Isotretinoin

updated

Isotretinoin is an FDA-approved oral retinoid for severe recalcitrant nodular acne, first approved as ACCUTANE in 1982, with a boxed warning for life-threatening birth defects and distribution only through the iPLEDGE REMS. A Cochrane review pooled 31 randomized trials, and all but three had high risk of bias. A PubMed search on 9 October 2026 found no trial or cohort measuring isotretinoin efficacy in anabolic steroid users, so the claim that it is the only treatment that works for steroid-driven acne is not supported.

Retinoid

  • FDA first approved isotretinoin as ACCUTANE under NDA 018662 on 7 May 1982; ABSORICA followed on 25 May 2012 and ABSORICA LD on 5 November 2019.
  • The label covers severe recalcitrant nodular acne in non-pregnant patients 12 and older, reserved for acne unresponsive to conventional therapy including systemic antibiotics.
  • A boxed warning states that isotretinoin can cause life-threatening birth defects, and the drug is available only through the iPLEDGE REMS.
  • A Cochrane review of 31 randomized trials (3,836 participants) found no clear difference from oral antibiotics plus topical agents in inflammatory lesion count (RR 1.01, 95% CI 0.96 to 1.06; very low-quality evidence).
  • A PubMed search on 9 October 2026 returned 12 records on isotretinoin with anabolic steroid or bodybuilding terms; none was a trial or cohort measuring efficacy in steroid users.
  • In 96 women with nodulocystic acne, isotretinoin was similarly effective with and without polycystic ovary syndrome, the closest high-androgen comparison located.

What is isotretinoin approved to do?

FDA approved isotretinoin as ACCUTANE in 1982 for severe recalcitrant nodular acne. The label reserves it for patients 12 and older whose acne did not respond to conventional therapy including systemic antibiotics.

The ABSORICA and ABSORICA LD label covers severe recalcitrant nodular acne in non-pregnant patients 12 years and older with multiple inflammatory nodules 5 mm or greater in diameter. It is reserved for acne unresponsive to conventional therapy, including systemic antibiotics. The label version used here took effect on 19 August 2026.

FDA first approved isotretinoin as ACCUTANE (Hoffmann-La Roche) under NDA 018662 on 7 May 1982, as a new molecular entity. ABSORICA (NDA 021951) followed on 25 May 2012 and ABSORICA LD (NDA 211913) on 5 November 2019, and generic capsules are approved under ANDAs. The ACCUTANE NDA strengths are now listed as discontinued, with a Federal Register determination that they were not withdrawn for safety or effectiveness reasons.

A boxed warning states that isotretinoin can cause life-threatening birth defects, and the drug is available only through the iPLEDGE REMS. The REMS requires contraception and repeated pregnancy testing for patients who can get pregnant, and patients who cannot get pregnant must not share the drug or donate blood. The testing intervals differ between label versions, so this page does not list them.

Isotretinoin is 13-cis-retinoic acid (C20H28O2, 300.4 g/mol, CAS 4759-48-2). ABSORICA and ABSORICA LD differ in bioavailability and are not interchangeable mg for mg.

ABSORICA label, version effective 19 August 2026: indication, boxed warning, warnings, PK

FDA prescribing information

DailyMed, U.S. National Library of Medicine. ABSORICA and ABSORICA LD (isotretinoin) oral capsules, prescribing information, label version effective 19 August 2026. Set ID 3ef0cff8-19c1-4441-b780-fca6c7ee1615.

The label approves isotretinoin for severe recalcitrant nodular acne in non-pregnant patients 12 years and older with multiple inflammatory nodules 5 mm or greater in diameter, reserved for acne unresponsive to conventional therapy including systemic antibiotics. A boxed warning states that isotretinoin can cause life-threatening birth defects, that the risk is extremely high if pregnancy occurs while taking any amount even for short periods, and that the drug is available only through the iPLEDGE REMS. The label says the exact mechanism is unknown; isotretinoin is a retinoid that inhibits sebaceous gland function and keratinization, and the fall in sebum is temporary. Warnings cover depression, psychosis and, rarely, suicidal ideation, suicide attempts, suicide, and aggressive or violent behavior; intracranial hypertension (avoid tetracyclines); serious skin reactions; pancreatitis; lipid elevations; hearing impairment; hepatotoxicity; inflammatory bowel disease; bone mineral density loss and premature epiphyseal closure; ocular effects; and hypersensitivity. In a 20-week trial, 27 of 306 (9%) pediatric patients aged 12 and older had bone mineral density declines, and 9 of 289 (3%) had clinically significant bone age changes for which a drug effect could not be excluded. Acne fulminans and sexual dysfunction that may continue after stopping appear among reported adverse reactions. Mean elimination half-lives were 18 hours for isotretinoin and 38 hours for 4-oxo-isotretinoin after a single 40 mg ABSORICA dose. The label's efficacy trial compared ABSORICA with another isotretinoin capsule in 925 patients, with no placebo arm; 70% and 75% reached a 90% reduction in nodular lesions at week 20. ABSORICA and ABSORICA LD are not substitutable mg for mg.

Participants / model
Non-pregnant patients 12 and older with severe recalcitrant nodular acne; label PK participants
Treatment
ABSORICA and ABSORICA LD oral capsules
Follow-up
Label version effective 19 August 2026; efficacy comparison at week 20
Study design
FDA prescribing information
Funding
not stated in the source

The label's efficacy trial had no placebo arm. The page gives no label dosing or REMS interval details, which differ between label versions.

Read the original source
Drugs@FDA: ACCUTANE 1982, ABSORICA 2012, ABSORICA LD 2019

Regulatory record

U.S. Food and Drug Administration. Drugs@FDA application record for NDA 018662 (ACCUTANE), with related applications NDA 021951 (ABSORICA) and NDA 211913 (ABSORICA LD). Dates read from the openFDA Drugs@FDA records.

FDA first approved isotretinoin as ACCUTANE (Hoffmann-La Roche) under NDA 018662 on 7 May 1982 as a new molecular entity. The ACCUTANE NDA strengths are now listed as discontinued, with a Federal Register determination that they were not withdrawn for safety or effectiveness reasons. ABSORICA (NDA 021951) was approved on 25 May 2012 and ABSORICA LD (NDA 211913) on 5 November 2019. Generic capsules are approved under ANDAs.

Participants / model
Not a clinical population
Treatment
Drug applications
Follow-up
Approvals from 1982 to 2019
Study design
FDA application records
Funding
not stated in the source

These records give approval dates and status. Indications come from the product label.

Read the original source
PubChem CID 5282379: C20H28O2, 300.4 g/mol

Chemical identity record

National Center for Biotechnology Information. PubChem Compound Summary for CID 5282379, isotretinoin (13-cis-retinoic acid).

Isotretinoin is 13-cis-retinoic acid: PubChem CID 5282379, C20H28O2, 300.4 g/mol, CAS 4759-48-2. The label lists retinoic acid (tretinoin) and 4-oxo-isotretinoin among its circulating metabolites. ABSORICA and ABSORICA LD differ in bioavailability and are not interchangeable mg for mg.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecule
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Identity record only; it says nothing about efficacy or safety.

Read the original source

What did the acne studies find?

The first report in 14 patients saw 13 clear completely, with no control group. A Cochrane review of 31 randomized trials found no clear difference from oral antibiotics plus topical agents in inflammatory lesion count, and most trials had high risk of bias.

