Can 5-Alpha Reductase Inhibitors Transform Dermatology Treatment?

🔍 Key Finding 5-alpha reductase inhibitors (5ARIs) like finasteride and dutasteride are effective in treating androgenetic alopecia and other dermatological conditions related to hyperandrogenism, but their use may be limited by side effects, particularly in men, highlighting the need for careful consideration of individual patient characteristics and reproductive factors. Topical formulations may offer a safer alternative with comparable efficacy.

🔬 Methodology Overview

• Design: Narrative review
• Data Sources: Medline and Google Scholar
• Search Terms: “5-alpha reductase inhibitors” AND (“dermatology” OR “alopecia” OR “acne” OR “hirsutism”)
• Selection Criteria: Articles up to May 31, 2023, discussing the application of 5ARIs in dermatological conditions (androgenetic alopecia, acne, frontal fibrosing alopecia, hirsutism).
• Analysis Approach: Qualitative synthesis of findings from selected articles.
• Scope: Use of 5-alpha reductase inhibitors in dermatology, focusing on efficacy, safety, and implications for general dermatological practice.

📊 Results

• Androgenetic Alopecia (AGA) in Men: Finasteride 1mg daily demonstrated efficacy in reducing hair loss and promoting hair growth, with 58% of men showing improvement after 48 weeks in one study. Topical finasteride showed comparable efficacy to oral finasteride with a lower peak plasma concentration and less initial reduction in serum DHT.

• Androgenetic Alopecia (AGA) in Women: Results are mixed. Finasteride did not promote hair growth in normoandrogenic postmenopausal women in one study. However, other studies suggest potential benefits in normoandrogenic and hyperandrogenic women, with one retrospective cohort study showing improvement or stabilization of AGA in 68.9% of women taking finasteride 1.25mg daily for 3 years.

• Acne Vulgaris: Limited evidence suggests that 5α-reductase inhibitors (5ARIs) may be beneficial, but more research is needed. One study found no additional benefit of combining a type I 5ARI with minocycline compared to minocycline alone. Another study found finasteride 2.5mg daily more effective than montelukast 10mg daily in treating moderate acne in normoandrogenic women, with 88.6% of the finasteride group achieving near-complete clearance after 12 weeks.

• Frontal Fibrosing Alopecia (FFA): 5ARIs, particularly dutasteride, show promise. In a multicenter study, finasteride 2.5-5mg daily led to improvement in 47% and stabilization in 53% of FFA patients. Dutasteride 0.5mg weekly showed improvement in 44% and stabilization in 56% of patients. Another study found dutasteride to be the most effective systemic therapy for FFA, with an optimal dose of 5-7 capsules (0.5mg) per week.

• Hirsutism: Finasteride has shown efficacy in reducing hirsutism scores in women. Both 2.5mg and 5mg daily doses were found safe and effective in one study. A meta-analysis confirmed that finasteride, alone or with oral contraceptives, significantly improved hirsutism scores.

• Adverse Effects: 5ARIs can cause sexual, physical, and mental side effects in men, sometimes persisting after discontinuation (post-finasteride syndrome). In women, potential risks include fetal genital malformation if taken during pregnancy. Lower doses are recommended to minimize side effects.

💡 Clinical Impact 5α-reductase inhibitors (5ARIs) demonstrate efficacy in treating androgen-mediated dermatological conditions like acne, androgenetic alopecia, frontal fibrosing alopecia, and hirsutism, potentially expanding treatment options for these conditions; however, careful consideration of individual patient characteristics, reproductive factors, and potential adverse effects is necessary for safe and appropriate 5ARI use. Topical 5ARI formulations may improve patient adherence and minimize systemic side effects, warranting further investigation.

🤔 Limitations

• Poor long-term patient tolerance due to unwanted side effects with oral 5ARIs.
• Uncertain benefit of 5ARI usage in women with or without hyperandrogenism due to few studies with varying regimens and results.
• Lack of enhanced improvement observed for patients receiving combination treatment of minocycline and a type I 5ARI compared to minocycline alone for acne vulgaris.
• Limited specification of clinical or serological hyperandrogenism presence in women in studies evaluating finasteride and dutasteride for AGA.
• Lack of placebo comparison in studies of finasteride and dutasteride for AGA in women due to study methodology.
• Potential for serious adverse effects in men, including sexual, physical, and mental symptoms, which can persist after discontinuation (post-finasteride syndrome).
• Risk of male fetal genital malformation with finasteride use in women of reproductive age, pregnant women, or nursing mothers.
• Limited long-term safety data, especially regarding persistent effects in patients with epigenetic susceptibility.

✨ What It Means For You Dermatologists should consider 5-alpha reductase inhibitors (5ARIs) like finasteride and dutasteride for various hair and skin conditions, including androgenetic alopecia, acne, frontal fibrosing alopecia, and hirsutism, but should carefully weigh the benefits against potential adverse effects, especially sexual and reproductive health issues, and tailor treatment plans accordingly, potentially favoring topical formulations to minimize systemic side effects. For women, 5ARI use requires careful consideration of hormonal status, reproductive plans, and appropriate contraception due to potential risks.

Reference Escamilla-Cruz M, Magaña M, Escandón-Perez S, Bello-Chavolla OY. Use of 5-Alpha Reductase Inhibitors in Dermatology: A Narrative Review. Dermatol Ther (Heidelb). 2023;13:1721–1731. https://doi.org/10.1007/s13555-023-00974-4