Can I use clascoterone if I'm undergoing gender-affirming hormone therapy?

Clascoterone is a topical medication approved by the FDA in 2020 for treating acne vulgaris in patients 12 years of age and older. Its mechanism of action is based on locally blocking androgen receptors in the skin. This has sparked growing interest in its potential use by transmasculine, non-binary, or gender-fluid individuals undergoing gender-affirming hormone therapy with testosterone who are experiencing side effects such as severe acne. But what do the label and the published trials actually say about using clascoterone during hormone therapy? No trial has studied this population, so the honest answer is a partial one.

What clascoterone does (and what it doesn't do)

Unlike medications such as spironolactone or systemic anti-androgens, clascoterone is applied to the skin and acts mainly where it is applied. Systemic exposure is low but not zero: the FDA label reports that after two weeks of twice-daily application of roughly 6 grams per dose in adults with moderate to severe acne, mean peak plasma clascoterone was 4.5 ng/mL. The label does not describe clascoterone as lowering blood testosterone, and there is no published evidence that it reduces the systemic effects sought on testosterone therapy, such as voice deepening, increased muscle mass, or body hair growth.

The label does, however, list two systemic findings. Hypothalamic-pituitary-adrenal (HPA) axis suppression "may occur during or after treatment", and elevated potassium was seen in some subjects in the trials. So "no systemic effect at all" overstates what is known. Because clascoterone is a relatively new drug, there are no studies specifically involving transgender populations.

Clascoterone during testosterone therapy: interference or relief?

Acne is a common side effect in people starting testosterone therapy. This happens because the sebaceous glands, responsible for producing oil in the skin, respond to increased androgen levels. Clascoterone, by blocking androgen receptors locally, reduces the activity of these glands in specific areas such as the face and back, where hormonal acne usually appears. But blocking these receptors in the skin does not mean stopping the effects of testosterone throughout the body.

This is the reason many transmasculine or non-binary individuals are interested in it: relieving acne without halting the changes they want. To date, no published study has tested whether topical clascoterone alters the systemic effects of testosterone — the absence of a finding here reflects the absence of a study, not a clean result.

What the evidence shows — and what it does not

Clascoterone has been studied in adolescents and adults with acne vulgaris, but there are no published clinical trials in trans people undergoing testosterone treatment. What exists is pharmacokinetic and efficacy data in acne patients, from which only limited inferences can be drawn.

The efficacy evidence comes from two identically designed Phase 3 trials reported by Hebert and colleagues in JAMA Dermatology in 2020, which enrolled 1,440 subjects with facial acne vulgaris. After 12 weeks, treatment success on the Investigator's Global Assessment was reached by 18.8% and 20.9% of clascoterone-treated subjects, versus 8.7% and 6.6% on vehicle. The trials were sponsored by Cassiopea, the drug's developer.

The absorption evidence comes from the pharmacokinetic study summarised in the FDA label, in 20 adults and 22 adolescents with acne who applied the cream twice daily for two weeks. Plasma levels reached steady state by day 5. HPA-axis suppression, defined by a post-stimulation cortisol level at or below 18 mcg/dL, was recorded in 1 of 20 adults (5%) and 2 of 22 adolescents (9%) at day 14; all subjects returned to normal HPA-axis function four weeks after stopping. The label notes that large treated surface areas, prolonged use, and occlusive dressings all increase systemic absorption.

In the context of a gender-affirming transition, unwanted physical changes like severe acne can affect self-esteem and mental health. Qualitative studies have reported that trans people often face barriers in accessing appropriate dermatological treatment. A localized option like clascoterone is therefore of interest to people who want acne treated without changing their hormone regimen — but whether it is the right choice for any individual on hormone therapy is a decision for their prescriber, not something the published evidence answers.

User Experience

Clascoterone, a topical androgen-receptor inhibitor also known as Breezula (in hair-loss development) or Winlevi (approved for acne), is gaining attention among individuals undergoing gender-affirming hormone therapy (GAHT). Community discussions on Tressless reveal a growing curiosity about whether this medication can be used alongside testosterone or estrogen therapy—particularly among transmasculine and transfeminine individuals dealing with androgenic alopecia or hormonal acne. Community users note that it acts on androgen receptors in the skin and scalp rather than lowering circulating hormone levels. That is the property they say makes it appealing for people on GAHT who want to avoid systemic anti-androgens that might conflict with their hormonal regimen — it is a reason for interest, not a demonstration of safety in this group.

A user participating in a Phase 3 trial of clascoterone for scalp use described being part of a structured study, including marked scalp areas to monitor hair regrowth. That post does not say whether the user was on hormone therapy, and enrolment in a trial says nothing about safety during a transition. Another user considering joining a trial after failing with topical finasteride and experiencing side effects from oral finasteride described clascoterone as an attractive next step; the reason they gave was wanting to avoid systemic DHT suppression.

Long-term community feedback specifically from transgender individuals remains sparse. One user expressed interest in how clascoterone might fit into a broader routine that includes minoxidil, especially since they were avoiding oral finasteride and RU58841 due to side effects or hormone-related concerns. This highlights that many in the transgender community are navigating treatment with great care to balance hair preservation with gender identity goals. Although community posts rarely mention detailed endocrinological concerns, there is a consistent focus on avoiding systemic anti-androgens that might interfere with HRT. Clascoterone's low systemic absorption is what users cite in its favour here. One concern occasionally raised is about its strength compared to more potent anti-androgens, which users tend to describe as a trade-off they accept.

In summary, transgender users in the Tressless community report cautious interest in using clascoterone alongside hormone therapy, valuing its localized effect and low systemic exposure. They also say more targeted research and community data are needed.

There is no published trial of clascoterone in people on gender-affirming hormone therapy, so no claim about its safety in that group can be made from the evidence. What the label and the acne trials support is narrower: systemic exposure is low, no effect on blood testosterone has been described, and the main reported adverse effects are local skin reactions, with HPA-axis suppression and raised potassium seen in a small minority of subjects. Talk to a doctor or pharmacist before starting, stopping or combining clascoterone, particularly a provider who understands both dermatological health and the particular needs of gender-affirming hormone therapy.

References

Hebert, A., Thiboutot, D., Stein Gold, L., Cartwright, M., Gerloni, M., Fragasso, E., & Mazzetti, A. (2020). Efficacy and Safety of Topical Clascoterone Cream, 1%, for Treatment in Patients With Facial Acne: Two Phase 3 Randomized Clinical Trials. JAMA Dermatology, 156(6), 621–630. https://pubmed.ncbi.nlm.nih.gov/32320027/

Eichenfield, L., Hebert, A., Stein Gold, L., Cartwright, M., Gerloni, M., Fragasso, E., & Mazzetti, A. (2020). Open-label, long-term extension study to evaluate the safety of clascoterone (CB-03-01) cream, 1% twice daily, in patients with acne vulgaris. Journal of the American Academy of Dermatology, 83(2), 477–485. https://pubmed.ncbi.nlm.nih.gov/32348828/

U.S. Food & Drug Administration. (2020). Approval Letter for Winlevi (Clascoterone) Cream, 1%, NDA 213433. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2020/213433Orig1s000ltr.pdf

U.S. Food & Drug Administration. WINLEVI (clascoterone) cream, 1% — Prescribing Information. https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=WINLEVI

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