism in urine.
The body generates epiandrosterone through multiple biosynthetic routes, all branching from the broader adrenal steroid cascade. Epiandrosterone is naturally produced by the enzyme 5α-reductase from the adrenal hormone DHEA. It can also be produced from the natural steroids androstanediol via 17β-hydroxysteroid dehydrogenase or from androstanedione via 3β-hydroxysteroid dehydrogenase. Thus, three distinct enzymatic reactions can generate epiandrosterone from three different steroid precursors, making it a relatively common and readily formed metabolite within the androgen pathway.
Epiandrosterone was first isolated in 1931 by Adolf Friedrich Johann Butenandt and Kurt Tscherning. They distilled over 17,000 litres of male urine, from which they obtained 50 milligrams of crystalline androsterone (most likely mixed isomers), which was sufficient to find that the chemical formula was very similar to estrone. This landmark early-20th-century experiment, which required enormous quantities of urine to yield a tiny amount of crystalline material, was a foundational moment in steroid biochemistry. Adolf Butenandt went on to receive the Nobel Prize in Chemistry in 1939 in part for this body of work on sex hormones.
Because the initial 1931 isolation yielded mixed isomers, the precise structural differentiation between androsterone (3α) and epiandrosterone (3β) was a product of progressively refined analytical techniques in subsequent decades. The compound is now definitively catalogued in the NIST Standard Reference Database with a confirmed CAS Registry Number of 481-29-8.
Epiandrosterone does not have a history of use within classical herbal medicine traditions (such as Ayurveda, Traditional Chinese Medicine, or European folk herbalism), because it was not identified as a discrete chemical entity until 1931 and could not be isolated or administered in a meaningful way prior to modern analytical chemistry. Its presence in pine pollen — a substance used in some traditional East Asian medicine systems — is incidental to the pollen's traditional role, and no historical source specifically attributed therapeutic effects to epiandrosterone within that context.
Historically, its presence was first identified in human urine, and it was subsequently studied for its potential physiological effects. In early medicinal investigation, epiandrosterone was explored for its role in supporting male vitality, promoting a sense of well-being, and contributing to the maintenance of lean muscle mass. These early investigations were scientific rather than traditional, emerging from the mid-20th-century expansion of endocrinology and steroid biochemistry.
During the prohormone boom of the 1990s and onward, epiandrosterone became very popular because of its unique qualities and advantages. This era of commercial interest — driven by the passage of the Dietary Supplement Health and Education Act (DSHEA) of 1994 in the United States — led to widespread marketing of androgenic prohormones, including epiandrosterone, as legal alternatives to anabolic steroids. This commercial history represents the primary period during which epiandrosterone was deliberately consumed by humans for performance or body-composition purposes.
In the supplement marketplace (prior to its U.S. scheduling as a controlled substance), epiandrosterone appeared in several preparation forms:
As a single pure steroid compound rather than a botanical extract, epiandrosterone is itself the primary active entity. Its biological activity arises from both its own direct actions and its downstream conversion to more potent androgens. The key mechanistic elements established in the scientific literature are as follows:
One of the primary physiological functions of epiandrosterone is its role as a precursor to dihydrotestosterone (DHT), a potent androgen hormone. DHT is involved in the development of male sexual characteristics and is important for maintaining muscle mass, bone density, and libido. Epiandrosterone's conversion to DHT contributes to its androgenic effects, which may include promoting lean muscle growth and enhancing strength.
However, epiandrosterone itself is classified as a weak androgen. Epiandrosterone is only a weak androgen, but it is widely recognized to inhibit the pentose phosphate pathway and to decrease intracellular NADPH levels. This means much of its perceived androgenic potency is attributable to its metabolic conversion to DHT rather than to direct androgen receptor activation by epiandrosterone itself.
A well-documented biochemical mechanism of epiandrosterone — confirmed in preclinical and in vitro research — is its capacity to inhibit G6PD, the rate-limiting enzyme of the pentose phosphate pathway. The 17-ketosteroids (including epiandrosterone and DHEA) are known to inhibit glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme in the pentose phosphate pathway (PPP), and to reduce intracellular NADPH levels.
DHEA and related steroids are potent, non-competitive inhibitors of mammalian glucose-6-phosphate dehydrogenase (G6PDH), the rate-limiting enzyme of the pentose phosphate pathway, which is a major source of five-carbon sugars as well as NADPH, a critical modulator of cellular redox potential. NADPH supplies reducing equivalents for several reactions that generate oxygen-free radicals, which, in addition to their mutagenicity, act as intermediate messengers that stimulate mitogenesis and upregulate inflammation.
