Acne vulgaris is a chronic condition whose pathogenesis is inextricably linked to androgenic influences on the sebaceous glands. In a recent review by J. Del Rosso et al., published in the Journal of Clinical and Aesthetic Dermatology in early 2026, the potential of topical hormonal therapy as a targeted approach to the hormonal component of the disease with minimal risk of systemic side effects was analyzed [1]. This approach is particularly relevant given that most acne patients have normal circulating hormone levels, while local androgen biosynthesis within the skin plays a key role.

Rationale and mechanisms of action

The effects of androgens in the skin are mediated through binding to androgen receptors expressed in sebocytes and keratinocytes [2]. This interaction triggers a cascade of reactions: from increased sebum production and the synthesis of proinflammatory cytokines to the modulation of keratinocyte differentiation, leading to comedogenesis. Traditional systemic agents, such as combined oral contraceptives or spironolactone, effectively block these processes. Still, their use is primarily limited to female patients due to the risk of feminizing effects in males and other systemic reactions.

Topical hormonal therapy is designed to address this issue. The core idea is to use molecules that actively interact with androgen receptors at the site of application but are rapidly metabolized upon entering the bloodstream or possess low systemic absorption. This allows the use of anti-androgens in patients of both sexes, including adolescents.

Current status: clascoterone

To date, clascoterone 1% cream is the first and only topical antiandrogen approved by the U.S. Food and Drug Administration (FDA) for the treatment of acne in patients aged 12 years or older. Its mechanism of action involves competitive binding to androgen receptors (AR), thereby inhibiting the action of dihydrotestosterone (DHT).

The drug's efficacy was confirmed in two large Phase III randomized controlled trials (RCTs) involving 1,440 patients [3]. After 12 weeks of twice-daily therapy, the clascoterone group demonstrated statistically significant superiority over the vehicle in terms of Investigator's Global Assessment (IGA) success rates and reductions in both inflammatory and noninflammatory lesion counts. Notably, the safety profile of clascoterone was comparable to the vehicle, and pharmacokinetic data confirmed minimal systemic exposure even when applied to large surface areas.

Experimental directions: spironolactone and flutamide

In addition to the approved clascoterone, other substances are being investigated. Topical spironolactone has been studied at various concentrations (1%-5%) and formulations (gels, creams, solutions). A systematic review of available data shows that in most small RCTs, topical spironolactone led to a significant reduction in the Acne Severity Index (ASI) or total lesion counts [4]. However, results remain inconsistent: some early studies did not record an effect on sebum excretion, and the lack of standardized commercial products and pharmacokinetic data limits its widespread adoption.

Another candidate is topical flutamide. In an RCT involving 54 patients, the use of 1% flutamide gel twice daily for 8 weeks resulted in a significant reduction in the number of papules and pustules compared to the vehicle [5]. Despite the absence of systemic side effects in this study, the risk of systemic absorption of flutamide via the topical route remains to be investigated in detail.

Clinical recommendations and practice

According to current guidelines from the American Academy of Dermatology, clascoterone is included in the list of recommended topical agents for acne treatment [2]. It can be used as monotherapy or as part of multimodal regimens, targeting pathogenetic mechanisms that were previously accessible only through systemic hormonal medications.

The limitations of the method primarily stem from the lack of long-term safety and efficacy data for agents such as spironolactone and flutamide. Furthermore, topical therapy requires high patient adherence, as its effects develop gradually.

Prospects

The field of topical hormonal therapy is recognized as highly promising. It allows for personalized treatment by offering hormonal intervention to male patients and women for whom systemic therapy is contraindicated. Future research will likely focus on optimizing delivery systems (e.g., using nanolipid carriers for spironolactone) and conducting large-scale RCTs to confirm the safety of new formulas. The introduction of such agents into practice could significantly alter management algorithms for patients with hormone-dependent forms of acne, making treatment safer and more targeted.

References

1. Del Rosso J.Q., Baldwin H., Layton A.M. Overview of the efficacy and safety of topical hormonal therapies for the treatment of acne vulgaris: a narrative review. J Clin Aesthet Dermatol 2026; 19(1): 34–40.
2. Reynolds R.V., Yeung H., Cheng C.E. et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol 2024; 90(5): 1006.e1–1006.e30.
3. Hebert A., Thiboutot D., Stein Gold L. et al. Efficacy and safety of topical clascoterone cream, 1%, for treatment in patients with facial acne: two Phase III randomized clinical trials. JAMA Dermatol 2020; 156(6): 621–630.
4. Rehan S.T., Khan Z., Abbas S. et al. Role of topical spironolactone in the treatment of acne: a systematic review of clinical trials — does this therapy open a path towards favorable outcomes? J Dermatol 2023; 50(2): 166–174.
5. Nassar A., Sayed A.E., Samy A. et al. Efficacy and safety of topical flutamide 1% gel as an adjunctive therapy in the treatment of patients with acne vulgaris. J Cutan Med Surg 2023; 27(5): 472–475.