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Epiandrosterone (3β-hydroxy-5α-androstan-17-one; also called isoandrosterone) is an endogenous 5-alpha-reduced steroid formed from dehydroepiandrosterone (DHEA) and androstenedione, and it is the 3-beta-hydroxyl epimer of androsterone. It circulates in humans predominantly as its sulfate ester and functions as a weak neurosteroid (a steroid that acts on neuronal receptors rather than classical nuclear hormone receptors), producing only mild modulation of the GABA-A receptor (the brain's principal inhibitory chloride ion channel) while inhibiting glycine receptors (another inhibitory ligand-gated channel concentrated in the spinal cord and brainstem). Beyond the nervous system it is a well-characterized uncompetitive inhibitor of glucose-6-phosphate dehydrogenase (G6PD, the rate-limiting enzyme of the pentose phosphate pathway) and a recognized urinary marker of 5-alpha-reductase activity. Because it can be metabolized toward dihydrotestosterone (DHT, the most potent natural androgen), it is also sold over the counter as a non-methylated androgen prohormone.
- Serves as an endogenous urinary and serum marker of 5-alpha-reductase pathway activity in clinical steroid profiling
- Provides weak positive modulation of GABA-A receptors that may contribute subtle inhibitory or calming tone
- Marketed as a non-methylated androgen prohormone that can be metabolized toward dihydrotestosterone, of interest for strength and body composition without estrogenic conversion
- Inhibits glucose-6-phosphate dehydrogenase, the basis for experimental anti-proliferative and metabolic effects in laboratory models
- Its brominated analogs have shown immune-modulating activity in infectious-disease research including HIV, malaria, and tuberculosis models
Overview
Endogenous 5-alpha-reduced DHEA/androstane metabolite; a weak GABA-A-modulating neurosteroid, a classic G6PD inhibitor, and a 5-alpha-reductase-pathway marker that is also marketed OTC as a non-methylated androgen prohormone.
- It is a textbook uncompetitive inhibitor of glucose-6-phosphate dehydrogenase, the rate-limiting enzyme of the pentose phosphate pathway, which is why it has been used as a research tool to starve rapidly dividing cells of NADPH.
- Its 16-alpha-bromo derivative, 16-alpha-bromoepiandrosterone (HE2000), reached human clinical trials as an immune modulator for HIV infection and malaria.
- It differs from the potent anticonvulsant neurosteroid androsterone by only a single stereocenter at carbon-3; that lone 3-alpha versus 3-beta flip is enough to change it from a strong GABA-A potentiator into a weak one.
- Because it is not readily aromatized, it is one of the few androgen prohormones marketed specifically for a low-estrogen, dihydrotestosterone-leaning metabolic route.
Mechanism
Epiandrosterone is an androstane neurosteroid whose activity is governed by the stereochemistry at carbon-3. Its parent, DHEA, is 5-alpha-reduced and 3-keto-reduced to yield the 3-beta-hydroxy-5-alpha configuration; the same enzymatic machinery (5-alpha-reductase followed by 3-alpha/3-beta-hydroxysteroid dehydrogenases, the AKR1C family) produces its more neuroactive 3-alpha epimer androsterone.
This single-stereocenter difference is decisive: 3-alpha-hydroxy A-ring-reduced steroids such as androsterone and allopregnanolone are potent positive modulators of the -A receptor, whereas the 3-beta-hydroxy orientation of epiandrosterone leaves it a comparatively weak GABA-A modulator. At the strychnine-sensitive glycine receptor, endogenous 5-alpha-androstanes including epiandrosterone act instead as inhibitors (negative modulators), so the molecule shifts inhibitory tone in opposite directions at two related channels.
