Androstenediol

• Hormone regulation
• Potential immune system support

• Potential radiation protection
• Possible anti-inflammatory effects

Absorption: When taken orally, androstenediol undergoes significant first-pass metabolism in the liver, resulting in low bioavailability (estimated at 3-6%). Sublingual administration partially bypasses this first-pass effect, potentially increasing bioavailability.

Distribution: Androstenediol is lipophilic and can distribute throughout the body, crossing cell membranes to reach intracellular targets. It may also bind to sex hormone-binding globulin (SHBG) in the bloodstream, though with lower affinity than testosterone.

Metabolism: Primarily metabolized in the liver through Phase I and Phase II reactions, including oxidation, reduction, hydroxylation, and conjugation with glucuronic acid or sulfate. The main metabolic pathways involve conversion to testosterone, estrogens, or direct conjugation for excretion.

Elimination: Metabolites are primarily excreted in urine, with a smaller portion eliminated through bile into feces. The elimination half-life is estimated to be 2-4 hours.

There is no established Recommended Dietary Allowance (RDA) or Adequate Intake (AI) for androstenediol as it is not considered an essential nutrient. As a controlled substance in many countries, it is not legally available as a dietary supplement. Historical supplement products typically contained 100-300 mg per day, though scientific evidence does not support effectiveness or safety at these doses. Natural endogenous production of androstenediol varies by individual, age, and health status.

Circadian Factors: Endogenous steroid hormone production follows a circadian rhythm, with peak levels typically occurring in the morning. Historical supplement protocols often recommended morning administration to align with this natural pattern, though there is limited evidence this timing affects outcomes.

Meal Timing: When historically used as a supplement, absorption was potentially improved when taken with meals containing moderate fat content, which may enhance dissolution and absorption of this lipophilic compound.

Exercise Timing: Some historical supplement protocols suggested taking androstenediol before or after exercise based on theoretical benefits, but clinical studies did not demonstrate significant performance or recovery advantages regardless of timing.

Description: Historical supplement use often involved ‘cycling’ protocols (periods of use followed by periods of abstinence) to potentially reduce side effects and prevent suppression of natural hormone production.

Common Protocols: Typical cycles ranged from 4-8 weeks of use followed by an equal or longer period without supplementation. However, there is no scientific evidence supporting the effectiveness or safety of these cycling protocols for androstenediol.

Women: Not recommended due to potential virilizing effects and hormonal disruption. Women are particularly sensitive to androgenic compounds and may experience side effects at lower doses than men.

Athletes: Banned by the World Anti-Doping Agency (WADA), the International Olympic Committee (IOC), and most professional sports organizations. Use can result in positive doping tests and sanctions.

Medical Conditions: Contraindicated in individuals with hormone-sensitive conditions including prostate issues, breast cancer, uterine cancer, ovarian cancer, endometriosis, and cardiovascular disease.

Androstenediol has poor oral bioavailability, estimated at approximately 3-6%

when taken in standard oral form.

This low bioavailability is primarily due to extensive first-pass metabolism in the liver, where a significant portion is converted to inactive metabolites before reaching systemic circulation. Studies have shown that even large oral doses (200-300 mg) produce only modest and transient increases in serum androstenediol levels, with minimal impact on testosterone concentrations in most individuals.

First Pass Metabolism: Undergoes extensive hepatic metabolism during first pass through the liver, significantly reducing the amount of active compound reaching systemic circulation

Enzymatic Degradation: Subject to degradation by intestinal and hepatic enzymes

Poor Water Solubility: As a steroid compound, androstenediol has limited water solubility, which can impair dissolution and absorption in the aqueous environment of the gastrointestinal tract

Historical supplement protocols often recommended taking androstenediol on an empty stomach to potentially speed absorption, or with meals containing fat to enhance dissolution. Sublingual formulations were typically administered 2-3 times daily due to the short half-life of the compound. However, clinical studies have not demonstrated significant performance or hormonal benefits regardless of timing strategies.

Individual Variation: Significant individual differences exist in the metabolism of androstenediol, influenced by genetic factors affecting enzyme activity, particularly 17β-hydroxysteroid dehydrogenase and 3β-hydroxysteroid dehydrogenase enzymes.

Enzyme Inducers Inhibitors: Certain medications and compounds can affect the enzymes involved in androstenediol metabolism. For example, some anti-epileptic drugs can induce liver enzymes, potentially increasing the metabolism and reducing the bioavailability of androstenediol.

Age Related Changes: Aging may affect the metabolism of steroid hormones, potentially altering the conversion rates between androstenediol and other hormones like testosterone and estrogens.

