5α-Reductase
The enzyme that converts testosterone to DHT. Two isoforms, three target tissues, and the pharmacological target of finasteride and dutasteride.
5α-reductase is a microsomal enzyme that catalyses the irreversible reduction of testosterone to dihydrotestosterone (DHT) by adding two hydrogen atoms across the 4,5-double bond of the A-ring. The conversion produces a more potent androgen — DHT binds the androgen receptor with approximately 3× the affinity of testosterone and dissociates more slowly, sustaining transcriptional activation longer per binding event.
Two isoforms with distinct tissue distributions:
– Type I (SRD5A1): expressed in skin (including scalp follicles), liver, and brain. Encoded on chromosome 5.
– Type II (SRD5A2): expressed in prostate, scalp, seminal vesicles, epididymis, and reproductive tract. The dominant isoform driving scalp DHT conversion. Encoded on chromosome 2.
The distinction matters pharmacologically. Finasteride is a Type II selective inhibitor — reduces serum DHT by ~70%, scalp DHT by ~60–70%. Dutasteride inhibits both isoforms — reduces serum DHT by ~95%, scalp DHT by ~90%. Olsen et al. 2006, J Am Acad Dermatol documented head-to-head superiority of dutasteride 0.5 mg/day over finasteride 1 mg/day for vertex hair count change at 24 weeks.
Clinical implication for AAS protocols:
Compounds that ARE 5α-reduced derivatives (stanozolol, oxandrolone, drostanolone, methenolone) bypass the enzyme entirely — they bind scalp and prostate androgen receptors directly without requiring conversion. Finasteride and dutasteride are pharmacologically irrelevant for these compounds and do not reduce scalp risk on cycles containing them. The same applies to trenbolone, which is a 19-nor 5α-reduced compound that binds AR directly with approximately 5× testosterone affinity.
For testosterone-dominant cycles (high-dose testosterone with no DHT-class additions), 5α-reductase inhibition is mechanistically appropriate and reduces scalp DHT exposure proportionally.
The nandrolone exception — why finasteride is contraindicated:
Nandrolone is reduced by 5α-reductase to dihydronandrolone (DHN) — a weaker androgen than DHT. Blocking the conversion with finasteride leaves the parent nandrolone available for AR binding at scalp tissue, paradoxically worsening rather than improving the scalp risk. Toorians et al. 1996, J Clin Endocrinol Metab documented the mechanism. Avoid 5α-reductase inhibitors during nandrolone protocols.
Side-effect profile of inhibition:
Documented sexual side effects (libido reduction, erectile dysfunction, ejaculate volume reduction) occur in 2–8% of users in RCT data; higher in user-reported surveys. Mechanism includes both direct DHT-deficiency effects and disruption of the 5α-reductase pathway producing allopregnanolone — a positive GABA-A modulator with anxiolytic effects. Post-finasteride syndrome (PFS) — persistent symptoms after cessation — is documented but uncommon.