Research cited in the Journal of Molecular and Cellular Cardiology (2002) confirmed that the DHEA metabolite epiandrosterone (EPI) inhibits the pentose phosphate pathway (PPP) and dilates isolated blood vessels pre-contracted by partial depolarization.
A study published in Endocrinology (1996) found that in isolated rat pancreatic islets and RINm5F insulinoma cells, epiandrosterone (EA) and DHEA inhibited [U-¹⁴C]glucose oxidation. Comparison of glucose oxidation patterns indicated that EA inhibited glycolysis and the pentose shunt contribution to glucose utilization. Notably, the effects of DHEA and EA on glucose oxidation were rapidly reversible.
Epiandrosterone may act as an L-type Ca²⁺ channel antagonist. This has been studied in cardiac tissue. Research demonstrated that a 17-ketosteroid, epiandrosterone, attenuates L-type Ca²⁺ currents (ICa-L) in cardiac myocytes and inhibits myocardial contractility. Because 17-ketosteroids are known to inhibit G6PD and to reduce intracellular NADPH levels, inhibition of G6PD was hypothesized to be a novel signaling mechanism which inhibits ICa-L and, therefore, cardiac contractile function.
In the Journal of Molecular and Cellular Cardiology study, EPI at concentrations of 10–100 μM dose-dependently decreased left-ventricular developed pressure (LVDP), the rate of myocardial contraction (+dp/dt), and the pressure rate product (PRP); at 100 μM EPI, LVDP (131±9 vs 34±7 mmHg), +dp/dt (1515±94 vs 542±185 mmHg/s), and PRP (37870±2471 vs 9498±2375 HR×mmHg/min) were all significantly (P<0.05) reduced. Electrophysiological analysis of single ventricular myocytes using whole-cell clamp showed EPI to dose-dependently (100 nM–100 μM) and reversibly inhibit L-type channel currents carried by Ba²⁺ (IBa) (IC50 = 42±6 μM) by as much as 50%. These findings are from isolated animal cardiac preparations and do not represent human clinical data.
By inhibiting G6PD and thereby suppressing the oxidative branch of the PPP, epiandrosterone reduces the intracellular supply of NADPH. These findings suggest that inhibiting G6PD activity and reducing NADPH levels alters metabolism and leads to inhibition of L-type Ca²⁺ channel activity. Notably, this pathway may be involved in modulating myocardial contractility under physiological and pathophysiological conditions during which the PPP-derived NADPH redox is modulated (e.g., ischemia-reperfusion and heart failure).
Additionally, inhibition of G6PD by epiandrosterone or DHEA reduces NADPH levels in the isolated rat heart and in pulmonary and coronary arteries, exerts a negative inotropic effect in rat hearts, attenuates angiotensin II- and hypoxia-induced pulmonary vasoconstriction in isolated lungs, and relaxes isolated vessels. All of these mechanistic observations derive from preclinical (animal and in vitro) models.
Epiandrosterone can be hydroxylated in several tissues to produce downstream neuroactive steroids. It has been demonstrated that neuroprotective effects of DHEA may be mediated by its 7α- and 7β-hydroxy derivatives. Epiandrosterone is also converted to 7β-hydroxy epiandrosterone (7β-OH EPIA) in numerous tissues.
A study published in Neuropathology and Applied Neurobiology (2004, PubMed PMID 15006696) investigated the 7β-hydroxylated metabolite specifically. The aim was to establish whether treatment with 7β-hydroxy epiandrosterone has a neuroprotective effect in animal models of Alzheimer's disease lesions. Intra-amygdaloid administration of amyloid beta [Aβ(25-35)] increased the number of tau-positive cells in the ipsilateral hippocampus. Intracerebroventricular administration of ethylcholine aziridinium (AF64A) caused cholinergic damage in the septum and glial lesions in the lateral septal nucleus and hippocampus. These effects were almost completely prevented when animals were treated subcutaneously twice daily for 10 days with 0.1 mg/kg 7β-hydroxy epiandrosterone. These findings indicate that 7β-hydroxy epiandrosterone has powerful cytoprotective effects, suggesting that this neurosteroid may have therapeutic potential in various neurodegenerative conditions such as Alzheimer's disease, and that 7β-hydroxy steroids may constitute a novel class of endogenous neuroprotective agents. These results were obtained exclusively in rodent models; no human clinical trials have examined this application.