Androstenediol has significant safety concerns that have led to its classification as a controlled substance in many countries. While it is a naturally occurring hormone in the human body, exogenous supplementation presents various risks due to its potential conversion to testosterone and estrogens, as well as possible direct effects. The safety profile is complicated by limited long-term human studies and variable product quality when it was available as a supplement.

• [“Acne”,”Oily skin”,”Hair loss (in men predisposed to male pattern baldness)”,”Mood changes”,”Headaches”,”Gastrointestinal discomfort”]
• [“Gynecomastia (male breast development) due to conversion to estrogens”,”Increased blood pressure”,”Decreased HDL (good) cholesterol”,”Increased LDL (bad) cholesterol”,”Water retention”,”Testicular atrophy (with prolonged use)”,”Reduced sperm production”]
• [“Liver toxicity”,”Cardiovascular complications”,”Blood clots”,”Stroke”,”Heart attack (in predisposed individuals)”]

Women:

• Virilization (development of male characteristics)
• Deepening of voice (potentially irreversible)
• Facial hair growth
• Clitoral enlargement
• Menstrual irregularities
• Potential fertility issues
• Male-pattern baldness

Men:

• Testicular atrophy
• Reduced sperm count and fertility
• Gynecomastia (breast development)
• Potential suppression of natural testosterone production with prolonged use

• Hormone-sensitive conditions (breast cancer, prostate cancer, endometriosis, uterine fibroids)
• Cardiovascular disease
• Liver disease or impaired liver function
• Kidney disease
• High cholesterol
• High blood pressure
• History of stroke or blood clots
• Sleep apnea
• Polycythemia (abnormally high red blood cell count)
• Pregnancy and breastfeeding
• Children and adolescents (under 18 years)

No established safe upper limit. Historical supplement doses ranged from 100-300 mg daily, but even these doses have demonstrated safety concerns in research studies, particularly regarding hormonal imbalances and cardiovascular risk factors.

Acute Toxicity: Limited data on acute toxicity in humans. Animal studies suggest relatively low acute toxicity, but human cases of overdose are poorly documented.

Chronic Toxicity: Prolonged use may lead to hormonal imbalances, liver stress, cardiovascular changes, and potential suppression of natural hormone production. Long-term safety studies in humans are lacking.

Pregnant Women: Contraindicated due to potential masculinization of female fetuses and other developmental concerns.

Breastfeeding Women: Contraindicated due to potential transfer to infant through breast milk and unknown effects on development.

Children Adolescents: Contraindicated due to potential interference with normal growth and development, including premature closure of growth plates and disruption of natural hormonal development.

Elderly: Potentially higher risk of adverse effects due to age-related changes in metabolism and increased prevalence of conditions that may be exacerbated by hormonal fluctuations.

Liver Impairment: Higher risk of adverse effects due to reduced metabolism and clearance of the compound.

Kidney Impairment: Potential for altered clearance of metabolites, possibly increasing risk of adverse effects.

Recommended Tests:

• Liver function tests
• Lipid profile (cholesterol, triglycerides)
• Complete blood count
• Hormone panel (testosterone, estradiol, etc.)
• Blood pressure monitoring
• Prostate-specific antigen (PSA) in men over 40

Monitoring Frequency: Would require baseline testing before use and regular monitoring during use if prescribed medically. For historical supplement use, monthly monitoring was recommended but rarely implemented.

Classification: Schedule III Controlled Substance

Details: Androstenediol is classified as a Schedule III controlled substance in the United States under the Anabolic Steroid Control Act of 2004, which amended the Controlled Substances Act to include androstenediol and related compounds. This classification places it in the same category as anabolic steroids and testosterone, despite its generally weaker direct androgenic effects.

Supplement Status: Not permitted to be marketed or sold as a dietary supplement in the United States. Prior to 2004, it was available as a dietary supplement under the provisions of the Dietary Supplement Health and Education Act (DSHEA) of 1994.

Prescription Status: Technically available by prescription, but no FDA-approved pharmaceutical products containing androstenediol are currently marketed for medical use in the United States.

Research Use: May be used for legitimate research purposes with appropriate DEA licensing and controls.

Wada Status: Prohibited substance, Listed on the World Anti-Doping Agency (WADA) Prohibited List under Anabolic Agents (S1), prohibited at all times (in and out of competition)., Detectable through urine testing using gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-mass spectrometry (LC-MS). Carbon isotope ratio testing may be used to distinguish between endogenous and exogenous sources.

Olympic Status: Prohibited in accordance with WADA regulations

Professional Sports: Banned by most major professional sports leagues and governing bodies, including the NFL, MLB, NBA, NHL, FIFA, and others.

