3-Alpha-Hydroxyetioallocholan-17-one (Androsterone): A Comprehensive Reference
1. Identity and Chemical Profile
Nomenclature and Chemical Identity
3-Alpha-Hydroxyetioallocholan-17-one is the systematic chemical name for the endogenous androstane steroid more widely recognized as androsterone. Androsterone, or 3α-hydroxy-5α-androstan-17-one, is an endogenous steroid hormone, neurosteroid, and putative pheromone. The compound belongs to the androstane series of C19 steroids, meaning it contains 19 carbon atoms arranged in the characteristic four-ring steroid nucleus (three six-membered cyclohexane rings and one five-membered cyclopentane ring).
Its CAS Registry Number is 53-41-8, and its molecular formula is C19H30O2 with a molecular weight of 290.4403. The IUPAC systematic name is (3R,5S,8R,9S,10S,13S,14S)-3-hydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,14,15,16-tetradecahydrocyclopenta[a]phenanthren-17-one.
The compound carries numerous synonyms in the scientific and regulatory literature. These include:
- Androsterone (most common trivial name)
- 3α-Hydroxy-5α-androstan-17-one
- 5α-Androstan-3α-ol-17-one
- 5α-Androstane-3α-ol-17-one
- cis-Androsterone
- 3-Epihydroxyetioallocholan-17-one
- D-Epiandrosterone
- 3-Epiandrosterone
- Androkinin / Androkinine
- 5α-Androstan-17-one, 3α-hydroxy-
It is a metabolite of testosterone or androstenedione with a 3-alpha-hydroxyl group and without the double bond. The 3-beta hydroxyl isomer is epiandrosterone.
The defining structural features that distinguish 3-alpha-hydroxyetioallocholan-17-one from its close isomers are: (1) the 5α configuration at carbon 5 (the A/B ring junction is trans, producing a flat, extended molecule), and (2) the 3α orientation of the hydroxyl group. Androsterone's 3β-isomer is epiandrosterone, and its 5β-epimer is etiocholanolone.
Natural Sources
The compound is primarily an endogenous human metabolite but is also found in certain botanical sources. Androsterone has been shown to naturally occur in pine pollen, celery, truffles, and is well known in many animal species. It is also found in human urine, skin secretions, and axillary tissue. Androsterone is found in the human axilla and skin as well as in the urine. It may also be secreted by human sebaceous glands.
An important distinction regarding plant sources: celery is claimed to contain androsterone; however, this is a mistake. Celery actually contains androstenone, which has a different structure to androsterone and is otherwise unrelated. Nonetheless, in one study, androsterone was found in 60–80% of the plant species investigated (Janeczko & Skoczowski 2005).
Common Forms and Preparations
As a dietary supplement ingredient, 3-alpha-hydroxyetioallocholan-17-one is commercially available in several forms. It is sourced as a pure chemical powder (the active pharmaceutical ingredient or API) and formulated into oral capsules and tablets. It also appears as a component in multi-ingredient supplements, particularly those marketed for androgen support or hormonal health. The compound has also been produced in injectable and suspension forms for research and pharmaceutical purposes. DHEA and androstenedione are metabolized primarily to androsterone and related conjugates, and this metabolic relationship has informed the use of precursor compounds in supplement contexts where androsterone itself is the target metabolite. As a research reagent, it has been supplied to research institutions and pharmaceutical companies for use in studies involving androgens, estrogens, cholestins, progestins, hormones, and metabolites synthesized to purified standards.
2. History of Discovery and Scientific Development
Isolation and Early Characterization
Discovered in 1931 by Adolf Butenandt, who isolated it from the urine of a male donor, androsterone was one of the first steroids identified and named for its androgenic properties ("andro" from male and "sterone" from steroid ketone). The isolation was an extraordinary technical achievement for its time. It 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 got 50 milligrams of crystalline androsterone, which was sufficient to find that the chemical formula was very similar to estrone.