In the first report, 14 patients with treatment-resistant cystic and conglobate acne took oral 13-cis-retinoic acid for 4 months at an average 2.0 mg/kg/day. Thirteen cleared completely and one improved by 75%, with remissions lasting up to 20 months after stopping at the time of writing. Toxicity was mostly skin and mucous membrane, dose dependent and reversible. The study had no control group.

A Cochrane review included 31 randomized trials with 3,836 participants aged 12 to 55 with mild to severe acne, and all but three trials had high risk of bias in at least one domain. Against oral antibiotics plus topical agents in moderate or severe acne, isotretinoin made no clear difference in investigator-assessed inflammatory lesion count (3 trials, 400 participants; RR 1.01, 95% CI 0.96 to 1.06; very low-quality evidence). It may slightly improve physician-assessed severity (RR 1.15, 95% CI 1.00 to 1.32; 351 participants). In one 150-participant trial in severe acne, 58%, 80% and 90% reached a 95% drop in inflammatory lesions on 0.1, 0.5 and 1 mg/kg/day.

The label's efficacy trial compared ABSORICA with another isotretinoin capsule in 925 patients and had no placebo arm; 70% and 75% reached a 90% reduction in nodular lesions at week 20.

First report: 14 patients, 13 cleared, no control group

Human study

Peck GL et al. N Engl J Med. 1979;300(7):329-33. PMID 153472.

Thirteen of 14 patients cleared completely and one improved by 75%, with remissions lasting up to 20 months after stopping at the time of writing. Toxicity was mostly skin and mucous membrane, dose dependent, and reversible.

Participants / model
14 patients with treatment-resistant cystic and conglobate acne
Treatment
Oral isotretinoin (13-cis-retinoic acid), average 2.0 mg/kg/day for 4 months
Follow-up
4 months of treatment
Study design
Original uncontrolled clinical study
Funding
not stated in the source

There was no control group. Endpoints were nodule and cyst counts, remission and toxicity.

Read the original source
Cochrane review: 31 randomized trials, 3,836 participants

Systematic review and meta-analysis

Costa CS et al. Cochrane Database Syst Rev. 2018;11(11):CD009435. PMID 30484286.

The review included 31 randomized trials with 3,836 participants aged 12 to 55 with mild to severe acne; all but three trials had high risk of bias in at least one domain. Against oral antibiotics plus topical agents in moderate or severe acne, isotretinoin made no clear difference in investigator-assessed inflammatory lesion count (3 trials, 400 participants; RR 1.01, 95% CI 0.96 to 1.06; very low-quality evidence), may slightly improve physician-assessed severity (RR 1.15, 95% CI 1.00 to 1.32; 351 participants), and caused more less serious adverse effects such as dry lips or skin, cheilitis, vomiting and nausea (RR 1.67, 95% CI 1.42 to 1.98). In one 150-participant trial in severe acne, 58%, 80% and 90% reached a 95% drop in inflammatory lesions on 0.1, 0.5 and 1 mg/kg/day. No included trial reported birth defects.

Participants / model
3,836 people aged 12 to 55 with acne in 31 randomized trials
Treatment
Oral isotretinoin versus placebo, antibiotics or other regimens
Follow-up
Varied by trial; not stated in the source
Study design
Cochrane systematic review of randomized trials
Funding
not stated in the source

The trials were mostly at high risk of bias, and the lesion-count comparison was very low-quality evidence.

Read the original source
ABSORICA label, version effective 19 August 2026: indication, boxed warning, warnings, PK

FDA prescribing information

DailyMed, U.S. National Library of Medicine. ABSORICA and ABSORICA LD (isotretinoin) oral capsules, prescribing information, label version effective 19 August 2026. Set ID 3ef0cff8-19c1-4441-b780-fca6c7ee1615.

The label approves isotretinoin for severe recalcitrant nodular acne in non-pregnant patients 12 years and older with multiple inflammatory nodules 5 mm or greater in diameter, reserved for acne unresponsive to conventional therapy including systemic antibiotics. A boxed warning states that isotretinoin can cause life-threatening birth defects, that the risk is extremely high if pregnancy occurs while taking any amount even for short periods, and that the drug is available only through the iPLEDGE REMS. The label says the exact mechanism is unknown; isotretinoin is a retinoid that inhibits sebaceous gland function and keratinization, and the fall in sebum is temporary. Warnings cover depression, psychosis and, rarely, suicidal ideation, suicide attempts, suicide, and aggressive or violent behavior; intracranial hypertension (avoid tetracyclines); serious skin reactions; pancreatitis; lipid elevations; hearing impairment; hepatotoxicity; inflammatory bowel disease; bone mineral density loss and premature epiphyseal closure; ocular effects; and hypersensitivity. In a 20-week trial, 27 of 306 (9%) pediatric patients aged 12 and older had bone mineral density declines, and 9 of 289 (3%) had clinically significant bone age changes for which a drug effect could not be excluded. Acne fulminans and sexual dysfunction that may continue after stopping appear among reported adverse reactions. Mean elimination half-lives were 18 hours for isotretinoin and 38 hours for 4-oxo-isotretinoin after a single 40 mg ABSORICA dose. The label's efficacy trial compared ABSORICA with another isotretinoin capsule in 925 patients, with no placebo arm; 70% and 75% reached a 90% reduction in nodular lesions at week 20. ABSORICA and ABSORICA LD are not substitutable mg for mg.

Participants / model
Non-pregnant patients 12 and older with severe recalcitrant nodular acne; label PK participants
Treatment
ABSORICA and ABSORICA LD oral capsules
Follow-up
Label version effective 19 August 2026; efficacy comparison at week 20
Study design
FDA prescribing information
Funding
not stated in the source

The label's efficacy trial had no placebo arm. The page gives no label dosing or REMS interval details, which differ between label versions.

Read the original source

Is isotretinoin the only treatment that works for steroid-driven acne?

No study found supports that. A PubMed search on 9 October 2026 returned 12 records on isotretinoin with anabolic steroid or bodybuilding terms, and none was a trial or cohort measuring efficacy in steroid users.

Sellers describe isotretinoin as the only treatment that works for severe nodular or cystic acne driven by anabolic-androgenic steroids, especially DHT-derived compounds, with weaker results while androgen levels stay high.

The PubMed search used isotretinoin with anabolic, bodybuilding or bodybuilder terms and returned 12 records: case reports, one case series, narrative reviews, a viewpoint, a laboratory Demodex study and unrelated drug-safety reviews. None was a trial or cohort measuring isotretinoin efficacy in anabolic steroid users, and none compared isotretinoin with other treatments in that group. A second search pairing acne and isotretinoin with named steroids (stanozolol, drostanolone, oxymetholone, mesterolone, trenbolone, methenolone) or the terms dihydrotestosterone-derived and DHT-derived returned 0 records.

No record supports isotretinoin as the only intervention that works, a special role for DHT-derived compounds, or blunted efficacy while androgens stay high. A narrative review from Germany reported acne in about 50% of anabolic-androgenic steroid users and noted that steroids can induce acne conglobata and acne fulminans, but it tests no treatment.

PubMed search, 9 October 2026: 12 records, none measuring efficacy in steroid users

PubMed search record

PubMed search run on 9 October 2026: isotretinoin[tiab] AND (anabolic[tiab] OR bodybuilding[tiab] OR bodybuilder[tiab] OR bodybuilders[tiab]). 12 records returned. A second search pairing acne and isotretinoin with named steroids (stanozolol, drostanolone, oxymetholone, mesterolone, trenbolone, methenolone) or the terms dihydrotestosterone-derived and DHT-derived returned 0 records.