Collegiate Sports: Banned by the NCAA (National Collegiate Athletic Association) and similar organizations worldwide.

Pharmaceutical: If manufactured as a pharmaceutical product, would require standard prescription drug labeling including indications, dosage, contraindications, warnings, and adverse effects. However, no approved pharmaceutical products containing androstenediol are currently marketed in most countries.

Research Chemicals: Must be labeled as research chemicals not for human consumption, with appropriate hazard information and controlled substance designations.

Historical Supplement Labeling: Prior to regulatory changes, supplement products were required to include a statement that the product contained a steroid hormone precursor, though compliance with this requirement was variable.

Restrictions: As a controlled substance in many countries, import and export typically require special permits and are limited to legitimate medical, scientific, or research purposes.

Personal Use: Personal importation is generally prohibited or strictly limited in most countries where androstenediol is classified as a controlled substance.

Penalties: Unauthorized import, export, or trafficking may carry significant legal penalties similar to those for other controlled substances.

Trends: Unlikely to see regulatory relaxation given the current approach to steroid hormone regulation. May see continued harmonization of international regulations.

Potential Changes: Any legitimate medical applications that emerge from research (such as radiation countermeasures) would likely be developed as specific pharmaceutical formulations subject to standard drug approval processes rather than changing the overall regulatory status of the compound.

Not applicable for consumer use

When available as a dietary supplement (pre-2004 in the US), androstenediol typically cost $30-60 for a 30-day supply at common dosages (100-300 mg daily), placing it in the moderate to high price range compared to other supplements.

Consumer Availability: Not legally available for consumer purchase in most countries due to classification as a controlled substance.

Research Chemical Cost: For legitimate research purposes, high-purity androstenediol typically costs $200-500 per gram from specialized chemical suppliers, requiring appropriate licensing and documentation.

Black Market: May be available through illicit channels at highly variable prices and with significant concerns regarding quality, purity, and legal risk. Not recommended due to legal and health risks.

Athletic Performance: Not cost-effective at any price point, as clinical studies have consistently shown minimal to no significant benefits for muscle growth, strength, or athletic performance compared to placebo.

Hormone Support: Not established as cost-effective for hormone support compared to other interventions, including lifestyle modifications and, when medically indicated, approved hormone therapies.

Experimental Applications: Cost-effectiveness for experimental applications such as radiation protection cannot be meaningfully assessed as these remain in research stages without established effective doses or approved medical uses.

Cost Benefit Assessment: Given the lack of demonstrated efficacy for common desired outcomes, combined with potential health risks and legal issues, androstenediol supplementation cannot be considered cost-effective for consumer use at any price point.

Alternatives Comparison: Evidence-based alternatives such as proper nutrition, training optimization, adequate recovery, and permitted supplements with established efficacy (e.g., creatine, protein, caffeine) offer superior cost-effectiveness., For individuals with clinically low testosterone, physician-supervised treatments with approved medications offer better efficacy, safety monitoring, and potentially better cost-effectiveness despite higher initial costs., Basic health interventions including adequate sleep, stress management, balanced nutrition, and regular exercise have stronger evidence for supporting optimal hormone levels at minimal direct cost.

Prescription Coverage: Not relevant as there are no approved pharmaceutical products containing androstenediol for medical use in most countries.

Alternative Treatments: Medically necessary hormone therapies using approved medications may be covered by insurance when prescribed for diagnosed conditions, offering a more cost-effective approach for those with legitimate medical needs.

Synthesis Costs: Laboratory synthesis of androstenediol is moderately complex but feasible at scale. Production costs are not prohibitive, with raw material and processing expenses estimated at $50-100 per gram for pharmaceutical-grade material when produced at commercial scale.

Scaling Factors: Economies of scale apply to larger production volumes, but regulatory requirements for controlled substances add significant compliance costs and administrative burden.

Research Grade Premium: Research-grade material commands a premium price due to higher purity requirements, smaller production volumes, and the specialized market with regulatory compliance costs.

Supplement Era: During its availability as a dietary supplement (late 1990s to 2004), prices gradually decreased as more manufacturers entered the market, following typical patterns for supplement products.

Post Regulation: After classification as a controlled substance, legitimate market availability became restricted to research purposes at significantly higher prices reflecting the specialized nature of this market and regulatory compliance costs.

Market Transformation: Regulatory changes effectively eliminated the legal consumer market for androstenediol, shifting any remaining demand to either black market sources or to legal alternatives marketed for similar purposes.

