Androstenedione, often shortened to “andro” or 4-AD, is a steroid hormone the body makes in the adrenal glands and the gonads (testes and ovaries). It sits one enzyme step away from both testosterone and estrone, which is why it was sold in the late 1990s as a “natural” way to raise testosterone. It drew wide public attention after baseball player Mark McGwire’s use of it became known during his 1998 home run record season (Brown et al., J Health Commun 2003).
The controlled trials that followed did not support the marketing. In men, androstenedione reliably raised estrogens and lowered HDL (“good”) cholesterol, but its effect on testosterone was small, inconsistent and short-lived, and it did not add muscle or strength to resistance training. Since January 20, 2005, it has been a Schedule III controlled substance in the US, and it is prohibited in sport at all times.
This page summarizes what the clinical trials, the FDA and the DEA report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Class | Endogenous C19 steroid; direct precursor of testosterone and estrone (a “prohormone”) |
| Chemical name | Androst-4-ene-3,17-dione; C₁₉H₂₆O₂; 286.4 g/mol |
| Route studied | Oral |
| Doses used in trials | 50–300 mg/day, for a single day up to 12 weeks |
| Half-life | No half-life for oral androstenedione was reported in the trials reviewed here; blood testosterone was back to baseline 24 h after a dose |
| Main hormonal effect in men | Consistent rise in estradiol and estrone; total testosterone unchanged in most trials |
| Muscle and strength | No added benefit over placebo in randomized trials |
| US status | Schedule III anabolic steroid (21 CFR 1308.13) since January 20, 2005; formerly sold as a dietary supplement |
| WADA status | Prohibited at all times (S1.1 anabolic androgenic steroids) |
What it is
Androstenedione is androst-4-ene-3,17-dione, with the formula C₁₉H₂₆O₂ and a molecular weight of 286.4 g/mol (PubChem). It is a normal hormone in both sexes. FDA describes it as a weak androgen and a prohormone that is an intermediate in the biosynthesis of testosterone, estrone and estradiol from DHEA (FDA CFSAN memorandum, 2022).
Its place in the pathway explains most of what the trials found:
| Conversion | Product | Why it matters |
|---|---|---|
| Conversion to testosterone | Testosterone | The effect users wanted |
| Aromatization (by the aromatase enzyme) | Estrone, then estradiol | The effect seen most consistently in men |
| Formation from DHEA | Androstenedione itself | DHEA is one step further back (see DHEA) |
Androstenedione also acts on the androgen receptor directly, but weakly. In cell culture it behaved as a partial agonist/antagonist: it bound the full-length receptor with affinities of 30–70 nM and partly blocked DHT-driven gene expression, by up to 30% (Chen et al., J Steroid Biochem Mol Biol 2004). Whether this matters at doses people take is not known.
The name “4-AD” is not standardized. Some sellers have also used it for 4-androstenediol, a different compound. Androstenedione is also distinct from 1-androstenedione (1-AD), which has its double bond in a different position (androst-1-ene rather than androst-4-ene).
How it works in the body
When androstenedione is swallowed, much of it is converted before it reaches the general circulation. In a randomized study of 37 men given 0, 100 or 300 mg/day for 7 days, urinary testosterone metabolites rose many-fold, and serum testosterone glucuronide (an inactive, water-soluble form made for excretion) rose far more than serum testosterone itself (Leder et al., JCEM 2001). The authors concluded that oral androstenedione is largely turned into testosterone glucuronide and other androgen metabolites before release into the bloodstream.
| Measure | Control | 100 mg/day | 300 mg/day |
|---|---|---|---|
| Change in serum testosterone glucuronide AUC (day 1, 16 men) | −18% | +579% | +1267% |
| Urinary androsterone excretion, mean of days 1 and 7 (µg/h) | 215 | 3,836 | 8,142 |
| Urinary etiocholanolone excretion, mean of days 1 and 7 (µg/h) | 175 | 4,306 | 10,070 |
The response also seems to fade with continued use. In a crossover trial in 8 men aged 40–48 taking 200 mg/day, the rise in serum androstenedione after a dose (area under the curve) was 108.3 nmol/L on day 0 but 43.4 nmol/L on day 28, versus 2.1 nmol/L on placebo (units as reported) (Beckham & Earnest, Br J Sports Med 2003). Testosterone did not change at either time point.
Effects are short-lived. In the 7-day trial in young men, testosterone measured 24 hours after the last dose had not changed from baseline even in the group that showed a rise during the day (Leder et al., JAMA 2000). No formal elimination half-life for oral androstenedione was reported in the trials cited here, so we do not give one.