The first search returned 12 records: case reports, one case series, narrative reviews, a viewpoint, a laboratory Demodex study and unrelated drug-safety reviews. None was a trial or cohort measuring isotretinoin efficacy in anabolic steroid users, and none compared isotretinoin with other treatments in that group. The second search returned 0 records. No record supports isotretinoin as the only intervention that works, a special role for DHT-derived compounds, or blunted efficacy while androgens stay high.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Search run on 9 October 2026
Study design
Literature search
Funding
not stated in the source

A search result shows what PubMed returned on that date. It is not proof that no unindexed study exists.

Read the original source
Narrative review: acne in about 50% of steroid users

Human study

Melnik B et al. J Dtsch Dermatol Ges. 2007;5(2):110-7. PMID 17274777.

A narrative review from Germany reported that acne occurs in about 50% of anabolic-androgenic steroid users and is a clinical sign of steroid use, especially in men aged 18 to 26, and that steroid use can induce acne conglobata and acne fulminans. It does not test any treatment.

Participants / model
Anabolic-androgenic steroid users, mainly fitness-center members in Germany
Treatment
Illicit anabolic-androgenic steroids
Follow-up
not stated in the source
Study design
Narrative review
Funding
not stated in the source

The review describes acne frequency and forms. It tests no treatment.

Read the original source

What do reports show when androgen levels are high?

A 96-woman study found similar on-treatment efficacy with and without polycystic ovary syndrome, and the steroid-specific reports are single cases or small series. One case worsened on isotretinoin.

In 96 women with nodulocystic acne, 46 with polycystic ovary syndrome (an endogenous androgen-excess state) and 50 without, isotretinoin at 0.5 to 1 mg/kg to a cumulative 120 to 150 mg/kg was similarly effective in both groups. Eight patients relapsed in the first post-treatment year and 16 in the second, and PCOS was associated with relapse in the second year. This is the closest high-androgen comparison located. It involves women with PCOS, not people using anabolic steroids, and it found no loss of on-treatment efficacy.

In a case report, a 22-year-old with severe bodybuilding acne caused by anabolic steroid use was treated with isotretinoin, which paradoxically led to exacerbation and pyogenic granuloma-like lesions. The abstract does not say whether steroid use continued, and one case cannot show how often this happens.

A case series of four children with acne fulminans, with a literature review, listed isotretinoin itself as a trigger in three of the four cases, and suggested testosterone and anabolic steroid use and cessation as triggers. The recommended treatment was oral corticosteroids combined with low-dose isotretinoin, with no consensus; all four patients responded to that combination.

A scoping review of 16 publications on transmasculine patients receiving testosterone reported that acne tends to peak about 6 months after testosterone starts, that severe cases can be treated with isotretinoin, and that acne may recur after isotretinoin stops when hormone therapy continues. This concerns prescribed testosterone and is review-level, not a measured efficacy comparison.

96 women: similar response with and without PCOS

Human study

Cakir GA et al. Int J Dermatol. 2013;52(3):371-6. PMID 22998438.

In 96 women with nodulocystic acne, 46 with polycystic ovary syndrome (an endogenous androgen-excess state) and 50 without, isotretinoin was similarly effective in both groups. Eight patients relapsed in the first post-treatment year and 16 in the second; PCOS was associated with relapse in the second year.

Participants / model
96 women with nodulocystic acne, 46 with PCOS
Treatment
Oral isotretinoin 0.5 to 1 mg/kg to a cumulative 120 to 150 mg/kg
Follow-up
Relapse followed for 2 years after treatment
Study design
Original comparative clinical study
Funding
not stated in the source

This is the closest high-androgen comparison located. It involves women with PCOS, not people using anabolic steroids, and it found no loss of on-treatment efficacy.

Read the original source
Case report: one 22-year-old, worsening on isotretinoin

Case report

Voelcker V et al. Int Wound J. 2010;7(3):199-201. PMID 20602651.

A 22-year-old with severe bodybuilding acne caused by anabolic steroid use was treated with isotretinoin, which paradoxically led to exacerbation and pyogenic granuloma-like lesions.

Participants / model
One 22-year-old patient
Treatment
Oral isotretinoin after anabolic steroid exposure (the abstract does not say whether steroid use continued)
Follow-up
not stated in the source
Study design
Case report
Funding
not stated in the source

One case cannot show how often this happens.

Read the original source
Acne fulminans: 4 children plus published cases

Case report

Alakeel A et al. Pediatr Dermatol. 2016;33(6):e388-e392. PMID 27699859.

A case series of four children with acne fulminans plus a literature review lists isotretinoin itself as a trigger (three of the four cases), with use and cessation of testosterone and anabolic steroid intake also suggested. The recommended treatment is oral corticosteroids combined with low-dose isotretinoin, with no consensus; all four patients responded to that combination.

Participants / model
Two boys and two girls with acne fulminans; published cases
Treatment
Oral corticosteroids plus low-dose oral isotretinoin
Follow-up
not stated in the source
Study design
Case series and literature review
Funding
not stated in the source

Endpoints were triggers and treatment response. The series is four patients.

Read the original source
Scoping review: 16 publications on acne during testosterone

Human study

Strock D et al. JMIR Dermatol. 2023;6:e45351. PMID 37616418.

A scoping review of 16 publications on transmasculine patients receiving testosterone reported that acne tends to peak about 6 months after testosterone starts, that severe cases can be treated with isotretinoin, and that acne may recur after isotretinoin stops when hormone therapy continues.

Participants / model
Transmasculine patients on testosterone, from 16 publications
Treatment
Oral isotretinoin during gender-affirming testosterone
Follow-up
not stated in the source
Study design
Scoping review
Funding
not stated in the source

This concerns prescribed testosterone and is review-level, not a measured efficacy comparison.

Read the original source

How does isotretinoin work, and what does the body do with it?

The label says the exact mechanism is unknown. Isotretinoin is a retinoid that inhibits sebaceous gland function and keratinization, and after a single 40 mg dose the mean elimination half-life was 18 hours.

The label says the exact mechanism is unknown. Isotretinoin is a retinoid that inhibits sebaceous gland function and keratinization, and the fall in sebum is temporary.

After a single 40 mg ABSORICA dose, mean elimination half-lives were 18 hours for isotretinoin and 38 hours for its metabolite 4-oxo-isotretinoin. The label also lists retinoic acid (tretinoin) among the circulating metabolites.

Nothing in the sources reviewed tests whether the mechanism changes when androgen levels are high. The only comparison located, in women with polycystic ovary syndrome, found similar on-treatment efficacy.

ABSORICA label, version effective 19 August 2026: indication, boxed warning, warnings, PK

FDA prescribing information

DailyMed, U.S. National Library of Medicine. ABSORICA and ABSORICA LD (isotretinoin) oral capsules, prescribing information, label version effective 19 August 2026. Set ID 3ef0cff8-19c1-4441-b780-fca6c7ee1615.

