Methoxydienone (Methoxygonadiene): A Comprehensive Reference Article
1. Identity and Chemical Characterization
Names and Nomenclature
Methoxydienone, also known as methoxygonadiene, as well as 3-methoxy-17-dehydro-18-methyl-19-nor-δ2,5(10)-testosterone or 13β-ethyl-3-methoxygona-2,5(10)-dien-17-one, is a synthetic anabolic-androgenic steroid (AAS) and progestogen of the 19-nortestosterone group related to levonorgestrel, and was never marketed. In the dietary supplement industry and among bodybuilders, it has been sold under the trade name "Max LMG" and the identifier "Methadrol."
Its molecular formula is C20H28O2 with a molecular weight of approximately 300.44 g/mol, and its CAS registry number is 2322-77-2. The EINECS number is 219-034-4.
In its pure form, it is a crystalline compound with a melting point of 150–160°C. Its appearance is that of a white crystalline powder, with a density of approximately 1.09 g/cm³ and a boiling point of 448°C.
Structural Features
Methoxydienone is not 17α-alkylated; instead it features a ketone at the C17 position. It is a progestin-derived steroid and not a 17-alpha alkylated steroid. It is structurally related to RU-486 and acts as an antiprogesterone, decreasing estrogen-like effects. Its characteristic methoxy group is located at the C3 position, and an ethyl substituent is present at C13, placing it structurally within the 18-methyl (or 13β-ethyl) 19-nortestosterone family.
Methoxydienone (methoxygonadiene) is classified alongside other androgen precursors or prohormones — including dehydroepiandrosterone (DHEA), androstenediol, androstenedione, and dienedione — that are relatively weak AAS when considered as oral preparations due to their prohormone character.
Natural Source
Methoxydienone is a fully synthetic compound. It has no established botanical or natural origin. It is a synthetic AAS and progestogen that was never marketed, and was synthesized in the 1960s and 1970s by chemist Herchel Smith and his colleagues while they were developing progestins for use in oral contraceptives. Claims circulating in some sources about a natural origin (e.g., tomato juice) are not corroborated by peer-reviewed scientific literature and should be regarded as unverified.
Common Forms and Preparations
Methoxydienone has been sold on the Internet as a designer steroid. It has been identified as a labeled ingredient in at least ten commercial products under the chemical name 13β-ethyl-3-methoxy-gona-2,5(10)-dien-17-one. It is predominantly encountered in oral capsule or tablet form as part of "prohormone" or "testosterone booster" supplement stacks, typically marketed to bodybuilders and strength athletes.
2. Historical Development and Context
Pharmaceutical Origins
In the 1960s and 1970s, organic chemist Herchel Smith and colleagues filed a series of patents leading to the development of some of the first synthetic oral contraceptives. One of these early experimental compounds was methoxygonadiene (18-methyl-19-nortestosterone).
Originally developed in the 1960s, methoxydienone was investigated for its potential anabolic effects. Though methoxydienone was never widely adopted in mainstream medicine, its inclusion in various nutritional and sports supplements underscored its valued anabolic properties.
Emergence as a Dietary Supplement
Colloquially referred to by various misleading monikers — "pro-hormones," "natural steroids," "testosterone boosters" — designer anabolic steroids have been popular for over a decade as a way to achieve classic anabolic steroid-like results from products sold in the legal marketplace.
Despite the broad spectrum of adverse effects and legal consequences, AAS are illicitly marketed and distributed in many countries. To circumvent existing laws, the chemical structure of AAS is modified and these designer steroids are sold as nutritional supplements mainly over the Internet.
Methoxygonadiene was identified by a 2015 systematic search as a labeled ingredient in ten products. There is no documented tradition of methoxydienone use in any indigenous, folk, or pre-modern medical system; its history is entirely confined to the post-1960s pharmaceutical and later sports supplement era.
3. Pharmacology: Active Compound and Mechanisms of Action
Classification as an Anabolic-Androgenic Steroid and Progestogen
Methoxydienone is a type of chemical known as an anabolic steroid. It is converted in the body to testosterone and other sex hormones. As a member of the 19-nortestosterone group, it shares structural and pharmacological kinship with compounds like nandrolone and levonorgestrel.
Designer steroids share a common mechanism of action with testosterone, acting at the androgen receptor. Their anabolic (promoting muscle growth) and androgenic (inducing masculine characteristics) effects result from androgen receptor activation in target tissues.
Anabolic-to-Androgenic Ratio
Related to the levonorgestrel family of progestins, methoxygonadiene is a potent anabolic by injection with an anabolic:androgenic ratio of approximately 54:27 vs. testosterone propionate and 90:625 vs. 19-nortestosterone (nandrolone), based on preclinical data from Edgren et al., 1966. These figures, derived from animal models, indicate that the compound's anabolic effects substantially exceed its androgenic effects relative to the comparator compounds in certain assay systems.
