4-Androstenediol (androst-4-ene-3β,17β-diol), sold as “4-Andro” or “4-AD diol,” is a steroid that differs from testosterone at a single position. It was marketed in the US as an over-the-counter “prohormone” supplement in the late 1990s and early 2000s, on the idea that the body converts it into testosterone (Uralets & Gillette, J Anal Toxicol 1999).
The most important fact: 4-androstenediol was never an approved medicine, and the human evidence on it is very thin. The only controlled study we found that names the 4-ene compound explicitly and measures blood hormones gave single doses and lasted 90 minutes. It has been a Schedule III controlled substance in the US since January 20, 2005, and it is banned in sport at all times.
This page summarizes what the small human studies, doping-control research and regulators report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Class | Androgen precursor (“prohormone”); 4-ene isomer of androstenediol |
| Chemical name | Androst-4-ene-3β,17β-diol |
| Formula / weight | C₁₉H₃₀O₂, 290.4 g/mol (PubChem CID 136297) |
| Approval | Never an approved drug; no medical indication or labeled dose |
| Route (as sold) | Oral supplement |
| Dose in the one explicit 4-ene human study | Single 200 mg oral dose in 8 young men |
| Half-life | Not reported in the human studies reviewed here; urinary steroid changes returned to normal by 24 h after an oral dose |
| Androgen receptor | Binds it directly in cell culture, as a partial agonist/antagonist |
| US status | Schedule III anabolic steroid (21 CFR 1308.13), named in the Anabolic Steroid Control Act of 2004 |
| WADA status | Prohibited at all times (S1.1 anabolic androgenic steroids); non-specified substance |
What it is
4-Androstenediol is a 19-carbon steroid with hydroxyl (OH) groups at carbons 3 and 17, both in the β position, and a double bond between carbons 4 and 5 of the A-ring (PubChem). That puts it next to testosterone and androstenedione in structure:
| Compound | Chemical name | Group at C3 | Group at C17 |
|---|---|---|---|
| 4-Androstenediol (4-Andro) | Androst-4-ene-3β,17β-diol | Hydroxyl | Hydroxyl |
| Testosterone | 17β-hydroxyandrost-4-en-3-one | Ketone | Hydroxyl |
| Androstenedione (4-AD) | Androst-4-en-3,17-dione | Ketone | Ketone |
| 5-Androstenediol | Androst-5-ene-3β,17β-diol | Hydroxyl | Hydroxyl (double bond at C5–C6 instead) |
Chemical names in the table are taken from the US Schedule III list (21 CFR 1308.13).
Turning the 3β-hydroxyl into a ketone gives testosterone, which is why 4-androstenediol was sold as a testosterone precursor. Conversion of 4-androstenediol to testosterone, and formation of 4-androstenediol from DHEA, were shown in rat testis tissue in vitro in 1966 (Inaba & Nakao, Endocrinol Jpn 1966). For the steroids one step further back, see DHEA.
It also acts on the androgen receptor itself. In human cell lines, 4-androstenediol bound the full-length androgen receptor with affinities of 30–70 nM and behaved as a partial agonist: it switched on androgen-responsive genes, but also blocked DHT- or R1881-driven PSA expression by up to 30% (Chen et al., J Steroid Biochem Mol Biol 2004). These are cell-culture results; whether they matter at the doses people took is not known.
Name confusion
“Androstenediol” on its own is ambiguous, and supplement names were not standardized:
- 4-androstenediol and 5-androstenediol are separate compounds, listed separately by both the DEA and WADA. Reviews of the era also treated them as distinct “Andro” products (Broeder, Can J Appl Physiol 2003).
- “4-AD” usually means androstenedione, but some sellers used it for 4-androstenediol.
- 1-Androstenediol (1-Andro) is a different, synthetic 5α-steroid with its double bond at carbon 1. It is meant to convert to 1-testosterone, not testosterone.
How it works in the body
Taken by mouth, most 4-androstenediol is broken down before it reaches the circulation. In urine excretion studies in men, Uralets and Gillette found that first-pass metabolism in the liver rapidly converted oral 4-androstenediol (and androstenedione) mostly into inactive androsterone and etiocholanolone (J Anal Toxicol 1999). Their findings:
- Urinary steroids (androsterone, etiocholanolone, related androstanediols, testosterone and epitestosterone) rose by one to two orders of magnitude, then returned to normal by 24 h after the dose.
- Testosterone/epitestosterone (T/E) ratio. Testosterone rose faster than epitestosterone, so the average man could exceed the doping-test cutoff of 6:1 that applied at the time.
- Ethnic difference. In eastern Asian men, neither compound raised urinary testosterone or the T/E ratio.
- Compared with androstenedione, the authors described 4-androstenediol as the more effective testosterone booster, because of its different metabolic route.
No elimination half-life for 4-androstenediol in humans was reported in the studies reviewed here.