Regulatory status
Androstenedione was sold in the US as a dietary supplement until the Anabolic Steroid Control Act of 2004 (Public Law 108-358). The President signed it on October 22, 2004, and it took effect on January 20, 2005. The Act listed 59 specific substances, including 4-androstenedione, as anabolic steroids, which made them Schedule III controlled substances (DEA final rule, Federal Register 2005). Before the Act passed, FDA had called for a ban on androstenedione sales (Brown et al., Med Sci Sports Exerc 2006).
Today 4-androstenedione (androst-4-en-3,17-dione) appears by name in the federal Schedule III list of anabolic steroids (21 CFR 1308.13).
In 2022, FDA’s food safety center reviewed whether androstenedione could be used in food. It concluded that the available data do not support its safety for the general public, and that adding it to food is use of an unsafe food additive, which makes the food adulterated under the Federal Food, Drug, and Cosmetic Act (FDA CFSAN memorandum, 2022).
In sport, the WADA 2026 Prohibited List names androstenedione (androst-4-ene-3,17-dione) under S1.1 anabolic androgenic steroids. It is prohibited in and out of competition, as a non-specified substance, when administered exogenously.
What the research shows
Testosterone and estrogen in men
The trials below gave androstenedione to healthy men with normal testosterone levels.
| Trial | Design, n | Dose and duration | Total testosterone | Estrogens |
|---|---|---|---|---|
| King et al., JAMA 1999 | RCT, 20 men aged 19–29 training | 300 mg/day, 8 weeks | No change (free or total) | Estradiol 220 → 310 pmol/L at week 2; estrone up |
| Leder et al., JAMA 2000 | Open-label RCT, 42 men aged 20–40 | 0, 100 or 300 mg/day, 7 days | AUC −2%, −4%, +34% (significant only at 300 mg) | Estradiol AUC +4%, +42%, +128% |
| Brown et al., JCEM 2000 | Double-blind RCT, 55 men aged 30–56 | 100 mg three times daily, 28 days | No change; free testosterone +45%, DHT +83% | Estradiol +68% |
| Broeder et al., Arch Intern Med 2000 | Double-blind RCT, 50 men aged 35–65 (includes an androstenediol arm) | 200 mg/day, 12 weeks | +16% at 1 month, back to baseline by week 12 | Estrone and estradiol up |
| Rasmussen et al., JCEM 2000 | Controlled study, 6 treated men | 100 mg/day, 5 days | No change | Estradiol up |
The pattern is consistent: estrogens rose in every trial listed, while total testosterone either did not change or rose only briefly (at 300 mg/day for 7 days, and by 16% at 1 month on 200 mg/day before returning to baseline). Individual responses varied widely (Leder et al., JAMA 2000). In the 12-week Andro Project, luteinizing hormone (LH, the pituitary signal that drives testicular testosterone production) fell by 18–33%. The authors attributed the return of testosterone to baseline to more aromatization plus suppression of the body’s own production (Broeder et al., 2000).
A 2022 meta-analysis of eight randomized trials found that androstenedione raised estradiol and lowered HDL cholesterol, with no significant effect on testosterone, body weight or BMI (Pang et al., Hormones 2022).
Muscle, strength and body composition
No randomized trial found that androstenedione improved training results beyond placebo:
- Young men, 8 weeks. Knee extension strength, type 2 muscle fiber size, lean mass and fat loss all improved similarly with androstenedione 300 mg/day and placebo (King et al., 1999).
- Men aged 35–65, 12 weeks. Neither androstenedione nor androstenediol at 200 mg/day enhanced strength or body composition compared with placebo (Broeder et al., 2000).
- Trained men around 48 years old, 12 weeks. In 40 men, 100 mg/day of androstenedione or DHEA produced small gains in lean mass (0.5 kg with androstenedione) and strength that did not differ from placebo (Wallace et al., Med Sci Sports Exerc 1999).
- Muscle protein turnover. Five days of 100 mg/day did not change muscle protein synthesis, breakdown or net balance across the leg, measured with stable-isotope infusion and biopsies (Rasmussen et al., 2000).
A 2006 review of the prohormone literature concluded that androstenedione and related supplements do not produce anabolic or ergogenic effects in men and may raise health risks (Brown et al., 2006).
Women
Women showed much larger relative rises in testosterone than men.
- Postmenopausal women. In a randomized study of 30 women, a single 50 mg or 100 mg dose raised testosterone AUC by 185% and 457%. Peak testosterone exceeded the upper limit of normal in 4 of 10 women at 50 mg and 6 of 10 at 100 mg. Estrone rose but estradiol did not (Leder et al., JCEM 2002).
