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Androstenediol (androst-5-ene-3β,17β-diol, commonly abbreviated 5-androstenediol or 5-AED) is an endogenous Δ5 androstane steroid formed as a direct metabolite of dehydroepiandrosterone (DHEA, the most abundant circulating adrenal steroid). It sits at a branch point in steroidogenesis, functioning both as a weak, ERβ-preferring estrogen (a steroid that activates the estrogen receptor) and as a prohormone that can be converted onward to testosterone. Its most distinctive documented activity is immunomodulatory and hematopoietic; under the development code Neumune it was investigated as a radiation countermeasure that accelerates recovery of white blood cells and platelets after whole-body irradiation. Its inclusion in the neurosteroid grouping is one of exhaustiveness, since unlike allopregnanolone it has only a marginal classic neurosteroid profile at the GABA-A and NMDA receptors, and its central effects are attributed mainly to estrogen receptor beta signaling.
- Stimulates myelopoiesis and accelerates recovery of neutrophils and platelets after radiation-induced bone marrow suppression in animal models
- Induces G-CSF and activates NF-κB to promote survival of irradiated hematopoietic progenitor cells
- Anti-inflammatory activity in mucosal injury models via ERβ-dependent suppression of TLR4/NF-κB signaling
- Enhances innate immune cell function and resistance to bacterial infection and endotoxin in rodents
- ERβ-mediated neuroprotection reported against isoflurane-induced neurocognitive injury in neonatal rodents
- Serves as an intracrine prohormone reservoir feeding local testosterone and estrogen production
- Androgenic effects including acne and unwanted hair growth from downstream conversion to testosterone
- Estrogenic effects including possible gynecomastia and fluid retention
- Disruption of endogenous hormone balance and hypothalamic-pituitary feedback
- Injection-site reactions with the parenteral formulations used in research
Overview
An endogenous DHEA metabolite best known as a weak ERβ-preferring estrogen and an immunostimulating radiation countermeasure (Neumune), included here as a borderline, niche neurosteroid rather than a classic GABAergic one.
- Under the development code Neumune, 5-androstenediol was advanced by Hollis-Eden Pharmaceuticals as a radiation countermeasure and tested in irradiated rhesus monkeys, where it accelerated recovery of neutrophils and platelets after radiation-induced myelosuppression.
- Despite being grouped with neurosteroids, crystallography shows androstenediol is only about 3-fold selective for ERβ over ERα and stabilizes the receptor's active conformation almost identically to estradiol, so its label as a 'selective' estrogen is only modest.
- It was openly sold as an over-the-counter prohormone until androstenediols were folded into the US Anabolic Steroid Control Act of 2004, moving the same molecule from supplement shelf to controlled substance.
- In women with polycystic ovary syndrome, the endometrial conversion of DHEA to 5-androstenediol is increased, illustrating how local (intracrine) steroid metabolism can shift in disease tissue.
Mechanism
Androstenediol is biosynthesized from dehydroepiandrosterone (DHEA) by 17β-hydroxysteroid dehydrogenase (17β-HSD, an enzyme that reduces the 17-keto group of DHEA to a 17β-hydroxyl); isoforms including HSD17B1, HSD17B3, HSD17B7 and HSD17B12 have been implicated in this reduction. It occupies a pivotal position in the Δ5 (5-ene) steroid pathway, since 3β-hydroxysteroid dehydrogenase (3β-HSD, which isomerizes Δ5 steroids to Δ4 steroids) can convert androstenediol directly to testosterone, giving it genuine prohormone character.
It can also be sulfated or serve as an aromatization substrate, and its tissue fate is highly intracrine (produced and acting within the same local tissue rather than as a circulating hormone). At the receptor level androstenediol is a weak ; crystallographic work on the human estrogen receptor binding domains shows it is only about 3-fold selective for estrogen receptor beta (ERβ) over estrogen receptor alpha (ERα), binds in a nearly identical pose in both subtypes, and stabilizes the active conformation and the activation function 2 (AF2) coactivator surface much as estradiol does.
