Clascoterone
CB-03-01 · Cortexolone 17α-propionate · Winlevi · Breezula
Last updated
At a glance
Overview
Why Clascoterone#
Clascoterone is the first topical androgen receptor antagonist with phase 3 data behind it for both acne and androgenetic alopecia — a molecule that competes with DHT at the receptor in scalp dermal papilla cells and sebocytes, then falls apart in plasma into an inactive metabolite before it can do anything systemic. For the looksmaxxing and physique-focused community, that's the entire pitch: AR blockade at the follicle without the libido, mood, and post-finasteride risks that drive people off oral 5α-reductase inhibitors in the first place.
The compound earned its reputation along two tracks. Winlevi (1% cream) is FDA-approved for acne and has become a quiet favorite for managing gear-acne on the back and shoulders without resorting to isotretinoin. Breezula (5% solution), the AGA-targeted formulation, posted strongly positive SCALP-1 and SCALP-2 phase 3 readouts in late 2025 — placing it alongside finasteride and minoxidil as a real, evidence-backed pillar in the hair-retention stack rather than another RU58841-tier research chemical with anecdote and a vendor list.
"The SCALP-1 and SCALP-2 trials demonstrated 539% and 168% greater target area hair count improvements with clascoterone 5% solution versus vehicle at 6 months." — Dermatology Times (2025)
Where it really shines is on cycle. On 19-nor or non-aromatizing AAS — nandrolone, trenbolone, mesterolone — scalp damage isn't driven primarily by DHT, so finasteride/dutasteride do little to protect the hairline. AR blockade at the follicle is the only level where the signal can be intercepted, and clascoterone is now the most rigorously studied option for doing exactly that.
The sections below cover the mechanism in detail, the 5% solution scalp protocol (and how it diverges from off-label Winlevi use), pharmacokinetics and why systemic exposure stays negligible, stacking with minoxidil, RU58841, and microneedling, the side-effect profile, sourcing routes while Breezula remains pre-approval, and the most common mistakes documented in community practice.
How Clascoterone works
Local AR Antagonism Without the Systemic Hit#
Clascoterone is a topical androgen receptor antagonist — structurally a cortexolone 17α-propionate ester that binds the AR in scalp dermal papilla cells and sebocytes and competitively blocks dihydrotestosterone (DHT) from activating it. Affinity at the AR is comparable to DHT itself, but instead of triggering the downstream transcription program that drives follicular miniaturization and sebum output, clascoterone occupies the receptor and shuts the signal off.
This is the mechanistic line that separates it from finasteride and dutasteride. The 5-AR inhibitors work upstream — they reduce conversion of testosterone to DHT systemically, which lowers serum DHT 60–90% and is the source of the libido, mood, and post-finasteride syndrome reports. Clascoterone leaves the entire 5-AR axis intact and intervenes at the receptor level, in the tissue, where the hair actually lives.
"Clascoterone binds the AR and blocks dihydrotestosterone-induced gene activation, leading to a reduction in sebum production and inflammatory cytokines in sebocytes." — Rosette C et al., J Drugs Dermatol, 2019
The "Self-Destruct" Metabolism#
The reason topical clascoterone does not behave like topical RU58841 with respect to systemic exposure is that the molecule is engineered to fall apart the moment it leaves skin. Plasma and tissue esterases hydrolyze the 17α-propionate ester into cortexolone (11-deoxycortisol), which is inactive at the AR. The drug exists as an AR antagonist locally in the scalp; anything absorbed into circulation is degraded within hours.
"After topical administration, plasma concentrations of clascoterone remained low and rapidly declined, reflecting a short elimination half-life and supporting minimal systemic exposure." — Mazzetti A et al., J Drugs Dermatol, 2019
Plasma half-life sits around 3–4 hours after topical absorption. Steady-state plasma concentrations in the maximal-use PK study (1% cream BID over acne-affected face/back/chest) stayed in the low ng/mL range. For scalp-only application surface areas, systemic exposure is meaningfully lower — which is the entire selling point versus oral 5-AR inhibitors and versus RU58841 (where the systemic exposure profile is the unknown people argue about).