Detection in sport
In urine, a major form of the drug is a sulfate conjugate. Australian anti-doping researchers proposed two breakdown products, androst-2,4-diene-17-one and androst-3,5-diene-17-one, as screening markers of 4-androstenediol use. Suspicious samples are then confirmed by carbon isotope ratio testing (GC-C-IRMS), which separates synthetic steroid from steroid the body made (Cawley et al., Forensic Sci Int 2011).
Regulatory status
4-Androstenediol was never approved as a drug. It was sold as a dietary supplement until Congress named it as one of 59 specific anabolic steroids in the Anabolic Steroid Control Act of 2004. The Act took effect on January 20, 2005, and the DEA’s conforming rule notes that many of these steroids had previously been marketed as dietary supplements (DEA final rule, Fed Regist 2005). It is now listed by name in Schedule III as “4-androstenediol (3β,17β-dihydroxy-androst-4-ene)” (21 CFR 1308.13).
The WADA 2026 Prohibited List names 4-androstenediol (androst-4-ene-3β,17β-diol) under S1.1 anabolic androgenic steroids, prohibited at all times when administered exogenously (WADA 2026 Prohibited List).
What the research shows
The one explicit 4-ene study
In a randomized, double-blind, placebo-controlled crossover study, 8 young men (mean age 23.8) took single 200 mg oral doses of 4-androstenediol, androstenedione and placebo, a week apart. Blood was drawn for 90 minutes (Earnest et al., Eur J Appl Physiol 2000):
| Mean AUC over 90 min | Placebo | 4-Androstenediol 200 mg | Androstenedione 200 mg |
|---|---|---|---|
| Serum androstenedione (nmol/L) | 484 | 900 | 2,177 |
| Total testosterone (nmol/L) | 1,418.5 | 1,602.9 | 1,632.5 |
| Free testosterone (pmol/L) | 4,974.6 | 5,632.0 | 6,114.0 |
Androstenedione raised total testosterone above placebo (p under 0.05). The 4-androstenediol results did not differ significantly from androstenedione, but the abstract does not report a direct comparison of 4-androstenediol with placebo. The link between the precursor and testosterone over time was weaker for 4-androstenediol (r = 0.69, not significant) than for androstenedione (r = 0.91). The authors concluded only that 4-androstenediol “perhaps” raises testosterone. The study did not measure estrogens, muscle, strength or any longer-term outcome.
Studies of “androstenediol” where the isomer is not stated
Several larger studies from the same period tested a product called “androstenediol.” Their abstracts do not say whether it was the 4-ene or 5-ene isomer, and we could not access the full texts to check. They are summarized here because they are the main controlled data on androstenediol supplements, but they should not be read as confirmed 4-androstenediol data.
| Study | Design | Androstenediol dose | Main hormone findings | Training outcomes |
|---|---|---|---|---|
| Broeder et al., Arch Intern Med 2000 (Andro Project) | Double-blind RCT, 50 men aged 35–65, with high-intensity resistance training | 200 mg/day orally for 12 weeks | Estrone and estradiol rose in the androstenediol and androstenedione groups | No added gain in strength or body composition vs placebo |
| Brown et al., J Am Coll Nutr 2001 | RCT, 55 men aged 30–58 | 300 mg/day plus herbal extracts, 28 days | Total testosterone unchanged; free testosterone +37%, androstenedione +174%, DHT +57%, estradiol +86% | Not studied |
| Brown et al., J Appl Physiol 2002 | Double-blind crossover, 8 trained young men | Single 20 mg sublingual cyclodextrin tablet | Total testosterone peaked at 47.9 nmol/L at 60 min (baseline 25.6); estradiol also rose | Not studied |
| Brown & McKenzie, Eur J Appl Physiol 2006 | Double-blind crossover, 6 trained young men | Single sublingual dose (21.4 mg) | Total testosterone about +115% at 60 min, back to baseline by 240 min; estradiol up about 45% at 120 min, back to baseline by 720 min | A single exercise session did not change the response |
Two patterns are clear from these studies. Oral doses gave small or no lasting rises in total testosterone but consistent rises in estrogens. The sublingual form, which partly bypasses the liver, raised testosterone sharply but only for a few hours. In the herbal-combination trial, adding saw palmetto, chrysin and other extracts did not prevent the rise in estradiol and DHT.
Muscle and performance
No trial that clearly used 4-androstenediol has measured muscle mass or strength. Reviews of the prohormone research concluded that oral androstenedione and androstenediol at the doses studied (below 300 mg/day, for up to 12 weeks) did not improve body composition or performance (Ziegenfuss et al., Can J Appl Physiol 2002; Brown et al., Med Sci Sports Exerc 2006).
Side effects and risks
There are no long-term safety data for 4-androstenediol. The risks below come from the androstenediol studies above, with the isomer caveat already noted, and from the class.