Discovery of androsterone dates back to 1931, when Butenandt reported the isolation of a compound from a male policeman's urine and named it androsterone (andro = male, ster = sterol, one = ketone). The achievement was immediately recognized as scientifically significant. The isolation of androsterone by Adolf Butenandt in 1931 paved the way for discovery of more potent androgens.
This breakthrough contributed to early understandings of steroid chemistry and endocrinology, with its structure later confirmed through synthesis efforts. The chemical synthesis followed rapidly: Ruzicka et al. (1934) succeeded in converting cholesterol to androsterone and its three isomers, using selective reductive and oxidative methods. This work led to the establishment of the chemical structure of androsterone and its relationship to other sterols.
By 1939, research demonstrated that androsterone is a key urinary metabolite of testosterone, with studies showing its formation through metabolic conversion in humans after testosterone administration. These discoveries ultimately contributed to Adolf Butenandt receiving the Nobel Prize in Chemistry. Together with colleague Leopold Ruzicka, Butenandt won the Nobel Prize for Chemistry in 1939, but the Nazi government forced him to refuse it. He finally received the award in 1949 for his discovery and isolation of the hormones estrogen and androsterone, among others.
Subsequent research over the 20th century expanded the understanding of androsterone as not merely a metabolic waste product, but as a biologically active molecule in its own right, with neurosteroid properties recognized in the latter decades of the century.
Traditional Use Context
3-Alpha-hydroxyetioallocholan-17-one does not carry a traditional herbal or folk-medicine history as an isolated compound; it was unknown as a distinct chemical entity before 1931. However, the broader context of pine pollen — one of the plant sources in which androsterone has been detected — does have traditional use. Human clinical trials demonstrate conventional parallels in the lung-nourishing and phlegm-resolving properties of pine pollen therapy, which is topically effective in inflammatory skin conditions such as eczema, eruptions, bedsores, and diaper rash, and orally beneficial for arthritis and immune modulation; while cardiovascular support mirrors pine pollen's anabolic effects. The traditional use of pine pollen, however, was not attributed to its androsterone content specifically, but rather to the whole-plant preparation.
3. Biochemistry, Biosynthesis, and Metabolic Pathways
Endogenous Biosynthesis
In the human body, 3-alpha-hydroxyetioallocholan-17-one is a terminal metabolite in the androgen cascade rather than a biosynthetic precursor. Androsterone and its 5β-isomer, etiocholanolone, are produced in the body as metabolites of testosterone. Testosterone is converted to 5α-dihydrotestosterone and 5β-dihydrotestosterone by 5α-reductase and 5β-reductase, respectively. The enzyme 3α-hydroxysteroid dehydrogenase converts the reduced forms to 3α-androstanediol and 3β-androstanediol, which are subsequently converted by 17β-hydroxysteroid dehydrogenase to androsterone and etiocholanolone, respectively.
5α-Reductase (5α-R) and 5β-reductase (5β-R) catalyze the rate-limiting irreversible initial steps, which are followed by sequential reductions by 3α-hydroxysteroid dehydrogenase (3α-HSD) and 17β-hydroxysteroid dehydrogenase (17β-HSD). Androsterone can also be formed from androstenedione directly: androsterone [(3α,5α)-3-hydroxyandrostan-17-one] and its 5β-epimer etiocholanolone [(3α,5β)-3-hydroxyandrostan-17-one], are the major excreted metabolites of testosterone.
An additional metabolic route exists in which androsterone can be re-converted to more potent androgens: it can be converted back into DHT via 3α-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase, bypassing conventional intermediates such as androstanedione and testosterone, and as such can be considered to be a metabolic intermediate in its own right.
Excretion and Conjugation
After formation, androsterone is conjugated in the liver to facilitate renal excretion. Testosterone glucuronide (TG), androsterone glucuronide (AG), etiocholanolone glucuronide (EtioG), and dihydrotestosterone glucuronide (DHTG) are the major metabolites of testosterone (T), which are excreted in urine and bile. Glucuronides can be deconjugated to active androgen in the gut lumen after biliary excretion, which in turn can affect physiological levels of androgens.