Why It Matters on an AAS Cycle#
On a test-only cycle, finasteride or dutasteride blunts scalp DHT and protects the hairline reasonably well. On a 19-nor or non-DHT-substrate cycle, 5-AR inhibition does nothing — nandrolone, trenbolone, and oxandrolone are not 5-AR substrates the way testosterone is, so blocking 5-AR doesn't reduce the AR activation those compounds drive in scalp tissue. The only level at which their hair signal can be intercepted is at the receptor itself.
This is where a topical AR antagonist becomes the structurally correct choice. Clascoterone (or RU58841, or pyrilutamide) sits on the AR in the dermal papilla and competitively excludes whatever androgen is binding — DHT, testosterone, nandrolone, trenbolone, MENT — without touching the systemic hormone profile that the lifter is paying for.
| Mechanism | Oral Finasteride/Dutasteride | Topical Clascoterone | Topical RU58841 |
|---|---|---|---|
| Site of action | Systemic 5-AR enzyme | Scalp AR | Scalp AR |
| Blocks non-DHT AAS at follicle? | No | Yes | Yes |
| Serum DHT impact | -60–90% | Negligible | Negligible |
| Sexual / mood side effect risk | Documented | Not observed in trials | Anecdotal |
| Phase 3 data behind it | Yes (for AGA) | Yes (2025 SCALP-1/2) | No |
Dermal Papilla and Sebocyte Signaling#
In dermal papilla cells, AR activation by DHT drives the transcription of TGF-β, DKK-1, and IL-6 — paracrine factors that shorten anagen, drive surrounding follicles into telogen, and produce the progressive miniaturization that defines AGA. Clascoterone occupies the AR in those cells, the transcription program does not fire, and the follicle is allowed to remain in anagen at a normal terminal diameter.
In sebocytes, the same AR-blockade mechanism cuts lipogenesis and inflammatory cytokine output (IL-1β, IL-6, IL-8). That is the basis of the Winlevi acne indication and the reason the 1% cream stacks well with topical retinoids for users dealing with gear acne on shoulders and back.
Clinical Confirmation of the Mechanism#
The mechanism translated cleanly into endpoints across both indications. In acne, phase 3 trials demonstrated significant reductions in inflammatory and non-inflammatory lesion counts versus vehicle at 12 weeks, with tolerability comparable to vehicle:
"Clascoterone cream, 1%, applied twice daily, demonstrated a significant reduction in inflammatory and noninflammatory lesion counts compared to vehicle, with a comparable safety profile." — Hebert A et al., JAMA Dermatology, 2020
In AGA, the phase II read-out validated that the AR-blockade story required a higher concentration to reach dermal papilla cells than to reach sebocytes:
"Phase II data in men showed clascoterone 7.5% solution BID resulted in statistically significant improvement in target area hair count, while 5% BID reached significance in women under 30." — Dominguez-Santas M et al., JEADV Clinical Practice, 2022
The 2025 phase 3 SCALP-1 and SCALP-2 trials then settled on the 5% solution BID as the registration dose in men, with topline results reporting target-area hair count improvements of 539% and 168% versus vehicle at 6 months:
"The SCALP-1 and SCALP-2 trials demonstrated 539% and 168% greater target area hair count improvements with clascoterone 5% solution versus vehicle at 6 months." — Cosmo Pharmaceuticals topline, Dermatology Times, 2025
The Practical Translation#
The mechanism dictates the protocol. Because the molecule acts locally and is destroyed peripherally, clascoterone is applied continuously — 1 mL of 5% solution BID for the scalp, or 1% cream BID for acne — with no PCT, no holiday cycling, and no HPG suppression to monitor. Because dermal papilla cells turn over slowly and the AGA response curve is driven by re-entry into anagen, visible response takes 4–6 months and full effect closer to 12. And because the AR signal returns the moment receptor occupancy ends, gains reverse on discontinuation, just as with finasteride and minoxidil — this is a long-term commitment, not a course of treatment.