- Young women using hormonal contraception. In a double-blind crossover study of 10 women given a purified 100 mg dose, testosterone AUC rose about 16-fold, and peak testosterone reached 14–54 nmol/L, well above the female reference range. On average 12.5% (range 7.8–21.6%) of the dose was converted to testosterone (Bassindale et al., JCEM 2004).
These were short, single-dose studies. No trial has measured the long-term effects of regular use in women.
Side effects and risks
Cholesterol
Lower HDL cholesterol was the most repeated adverse finding:
| Trial | HDL change |
|---|---|
| King et al., 1999 (300 mg/day) | 42 → 37 mg/dL after 2 weeks, staying low through week 8 |
| Brown et al., 2000 (300 mg/day) | −10% over 28 days |
| Broeder et al., 2000 (200 mg/day) | HDL adversely affected; (LDL/HDL)/(apoA/apoB) lipid ratio +10.5%, while HDL rose 5.1% on placebo |
One 12-week trial at 100 mg/day found no significant lipid changes (Wallace et al., 1999). The 2022 meta-analysis still found a significant pooled fall in HDL (Pang et al., 2022).
Estrogen effects and suppression of natural testosterone
Because androstenedione raises estradiol in men, it carries the risks of excess estrogen. FDA’s 2022 review lists feminizing effects such as gynecomastia (breast tissue growth) in males and, in adolescents, possible early closure of growth plates (FDA CFSAN memorandum, 2022).
It is not “non-suppressive.” LH fell by 18–33% over 12 weeks in the Andro Project (Broeder et al., 2000). A published case report described a 29-year-old bodybuilder with impotence and severe oligospermia (very low sperm count) while using androstenedione. Symptoms and semen results returned to normal at 6 months after he stopped (Ritter et al., Fertil Steril 2005).
Women and children
In women, single doses pushed testosterone above the normal female range in many participants (Leder et al., 2002; Bassindale et al., 2004). FDA’s review notes that excess androgen exposure during pregnancy can virilize a developing female fetus, and that supraphysiological sex hormone levels in children can cause early puberty (FDA CFSAN memorandum, 2022).
Cancer findings in animals
The National Toxicology Program gave androstenedione by stomach tube to rats and mice for 2 years at up to 50 mg/kg (NTP TR-560, 2010). These are animal results and have not been shown in people:
- Mice: clear evidence of carcinogenic activity, based on liver tumors (hepatocellular adenoma and carcinoma) in both sexes and hepatoblastoma in males.
- Rats: equivocal evidence, based on lung tumors in males and mononuclear cell leukemia in females.
- Genetic toxicity: not mutagenic in bacterial tests.
FDA cited these results in 2022 alongside reports of potential reproductive, developmental and cardiovascular toxicity in concluding that the data do not support its safety as a food ingredient (FDA CFSAN memorandum, 2022).
Quality, contamination and drug testing
When androstenedione was sold over the counter, product quality was poor. A UCLA study analyzed 7 brands. One contained no androstenedione, one contained 10 mg of testosterone, and four more contained 90% or less of the labeled amount (Catlin et al., JAMA 2000).
The same study found that the androstenedione used in the trial, pure at a 0.1% detection limit, contained 19-norandrostenedione at the 0.001% level. That was enough to put the nandrolone marker 19-norandrosterone above the 2.0 ng/mL reporting cutoff in 20 of 24 men taking 100 or 300 mg/day. In other words, androstenedione use could produce a positive test for nandrolone.
The standard testosterone-to-epitestosterone (T/E) ratio screen is unreliable for androstenedione itself. After 28 days at 300 mg/day, the mean T/E ratio rose from 1.2 to 4.0, but only 1 of the men exceeded the cutoff then in use (over 6.0) (Brown et al., JCEM 2004).
Key takeaways
- A natural hormone, not a proven muscle builder. Androstenedione is the direct precursor of testosterone and estrone, but randomized trials found no added gain in strength, muscle fiber size or lean mass over placebo.
- Estrogen rises more reliably than testosterone. In men, estradiol rose in every trial, while total testosterone was unchanged in most trials and any rise was brief.
- HDL cholesterol falls. Several trials and a 2022 meta-analysis found lower HDL, and LH suppression was seen with longer use.
- Women respond strongly. Single doses pushed testosterone above the normal female range in many women.
- Animal cancer signal. A 2-year NTP study found clear evidence of liver tumors in mice; human data on cancer are lacking.
- Controlled and banned in sport. It has been a US Schedule III anabolic steroid since 2005 and is on the WADA Prohibited List.