The label approves isotretinoin for severe recalcitrant nodular acne in non-pregnant patients 12 years and older with multiple inflammatory nodules 5 mm or greater in diameter, reserved for acne unresponsive to conventional therapy including systemic antibiotics. A boxed warning states that isotretinoin can cause life-threatening birth defects, that the risk is extremely high if pregnancy occurs while taking any amount even for short periods, and that the drug is available only through the iPLEDGE REMS. The label says the exact mechanism is unknown; isotretinoin is a retinoid that inhibits sebaceous gland function and keratinization, and the fall in sebum is temporary. Warnings cover depression, psychosis and, rarely, suicidal ideation, suicide attempts, suicide, and aggressive or violent behavior; intracranial hypertension (avoid tetracyclines); serious skin reactions; pancreatitis; lipid elevations; hearing impairment; hepatotoxicity; inflammatory bowel disease; bone mineral density loss and premature epiphyseal closure; ocular effects; and hypersensitivity. In a 20-week trial, 27 of 306 (9%) pediatric patients aged 12 and older had bone mineral density declines, and 9 of 289 (3%) had clinically significant bone age changes for which a drug effect could not be excluded. Acne fulminans and sexual dysfunction that may continue after stopping appear among reported adverse reactions. Mean elimination half-lives were 18 hours for isotretinoin and 38 hours for 4-oxo-isotretinoin after a single 40 mg ABSORICA dose. The label's efficacy trial compared ABSORICA with another isotretinoin capsule in 925 patients, with no placebo arm; 70% and 75% reached a 90% reduction in nodular lesions at week 20. ABSORICA and ABSORICA LD are not substitutable mg for mg.

Participants / model
Non-pregnant patients 12 and older with severe recalcitrant nodular acne; label PK participants
Treatment
ABSORICA and ABSORICA LD oral capsules
Follow-up
Label version effective 19 August 2026; efficacy comparison at week 20
Study design
FDA prescribing information
Funding
not stated in the source

The label's efficacy trial had no placebo arm. The page gives no label dosing or REMS interval details, which differ between label versions.

Read the original source
PubChem CID 5282379: C20H28O2, 300.4 g/mol

Chemical identity record

National Center for Biotechnology Information. PubChem Compound Summary for CID 5282379, isotretinoin (13-cis-retinoic acid).

Isotretinoin is 13-cis-retinoic acid: PubChem CID 5282379, C20H28O2, 300.4 g/mol, CAS 4759-48-2. The label lists retinoic acid (tretinoin) and 4-oxo-isotretinoin among its circulating metabolites. ABSORICA and ABSORICA LD differ in bioavailability and are not interchangeable mg for mg.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecule
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Identity record only; it says nothing about efficacy or safety.

Read the original source
96 women: similar response with and without PCOS

Human study

Cakir GA et al. Int J Dermatol. 2013;52(3):371-6. PMID 22998438.

In 96 women with nodulocystic acne, 46 with polycystic ovary syndrome (an endogenous androgen-excess state) and 50 without, isotretinoin was similarly effective in both groups. Eight patients relapsed in the first post-treatment year and 16 in the second; PCOS was associated with relapse in the second year.

Participants / model
96 women with nodulocystic acne, 46 with PCOS
Treatment
Oral isotretinoin 0.5 to 1 mg/kg to a cumulative 120 to 150 mg/kg
Follow-up
Relapse followed for 2 years after treatment
Study design
Original comparative clinical study
Funding
not stated in the source

This is the closest high-androgen comparison located. It involves women with PCOS, not people using anabolic steroids, and it found no loss of on-treatment efficacy.

Read the original source

What risks do the label and studies report?

The label carries a boxed warning for life-threatening birth defects and lists warnings for depression, psychosis, suicidality, intracranial hypertension, serious skin reactions, pancreatitis, lipid elevations, hearing impairment, hepatotoxicity, inflammatory bowel disease, bone effects and eye effects.

The boxed warning states that isotretinoin can cause life-threatening birth defects, that the risk is extremely high if pregnancy occurs while taking any amount even for short periods, and that the drug is available only through the iPLEDGE REMS.

Label warnings cover depression, psychosis and, rarely, suicidal ideation, suicide attempts, suicide, and aggressive or violent behavior; intracranial hypertension (the label says to avoid tetracyclines); serious skin reactions; pancreatitis; lipid elevations; hearing impairment; hepatotoxicity; inflammatory bowel disease; bone mineral density loss and premature epiphyseal closure; ocular effects; and hypersensitivity. Acne fulminans and sexual dysfunction that may continue after stopping appear among the reported adverse reactions. No incidence figures are given here for inflammatory bowel disease, hearing loss or epiphyseal closure beyond the label trial numbers below.

In a 20-week label trial in patients aged 12 and older, 27 of 306 (9%) had bone mineral density declines, and 9 of 289 (3%) had clinically significant bone age changes for which a drug effect could not be excluded.

In the Cochrane review, isotretinoin caused more less serious adverse effects than oral antibiotics plus topical agents, such as dry lips or skin, cheilitis, vomiting and nausea (RR 1.67, 95% CI 1.42 to 1.98). No included trial reported birth defects. In the single case report of steroid-associated acne, isotretinoin was followed by worsening, and one case cannot show how often that happens.

ABSORICA label, version effective 19 August 2026: indication, boxed warning, warnings, PK

FDA prescribing information

DailyMed, U.S. National Library of Medicine. ABSORICA and ABSORICA LD (isotretinoin) oral capsules, prescribing information, label version effective 19 August 2026. Set ID 3ef0cff8-19c1-4441-b780-fca6c7ee1615.

The label approves isotretinoin for severe recalcitrant nodular acne in non-pregnant patients 12 years and older with multiple inflammatory nodules 5 mm or greater in diameter, reserved for acne unresponsive to conventional therapy including systemic antibiotics. A boxed warning states that isotretinoin can cause life-threatening birth defects, that the risk is extremely high if pregnancy occurs while taking any amount even for short periods, and that the drug is available only through the iPLEDGE REMS. The label says the exact mechanism is unknown; isotretinoin is a retinoid that inhibits sebaceous gland function and keratinization, and the fall in sebum is temporary. Warnings cover depression, psychosis and, rarely, suicidal ideation, suicide attempts, suicide, and aggressive or violent behavior; intracranial hypertension (avoid tetracyclines); serious skin reactions; pancreatitis; lipid elevations; hearing impairment; hepatotoxicity; inflammatory bowel disease; bone mineral density loss and premature epiphyseal closure; ocular effects; and hypersensitivity. In a 20-week trial, 27 of 306 (9%) pediatric patients aged 12 and older had bone mineral density declines, and 9 of 289 (3%) had clinically significant bone age changes for which a drug effect could not be excluded. Acne fulminans and sexual dysfunction that may continue after stopping appear among reported adverse reactions. Mean elimination half-lives were 18 hours for isotretinoin and 38 hours for 4-oxo-isotretinoin after a single 40 mg ABSORICA dose. The label's efficacy trial compared ABSORICA with another isotretinoin capsule in 925 patients, with no placebo arm; 70% and 75% reached a 90% reduction in nodular lesions at week 20. ABSORICA and ABSORICA LD are not substitutable mg for mg.

Participants / model
Non-pregnant patients 12 and older with severe recalcitrant nodular acne; label PK participants
Treatment
ABSORICA and ABSORICA LD oral capsules
Follow-up
Label version effective 19 August 2026; efficacy comparison at week 20
Study design
FDA prescribing information
Funding
not stated in the source

The label's efficacy trial had no placebo arm. The page gives no label dosing or REMS interval details, which differ between label versions.

Read the original source
Cochrane review: 31 randomized trials, 3,836 participants

Systematic review and meta-analysis

Costa CS et al. Cochrane Database Syst Rev. 2018;11(11):CD009435. PMID 30484286.