The enzymes responsible for conjugation include members of the UDP-glucuronosyltransferase (UGT) superfamily. Major endogenous substrates for UGT2B17 are C19 androgen steroids, such as testosterone, androsterone, and etiocholanolone. Androsterone is also excreted as a sulfate conjugate: steroid androgens such as androsterone, etiocholanolone, testosterone, and epitestosterone may also be excreted as sulfates, with a sulfate to glucuronide ratio nearing 1:1.
A recent study quantifying androgen metabolites and their sulfo- and glucoconjugates in serum showed that T and DHT circulate predominantly in their unconjugated form, while their metabolites androsterone (AST, 5α-androstan-3α-ol-17-one), epiandrosterone, and 3α-adiol were mostly conjugated, each with specific preferences for sulfation or glucuronidation.
Orally administered androstenedione substantially increases androsterone output. A clinical study in young men found that in the control group, mean excretion rates for androsterone were 215 ± 26 μg/h; in the 100 mg androstenedione group, mean excretion rates for androsterone were 3,836 ± 458 μg/h; and in the 300 mg androstenedione group, mean excretion rates for androsterone were 8,142 ± 1,362 μg/h. This study concluded that the administration of both 100 and 300 mg androstenedione increases the excretion rates of conjugated testosterone, androsterone, etiocholanolone, and dihydrotestosterone and the serum levels of testosterone glucuronide in men. The magnitude of these increases is much greater than the changes observed in serum total testosterone concentrations. These findings demonstrate that orally administered androstenedione is largely metabolized to testosterone glucuronide and other androgen metabolites before release into the general circulation.
4. Active Compounds and Mechanisms of Action
Androgenic Activity
Androsterone is a weak androgen with a potency that is approximately 1/7 that of testosterone. It exerts this androgenic activity through binding to the androgen receptor, the canonical intracellular nuclear receptor through which androgens exert their genomic effects. Androgens exert their effect through binding to the androgen receptor to modulate many different biological processes. The relatively weak androgenic potency of androsterone compared to testosterone or dihydrotestosterone is a function of its binding affinity for the androgen receptor and the rate at which it dissociates from the receptor.
As noted above, androsterone can serve as a metabolic precursor to the more potent androgen DHT under certain enzymatic conditions via 3α-HSD and 17β-HSD, which may amplify its physiological androgenic impact in peripheral tissues beyond what its direct receptor-binding affinity would suggest.
Neurosteroid and GABAergic Activity
Androsterone is also known to be an inhibitory androstane neurosteroid, acting as a positive allosteric modulator of the GABAA receptor, and possesses anticonvulsant effects. This mechanism is central to the most-studied pharmacological properties of the compound.
The GABAA receptor subtype regulates neuronal excitability and rapid mood changes, such as anxiety, panic, and stress response. GABAA receptors are chloride ion channels; as a result, activation of the receptor induces increased inward chloride ion flux, resulting in membrane hyperpolarization and neuronal inhibition. By acting as a positive allosteric modulator at this receptor, androsterone enhances GABA-mediated chloride influx, thereby increasing inhibitory neurotransmission in the central nervous system.
A noteworthy structural–activity finding concerns the stereochemistry of this effect: the unnatural enantiomer of androsterone is more potent as a positive allosteric modulator of GABAA receptors and as an anticonvulsant than the natural form. This is unusual, as neurosteroids typically exhibit enantioselectivity favoring the natural form; such neurosteroids typically show enantioselectivity in which the natural form is more potent than the corresponding unnatural enantiomer. For 5α,3α-A and 5β,3α-A, the unnatural enantiomers are more potent at GABAA receptors than the natural forms.
Androsterone is also found in brain tissue: 5alpha,3alpha-A has been found in adult brain, and both metabolites, which also can be derived from androstenedione, are present in substantial quantities in serum along with their glucuronide and sulfate conjugates.
Olfactory and Putative Pheromonal Activity
Androsterone is described as having a musky odor similar to that of androstenol. Androsterone has been found to affect human behavior when smelled. The compound is detected in human axillary secretions and may act as a putative chemosignal, though its status as a true pheromone in humans remains scientifically unresolved.