Epiandrosterone occupies a node in the androgen biosynthetic pathway. It is a downstream metabolite of DHEA and an upstream precursor to DHT. It is formed in peripheral tissues, from which it is released into the circulation and is ultimately excreted in the urine. Through its conversion to DHT — one of the most potent endogenous androgens — epiandrosterone participates indirectly in the regulation of androgen-dependent processes, including male sexual differentiation, spermatogenesis, and libido-related physiology.
Epiandrosterone is used for weight loss and to improve athletic performance, but there is no good scientific evidence to support these uses. The theoretical basis for ergogenic claims rests on the DHT conversion pathway: because DHT is a potent androgen receptor agonist, it could theoretically stimulate anabolic processes in muscle tissue at physiologically relevant concentrations. However, as of the time of writing, no published, peer-reviewed, randomized controlled trial (RCT) specifically evaluating epiandrosterone itself as a dietary supplement in humans for body composition or strength outcomes has been identified in the authoritative literature. In short, epiandrosterone is real biology — but as an endogenous weak androgen and metabolite, not a clinically validated performance enhancer.
The closely related compound 1-epiandrosterone (also written as 1-androsterone; its systematic name is 3β-hydroxy-5α-androst-1-en-17-one) has been studied in one small randomized trial. In a randomized, placebo-controlled trial involving 17 resistance-trained men over 4 weeks, supplementation with 330 mg/day of 1-androsterone resulted in a 6.3% increase in lean body mass (approximately 4.6 kg), a 24.6% decrease in fat mass, and a 14.3% improvement in back squat one-repetition maximum strength, significantly exceeding placebo outcomes. However, the study did not directly assess serum testosterone elevations or broader athletic performance metrics, and it highlighted potential health risks that could offset benefits. Larger and longer-term studies are needed to confirm ergogenic effects. It must be emphasized that 1-epiandrosterone and epiandrosterone are structurally distinct compounds, and the results of that trial cannot be assumed to apply to epiandrosterone (3β-hydroxy-5α-androstan-17-one).
The cardiovascular research on epiandrosterone is entirely preclinical. The compound's capacity to inhibit G6PD and reduce NADPH has implications for myocardial and vascular function. Studies in isolated rat hearts and aortic preparations showed dose-dependent reduction in cardiac contractile parameters (see the Mechanisms section above). This pathway may be involved in modulating myocardial contractility under physiological and pathophysiological conditions during which PPP-derived NADPH redox is modulated, such as ischemia-reperfusion and heart failure. There are no human clinical trials on epiandrosterone's cardiovascular effects.
An in vitro and ex vivo study published in Endocrinology in 1996 (Laychock SG, Bauer AL) investigated epiandrosterone's effects on pancreatic beta cells. Isolated rat islets or RINm5F insulinoma cells treated with interleukin-1 beta (IL-1β) for 18 hours showed reduced glucose-sensitive insulin release and increased nitrite formation. Islets cultured with IL-1β and epiandrosterone and then washed responded with a concentration-dependent reversal of the effects of IL-1β on insulin release in the presence of glucose stimulus. In contrast, when EA was not washed from the islets before determination, the presence of EA inhibited insulin release in both freshly isolated and cultured islets. Nitrite formation in islets and RINm5F cells in response to IL-1β was also significantly reduced during culture with EA or DHEA, although nitrite levels were still elevated above control values. These findings suggest a complex, bidirectional relationship between epiandrosterone and pancreatic beta-cell function that is context- and concentration-dependent. This is preclinical data only.
As described in the mechanism section, epiandrosterone's primary neuroactive interest lies in its 7β-hydroxylated metabolite. The preclinical evidence (rodent models) for 7β-hydroxy-epiandrosterone is described above. For epiandrosterone itself, it has been studied for potential neuroprotective effects, supporting cognitive function and potentially mitigating neurodegenerative diseases. However, these claims derive from preclinical investigation, not human clinical trials.