Protocol
| Level | Dose | Frequency | Notes |
|---|---|---|---|
| Low | 25–50 mg | Twice daily | Documented entry-level range |
| Mid | 50–100 mg | Twice daily | Most commonly studied range |
| High | 100–150 mg | Twice daily | Scalp AGA protocols apply ~1 mL of 5% solution BID (≈50 mg per application, 100 mg/day total). Acne use is 1% cream BID to affected areas. Continuous dosing — AGA gains reverse on discontinuation. |
Cycle length & outcomes
Documented cycle
24–104 weeks
Plateau after
52 wks
Cycle Notes#
Clascoterone is not a "cycle" in the AAS sense — it's a chronic topical with a response curve measured in months, not weeks. The follicle takes 12–16 weeks to show objective response, the SCALP-1/SCALP-2 phase 3 program measured primary endpoints at 6 months, and gains reverse on discontinuation the same way they do with finasteride and minoxidil. The framing is "permanent residency in the hair-retention stack," not "8-week blast."
There is no loading phase, no taper, and no PCT — absorption is minimal and the parent compound is hydrolyzed peripherally to AR-inactive cortexolone, so the HPG axis is untouched at scalp doses.
| Goal | Concentration | Daily Application | Minimum Commitment |
|---|---|---|---|
| Off-label scalp monotherapy (AGA, no fin) | 5% hydroalcoholic solution | 1 mL BID (~100 mg/day) | 6–12 months, then continuous |
| AAS hair-retention adjunct | 5% solution + minoxidil ± RU58841 | 1 mL BID | Duration of cycle + indefinite |
| Female AGA (<30 phenotype) | 5% solution | 1 mL BID | 6–12 months, then continuous |
| Gear acne (back/chest/shoulders) | 1% cream (Winlevi) | Thin layer BID | 12 weeks → reassess |
| Aggressive responder protocol | 7.5% solution | 1 mL BID | 6–12 months, then continuous |
| Underdose / "available now" route | 1% cream off-label on scalp | 1–2 g/day split BID | 6+ months (expect weaker signal) |
Onset timing. Expect nothing visible at week 4. Shed normalization and reduced miniaturization show up around weeks 8–12. Objective target-area hair count improvement is a month 4–6 event in the phase 3 data:
"The SCALP-1 and SCALP-2 trials demonstrated 539% and 168% greater target area hair count improvements with clascoterone 5% solution versus vehicle at 6 months." — Cosmo Pharmaceuticals topline, Dermatology Times (2025)
The most common reason users abandon clascoterone is quitting at the 4–6 month mark when the curve is about to turn. Standardized monthly photos (same lighting, same angle, same hair length) are the only honest assessment.
Loading. None. The 5% solution is run at full concentration from day one. Some users with sensitive scalps front-load with one application per day for the first 7–10 days to let the ethanol/PG vehicle acclimate the skin, then move to BID. This is a tolerability accommodation, not a pharmacology one.
Tapering. None on discontinuation either — but gains regress. The follicle reverts to its DHT-driven miniaturization trajectory once AR blockade is removed, typically over 3–6 months. This is identical to the finasteride and minoxidil exit curve. Plan to run it indefinitely, or don't start.
Concurrent AAS cycles. This is where clascoterone earns its slot in the stack. On 19-nor and non-DHT-derivative compounds (nandrolone, trenbolone), oral 5-AR inhibitors are mechanistically useless for the scalp because these compounds aren't 5-AR substrates the way testosterone is. Topical AR blockade at the follicle is the only level where the signal can be intercepted. Initiate the 5% solution at least 8 weeks before a hair-aggressive cycle, so the protective effect is established before the AR signal surges.