5. Scientific Evidence by Area of Use
5.1 Anticonvulsant and Neurological Activity
The most substantial preclinical evidence for 3-alpha-hydroxyetioallocholan-17-one concerns its anticonvulsant properties. Androsterone (5alpha-androstan-3alpha-ol-17-one; 5alpha,3alpha-A), a neurosteroid that acts as a positive allosteric modulator of GABA(A) receptors, has anticonvulsant properties. Although of low potency, the steroids are present in high abundance and could represent endogenous modulators of seizure susceptibility.
A key preclinical study investigated the anticonvulsant activity of androsterone and its epimer etiocholanolone: the anticonvulsant activity of 5alpha,3alpha-A and 5beta,3alpha-A was investigated in electrical and chemoconvulsant seizure models in mice. The results demonstrated dose-dependent effects, with a dose of 100 mg/kg in the 6 Hz electrical stimulation (32 mA, 3 s) model producing protective effects.
In additional mouse studies: androsterone, when administered alone (80 mg/kg), elevated the seizure threshold. This was not observed at lower doses (5–40 mg/kg). Studies also examined the combination of androsterone with established antiepileptic drugs (AEDs). When combined with AEDs, androsterone (at 40 mg/kg) significantly enhanced the anticonvulsant activity of phenobarbital, gabapentin, and carbamazepine, but it did not affect the protective activity of phenytoin, lamotrigine, oxcarbazepine, topiramate, or valproate. The observed lack of androsterone's effect on the brain total concentration of AEDs suggests that the positive effect of this neurosteroid was not connected with pharmacokinetic interactions.
Androsterone not only elevated the threshold but significantly enhanced the protective action of carbamazepine, gabapentin, and phenobarbital against maximal electroshock in mice.
The broader neurosteroid context informs androsterone's role: animal studies have shown that testosterone can cause convulsive episodes to be aggravated, but it was also demonstrated to possess anticonvulsant properties which were connected with its transformation to various metabolites. The first case is a testosterone metabolism to 5α-DHT by 5α-reductase, which is then reduced by 3α-hydroxysteroid oxidoreductase enzyme, resulting in the synthesis of the anticonvulsant metabolite 3α-androstanediol, a potent GABA-A receptor modulating neurosteroid.
Evidence strength assessment: All anticonvulsant evidence for androsterone is derived from preclinical animal models (primarily mice) using injected doses. No controlled human clinical trials of androsterone for epilepsy or seizure disorders have been identified in the peer-reviewed literature. The mechanistic rationale (positive allosteric modulation of GABAA receptors) is well-established at the cellular level, but translation to human therapeutic outcomes has not been demonstrated.
5.2 Androgenic / Hormonal Effects
As a weak androgen, androsterone is a physiologically relevant contributor to the body's androgen milieu, albeit of modest potency. Its direct androgenic activity at approximately 1/7 that of testosterone is established from classical bioassays and receptor binding studies. Its clinical relevance as an exogenous supplement ingredient for androgenic effects has not been demonstrated in controlled human trials. The clinical significance of androstenedione supplementation — which increases androsterone excretion markedly — has been the subject of human studies, but these focused on androstenedione rather than androsterone directly.
In terms of urinary markers relevant to androgen status, the androsterone glucuronide to epitestosterone glucuronide ratio may serve as a complementary biomarker to reveal testosterone abuse, illustrating the role androsterone measurements play in clinical and sports antidoping contexts.
5.3 Putative Pheromonal and Behavioral Effects
Androsterone is a putative human pheromone, found in axillary secretions and discussed in the chemosensory literature. Androsterone has been found to affect human behavior when smelled. However, the evidence for classical pheromone signaling in adult humans is limited and contested. Pheromones are substances which are secreted to the outside by an individual and received by a second individual of the same species. Many examples exist in animals but their role in humans remains uncertain since adults have no functioning vomeronasal organ, which processes pheromone signals in animals.
The available data on androsterone's specific behavioral effects in humans are insufficient to draw firm conclusions. It is important to distinguish androsterone from the structurally related (but chemically distinct) androstadienone and androstenone, which have been the subjects of more extensive pheromone research in humans.