The review included 31 randomized trials with 3,836 participants aged 12 to 55 with mild to severe acne; all but three trials had high risk of bias in at least one domain. Against oral antibiotics plus topical agents in moderate or severe acne, isotretinoin made no clear difference in investigator-assessed inflammatory lesion count (3 trials, 400 participants; RR 1.01, 95% CI 0.96 to 1.06; very low-quality evidence), may slightly improve physician-assessed severity (RR 1.15, 95% CI 1.00 to 1.32; 351 participants), and caused more less serious adverse effects such as dry lips or skin, cheilitis, vomiting and nausea (RR 1.67, 95% CI 1.42 to 1.98). In one 150-participant trial in severe acne, 58%, 80% and 90% reached a 95% drop in inflammatory lesions on 0.1, 0.5 and 1 mg/kg/day. No included trial reported birth defects.

Participants / model
3,836 people aged 12 to 55 with acne in 31 randomized trials
Treatment
Oral isotretinoin versus placebo, antibiotics or other regimens
Follow-up
Varied by trial; not stated in the source
Study design
Cochrane systematic review of randomized trials
Funding
not stated in the source

The trials were mostly at high risk of bias, and the lesion-count comparison was very low-quality evidence.

Read the original source
Case report: one 22-year-old, worsening on isotretinoin

Case report

Voelcker V et al. Int Wound J. 2010;7(3):199-201. PMID 20602651.

A 22-year-old with severe bodybuilding acne caused by anabolic steroid use was treated with isotretinoin, which paradoxically led to exacerbation and pyogenic granuloma-like lesions.

Participants / model
One 22-year-old patient
Treatment
Oral isotretinoin after anabolic steroid exposure (the abstract does not say whether steroid use continued)
Follow-up
not stated in the source
Study design
Case report
Funding
not stated in the source

One case cannot show how often this happens.

Read the original source

What happened in pregnancies exposed to isotretinoin?

Of 154 pregnancies with fetal exposure, 21 infants were malformed and the relative risk for selected major malformations was 25.6. FDA reports logged 6,740 pregnancies from 1997 to 2017, and pregnancies and fetal defects fell after iPLEDGE began but persisted.

In 154 human pregnancies with fetal isotretinoin exposure, outcomes were 95 elective abortions, 26 infants without major malformations, 12 spontaneous abortions and 21 malformed infants. Exposure carried a relative risk of 25.6 (95% CI 11.4 to 57.5) for a group of selected major malformations, in a pattern involving craniofacial, cardiac, thymic and central nervous system structures.

FDA adverse event reports included 6,740 pregnancies among women taking isotretinoin from 1997 to 2017. Reports peaked at 768 in 2006, the year iPLEDGE began, and settled at 218 to 310 a year after 2011. Estimated yearly pregnancy rates among females of childbearing potential ranged from 0.33% to 0.65%. Pregnancies, abortions and fetal defects fell after iPLEDGE began but persisted.

The FDA figures are spontaneous reports, not a registry of all exposures.

154 exposed pregnancies: 21 malformed infants, RR 25.6

Human study

Lammer EJ et al. N Engl J Med. 1985;313(14):837-41. PMID 3162101.

Among 154 human pregnancies with fetal isotretinoin exposure, outcomes were 95 elective abortions, 26 infants without major malformations, 12 spontaneous abortions and 21 malformed infants. Exposure carried a relative risk of 25.6 (95% CI 11.4 to 57.5) for a group of selected major malformations, in a pattern involving craniofacial, cardiac, thymic and central nervous system structures.

Participants / model
154 pregnancies with fetal isotretinoin exposure
Treatment
Maternal oral isotretinoin
Follow-up
not stated in the source
Study design
Original observational study
Funding
not stated in the source

Endpoints were pregnancy outcomes and major malformations.

Read the original source
FAERS: 6,740 reported pregnancies, 1997 to 2017

Human study

Tkachenko E et al. JAMA Dermatol. 2019;155(10):1175-1179. PMID 31314041.

FDA adverse event reports included 6,740 pregnancies among women taking isotretinoin from 1997 to 2017, peaking at 768 in 2006, the year iPLEDGE began, and settling at 218 to 310 reports a year after 2011. Estimated yearly pregnancy rates among females of childbearing potential ranged from 0.33% to 0.65%. Pregnancies, abortions and fetal defects fell after iPLEDGE began but persisted.

Participants / model
Women taking isotretinoin, FDA Adverse Event Reporting System reports
Treatment
Oral isotretinoin
Follow-up
Reports from 1997 to 2017
Study design
Original pharmacovigilance study
Funding
not stated in the source

These are spontaneous reports, not a registry of all exposures.

Read the original source

What do pooled studies find on depression and suicide?

In a meta-analysis of 25 studies, 1-year pooled absolute risks were below 0.5% each for completed suicide, attempt, ideation and self-harm, and 3.83% for depression. It does not replace the label's psychiatric warning for individual patients.

A meta-analysis of 25 studies (1,625,891 participants, average ages 16 to 38) found 1-year pooled absolute risks below 0.5% each for completed suicide, suicide attempt, suicidal ideation and self-harm, and 3.83% (95% CI 2.45 to 5.93) for depression among isotretinoin users. Isotretinoin was not associated with all psychiatric disorders (RR 1.08, 95% CI 0.99 to 1.19), and users had a lower risk of suicide attempt at 3 years (RR 0.86, 95% CI 0.77 to 0.95).

This is population-level evidence from randomized and observational studies. It does not replace the label's warning about depression, psychosis and suicidality for individual patients,.

Meta-analysis: 25 studies, 1,625,891 participants

Systematic review and meta-analysis

Tan NKW et al. JAMA Dermatol. 2024;160(1):54-62. PMID 38019562.

A meta-analysis of 25 studies (1,625,891 participants) found 1-year pooled absolute risks below 0.5% each for completed suicide, suicide attempt, suicidal ideation and self-harm, and 3.83% (95% CI 2.45 to 5.93) for depression among isotretinoin users. Isotretinoin was not associated with all psychiatric disorders (RR 1.08, 95% CI 0.99 to 1.19), and users had a lower risk of suicide attempt at 3 years (RR 0.86, 95% CI 0.77 to 0.95).

Participants / model
Isotretinoin users in randomized and observational studies, average ages 16 to 38
Treatment
Oral isotretinoin
Follow-up
1-year and 3-year outcomes
Study design
Systematic review and meta-analysis
Funding
not stated in the source

This is population-level evidence; it does not replace the label's psychiatric warning for individual patients.

Read the original source
ABSORICA label, version effective 19 August 2026: indication, boxed warning, warnings, PK

FDA prescribing information

DailyMed, U.S. National Library of Medicine. ABSORICA and ABSORICA LD (isotretinoin) oral capsules, prescribing information, label version effective 19 August 2026. Set ID 3ef0cff8-19c1-4441-b780-fca6c7ee1615.