One area in which epiandrosterone has received substantive scientific attention is as a urinary marker for detection of exogenous testosterone administration. Because epiandrosterone is a normal metabolic product of testosterone and DHT, its urinary sulfate conjugate and glucuronide conjugate ratios can shift when exogenous testosterone is administered. Research on this application is real and published in peer-reviewed sports medicine literature. Results showed that oral testosterone administration is detected for a much longer period of time with sulfate markers than with conventional urinary steroid profile markers. Androstanediol sulfate/dehydroandrosterone sulfate and epiandrosterone sulfate/dehydroandrosterone sulfate ratios were the most diagnostic parameters for longitudinal monitoring. For most subjects, sulfate markers allowed the detection of suspicious samples up to 144 hours.
Evidence strength: Very weak (no human RCTs specifically for epiandrosterone itself; preclinical and theoretical only).
Epiandrosterone is used for weight loss and to improve athletic performance, but there is no good scientific evidence to support its use. The mechanistic rationale — DHT upregulation — is physiologically plausible but remains unvalidated in rigorous human trials specifically for epiandrosterone. A compound that appears modestly active in a cell model may have negligible impact systemically, or it may sustain local androgen tone in select tissues without altering blood testosterone. That gap between local metabolism and whole-body effect is a central reason why many purported "prohormones" disappoint in rigorous trials or deliver unpredictable results across individuals.
Evidence strength: No human clinical evidence; theoretical only.
Claims regarding improved libido are based on the compound's conversion to DHT, which is known to play roles in male sexual function. However, no published human clinical trial has evaluated epiandrosterone specifically for this purpose. There is no good scientific evidence to support its use for reducing sexual problems.
Evidence strength: Preclinical only (in vitro and isolated animal organ preparations).
The mechanistic studies in rat cardiac preparations demonstrating L-type calcium channel blockade and G6PD inhibition are scientifically credible, published in peer-reviewed journals such as the Journal of Molecular and Cellular Cardiology. However, the concentrations used (100 μM) are pharmacologically high and may not reflect physiological or supplemental exposure in vivo. No human cardiovascular outcomes trials exist.
Evidence strength: Preclinical only (rodent models of Alzheimer's-like lesions, for the 7β-OH metabolite).
Findings from rodent studies indicate that 7β-hydroxy epiandrosterone has powerful cytoprotective effects, suggesting that this neurosteroid may have therapeutic potential in various neurodegenerative conditions such as Alzheimer's disease. This applies to the hydroxylated metabolite, not epiandrosterone per se, and there are no human data.
Evidence strength: Preclinical only (isolated pancreatic islets and insulinoma cell lines).
The 1996 Endocrinology study (Laychock and Bauer) showed context-dependent effects on insulin release and glucose oxidation in isolated rat islets. These findings are hypothesis-generating but require human investigation before any clinical conclusions can be drawn.
Evidence strength: Moderate to strong (analytical chemistry studies in human volunteers); this is not a therapeutic use but a forensic/diagnostic one.
Based on research findings, sulfate EAAS (endogenous anabolic androgenic steroid) metabolites including epiandrosterone sulfate provide a consistent improvement in the detectability of testosterone administration in both Caucasian and Asian populations. Sulfate metabolites of endogenous anabolic androgenic steroids have been shown to prolong the detection times compared with conventional urinary markers.
No well-designed human clinical dosing studies for epiandrosterone (3β-hydroxy-5α-androstan-17-one) as a supplement have been published in the peer-reviewed literature identified in this review. Accordingly, no evidence-based human dosing recommendation can be made.
There isn't enough reliable information to know what an appropriate dose of epiandrosterone might be.
In the preclinical cardiovascular research literature, epiandrosterone was studied at concentrations of 10–100 μM in isolated cardiac preparations and at 100 nM–100 μM in electrophysiological studies of ventricular myocytes. These are in vitro concentrations and do not translate directly to human oral dosing.
In animal neuroprotection studies, animals were treated subcutaneously twice daily for 10 days with 0.1 mg/kg of the metabolite 7β-hydroxy epiandrosterone — again, these are animal experimental doses, not human clinical doses.
For the structurally related 1-epiandrosterone (a distinct compound), the one identified human trial used 330 mg/day over 4 weeks. This figure should not be extrapolated to epiandrosterone without dedicated human pharmacokinetic and safety studies.
In the US, epiandrosterone is a Schedule III controlled substance that is not legal for use in supplements. Despite this, it is still found in some supplement products. It is also banned by the World Anti-Doping Agency (WADA).