5.4 Clinical Diagnostic Relevance
While not a therapeutic application of the compound as a supplement, the clinical measurement of 3-alpha-hydroxyetioallocholan-17-one (androsterone) in urine and serum is an established part of endocrinological practice. The goal of characterizing mechanisms of androsterone glucuronide elimination was to quantitatively understand how it is eliminated from liver, intestine, and kidney. Urinary androsterone levels are used to assess androgen metabolism in conditions including congenital adrenal hyperplasia, polycystic ovary syndrome, and in antidoping screening. An important indicator for steroid abuse is the steroid profile, of which the concentration ratio of testosterone glucuronide to epitestosterone glucuronide (T/E ratio) has been adopted for the detection of testosterone doping using gas chromatography/mass spectrometry (GC/MS).
6. Body Systems and Health Areas Associated with Androsterone
Central Nervous System
Through its positive allosteric modulation of GABAA receptors, androsterone is mechanistically linked to the regulation of neuronal excitability, seizure threshold, and inhibitory neurotransmission. Men with epilepsy often have sexual or reproductive abnormalities that are attributed to alterations in androgen levels, including subnormal free testosterone. Levels of the major metabolites of testosterone — androsterone, a neurosteroid that acts as a positive allosteric modulator of GABA(A) receptors, and its 5beta-epimer etiocholanolone — also may be reduced in epilepsy. This observation suggests that reduced endogenous androsterone may contribute to altered seizure susceptibility in some individuals, though this has not been established as a causal therapeutic target in human trials.
Endocrine and Reproductive Systems
Androsterone is a metabolite of testosterone and dihydrotestosterone (DHT). As part of the androgen cascade, it is produced in tissues throughout the body, including the liver (where it is predominantly glucuronidated), the gonads, adrenal glands, and peripheral tissues including skin and adipose. It contributes to the total androgen load of the body and reflects the activity of testosterone and DHT metabolism. Its role in maintaining male secondary sexual characteristics is indirect, as a weak androgen and as a metabolic precursor that can be re-converted to DHT.
Olfactory / Chemosensory System
As a compound found in axillary secretions and skin, androsterone is part of the chemosensory milieu of the human body. It is described as having a musky odor similar to that of androstenol. Its detection by other individuals and potential behavioral or neuroendocrine effects mediated through the olfactory system have been proposed, though these remain an area of ongoing and contested research.
7. Dosage Forms and Dosages Reported in Research
The following dosages are drawn directly from the scientific literature cited above and reflect doses used in preclinical or clinical studies. They do not represent clinical recommendations.
- Anticonvulsant effects in mice (preclinical): Androsterone administered alone at 80 mg/kg elevated the seizure threshold in mice. This was not observed at lower doses (5–40 mg/kg).
- Interaction with antiepileptic drugs in mice (preclinical): At a dose of 40 mg/kg, androsterone significantly enhanced the anticonvulsant activity of phenobarbital, gabapentin, and carbamazepine in mice.
- 6 Hz electrical stimulation model in mice (preclinical): A dose of 100 mg/kg was used in the 6 Hz electrical stimulation (32 mA, 3 s) model.
- Androsterone as an excretory product of androstenedione in humans (clinical study): In a control group of men, mean excretion rates for androsterone were 215 ± 26 μg/h. Following 100 mg oral androstenedione administration, mean androsterone excretion rates increased to 3,836 ± 458 μg/h.
No controlled human clinical trials have been published that define a dosage regimen for 3-alpha-hydroxyetioallocholan-17-one administered directly as a supplement for any indication. All animal study doses above have been administered via injection (intraperitoneal or subcutaneous routes) in rodents and cannot be directly extrapolated to human oral supplementation.
8. Safety Considerations and Interactions
Regulatory Status
In the United States, androsterone has been the subject of Drug Master Files (DMF) submitted to the FDA, reflecting its status as an active pharmaceutical ingredient in at least some formulations. The FDA regulates 3-alpha-hydroxyetioallocholan-17-one manufacturers to ensure that their products comply with relevant laws and regulations and are safe and effective to use. Manufacturers are required to adhere to Good Manufacturing Practices (GMP) to ensure that their products are consistently manufactured to meet established quality criteria.