Absence of Oral Bioavailability Data
Methoxydienone is not 17α-alkylated (instead featuring a ketone at the C17 position) and no data exist regarding its oral activity in humans. No data exist regarding the oral activity of methoxygonadiene in humans. This is a critically important gap: because the compound lacks 17α-alkylation — a structural modification that typically confers oral bioavailability to most known oral AAS — its pharmacokinetic behavior following oral ingestion in humans is completely uncharacterized in peer-reviewed literature.
Non-17α-alkylated testosterone derivatives such as testosterone itself, DHT, and nandrolone all have poor oral bioavailability due to extensive first-pass hepatic metabolism and hence are not orally active. Methoxydienone's prohormone classification stems from this structural reality: it may require metabolic conversion to an active androgen in order to produce biological effects.
Progestogenic Activity
Methoxydienone is a progestin-derived steroid and not a 17-alpha alkylated steroid. It is structurally related to RU-486 and acts as an antiprogesterone, decreasing estrogen-like effects.
The progestogenic activity of AAS such as methoxydienone serves to augment their antigonadotropic activity. This results in increased potency and effectiveness as antispermatogenic agents and, in effect, increased potency in producing azoospermia and reversible male infertility.
Metabolic Degradation
Methoxydienone was observed to slowly degrade by demethylation of the methoxy substituent in liquid solutions. While no compound-specific intermediates were identified that allowed differentiation from other 18-methyl steroids, the 18-methyl-19-nortestosterone metabolite proved to be a suitable marker for reliable detection in doping analysis.
General AAS Mechanisms Applicable to Methoxydienone
Anabolic steroids are synthetic derivatives of testosterone characterized by their ability to cause nitrogen retention and positive protein metabolism, thereby leading to increased protein synthesis and muscle mass. These mechanisms — operating through the androgen receptor — are shared by the broader class to which methoxydienone belongs.
Oxidative stress, apoptosis, and protein synthesis alteration are common mechanisms involved in AAS-related effects in the whole body. Cellular complications from AAS arise when activation of signaling proteins like mTOR and Akt leads to alteration in protein synthesis pathways, cell cycle dynamics, oxidative stress, and apoptosis, contributing to damage at the cellular level.
4. Scientific Evidence by Area of Application
4.1 Anabolic / Muscle-Building Effects
The anabolic potential of methoxydienone rests almost entirely on preclinical (animal) data. Originally developed in the 1960s, methoxydienone was investigated for its potential anabolic effects, with early animal studies suggesting significant muscle-building properties and a favorable anabolic-to-androgenic activity ratio.
Several side effects are linked with AAS abuse. Only little is known about the pharmacological effects and metabolism of unapproved steroids due to the absence of clinical studies. There are no peer-reviewed, controlled human clinical trials specifically evaluating methoxydienone's anabolic efficacy, dosing, or safety. All preclinical ratios derive from animal myotrophic assays comparing muscle tissue weight gain against prostate weight gain — a standard but indirect methodology not validated against human outcomes.
Evidence strength: Preliminary animal/preclinical data only. No human clinical trial evidence exists for muscle-building effects.
4.2 Athletic Performance Enhancement
Methoxydienone is used for weight loss, to improve athletic performance, to reduce sexual problems, and for many other uses, but there is no good scientific evidence to support its use. Its presence in sport supplements is driven by the theoretical androgen receptor agonism it shares with other AAS, not by demonstrated human performance outcomes.
Evidence strength: No human clinical evidence. Claims of athletic performance enhancement are not supported by published controlled trials.
4.3 Body Composition (Weight Loss)
Methoxydienone appears in supplements marketed partly for body fat reduction. Anabolic steroids as a class can alter body composition through androgen receptor-mediated effects on metabolism, but no studies specifically investigating methoxydienone's effects on adiposity or body composition in humans have been published in peer-reviewed literature. Only little is known about the pharmacological effects and metabolism of unapproved steroids due to the absence of clinical studies.
Evidence strength: Absent. No human data exist.
4.4 Hormonal and Reproductive Effects
By virtue of its progestogenic and androgenic properties, methoxydienone is expected to interact with the hypothalamic-pituitary-gonadal (HPG) axis. The hypothalamic-pituitary-gonadal (HPG) axis is one of the body systems that is mainly influenced by steroidal hormones. Fluctuations of the hormonal milieu result in alterations of reproductive function, which are made through changes in hypothalamic neurons expressing gonadotropin-releasing hormone (GnRH).
Supraphysiological doses of AAS downregulate testosterone production, and the external administration of androgens suppresses the hypothalamic-pituitary axis. Recent evidence suggests that anabolic steroid use may be the most common cause of hypogonadism in men of reproductive age.