Estrogen rise
Estrogens rose in every androstenediol study that measured them: estradiol by 86% over 4 weeks in the herbal-combination trial (Brown et al., 2001), and estrone and estradiol in the 12-week Andro Project (Broeder et al., 2000). Reviewers flagged this pattern as a concern for long-term use (Broeder, 2003).
Blood lipids
- HDL cholesterol (“good” cholesterol) fell by 0.14 mmol/L (about 5 mg/dL) over 4 weeks with the androstenediol-herbal product (Brown et al., 2001).
- Andro Project: both androstenediol and androstenedione worsened HDL and the estimated coronary heart disease risk (a 6.5% increase). The composite lipid ratio rose by 5.2% on androstenediol, while it fell by 12.3% on placebo (Broeder et al., 2000).
Hormone suppression and doping tests
In the Andro Project, luteinizing hormone (LH, the pituitary signal that drives testosterone production) was 18–33% lower during treatment. The abstract reports this in explaining why testosterone in the androstenedione group fell back to baseline, and lists down-regulation of the body’s own testosterone production as an effect of the precursors studied (Broeder et al., 2000). It does not give separate LH figures for the androstenediol group. Because oral 4-androstenediol can push the urinary T/E ratio above the doping cutoff in many men, an athlete taking it can test positive (Uralets & Gillette, 1999).
Unknowns
- No half-life, dose-response or long-term human data exist for the 4-ene compound.
- Effects in women have not been studied.
- Products sold as “androstenediol” did not always state the isomer, so what a given product contained cannot be assumed from its name.
Key takeaways
- One step from testosterone. 4-Androstenediol differs from testosterone only at carbon 3 and was sold as a testosterone-raising supplement.
- Very little direct human data. The only controlled study that names the 4-ene compound and measures blood hormones gave 8 men a single 200 mg dose and followed them for 90 minutes.
- Mostly broken down by the liver. Oral doses were largely converted to inactive metabolites, with urinary steroid changes back to normal by 24 h.
- Estrogens and lipids, not muscle. Androstenediol studies (isomer not stated) found estrogen rises and HDL falls, and no added strength or muscle with training.
- Controlled and banned. It has been Schedule III in the US since January 20, 2005, and is prohibited at all times by WADA.
Sources
- Uralets VP, Gillette PA. Over-the-counter anabolic steroids 4-androsten-3,17-dione; 4-androsten-3beta,17beta-diol; and 19-nor-4-androsten-3,17-dione: excretion studies in men. J Anal Toxicol. 1999;23(5):357–366. PubMed.
- National Center for Biotechnology Information. 4-Androstenediol (CID 136297). PubChem. PubChem.
- Code of Federal Regulations. 21 CFR 1308.13, Schedule III. 21 CFR 1308.13.
- Inaba M, Nakao T. Conversion of 4-androstenediol and 5-androstenediol to testosterone, and conversion of dehydroepiandrosterone to 4-androstenediol by rat testis in vitro. Endocrinol Jpn. 1966;13(2):160–172. PubMed.
- 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.
- Broeder CE. Oral andro-related prohormone supplementation: do the potential risks outweigh the benefits? Can J Appl Physiol. 2003;28(1):102–116. PubMed.
- Cawley AT, Trout GJ, Kazlauskas R, George AV. The potential of urinary androstdiene markers to identify 4-androstenediol (4-ADIOL) administration in athletes. Forensic Sci Int. 2011;208(1-3):129–138. 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.
- World Anti-Doping Agency. The 2026 Prohibited List. In effect from January 1, 2026. WADA 2026 Prohibited List.
- Earnest CP, Olson MA, Broeder CE, Breuel KF, Beckham SG. In vivo 4-androstene-3,17-dione and 4-androstene-3 beta,17 beta-diol supplementation in young men. Eur J Appl Physiol. 2000;81(3):229–232. 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.
- Brown GA, Vukovich MD, Martini ER, et al. Endocrine and lipid responses to chronic androstenediol-herbal supplementation in 30 to 58 year old men. J Am Coll Nutr. 2001;20(5):520–528. PubMed.
- Brown GA, Martini ER, Roberts BS, et al. Acute hormonal response to sublingual androstenediol intake in young men. J Appl Physiol. 2002;92(1):142–146. PubMed.
- Brown GA, McKenzie D. Acute resistance exercise does not change the hormonal response to sublingual androstenediol intake. Eur J Appl Physiol. 2006;97(4):404–412. PubMed.
- Ziegenfuss TN, Berardi JM, Lowery LM. Effects of prohormone supplementation in humans: a review. Can J Appl Physiol. 2002;27(6):628–646. PubMed.
- Brown GA, Vukovich M, King DS. Testosterone prohormone supplements. Med Sci Sports Exerc. 2006;38(8):1451–1461. PubMed.