Androgenic Effects as a Safety Concern
Because androsterone is a weak androgen and a potential precursor to more potent androgens such as DHT, exogenous supplementation with androsterone or its precursors carries the theoretical potential to alter the androgen-to-estrogen balance in both sexes. These concerns parallel those documented for closely related compounds. In women and adolescents, exogenous androgenic steroids can produce virilizing effects. In men, elevated androgenic compounds may suppress the hypothalamic-pituitary-gonadal axis through negative feedback. These concerns are inferred from the pharmacology of the compound class; no direct human safety studies of oral androsterone supplementation have been identified in the peer-reviewed literature.
GABAergic Pharmacodynamic Interactions
Given that androsterone acts as a positive allosteric modulator of GABAA receptors, there is a pharmacodynamic basis for potential additive effects with other GABAergic compounds, including benzodiazepines, barbiturates, ethanol, and other neurosteroids. Androsterone at 40 mg/kg significantly enhanced the anticonvulsant activity of phenobarbital and gabapentin in mice, but this effect was not connected with pharmacokinetic interactions, suggesting it is pharmacodynamic in nature. Whether this translates to meaningful drug interactions in humans at physiologically or supplementally relevant concentrations of androsterone is not established.
Antidoping Considerations
Androsterone is a metabolite monitored in antidoping programs. Steroid androgens such as androsterone, etiocholanolone, testosterone, and epitestosterone may also be excreted as sulfates. The measurement of androsterone glucuronide and its ratios to other steroids is used in doping control screening, as exogenous androgens markedly increase its urinary excretion. Athletes subject to antidoping testing should be aware that supplementation with androsterone or closely related precursors such as androstenedione may alter urinary steroid profiles in ways detectable by standard screening protocols.
Hepatic Metabolism and Enzyme Variability
The metabolism and excretion of androsterone are strongly influenced by genetic polymorphisms in UGT enzymes. The conspicuous interindividual differences in metabolism and urinary excretion of testosterone and its metabolites make it challenging to interpret steroid profiles. The variation in testosterone glucuronide excretion is strongly associated with a deletion polymorphism in the UDP-glucuronosyltransferase (UGT) 2B17 gene. These genetic differences mean that individuals may metabolize and clear androsterone at substantially different rates, creating variability in its physiological effects and urinary detection windows.
Absence of Formal Toxicological Data for Oral Androsterone
No formal toxicological studies (acute, subchronic, or chronic) examining orally administered androsterone as a dietary supplement have been identified in the peer-reviewed literature. The available safety data for related compounds (such as androstenedione) come from preclinical models. For example, the administration of androstenedione at three dose levels (5, 30, or 60 mg/kg body weight/day) in pregnant rats revealed no significant differences in biomarkers of hepatotoxicity, including aspartate aminotransferase, serum alanine aminotransferase, glutathione, and glutathione S-transferase, lipid peroxidation, lactate dehydrogenase, total microsomal P450, and nuclear DNA damage. Whether analogous data exist for androsterone directly has not been confirmed in the identified sources.
9. Summary of Evidence Limitations
The scientific literature on 3-alpha-hydroxyetioallocholan-17-one (androsterone) as an exogenously administered supplement is sparse relative to its extensive characterization as an endogenous metabolite and analytical marker. The following key evidence gaps exist:
- No controlled human clinical trials have evaluated androsterone as a supplement for any indication (androgen support, seizure prevention, pheromonal effects, or otherwise).
- Anticonvulsant evidence is limited to preclinical animal models using injected, suprapharmacological doses.
- Androgenic effects are established from classical receptor binding and in vivo bioassays but have not been quantified in human supplementation studies.
- Pheromonal activity in humans remains speculative; robust, replicated human behavioral trials specifically examining androsterone (as distinct from related androstenes) are not available in the identified sources.
- Safety and toxicology data for oral androsterone supplementation in humans are absent from the peer-reviewed literature reviewed for this article.
References
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