Inhibition of Human Steroid 5β-Reductase (AKR1D1) by Finasteride and Structure of the Enzyme-Inhibitor Complex

Finasteride and dutasteride are discussed for hair loss, with concerns about their effects on neurosteroids and potential side effects like depression. Alternatives like topical estrogen and lifestyle changes are considered, with varying opinions on mental health and hair regrowth.

The conversation is about managing allopregnanolone deficiency caused by 5-alpha-reductase inhibitors like finasteride or dutasteride. Specific treatments discussed for hair loss include Minoxidil, finasteride, and RU58841.

FCE 28260 (PNU 156765), an under-explored 5α-reductase inhibitor, showcases promising results in research by Giudici et al., outperforming well-known treatments like Finasteride in reducing the conversion of testosterone to DHT. Its superior efficacy, demonstrated through lower IC50 values in both natural and human recombinant enzyme studies, suggests it could offer more effective management of DHT-related conditions. Additionally, its lower molecular weight hints at better potential for topical application, potentially offering advantages in treating conditions such as androgenic alopecia. Despite its potential, it has not advanced in development, possibly due to financial limitations, leaving its therapeutic prospects and side effect profile largely unexplored.

The conversation discusses the molecular structures of compounds that reduce DHT levels, including finasteride and Ashwagandha. It explores the potential of using Ashwagandha topically as a 5a reductase inhibitor.

A 25-year-old male experienced significant hair regrowth after one year of using 0.5mg daily finasteride, with plans to add 1.25mg oral minoxidil and microneedling for further improvement. He also uses Nizoral shampoo weekly and reports no current side effects.

Androsterone may help with sexual and affective dysfunction from finasteride by replacing disrupted neurosteroids without increasing androgenic side effects. Controlled testing is needed to confirm its effectiveness and safety.