"Clascoterone binds the AR and blocks dihydrotestosterone-induced gene activation, leading to a reduction in sebum production and inflammatory cytokines in sebocytes." — Rosette et al., J Drugs Dermatol (2019)
On-cycle bloodwork. Not required for scalp use. The one edge case is users running >5 mL/day of 7.5% solution chronically (i.e. approaching the surface area of the maximal-use cream PK study) — a single AM cortisol check at the 8–12 week mark is reasonable, since transient HPA-axis suppression has been observed at large-surface-area dosing:
"After topical administration, plasma concentrations of clascoterone remained low and rapidly declined, reflecting a short elimination half-life and supporting minimal systemic exposure." — Mazzetti et al., J Drugs Dermatol (2019)
At standard 1 mL BID scalp dosing, this is clinically silent.
Microneedling night. Skip the evening application on microneedling days. Driving a hydroalcoholic solution through fresh 1.5 mm puncture channels has unknown systemic kinetics and burns. Resume the next morning.
Stack timing within the day. When co-applied with topical minoxidil, separate by ≥30 minutes — apply clascoterone first to dry scalp, let it absorb, then minoxidil. When stacked with RU58841 or pyrilutamide, alternate AM/PM (e.g. clascoterone AM, RU PM) rather than layering all three at once, which raises irritation without improving AR coverage.
Acne protocol exits. The 1% cream for gear acne is the one use case where a defined endpoint exists: 12 weeks BID to affected areas, reassess, continue if responding. Stackable with adapalene and benzoyl peroxide. Unlike isotretinoin, there's no cumulative dose target and no washout — discontinue when the acne clears, restart on the next cycle if it returns.
Risks & mistakes
Common (most users)#
- Scalp dryness, flaking, or mild erythema — almost always the hydroalcoholic vehicle (70:30 ethanol/PG), not the molecule itself. Mitigation: drop to once-daily for 1–2 weeks while the barrier adapts, then reintroduce BID. A bland ceramide moisturizer on off-hours helps; avoid layering retinoids on the scalp during the adaptation window.
- Transient pruritus or stinging on application — typically resolves within 5–10 minutes. Applying to a fully dry scalp (not immediately post-shower) cuts incidence sharply.
- Folliculitis or small pustules at application sites — usually a hygiene issue, not the drug. Wash hands before application, keep the dropper tip off the scalp, and rotate the precise application points across the thinning zone.
- Mild local scaling or seborrhea-like flaking — managed with a weekly ketoconazole 2% shampoo, which slots cleanly into a hair stack anyway.
- No libido, mood, or cognitive effects at scalp doses — this is the entire point of the molecule. The plasma half-life of 3–4 hours and rapid hydrolysis to inactive cortexolone are why the systemic anti-androgen profile that plagues oral finasteride does not materialize here (Mazzetti 2019).
Uncommon (dose-dependent or individual)#
- Persistent contact dermatitis — distinguishable from vehicle irritation by failure to resolve with frequency reduction. Switch the compounding vehicle (some users tolerate a 60:40 PG/ethanol blend better than 70:30) or, if using Winlevi cream off-label on scalp, swap to a solution format.
- Increased shedding in weeks 4–10 — the standard AGA "dread shed" as miniaturized follicles cycle out and are replaced. Not a side effect in the pharmacological sense; not a reason to stop. Photographing the scalp monthly under fixed lighting prevents the panic-quit at month 3 that ends most clascoterone trials prematurely (Tressless community).
- Theoretical HPA-axis shift — the maximal-use PK study of 1% cream applied over face, chest, and back showed transient, reversible reductions in morning cortisol with compensatory ACTH changes, fully resolved after discontinuation (Mazzetti 2019). At scalp-only surface areas this signal has not been clinically meaningful, but users running >5 mL/day of a 7.5% solution sit in the same total-dose range as the PK study and should check an AM cortisol once at the 8–12 week mark.
- Possible mild hyperkalemia signal — theoretical via the cortexolone metabolite acting as a weak mineralocorticoid antagonist. Not reported above vehicle in trials. A standard CMP catches it; relevant only for users already running spironolactone or ARBs.