The label approves isotretinoin for severe recalcitrant nodular acne in non-pregnant patients 12 years and older with multiple inflammatory nodules 5 mm or greater in diameter, reserved for acne unresponsive to conventional therapy including systemic antibiotics. A boxed warning states that isotretinoin can cause life-threatening birth defects, that the risk is extremely high if pregnancy occurs while taking any amount even for short periods, and that the drug is available only through the iPLEDGE REMS. The label says the exact mechanism is unknown; isotretinoin is a retinoid that inhibits sebaceous gland function and keratinization, and the fall in sebum is temporary. Warnings cover depression, psychosis and, rarely, suicidal ideation, suicide attempts, suicide, and aggressive or violent behavior; intracranial hypertension (avoid tetracyclines); serious skin reactions; pancreatitis; lipid elevations; hearing impairment; hepatotoxicity; inflammatory bowel disease; bone mineral density loss and premature epiphyseal closure; ocular effects; and hypersensitivity. In a 20-week trial, 27 of 306 (9%) pediatric patients aged 12 and older had bone mineral density declines, and 9 of 289 (3%) had clinically significant bone age changes for which a drug effect could not be excluded. Acne fulminans and sexual dysfunction that may continue after stopping appear among reported adverse reactions. Mean elimination half-lives were 18 hours for isotretinoin and 38 hours for 4-oxo-isotretinoin after a single 40 mg ABSORICA dose. The label's efficacy trial compared ABSORICA with another isotretinoin capsule in 925 patients, with no placebo arm; 70% and 75% reached a 90% reduction in nodular lesions at week 20. ABSORICA and ABSORICA LD are not substitutable mg for mg.

Participants / model
Non-pregnant patients 12 and older with severe recalcitrant nodular acne; label PK participants
Treatment
ABSORICA and ABSORICA LD oral capsules
Follow-up
Label version effective 19 August 2026; efficacy comparison at week 20
Study design
FDA prescribing information
Funding
not stated in the source

The label's efficacy trial had no placebo arm. The page gives no label dosing or REMS interval details, which differ between label versions.

Read the original source

Why does isotretinoin sit in S tier?

An FDA approval dating to 1982, more than four decades of use, a 31-trial Cochrane review and a safety profile managed through a REMS support the S for severe recalcitrant nodular acne. The grade does not cover the supplier's steroid-acne claim, which no study found tests.

The S applies to the labeled use. In the Cochrane review, all but three of the 31 trials had high risk of bias in at least one domain, and the birth defect risk is severe enough that the drug is only available through iPLEDGE.

The supplier's claim is a separate question. Steroid-associated acne appears only in reviews and case reports, one case worsened on isotretinoin, acne fulminans is treated with corticosteroids plus low-dose isotretinoin rather than isotretinoin alone, and the one high-androgen comparison, in women with polycystic ovary syndrome, found similar on-treatment efficacy with more relapse in the second year.

ABSORICA label, version effective 19 August 2026: indication, boxed warning, warnings, PK

FDA prescribing information

DailyMed, U.S. National Library of Medicine. ABSORICA and ABSORICA LD (isotretinoin) oral capsules, prescribing information, label version effective 19 August 2026. Set ID 3ef0cff8-19c1-4441-b780-fca6c7ee1615.

The label approves isotretinoin for severe recalcitrant nodular acne in non-pregnant patients 12 years and older with multiple inflammatory nodules 5 mm or greater in diameter, reserved for acne unresponsive to conventional therapy including systemic antibiotics. A boxed warning states that isotretinoin can cause life-threatening birth defects, that the risk is extremely high if pregnancy occurs while taking any amount even for short periods, and that the drug is available only through the iPLEDGE REMS. The label says the exact mechanism is unknown; isotretinoin is a retinoid that inhibits sebaceous gland function and keratinization, and the fall in sebum is temporary. Warnings cover depression, psychosis and, rarely, suicidal ideation, suicide attempts, suicide, and aggressive or violent behavior; intracranial hypertension (avoid tetracyclines); serious skin reactions; pancreatitis; lipid elevations; hearing impairment; hepatotoxicity; inflammatory bowel disease; bone mineral density loss and premature epiphyseal closure; ocular effects; and hypersensitivity. In a 20-week trial, 27 of 306 (9%) pediatric patients aged 12 and older had bone mineral density declines, and 9 of 289 (3%) had clinically significant bone age changes for which a drug effect could not be excluded. Acne fulminans and sexual dysfunction that may continue after stopping appear among reported adverse reactions. Mean elimination half-lives were 18 hours for isotretinoin and 38 hours for 4-oxo-isotretinoin after a single 40 mg ABSORICA dose. The label's efficacy trial compared ABSORICA with another isotretinoin capsule in 925 patients, with no placebo arm; 70% and 75% reached a 90% reduction in nodular lesions at week 20. ABSORICA and ABSORICA LD are not substitutable mg for mg.

Participants / model
Non-pregnant patients 12 and older with severe recalcitrant nodular acne; label PK participants
Treatment
ABSORICA and ABSORICA LD oral capsules
Follow-up
Label version effective 19 August 2026; efficacy comparison at week 20
Study design
FDA prescribing information
Funding
not stated in the source

The label's efficacy trial had no placebo arm. The page gives no label dosing or REMS interval details, which differ between label versions.

Read the original source
Drugs@FDA: ACCUTANE 1982, ABSORICA 2012, ABSORICA LD 2019

Regulatory record

U.S. Food and Drug Administration. Drugs@FDA application record for NDA 018662 (ACCUTANE), with related applications NDA 021951 (ABSORICA) and NDA 211913 (ABSORICA LD). Dates read from the openFDA Drugs@FDA records.

FDA first approved isotretinoin as ACCUTANE (Hoffmann-La Roche) under NDA 018662 on 7 May 1982 as a new molecular entity. The ACCUTANE NDA strengths are now listed as discontinued, with a Federal Register determination that they were not withdrawn for safety or effectiveness reasons. ABSORICA (NDA 021951) was approved on 25 May 2012 and ABSORICA LD (NDA 211913) on 5 November 2019. Generic capsules are approved under ANDAs.

Participants / model
Not a clinical population
Treatment
Drug applications
Follow-up
Approvals from 1982 to 2019
Study design
FDA application records
Funding
not stated in the source

These records give approval dates and status. Indications come from the product label.

Read the original source
Cochrane review: 31 randomized trials, 3,836 participants

Systematic review and meta-analysis

Costa CS et al. Cochrane Database Syst Rev. 2018;11(11):CD009435. PMID 30484286.

The review included 31 randomized trials with 3,836 participants aged 12 to 55 with mild to severe acne; all but three trials had high risk of bias in at least one domain. Against oral antibiotics plus topical agents in moderate or severe acne, isotretinoin made no clear difference in investigator-assessed inflammatory lesion count (3 trials, 400 participants; RR 1.01, 95% CI 0.96 to 1.06; very low-quality evidence), may slightly improve physician-assessed severity (RR 1.15, 95% CI 1.00 to 1.32; 351 participants), and caused more less serious adverse effects such as dry lips or skin, cheilitis, vomiting and nausea (RR 1.67, 95% CI 1.42 to 1.98). In one 150-participant trial in severe acne, 58%, 80% and 90% reached a 95% drop in inflammatory lesions on 0.1, 0.5 and 1 mg/kg/day. No included trial reported birth defects.

Participants / model
3,836 people aged 12 to 55 with acne in 31 randomized trials
Treatment
Oral isotretinoin versus placebo, antibiotics or other regimens
Follow-up
Varied by trial; not stated in the source
Study design
Cochrane systematic review of randomized trials
Funding
not stated in the source

The trials were mostly at high risk of bias, and the lesion-count comparison was very low-quality evidence.