Industry Adaptation: Supplement manufacturers that previously produced androstenediol products generally adapted by developing alternative products using permitted ingredients claimed to support hormone levels through different mechanisms.

Research Costs: Increased regulatory controls have raised the cost and administrative burden of legitimate research using androstenediol, potentially limiting scientific investigation.

Pure Compound: Pure androstenediol powder, properly stored, typically has a shelf life of 2-3 years before significant degradation occurs.

Commercial Formulations: Historical supplement formulations generally carried expiration dates of 1-2 years from manufacture, though stability could vary significantly based on formulation, packaging, and storage conditions.

Research Grade: Research-grade androstenediol stored under optimal conditions (sealed, protected from light, under inert gas, and refrigerated or frozen) may maintain >95% purity for 3-5 years.

Temperature: Optimal storage temperature is 2-8°C (refrigerated). Room temperature storage accelerates degradation, while freezing (-20°C) is recommended for long-term storage of pure compound.

Light Exposure: Androstenediol should be protected from light, particularly UV radiation, which can catalyze oxidation and degradation reactions.

Humidity: Should be stored in low-humidity environments, as moisture can accelerate hydrolysis and degradation reactions.

Container Type: Ideally stored in amber glass containers with airtight seals. For research applications, storage under inert gas (nitrogen or argon) further enhances stability.

Special Considerations: Repeated freeze-thaw cycles should be avoided as they can accelerate degradation. Once a container is opened, the contents should ideally be used within a shorter timeframe or repackaged into smaller containers to minimize exposure to air and moisture.

Primary Products: Oxidation typically produces ketones at hydroxyl positions (converting to androstenedione or similar compounds) and may lead to oxidation of double bonds forming epoxides or additional hydroxyl groups. These products generally have different biological activities than the parent compound.

Detection Methods: Changes in appearance (discoloration), HPLC analysis showing decreased purity and appearance of degradation peaks, and changes in melting point or spectroscopic properties can indicate degradation.

Safety Implications: Degradation products have not been extensively studied for safety, but may have different hormonal activities or potentially increased toxicity compared to the parent compound.

Oral Tablets Capsules: Generally more stable than liquid formulations, with typical shelf life of 1-2 years when properly formulated with appropriate excipients and stored in suitable containers.

Sublingual Formulations: Moderately stable but may be more susceptible to moisture and oxidation due to their formulation requirements. Typically have shorter shelf life than solid oral dosage forms.

Liquid Formulations: Most susceptible to degradation, particularly oxidation and microbial contamination. Require appropriate preservatives and antioxidants to maintain stability.

Stabilizing Excipients: Antioxidants (e.g., vitamin E, BHT), chelating agents (EDTA), and appropriate pH buffers can enhance stability in formulations. Microcrystalline cellulose and other inert fillers are commonly used in solid dosage forms to minimize reactivity.

Accelerated Testing: Exposure to elevated temperatures (40°C) and humidity (75% RH) for defined periods (typically 6 months) to predict long-term stability under normal conditions.

Real Time Testing: Storage under recommended conditions with periodic testing of identity, purity, and potency over the expected shelf life.

Photostability Testing: Exposure to defined light conditions to assess vulnerability to photodegradation.

Analytical Methods: HPLC, LC-MS, and spectroscopic methods (UV, IR, NMR) are commonly used to assess purity and identify degradation products during stability testing.

Synthesis Methods

Natural Sources

Commercial Forms

Quality Considerations

Sustainability Considerations

Scientific evidence for androstenediol is limited and mixed. Most clinical studies have focused on its use as a performance-enhancing supplement, with results generally showing minimal effectiveness for increasing testosterone or improving athletic performance. Some promising research exists in specialized areas such as radiation protection and immune modulation, but

these applications remain experimental. Overall, the body of evidence is characterized by small sample sizes, methodological limitations, and a lack of long-term safety data.

Limited current clinical trials specifically investigating androstenediol due to its controlled substance status in many countries. Most contemporary research focuses on synthetic derivatives with specific medical applications rather than the natural compound.

Testosterone Effects: Some studies report small, transient increases in testosterone with androstenediol supplementation, while others show no significant change. These discrepancies may relate to differences in dosing, administration routes, subject characteristics, and measurement timing.

Performance Effects: Anecdotal reports of performance benefits contrast with controlled studies showing minimal effects, highlighting the potential influence of placebo effects and publication bias in this field.

Small sample sizes in most studies, Short study durations limiting understanding of long-term effects, Variable product quality and composition in supplement-based studies, Limited research in women, Potential publication bias favoring positive results, Ethical constraints limiting certain types of human research due to controlled substance status, Methodological challenges in measuring transient hormonal changes