Evidence strength: No methoxydienone-specific human evidence; inferred from class-level AAS pharmacology and adverse event reports involving designer steroids as a group.
5. Body Systems and Health Areas
5.1 Musculoskeletal System
The principal claimed target of methoxydienone is skeletal muscle, where androgen receptor activation promotes myotrophic effects — nitrogen retention, enhanced protein synthesis, and ultimately increased muscle fiber cross-sectional area. These mechanisms are documented for the broader AAS class. Anabolic steroids are characterized by their ability to cause nitrogen retention and positive protein metabolism, leading to increased protein synthesis and muscle mass. No human data specific to methoxydienone confirm these effects clinically.
5.2 Endocrine and Reproductive System
AAS have side effects involving all organs, tissues, and body functions, especially long-term toxicity involving the cardiovascular system and the reproductive system, and their abuse is considered a public health issue.
Misuse of AAS results in severe infertility, with azoospermia observed in many users. Recovery of spermatogenesis may take 18–36 months, a period during which testosterone levels are often very low. Persistent hypogonadism, testicular atrophy, and impaired spermatogenesis have been frequently reported, and complete recovery of reproductive function is not invariably achieved. Histopathological and experimental findings suggest that structural gonadal alterations and epigenetic changes may contribute to prolonged fertility impairment.
5.3 Hepatic System
Hepatotoxicity is one of the major concerns regarding AAS treatment and abuse. Testosterone and its derivatives have been most often shown to induce a specific form of cholestasis, peliosis hepatis, and hepatic benign and malignant tumors.
Hepatotoxicity can be severe, with reported manifestations including intrahepatic cholestasis and peliosis hepatis, the latter of which may lead to subcapsular hematoma or spontaneous hepatic rupture in rare cases. These risks are attributed to the AAS class at large and, because methoxydienone lacks 17α-alkylation, the classical mechanism of 17α-alkylation-induced hepatotoxicity may apply differently, though its oral metabolism in humans remains unstudied.
5.4 Cardiovascular System
Chronic supraphysiological AAS exposure is associated with serious cardiovascular consequences, ranging from hypertension and lipid disorders to cardiomyopathy, atherosclerosis, and sudden cardiac death.
Long-term administration of high doses of AAS may lead to serious consequences such as hypogonadism, cardiac impairment, neurodegeneration, coronary artery disease, and sudden cardiac death. The most reported long-term side effects affect the cardiovascular system, such as cardiomyopathy and atherosclerotic disease. No cardiovascular studies specific to methoxydienone in humans have been published.
5.5 Renal System
Supraphysiologic and long-term use of AAS affects all organs, leading to cardiovascular, neurological, endocrine, gastrointestinal, renal, and hematologic disorders. Consumption of designer steroids including methoxygonadiene has been related to liver damage such as severe hepatotoxicity, cholestasis, and carcinoma, as well as other adverse effects including acute renal failure.
5.6 Neuropsychiatric Effects
Side effects of methoxydienone include infertility, behavioral changes, hair loss, and breast development (in men). Several experimental studies have focused on the mechanisms involved in neuropsychiatric effects of AAS. These include mood disturbances, aggression, and potential dependence phenomena — effects reported for the AAS class generally and inferred to apply to methoxydienone given its mechanism.
6. Dosage: Forms and Reported Amounts
Available Dose Forms
Methoxydienone circulates principally in oral capsule and tablet form in the sports supplement market, though raw powder is sold by chemical suppliers for research purposes. Identified uses in chemical commerce are for research and development only, not for medicinal, household, or other use.
Dosages
The appropriate dose of methoxydienone depends on several factors such as the user's age, health, and several other conditions. At this time there is not enough scientific information to determine an appropriate range of doses for methoxydienone.
No controlled clinical trials have established safe or effective dosing ranges for methoxydienone in humans. Anabolic:androgenic characterization was carried out using injected preparations in animal models, and no human pharmacokinetic dose-response studies have been published in the peer-reviewed literature.
7. Legal and Regulatory Status
United States
In the U.S., it is illegal to include anabolic steroids in supplement products. These drugs are now considered controlled substances in the United States (schedule 2 and 3), and many AAS have been withdrawn from the US market. The Designer Anabolic Steroid Control Act of 2014 (Public Law No. 113-260) further extended the scheduling framework specifically to cover designer steroids not enumerated in the original Anabolic Steroid Control Act.
Despite recent regulatory efforts that have banned specific compounds, many anabolic-androgenic steroids remain available in over-the-counter dietary supplements that are legally sold in the United States, a situation that regulatory agencies continue to address. The FDA has had a hard time keeping up with the tactics of the supplement industry, which releases one structurally slightly modified but effective AAS derivative after the other.