It is additionally a weak (AR) . Its immunomodulatory and radioprotective actions are mechanistically separable from its estrogenicity: in gamma-irradiated human hematopoietic progenitors it promotes survival by inducing nuclear factor kappa B (NF-κB, a master transcription factor of inflammation and survival) activation and granulocyte colony-stimulating factor (G-CSF, the that drives neutrophil production) expression, and in vivo it stimulates myelopoiesis and innate immune cell function.
In mucosal inflammation models it acts through ERβ to suppress TLR4-mediated / and NF-κB signaling, and it dampens AIM2 inflammasome activation, reducing pyroptotic tissue injury. Classic neurosteroid modulation of the -A receptor (the brain's principal inhibitory chloride channel) and the (an excitatory -gated channel involved in learning) is weak and poorly characterized for this molecule, so its central nervous system effects, such as protection against isoflurane-induced neurocognitive injury in neonatal rodents, are attributed primarily to ERβ activation rather than to ion-channel modulation.
receptor fingerprint
receptor beta (ERβ)Selective partial agonist (~3-fold over ERα)
NF-κB pathway (myeloid cells)Indirect activation
TLR4 / - signalingDownregulation (ERβ-dependent)
receptor alpha (ERα)Weak agonist
(AR)Weak ligand and prohormone to testosterone
AIM2 inflammasomeSuppression
-A / receptorsWeak, poorly characterized modulation
Dosingtypical ranges, not medical advice
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Safetyrisks and cautions, not medical advice
Human safety data for androstenediol are limited and derive largely from investigational radiation-countermeasure programs rather than from controlled chronic-use trials, so its long-term risk profile is not well established. As a molecule that feeds both androgen and estrogen pathways, supplemental use carries the predictable hazards of hormonal disruption, including androgenic effects such as acne and estrogenic effects such as gynecomastia and fluid retention, along with suppression of endogenous steroid feedback.
It is a controlled substance in several jurisdictions and is banned in sport by the World Anti-Doping Agency, so possession and use carry legal and competitive consequences independent of any biological risk. The former prohormone supplement market was associated with inconsistent purity and mislabeling. It should not be used during pregnancy or by individuals with hormone-sensitive conditions.
History
Androstenediol was characterized as an endogenous DHEA metabolite in classical steroid biochemistry, but modern interest arose in two distinct arenas. In the late 1990s and early 2000s it, together with the closely related androstenedione products, was marketed aggressively as an over-the-counter "prohormone" for muscle building, a market curtailed in the United States when the Anabolic Steroid Control Act of 2004 reclassified androstenediols as controlled substances.
In parallel, work by Loria, Ben-Nathan, Whitnall, Singh and colleagues established its immunomodulatory and radioprotective properties, leading Hollis-Eden Pharmaceuticals to develop it as the radiation countermeasure Neumune and to test it in irradiated nonhuman primates. Contemporary research, reviewed comprehensively by Fedotcheva and colleagues in 2024, has revisited 5-androstenediol as a candidate for acute radiation syndrome and as an immunostimulant during radiopharmaceutical therapy, while structural and mechanistic studies have clarified its ERβ-preferring estrogenic behavior.
Reputation
Within pharmacology androstenediol is a niche molecule with a split reputation. In radiation biology and biodefense it is regarded as a credible, if not fully advanced, hematopoietic radiation countermeasure notable for stimulating rather than merely protecting the immune system. In the supplement and bodybuilding world it is remembered as one of the prohormones swept up in the 2004 legal reclassification. Among neurosteroid researchers it is a peripheral figure, cited more for its ERβ estrogenicity and immunology than for any signature action at inhibitory or excitatory ion channels; it is best understood as a borderline, exhaustiveness-driven entry in a neurosteroid catalog rather than a canonical one.
Subjective profileweighing the evidence above
Skip it as a supplement. Its real interest is as a radiation countermeasure in animal work, and taken by choice it behaves like any prohormone; acne, possible gynecomastia and fluid retention, and suppression of your own hormone output, with no long-term human safety data to weigh against that.
Resources
This entry is here for reference.
