Transforming Dermatology with 5-Alpha Reductase Inhibitors

[madman]

Finasteride and dutasteride, known as 5-alpha reductase inhibitors (5ARIs), are used to treat benign prostatic hyperplasia and androgenetic alopecia. These drugs block the conversion of testosterone to dihydrotestosterone, which affects the neuroendocrine system. They have potential applications in dermatology for conditions associated with hyperandrogenism. This review focuses on the use of 5ARIs in treating androgenetic alopecia, acne, frontal fibrosing alopecia, and hirsutism. It also discusses the efficacy, safety profile, and implications of adverse events. The aim is to provide insights into the use of 5ARIs in general dermatology practice.




5-alpha reductases inhibitors:

• 5-alpha reductases (5a-Rs) are enzymes that convert steroid precursors into neuroactive steroids and functional hormones
• The 5a-R family includes three main isotypes (5a-R 1, 2, and 3) involved in steroidogenesis and two trans-2,3-enoylCoA reductases (TECR and TECR-like) with unclear functions
• The substrates for 5a-R include progesterone, corticosterone, deoxycorticosterone, cortisol, and aldosterone.
• 5a-R converts testosterone to dihydrotestosterone (DHT), which has a stronger impact on androgen receptors than testosterone
• 5-alpha reductase inhibitors (5ARIs) like finasteride and dutasteride block DHT production, reducing serum and prostate DHT levels
• 5ARIs are primarily used for benign prostatic hyperplasia but have expanded applications in dermatology, including androgenetic alopecia

Safety concerns and harmful effects:

• The use of 5ARIs for androgenetic alopecia (AGA) or benign prostatic hyperplasia in men is associated with serious adverse effects
• Adverse effects include sexual, physical, and mental symptoms, leading to post-finasteride syndrome (PFS)
• Scientific evidence supports the link between 5ARI use and adverse effects, including libido loss, erectile dysfunction, depression, anxiety, and suicidal ideation
• Symptoms generally improve after discontinuation, but patients with epigenetic susceptibility may experience persistent effects regardless of age or dosage
• Finasteride and minoxidil use in alopecia treatment result in significant adverse effect reports, negatively impacting the reproductive system in both genders
• Men commonly report sexual adverse effects, while women report reproductive toxicity effects such as fetal toxicity and induced abortion
• The FDA warns about potential adverse effects of finasteride, including increased risk of high-grade prostate cancer and male fetal genital malformation in women of reproductive age, pregnant women, or nursing mothers

Key Takeaways:

• The efficacy of 5ARIs for trichological conditions has been proven in studies, but their side effects limit their use
• The Indian Association of Dermatologists, Venereologists, and Leprologists (IADVL) advises caution when prescribing 5ARIs to patients with a history of low sperm count or infertility, especially if they plan to have children
• Lower doses of 5ARIs should be prescribed to minimize side effects, with a daily dose of 0.2 mg effectively suppressing DHT effects
• The 5a-reductase type II enzyme complex takes around 30 days to regenerate, so a gradual increase in dosage is suggested
• For women with AGA, reliable contraception and a pregnancy test before starting finasteride treatment are recommended due to the potential risk of fetal malformation
• Adhering to these guidelines ensures the safe and appropriate use of 5ARIs, considering individual patient characteristics and reproductive factors

5ARIs have a significant role in managing complex conditions like acne, male- and female-pattern AGA, FFA, and hirsutism. These conditions share a common mechanism involving androgenic hormones. 5ARIs offer antiandrogenic effects and have favorable safety and efficacy profiles. Future research should explore the topical application of 5ARIs in dermatological conditions to assess adherence and adverse effects. Incorporating 5ARIs into dermatology practice can potentially enhance patient outcomes.