The legal pathway by which epiandrosterone was scheduled relates to successive federal legislation. The Designer Anabolic Steroid Control Act of 2014 (H.R. 4771) expanded the list of anabolic steroids regulated by the Drug Enforcement Administration (DEA) to include about two dozen new substances and established new crimes relating to false labeling of steroids. The Act amended the Controlled Substances Act to add specified substances to the list of those included within the definition of "anabolic steroid," and provided that a drug or hormonal substance that has a chemical structure substantially similar to a listed anabolic steroid shall be considered to be an anabolic steroid if it has been created or manufactured with the intent of producing a substance that promotes muscle growth or otherwise causes a pharmacological effect similar to that of testosterone.
The Designer Anabolic Steroid Control Act of 2014 (P.L. 113–260) — DASCA — gives the DEA additional authority to identify and quickly respond when new designer anabolic steroids — illegal drugs — are falsely marketed as dietary supplements.
For competitive athletes worldwide, the World Anti-Doping Agency (WADA) explicitly lists epiandrosterone (and its 1-ene analog 1-epiandrosterone) among anabolic agents prohibited at all times. 1-Epiandrosterone is also banned by the National Collegiate Athletic Association (NCAA).
When taken by mouth, epiandrosterone is possibly unsafe for most people. Reported side effects include infertility, behavioral changes, and hair loss. Epiandrosterone might also lead to liver damage and heart disease.
Because epiandrosterone converts to DHT — which is more potent at the androgen receptor than testosterone — androgenic adverse effects are a concern. These include scalp hair loss in genetically predisposed individuals (androgenetic alopecia), acne, and potential virilization effects. Elevations in DHT may also suppress endogenous testosterone production via negative feedback on the hypothalamic-pituitary-gonadal (HPG) axis, potentially causing temporary hypogonadism and reduced sperm production, contributing to the reported infertility risk.
Since the 1950s, a significant number of studies and case reports have raised concerns regarding hepatotoxic effects — including cholestasis, hepatic neoplasms, hepatocyte toxicity, and peliosis hepatis — related to use of anabolic-androgenic steroids. Bodybuilding products were the most common cause for liver injury in those using herbal and dietary supplement (HDS) products. Supraphysiologic and long-term use of anabolic-androgenic steroids affects all organs, leading to cardiovascular, neurological, endocrine, gastrointestinal, renal, and hematologic disorders.
While these broader class effects for anabolic-androgenic steroids are well-documented in the medical literature, epiandrosterone-specific hepatotoxicity case data in the peer-reviewed literature were not identified in the sources consulted for this review.
Anabolic-androgenic steroids have side effects involving all organs, tissues, and body functions, with especially serious long-term toxicity involving the cardiovascular system and the reproductive system; their abuse is therefore considered a public health issue. The cardiovascular risk class effects include adverse lipid changes (reduction in HDL cholesterol), left ventricular hypertrophy, and increased thromboembolic risk — consistent with the broader anabolic steroid class. Epiandrosterone's specific cardiovascular risk profile in humans has not been formally characterized in clinical research.
Analyses of "test booster" and prohormone products have uncovered undisclosed steroids, improper dosing, or pharmaceutical contaminants. Even if a consumer believes they are purchasing epiandrosterone, the bottle may contain something else — or the amount may differ from the label by a wide margin. This compounds safety uncertainties because the actual substance and dose consumed may differ from what is stated.
Epiandrosterone is possibly unsafe when pregnant or breast-feeding. Its use should be avoided during these periods.
Laboratories can detect characteristic metabolites and altered steroid ratios from epiandrosterone use, and analytical methods continue to improve. For athletes subject to testing, possession or use is a high-risk choice irrespective of perceived potency.
Epiandrosterone is mainly transformed into 17β-hydroxylated derivatives, 7- or 16α-hydroxylated metabolites under NAD(P)H conditions, and 5α-androstane-3,17-dione under NAD(P)⁺ conditions. Hepatic metabolism is the primary route of biotransformation. A study by Chalbot and Morfin (Drug Metabolism and Disposition, 2005) specifically characterized the metabolism of epiandrosterone in human liver S9 fractions, identifying a range of hydroxylated metabolites including 7-hydroxylated derivatives. These metabolites are ultimately conjugated (glucuronidated or sulfonated) and excreted in urine, forming the basis for urinary steroid profiling in anti-doping testing.
The following are areas where the existing scientific record for epiandrosterone is absent or critically limited:
Health conditions that Epindrosterone may help support.
Body systems that Epindrosterone may help support.
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