Research
- 1974first citedUtilization of oxygen and reduced nicotinamide adenine dinucleotide phosphate by human placenta…
- 2024most active year5 papers
- 2026most recentAndrostenediol repelled isoflurane-induced behavioral and cognitive insults in neonatal rats: i…
- 1.Dehydroepiandrosterone and Its Metabolite 5-Androstenediol: New Therapeutic Targets and Possibilities for Clinical Application.
- 2.Structural comparison of androstenediol recognition by the human estrogen receptor ligand binding domains.
- 3.The potential value of 5-androstenediol in countering acute radiation syndrome.
- 4.Ameliorative effects of androstenediol against acetic acid-induced colitis in male wistar rats via inhibiting TLR4-mediated PI3K/Akt and NF-κB pathways through estrogen receptor β activation.
- 5.Androstenediol repelled isoflurane-induced behavioral and cognitive insults in neonatal rats: investigating the role of estrogen receptor beta.
- 6.Uncovering Common Anti-Inflammatory Targets of DHEA, 5-AED, Progesterone, and Gestobutanoyl.
- 7.5-Androstenediol promotes survival of gamma-irradiated human hematopoietic progenitors through induction of nuclear factor-kappaB activation and granulocyte colony-stimulating factor expression.
- 8.Administration of 5-androstenediol to mice: pharmacokinetics and cytokine gene expression.
- 9.5-androstenediol stimulates multilineage hematopoiesis in rhesus monkeys with radiation-induced myelosuppression.
- 10.Androstenediol and dehydroepiandrosterone protect mice against lethal bacterial infections and lipopolysaccharide toxicity.
- 11.Molecular specificity of 5-androstenediol as a systemic radioprotectant in mice.
- 12.Androstenediol stimulates myelopoiesis and enhances resistance to infection in gamma-irradiated mice.
28 listed here; entry last updated August 2026
Reviews
My notesprivate to this device
FAQ
Is androstenediol a true neurosteroid?
Only marginally. It is an endogenous steroid that can be made and act within nervous tissue, but unlike allopregnanolone it does not strongly modulate the GABA-A or NMDA receptors. Its documented central effects are attributed mainly to estrogen receptor beta activation, and it is included in the neurosteroid grouping for completeness rather than for a classic ion-channel profile.
How is it different from DHEA?
Androstenediol is a direct metabolite of DHEA, formed when the enzyme 17β-hydroxysteroid dehydrogenase reduces DHEA's 17-keto group to a hydroxyl. Compared with DHEA it is a somewhat more estrogenic molecule at ERβ and can be converted more directly to testosterone, but the two share overlapping anti-inflammatory and immunomodulatory targets.
What was Neumune?
Neumune was the investigational name for 5-androstenediol developed as a medical radiation countermeasure. In irradiated animals it stimulated the innate immune system and the production of G-CSF, speeding recovery of infection-fighting blood cells, which is why it was studied for acute radiation syndrome and biodefense stockpiling.
Can I buy it as a supplement?
No, not legitimately in the United States. Androstenediols were reclassified as controlled anabolic-type substances under the 2004 Anabolic Steroid Control Act, ending the over-the-counter prohormone market. Its use is also prohibited in sport under anti-doping rules.
Does it improve memory or mood like other neuroactive steroids?
There is no robust human evidence for cognitive or mood benefit. The relevant preclinical signal is ERβ-mediated neuroprotection in injury models, not the rapid anxiolytic or pro-cognitive GABAergic actions seen with steroids such as allopregnanolone or pregnenolone.
Limitations of the evidence
- Poorly characterized human safety profile outside investigational radiation-countermeasure trials
Adverse effects
- Androgenic effects including acne and unwanted hair growth from downstream conversion to testosterone
- Estrogenic effects including possible gynecomastia and fluid retention
- Disruption of endogenous hormone balance and hypothalamic-pituitary feedback
- Injection-site reactions with the parenteral formulations used in research
Notes and cautions
- Controlled-substance and anti-doping status in many jurisdictions
- Uncertain purity and mislabeling risk from the former prohormone supplement market