Sources
- Brown WJ, Basil MD, Bocarnea MC. The influence of famous athletes on health beliefs and practices: Mark McGwire, child abuse prevention, and Androstenedione. J Health Commun. 2003;8(1):41–57. PubMed.
- National Center for Biotechnology Information. Androstenedione, CID 6128. PubChem. PubChem.
- Center for Food Safety and Applied Nutrition, Office of Food Additive Safety. Regulatory status and review of available information pertaining to 4-androstenedione: lack of general recognition of safety for its use in foods. FDA memorandum, March 1, 2022. FDA.
- Chen F, Knecht K, Leu C, et al. Partial agonist/antagonist properties of androstenedione and 4-androsten-3beta,17beta-diol. J Steroid Biochem Mol Biol. 2004;91(4-5):247–257. PubMed.
- Leder BZ, Catlin DH, Longcope C, et al. Metabolism of orally administered androstenedione in young men. J Clin Endocrinol Metab. 2001;86(8):3654–3658. PubMed.
- Beckham SG, Earnest CP. Four weeks of androstenedione supplementation diminishes the treatment response in middle aged men. Br J Sports Med. 2003;37(3):212–218. PubMed.
- Leder BZ, Longcope C, Catlin DH, et al. Oral androstenedione administration and serum testosterone concentrations in young men. JAMA. 2000;283(6):779–782. PubMed.
- Drug Enforcement Administration. Implementation of the Anabolic Steroid Control Act of 2004. Final rule. Federal Register. December 16, 2005;70(241):74653–74658 (FR Doc 05-23907). govinfo.
- Brown GA, Vukovich M, King DS. Testosterone prohormone supplements. Med Sci Sports Exerc. 2006;38(8):1451–1461. PubMed.
- Code of Federal Regulations. 21 CFR 1308.13, Schedule III. 21 CFR 1308.13.
- World Anti-Doping Agency. The 2026 Prohibited List. In effect from January 1, 2026. WADA 2026 Prohibited List.
- King DS, Sharp RL, Vukovich MD, et al. Effect of oral androstenedione on serum testosterone and adaptations to resistance training in young men: a randomized controlled trial. JAMA. 1999;281(21):2020–2028. PubMed.
- Brown GA, Vukovich MD, Martini ER, et al. Endocrine responses to chronic androstenedione intake in 30- to 56-year-old men. J Clin Endocrinol Metab. 2000;85(11):4074–4080. PubMed.
- Broeder CE, Quindry J, Brittingham K, et al. The Andro Project: physiological and hormonal influences of androstenedione supplementation in men 35 to 65 years old participating in a high-intensity resistance training program. Arch Intern Med. 2000;160(20):3093–3104. PubMed.
- Rasmussen BB, Volpi E, Gore DC, Wolfe RR. Androstenedione does not stimulate muscle protein anabolism in young healthy men. J Clin Endocrinol Metab. 2000;85(1):55–59. PubMed.
- Pang Q, Jia A, Al Masri MK, et al. The effect of androstenedione supplementation on testosterone, estradiol, body composition, and lipid profile: a systematic review and meta-analysis of randomized controlled trials. Hormones (Athens). 2022;21(4):545–554. PubMed.
- Wallace MB, Lim J, Cutler A, Bucci L. Effects of dehydroepiandrosterone vs androstenedione supplementation in men. Med Sci Sports Exerc. 1999;31(12):1788–1792. PubMed.
- Leder BZ, Leblanc KM, Longcope C, et al. Effects of oral androstenedione administration on serum testosterone and estradiol levels in postmenopausal women. J Clin Endocrinol Metab. 2002;87(12):5449–5454. PubMed.
- Bassindale T, Cowan DA, Dale S, et al. Effects of oral administration of androstenedione on plasma androgens in young women using hormonal contraception. J Clin Endocrinol Metab. 2004;89(12):6030–6038. PubMed.
- Ritter RH, Cryar AK, Hermans MR. Oral androstenedione-induced impotence and severe oligospermia. Fertil Steril. 2005;84(1):217. PubMed.
- National Toxicology Program. Toxicology and carcinogenesis studies of androstenedione (CAS No. 63-05-8) in F344/N rats and B6C3F1 mice (gavage studies). Natl Toxicol Program Tech Rep Ser. 2010;(560). PubMed.
- Catlin DH, Leder BZ, Ahrens B, et al. Trace contamination of over-the-counter androstenedione and positive urine test results for a nandrolone metabolite. JAMA. 2000;284(20):2618–2621. PubMed.
- Brown GA, Vukovich MD, King DS. Urinary excretion of steroid metabolites after chronic androstenedione ingestion. J Clin Endocrinol Metab. 2004;89(12):6235–6238. PubMed.