Rare but serious#
- Severe allergic contact dermatitis — vesicular, weeping, or spreading beyond application sites. Stop the compound, treat with a short course of topical steroid, and do not rechallenge with the same vehicle.
- Symptomatic adrenal insufficiency — fatigue, nausea, postural lightheadedness, hyponatremia after months of high-surface-area dosing. Not documented in scalp-only protocols but mechanistically plausible at extreme off-label total daily doses. AM cortisol and ACTH confirm; discontinue and the axis recovers within ~4 weeks per the published PK data (Mazzetti 2019).
- Pediatric / adolescent hormonal-maturation concerns — the basis of the EMA CHMP negative opinion for Winlevi in minors. Not relevant to adult physique-focused users but the reason the European label is more restrictive than the FDA label.
Hard contraindications#
- Pregnancy, or any realistic possibility of pregnancy. Topical anti-androgens carry theoretical risk to male fetal genital development. This line does not get crossed.
- Application to broken, abraded, sunburned, or actively microneedled skin. Systemic kinetics through a breached barrier are not characterized. Skip clascoterone the night of microneedling and resume the following day.
- Same-session co-application with high-irritation vehicles (e.g. tretinoin solution on the scalp, fresh minoxidil application on wet scalp). Separate by at least 30 minutes.
- Known hypersensitivity to the 17α-propionate ester or to the ethanol/propylene glycol vehicle.
Gender, fertility, and PCT considerations#
Clascoterone is one of the few hair compounds that is genuinely safe across both sexes at scalp doses. Phase II AGA data showed the strongest female response in the <30 cohort at 5% solution BID (Dominguez-Santas 2022), and the negligible systemic absorption means it does not interfere with menstrual cycles, ovulation, or libido the way oral spironolactone can.
For male users planning near-term conception, this is the principal advantage over oral finasteride or dutasteride — semen quality and sperm count are not on the table, because there is no meaningful 5-AR inhibition and no systemic AR antagonism. The molecule is engineered to disintegrate the moment it leaves skin.
PCT: none required. Clascoterone does not suppress the HPG axis, does not require holiday cycling, and slots into any AAS protocol without ancillary support. The cost of admission is that gains reverse on discontinuation — like every AGA therapy, this is a permanent topical, not a course of treatment.
Stack & combine
Multipliers applied when these compounds run together. Values > 1 indicate a bonus on that axis. Tap a partner to expand the mechanism.
| Partner | Type | Lean | Fat loss | Recovery |
|---|---|---|---|---|
| synergistic | ×1.00 | ×1.00 | ×1.00 |
FAQ — Clascoterone
Research & citations
5 studies cited on this page.
Conclusion
Clascoterone (CB-03-01) is the leading topical androgen receptor antagonist with strong phase 3 data for androgenetic alopecia — a legit option for hair retention, especially when systemic 5-AR inhibitors are off the table or AAS cycles are in play.
Key takeaways:
- Gold-standard AGA protocol: 5% hydroalcoholic solution, ~1 mL BID to thinning scalp regions (≈100 mg/day total)
- Results require patience — 4–6 months until objective changes, continuous dosing to maintain gains
- Stacks rationally with topical/oral minoxidil and weekly microneedling; typical to combine with RU58841 or pyrilutamide on AAS
- Local skin effects (irritation, dryness) are the main risk; systemic side effects are negligible at scalp doses (Mazzetti et al. 2019, Hebert et al. 2020)
- No PCT or holiday cycling required — this is a lifetime protocol, on par with minoxidil and finasteride for chronic use
- Particularly attractive in users who experienced sexual or cognitive side effects on oral finasteride, or those seeking a non-systemic AR blockade during AAS/variant cycles
For physique-focused users and looksmaxxers serious about retaining hair under high-androgen conditions, clascoterone belongs at the core of the modern scalp protocol.