World Anti-Doping Agency (WADA)
Methoxydienone and related chemicals are banned by the World Anti-Doping Agency (WADA). All anabolic agents, including anabolic-androgenic steroids, are permanently banned due to their muscle growth and strength effects. This also covers all prohormones even if the drugs are not specifically listed on the prohibited list.
Substances prohibited by WADA fall into categories including S1 anabolic agents, among others. Methoxygonadiene/methoxydienone falls under the S1 category of anabolic agents in the WADA Prohibited List.
8. Safety Considerations and Known Adverse Effects
General Safety Profile
When taken by mouth, methoxydienone is possibly unsafe for most people. Side effects include infertility, behavioral changes, hair loss, and breast development (in men). Methoxydienone can also lead to liver damage and heart disease.
Class-Level Adverse Effects Documented for Designer Steroids Including Methoxygonadiene
The 2015 systematic review published in Andrology by Rahnema et al. identified the following adverse effects attributed to the class of designer steroids sold in supplements — including methoxygonadiene specifically — based on available case reports and pharmacological data:
- Severe side effects including hepatotoxicity, cholestasis, renal failure, hypogonadism, gynecomastia, and infertility have been reported secondary to the use of these products.
- While some of these side effects may be reversible, more aggressive use may result in more permanent end-organ damage.
- Recent evidence suggests that anabolic steroid use may be the most common cause of hypogonadism in men of reproductive age.
Hepatotoxicity
Hepatotoxicity can be severe, with reported manifestations including intrahepatic cholestasis and peliosis hepatis, the latter of which may lead to subcapsular hematoma or spontaneous hepatic rupture in rare cases. For methoxydienone specifically, the absence of 17α-alkylation may theoretically reduce (but does not eliminate) hepatic risk, since hepatotoxicity with AAS is a multi-pathway phenomenon not exclusively tied to alkylation status. Its precise hepatotoxic mechanism in humans remains undescribed in clinical literature.
Cardiovascular Risks
AAS abuse has been recurrently associated with an increased risk of thrombosis and is detrimental to cardiovascular health; however, the association has primarily been based on case reports. Supplementation with testosterone or related compounds may cause serious adverse effects, including altered blood lipid profiles, hypertension, and cardiovascular conditions.
Reproductive and Endocrine Harms
The progestogenic activity of drugs like methoxydienone serves to augment their antigonadotropic activity. This results in increased potency and effectiveness as antispermatogenic agents, increasing potency in producing azoospermia and reversible male infertility.
Persistent hypogonadism, testicular atrophy, and impaired spermatogenesis have been frequently reported, and complete recovery of reproductive function is not invariably achieved. Histopathological and experimental findings suggest that structural gonadal alterations and epigenetic changes may contribute to prolonged fertility impairment.
Multi-System Toxicity
Anabolic-androgenic steroid toxicity represents a diffuse endocrine-metabolic disorder rather than isolated organ-specific pathology. The recurring interplay of oxidative stress, inflammatory activation, and disrupted cellular signalling provides a unifying mechanistic framework linking renal, musculoskeletal, cutaneous, immunological, respiratory, gastrointestinal, and reproductive dysfunctions to those already described in cardiovascular, hepatic, and gonadal tissues.
Doping Detection
Methoxydienone was observed to slowly degrade by demethylation of the methoxy substituent in liquid solutions. While no compound-specific intermediates were identified that allowed differentiation from other 18-methyl steroids, the 18-methyl-19-nortestosterone metabolite proved to be a suitable marker for reliable detection in doping analysis. This indicates that methoxydienone can be detected in anti-doping urine analysis through its metabolic breakdown products.
Contamination Risk
Black market products further increase the risk for hepatitis B, hepatitis C, and HIV infection through contamination, heavy metal exposure, substitution with veterinary formulations, inaccurate dosing, and non-sterile injection practices. The large number of designer steroid findings in dietary supplements and the detection of new compounds combined with legal loopholes for their distribution in many countries show that stricter regulations and better information policy are needed.
9. State of the Evidence: Summary Assessment
The totality of available peer-reviewed evidence on methoxydienone can be summarized as follows:
- Animal/Preclinical evidence: Anabolic activity established by early (1960s) animal assays showing an anabolic:androgenic ratio of approximately 54:27 relative to testosterone propionate and 90:625 relative to nandrolone, by injection.
- Human clinical evidence: Absent. No controlled clinical trials have been conducted in humans on methoxydienone's efficacy, dosing, pharmacokinetics, or safety.
- Oral bioavailability: Unknown and unstudied. Its non-17α-alkylated structure raises significant doubt about oral activity.
- Safety: Only little is known about the pharmacological effects and metabolism of unapproved steroids due to the absence of clinical studies. Known risks are inferred from the AAS class and from adverse event reporting involving designer steroid products that included methoxygonadiene.
- Regulatory: Classified as a controlled substance and/or banned substance under U.S. law and WADA rules.
References
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