Read the original source
PubMed search, 9 October 2026: 12 records, none measuring efficacy in steroid users

PubMed search record

PubMed search run on 9 October 2026: isotretinoin[tiab] AND (anabolic[tiab] OR bodybuilding[tiab] OR bodybuilder[tiab] OR bodybuilders[tiab]). 12 records returned. A second search pairing acne and isotretinoin with named steroids (stanozolol, drostanolone, oxymetholone, mesterolone, trenbolone, methenolone) or the terms dihydrotestosterone-derived and DHT-derived returned 0 records.

The first search returned 12 records: case reports, one case series, narrative reviews, a viewpoint, a laboratory Demodex study and unrelated drug-safety reviews. None was a trial or cohort measuring isotretinoin efficacy in anabolic steroid users, and none compared isotretinoin with other treatments in that group. The second search returned 0 records. No record supports isotretinoin as the only intervention that works, a special role for DHT-derived compounds, or blunted efficacy while androgens stay high.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Search run on 9 October 2026
Study design
Literature search
Funding
not stated in the source

A search result shows what PubMed returned on that date. It is not proof that no unindexed study exists.

Read the original source
96 women: similar response with and without PCOS

Human study

Cakir GA et al. Int J Dermatol. 2013;52(3):371-6. PMID 22998438.

In 96 women with nodulocystic acne, 46 with polycystic ovary syndrome (an endogenous androgen-excess state) and 50 without, isotretinoin was similarly effective in both groups. Eight patients relapsed in the first post-treatment year and 16 in the second; PCOS was associated with relapse in the second year.

Participants / model
96 women with nodulocystic acne, 46 with PCOS
Treatment
Oral isotretinoin 0.5 to 1 mg/kg to a cumulative 120 to 150 mg/kg
Follow-up
Relapse followed for 2 years after treatment
Study design
Original comparative clinical study
Funding
not stated in the source

This is the closest high-androgen comparison located. It involves women with PCOS, not people using anabolic steroids, and it found no loss of on-treatment efficacy.

Read the original source

Studies and sources

ABSORICA label, version effective 19 August 2026: indication, boxed warning, warnings, PK

FDA prescribing information

DailyMed, U.S. National Library of Medicine. ABSORICA and ABSORICA LD (isotretinoin) oral capsules, prescribing information, label version effective 19 August 2026. Set ID 3ef0cff8-19c1-4441-b780-fca6c7ee1615.

The label approves isotretinoin for severe recalcitrant nodular acne in non-pregnant patients 12 years and older with multiple inflammatory nodules 5 mm or greater in diameter, reserved for acne unresponsive to conventional therapy including systemic antibiotics. A boxed warning states that isotretinoin can cause life-threatening birth defects, that the risk is extremely high if pregnancy occurs while taking any amount even for short periods, and that the drug is available only through the iPLEDGE REMS. The label says the exact mechanism is unknown; isotretinoin is a retinoid that inhibits sebaceous gland function and keratinization, and the fall in sebum is temporary. Warnings cover depression, psychosis and, rarely, suicidal ideation, suicide attempts, suicide, and aggressive or violent behavior; intracranial hypertension (avoid tetracyclines); serious skin reactions; pancreatitis; lipid elevations; hearing impairment; hepatotoxicity; inflammatory bowel disease; bone mineral density loss and premature epiphyseal closure; ocular effects; and hypersensitivity. In a 20-week trial, 27 of 306 (9%) pediatric patients aged 12 and older had bone mineral density declines, and 9 of 289 (3%) had clinically significant bone age changes for which a drug effect could not be excluded. Acne fulminans and sexual dysfunction that may continue after stopping appear among reported adverse reactions. Mean elimination half-lives were 18 hours for isotretinoin and 38 hours for 4-oxo-isotretinoin after a single 40 mg ABSORICA dose. The label's efficacy trial compared ABSORICA with another isotretinoin capsule in 925 patients, with no placebo arm; 70% and 75% reached a 90% reduction in nodular lesions at week 20. ABSORICA and ABSORICA LD are not substitutable mg for mg.

Participants / model
Non-pregnant patients 12 and older with severe recalcitrant nodular acne; label PK participants
Treatment
ABSORICA and ABSORICA LD oral capsules
Follow-up
Label version effective 19 August 2026; efficacy comparison at week 20
Study design
FDA prescribing information
Funding
not stated in the source

The label's efficacy trial had no placebo arm. The page gives no label dosing or REMS interval details, which differ between label versions.

Read the original source
Drugs@FDA: ACCUTANE 1982, ABSORICA 2012, ABSORICA LD 2019

Regulatory record

U.S. Food and Drug Administration. Drugs@FDA application record for NDA 018662 (ACCUTANE), with related applications NDA 021951 (ABSORICA) and NDA 211913 (ABSORICA LD). Dates read from the openFDA Drugs@FDA records.

FDA first approved isotretinoin as ACCUTANE (Hoffmann-La Roche) under NDA 018662 on 7 May 1982 as a new molecular entity. The ACCUTANE NDA strengths are now listed as discontinued, with a Federal Register determination that they were not withdrawn for safety or effectiveness reasons. ABSORICA (NDA 021951) was approved on 25 May 2012 and ABSORICA LD (NDA 211913) on 5 November 2019. Generic capsules are approved under ANDAs.

Participants / model
Not a clinical population
Treatment
Drug applications
Follow-up
Approvals from 1982 to 2019
Study design
FDA application records
Funding
not stated in the source

These records give approval dates and status. Indications come from the product label.

Read the original source
First report: 14 patients, 13 cleared, no control group

Human study

Peck GL et al. N Engl J Med. 1979;300(7):329-33. PMID 153472.

Thirteen of 14 patients cleared completely and one improved by 75%, with remissions lasting up to 20 months after stopping at the time of writing. Toxicity was mostly skin and mucous membrane, dose dependent, and reversible.

Participants / model
14 patients with treatment-resistant cystic and conglobate acne
Treatment
Oral isotretinoin (13-cis-retinoic acid), average 2.0 mg/kg/day for 4 months
Follow-up
4 months of treatment
Study design
Original uncontrolled clinical study
Funding
not stated in the source

There was no control group. Endpoints were nodule and cyst counts, remission and toxicity.

Read the original source
Cochrane review: 31 randomized trials, 3,836 participants

Systematic review and meta-analysis

Costa CS et al. Cochrane Database Syst Rev. 2018;11(11):CD009435. PMID 30484286.

The review included 31 randomized trials with 3,836 participants aged 12 to 55 with mild to severe acne; all but three trials had high risk of bias in at least one domain. Against oral antibiotics plus topical agents in moderate or severe acne, isotretinoin made no clear difference in investigator-assessed inflammatory lesion count (3 trials, 400 participants; RR 1.01, 95% CI 0.96 to 1.06; very low-quality evidence), may slightly improve physician-assessed severity (RR 1.15, 95% CI 1.00 to 1.32; 351 participants), and caused more less serious adverse effects such as dry lips or skin, cheilitis, vomiting and nausea (RR 1.67, 95% CI 1.42 to 1.98). In one 150-participant trial in severe acne, 58%, 80% and 90% reached a 95% drop in inflammatory lesions on 0.1, 0.5 and 1 mg/kg/day. No included trial reported birth defects.

Participants / model
3,836 people aged 12 to 55 with acne in 31 randomized trials
Treatment
Oral isotretinoin versus placebo, antibiotics or other regimens
Follow-up
Varied by trial; not stated in the source
Study design
Cochrane systematic review of randomized trials
Funding
not stated in the source

The trials were mostly at high risk of bias, and the lesion-count comparison was very low-quality evidence.