The circulating sulfate ester, epiandrosterone sulfate, is structurally analogous to DHEA sulfate and is expected to share its profile as a negative -A modulator with additional modulation of the receptor and putative sigma-1 receptor signaling, though direct potency data for the epiandrosterone ester are sparse. Metabolically, epiandrosterone sits on the periphery of the androgen network: it interconverts with androsterone and 5-alpha-androstane-3-beta,17-beta-diol and can be oxidized at carbon-17 and re-reduced at carbon-3 to feed toward dihydrotestosterone, which is why it behaves as an androgen prohormone and why it is not appreciably aromatized to estrogens.
A distinct, non-receptor mechanism is its uncompetitive inhibition of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase; by throttling the oxidative pentose phosphate pathway it lowers NADPH and ribose-5-phosphate supply, the biochemical basis for its experimental anti-proliferative, metabolic, and immune-modulating effects and for the development of its 16-alpha-bromo analog.
receptor fingerprint
5-alpha-reductase pathwayDownstream metabolite and activity marker (as the sulfate)
Glycine receptorInhibition (negative modulation of inhibitory current)
Glucose-6-phosphate dehydrogenaseUncompetitive inhibition
Glucose-6-phosphate dehydrogenase (G6PD)Uncompetitive inhibition of the pentose phosphate pathway enzyme
17-beta-hydroxysteroid / carbonyl reductasesSubstrate for interconversion with oxo and hydroxy metabolites
-A receptorWeak positive allosteric modulation (potentiation of chloride current)
Indirect agonism via metabolic conversion toward dihydrotestosterone
Modulation by the circulating sulfate ester (DHEA-sulfate-like profile)
Sigma-1 receptorPutative agonism by the sulfate ester
Dosingtypical ranges, not medical advice
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Safetyrisks and cautions, not medical advice
Everything that matters follows from where epiandrosterone goes: it is a precursor to dihydrotestosterone and it does not aromatise. That removes the oestrogenic problems and leaves the androgenic ones, meaning acne, oily skin, accelerated male-pattern hair loss in the susceptible, prostate effects, suppression of the body's own testosterone, and virilising effects in women. No controlled human safety trial of epiandrosterone itself exists, so the numbers are borrowed. A four-week trial of the adjacent prohormone 1-androsterone found HDL down 39 percent, LDL up 33 percent and AST roughly doubled.
History
Epiandrosterone belongs to the first generation of crystalline urinary androgens characterized during the foundational era of steroid chemistry in the 1930s, alongside its isomer androsterone; the "iso" and "epi" names reflect its status as a stereoisomer distinguished by the orientation of the 3-hydroxyl group. Its inhibition of glucose-6-phosphate dehydrogenase became a subject of biochemical study in the mid-twentieth century and made it a standard tool compound for probing the pentose phosphate pathway.
Interest broadened in the 2000s when a synthetic derivative, 16-alpha-bromoepiandrosterone (developmental code HE2000), was advanced into human clinical trials as an immune-modulating agent for HIV and malaria, and a related oral analog (HE3286) was studied for inflammatory disease. In parallel, the parent compound entered the sports-supplement market as a legal, non-methylated prohormone after methylated designer steroids were restricted.
Reputation
Epiandrosterone occupies two largely separate reputations. In steroid biochemistry and endocrinology it is respected as a reliable urinary index of 5-alpha-reductase activity and as a classic small-molecule inhibitor of G6PD, with its brominated analogs drawing attention in infectious-disease and immunology research. In the fitness community it is regarded as one of the milder, non-liver-toxic prohormones, valued for a "dry" androgenic profile because it resists aromatization to estrogen. Its standing as a nootropic or mood agent is minor and speculative; unlike the potent GABAergic neurosteroids, its weak receptor activity means any central effects are subtle and poorly documented in humans.
Subjective profileweighing the evidence above
Milder than most prohormones and non-methylated, which is the main thing in its favor, but the human evidence that it does much for strength or leanness is thin and the supplement quality is variable. If a DHT-leaning androgen is genuinely the goal, expect the usual androgenic tradeoffs.
Resources
This entry is here for reference.
