Antifungal “Azole” Class

Azole antifungals (the “-azole” drugs like fluconazole, clotrimazole, miconazole, ketoconazole, etc.) treat fungal overgrowth by blocking the fungus’s ability to build a healthy cell membrane. They do this by inhibiting lanosterol 14α-demethylase (CYP51), a fungal cytochrome P450 enzyme needed to make ergosterol (a core fungal membrane sterol). When ergosterol production is disrupted, toxic sterol intermediates build up and the fungus can’t grow normally.

Why they get discussed as “anti-androgenic”: azoles bind to cytochrome P450 enzymes, and some of them can also inhibit human steroidogenic enzymes (at least in certain contexts), which can suppress androgen production. Ketoconazole is the clearest example—medical literature describes it as inhibiting multiple steroidogenesis enzymes (including CYP17A1) and reducing adrenal/gonadal steroid output, which is why it’s historically been used as an androgen-synthesis inhibitor in endocrine/oncology contexts (1) Other azoles are generally much weaker in this regard (e.g., fluconazole has been reported to have little effect on testosterone biosynthesis at typical exposures), though lab studies show endocrine pathway inhibition can occur in vitro, and clotrimazole has been shown to inhibit steroidogenic enzymes like CYP17A1 in experimental systems (1). For a PFS/PSSD/PAS audience, the clean takeaway is: not all azoles are equal, topical exposure is usually lower than systemic exposure, but because some azoles can touch steroid/androgen pathways (at least theoretically), a subset of sensitive people report flares and choose to avoid them.

(1) https://pmc.ncbi.nlm.nih.gov/articles/PMC3644858/

Crash Anecdotes:

https://www.reddit.com/r/PSSD/comments/120ho4h/warning_about_anti_fungal_ointments/

https://www.reddit.com/r/PSSD/comments/uobqmj/fluconazole_antifungal/

My Personal Risk Ranking:

Moderate Risk of Permanent Worsening (for PFS/PSSD/PAS):
If you currently have PFS/PSSD/PAS, these substances may carry an moderate risk of worsening symptoms—potentially in a lasting way—and is best avoided.