Read the original source
154 exposed pregnancies: 21 malformed infants, RR 25.6

Human study

Lammer EJ et al. N Engl J Med. 1985;313(14):837-41. PMID 3162101.

Among 154 human pregnancies with fetal isotretinoin exposure, outcomes were 95 elective abortions, 26 infants without major malformations, 12 spontaneous abortions and 21 malformed infants. Exposure carried a relative risk of 25.6 (95% CI 11.4 to 57.5) for a group of selected major malformations, in a pattern involving craniofacial, cardiac, thymic and central nervous system structures.

Participants / model
154 pregnancies with fetal isotretinoin exposure
Treatment
Maternal oral isotretinoin
Follow-up
not stated in the source
Study design
Original observational study
Funding
not stated in the source

Endpoints were pregnancy outcomes and major malformations.

Read the original source
FAERS: 6,740 reported pregnancies, 1997 to 2017

Human study

Tkachenko E et al. JAMA Dermatol. 2019;155(10):1175-1179. PMID 31314041.

FDA adverse event reports included 6,740 pregnancies among women taking isotretinoin from 1997 to 2017, peaking at 768 in 2006, the year iPLEDGE began, and settling at 218 to 310 reports a year after 2011. Estimated yearly pregnancy rates among females of childbearing potential ranged from 0.33% to 0.65%. Pregnancies, abortions and fetal defects fell after iPLEDGE began but persisted.

Participants / model
Women taking isotretinoin, FDA Adverse Event Reporting System reports
Treatment
Oral isotretinoin
Follow-up
Reports from 1997 to 2017
Study design
Original pharmacovigilance study
Funding
not stated in the source

These are spontaneous reports, not a registry of all exposures.

Read the original source
Meta-analysis: 25 studies, 1,625,891 participants

Systematic review and meta-analysis

Tan NKW et al. JAMA Dermatol. 2024;160(1):54-62. PMID 38019562.

A meta-analysis of 25 studies (1,625,891 participants) found 1-year pooled absolute risks below 0.5% each for completed suicide, suicide attempt, suicidal ideation and self-harm, and 3.83% (95% CI 2.45 to 5.93) for depression among isotretinoin users. Isotretinoin was not associated with all psychiatric disorders (RR 1.08, 95% CI 0.99 to 1.19), and users had a lower risk of suicide attempt at 3 years (RR 0.86, 95% CI 0.77 to 0.95).

Participants / model
Isotretinoin users in randomized and observational studies, average ages 16 to 38
Treatment
Oral isotretinoin
Follow-up
1-year and 3-year outcomes
Study design
Systematic review and meta-analysis
Funding
not stated in the source

This is population-level evidence; it does not replace the label's psychiatric warning for individual patients.

Read the original source
Narrative review: acne in about 50% of steroid users

Human study

Melnik B et al. J Dtsch Dermatol Ges. 2007;5(2):110-7. PMID 17274777.

A narrative review from Germany reported that acne occurs in about 50% of anabolic-androgenic steroid users and is a clinical sign of steroid use, especially in men aged 18 to 26, and that steroid use can induce acne conglobata and acne fulminans. It does not test any treatment.

Participants / model
Anabolic-androgenic steroid users, mainly fitness-center members in Germany
Treatment
Illicit anabolic-androgenic steroids
Follow-up
not stated in the source
Study design
Narrative review
Funding
not stated in the source

The review describes acne frequency and forms. It tests no treatment.

Read the original source
Case report: one 22-year-old, worsening on isotretinoin

Case report

Voelcker V et al. Int Wound J. 2010;7(3):199-201. PMID 20602651.

A 22-year-old with severe bodybuilding acne caused by anabolic steroid use was treated with isotretinoin, which paradoxically led to exacerbation and pyogenic granuloma-like lesions.

Participants / model
One 22-year-old patient
Treatment
Oral isotretinoin after anabolic steroid exposure (the abstract does not say whether steroid use continued)
Follow-up
not stated in the source
Study design
Case report
Funding
not stated in the source

One case cannot show how often this happens.

Read the original source
Acne fulminans: 4 children plus published cases

Case report

Alakeel A et al. Pediatr Dermatol. 2016;33(6):e388-e392. PMID 27699859.

A case series of four children with acne fulminans plus a literature review lists isotretinoin itself as a trigger (three of the four cases), with use and cessation of testosterone and anabolic steroid intake also suggested. The recommended treatment is oral corticosteroids combined with low-dose isotretinoin, with no consensus; all four patients responded to that combination.

Participants / model
Two boys and two girls with acne fulminans; published cases
Treatment
Oral corticosteroids plus low-dose oral isotretinoin
Follow-up
not stated in the source
Study design
Case series and literature review
Funding
not stated in the source

Endpoints were triggers and treatment response. The series is four patients.

Read the original source
96 women: similar response with and without PCOS

Human study

Cakir GA et al. Int J Dermatol. 2013;52(3):371-6. PMID 22998438.

In 96 women with nodulocystic acne, 46 with polycystic ovary syndrome (an endogenous androgen-excess state) and 50 without, isotretinoin was similarly effective in both groups. Eight patients relapsed in the first post-treatment year and 16 in the second; PCOS was associated with relapse in the second year.

Participants / model
96 women with nodulocystic acne, 46 with PCOS
Treatment
Oral isotretinoin 0.5 to 1 mg/kg to a cumulative 120 to 150 mg/kg
Follow-up
Relapse followed for 2 years after treatment
Study design
Original comparative clinical study
Funding
not stated in the source

This is the closest high-androgen comparison located. It involves women with PCOS, not people using anabolic steroids, and it found no loss of on-treatment efficacy.

Read the original source
Scoping review: 16 publications on acne during testosterone

Human study

Strock D et al. JMIR Dermatol. 2023;6:e45351. PMID 37616418.

A scoping review of 16 publications on transmasculine patients receiving testosterone reported that acne tends to peak about 6 months after testosterone starts, that severe cases can be treated with isotretinoin, and that acne may recur after isotretinoin stops when hormone therapy continues.

Participants / model
Transmasculine patients on testosterone, from 16 publications
Treatment
Oral isotretinoin during gender-affirming testosterone
Follow-up
not stated in the source
Study design
Scoping review
Funding
not stated in the source

This concerns prescribed testosterone and is review-level, not a measured efficacy comparison.

Read the original source
PubChem CID 5282379: C20H28O2, 300.4 g/mol

Chemical identity record

National Center for Biotechnology Information. PubChem Compound Summary for CID 5282379, isotretinoin (13-cis-retinoic acid).

Isotretinoin is 13-cis-retinoic acid: PubChem CID 5282379, C20H28O2, 300.4 g/mol, CAS 4759-48-2. The label lists retinoic acid (tretinoin) and 4-oxo-isotretinoin among its circulating metabolites. ABSORICA and ABSORICA LD differ in bioavailability and are not interchangeable mg for mg.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecule
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Identity record only; it says nothing about efficacy or safety.

Read the original source

Why is Isotretinoin in S tier?

S fits an approved medicine with more than four decades of use, randomized trials pooled in a 31-trial Cochrane review, and a well-characterized safety profile managed through a REMS. The grade covers severe recalcitrant nodular acne, not the supplier's claim about anabolic-steroid acne, which no study found tests. The birth defect risk is severe enough that the drug is only available through iPLEDGE.