Research
- 1966first citedAndrostenedione production and interconversion rates measured in peripheral blood and studies o…
- 2006controlled trialImprovement in immune parameters and human immunodeficiency virus-1 viral response in individua…
- 2024most active year4 papers
- 2025most recentProposing Bromo-Epi-Androsterone for Host-Directed Therapy Against Tuberculosis
- 1.Neurosteroids as Selective Inhibitors of Glycine Receptor Activity: Structure-Activity Relationship Study on Endogenous Androstanes and Androstenes
- 2.Anticonvulsant activity of androsterone and etiocholanolone
- 3.5β-Dihydrosteroids: Formation and Properties
- 4.17beta-Nitro-5alpha-androstan-3alpha-ol and its 3beta-methyl derivative: neurosteroid analogs with potent anticonvulsant and anxiolytic activities
- 5.Neurosteroids and GABA-A Receptor Function
- 6.Neuroactive Steroids: Receptor Interactions and Responses
- 7.Non-stereo-selective cytosolic human brain tissue 3-ketosteroid reductase is refractory to inhibition by AKR1C inhibitors
- 8.Characterization and measurement of dehydroepiandrosterone sulfate in rat brain
- 9.Memory-enhancing effects in male mice of pregnenolone and steroids metabolically derived from it.
- 10.Androstenedione production and interconversion rates measured in peripheral blood and studies on the possible site of its conversion to testosterone.
- 11.The conversion of testosterone to 5-alpha-androstan-17-beta-ol-3-one (dihydrotestosterone) by skin slices of man
- 12.Human metabolic individuality in biomedical and pharmaceutical research
31 listed here; entry last updated August 2026
Reviews
My notesprivate to this device
FAQ
Is epiandrosterone the same as androsterone?
No. They are 3-epimers, meaning they share the same skeleton but differ in the orientation of the hydroxyl group at carbon-3; epiandrosterone is 3-beta-hydroxy while androsterone is 3-alpha-hydroxy. That single difference makes androsterone a much stronger GABA-A modulator and anticonvulsant, and epiandrosterone a comparatively weak one.
Will epiandrosterone sedate or intoxicate me like allopregnanolone?
No. Its 3-beta configuration gives it only weak positive activity at the GABA-A receptor, so it does not produce the pronounced sedative, anxiolytic, or intoxicating effects associated with potent 3-alpha neurosteroids such as allopregnanolone or the drug brexanolone.
How is it related to DHEA and dihydrotestosterone?
Epiandrosterone is a 5-alpha-reduced metabolite of DHEA and androstenedione, and through interconversion with androsterone and androstanediol it can be routed toward dihydrotestosterone, the most potent natural androgen. This prohormone route is why it is sold as a supplement and why it is banned in sport.
What is the connection to G6PD and the pentose phosphate pathway?
Independent of any hormone receptor, epiandrosterone directly inhibits glucose-6-phosphate dehydrogenase, the first and rate-limiting enzyme of the oxidative pentose phosphate pathway. By reducing production of NADPH and ribose-5-phosphate it can slow the growth of rapidly dividing cells, which underlies research interest in metabolic and anti-proliferative applications.
Is it detectable in anti-doping tests?
Yes. Epiandrosterone and its ratios to related steroids are part of the urinary steroid profile that anti-doping laboratories monitor, and supplementation can flag the athlete biological passport as evidence of exogenous androgen use.
Limitations of the evidence
- Limited controlled human safety data and variable, unregulated supplement quality
Notes and cautions
- Androgenic effects when used as a prohormone, including acne, oily skin, and accelerated scalp hair loss in genetically predisposed individuals
- Potential suppression of endogenous testosterone production with prolonged or high-dose supplementation
- Downstream conversion products can perturb the broader androgen balance despite minimal direct estrogen conversion
- Theoretical interference with NADPH-dependent antioxidant defense through pentose phosphate pathway inhibition at high exposure
- Prohibited in competitive sport as an anabolic-androgenic agent and detectable on steroid-profile doping tests