Which enzyme is responsible for the conversion of testosterone to dihydrotestosterone in benign prostatic hyperplasia?

Explanation

## Role of 5-Alpha Reductase in BPH **Key Point:** 5-alpha reductase (5-AR) catalyzes the conversion of testosterone to dihydrotestosterone (DHT), the more potent androgen that drives prostatic hyperplasia. ### Enzyme Isoforms - **Type 1 5-AR:** Expressed in skin and liver; minor role in prostate - **Type 2 5-AR:** Predominant isoform in prostate; main driver of BPH - **Type 3 5-AR:** Recently identified; role still being clarified ### Biochemical Pathway ``` Testosterone --[5-α reductase]--> Dihydrotestosterone (DHT) ↓ Binds to androgen receptor ↓ Stromal cell proliferation ↓ Nodular hyperplasia of prostate ``` ### Clinical Significance - DHT is 5–10 times more potent than testosterone at the androgen receptor - DHT accumulates in prostatic tissue with age - Increased DHT sensitivity in stromal cells drives BPH - **Therapeutic target:** 5-AR inhibitors (finasteride, dutasteride) reduce DHT by 70–90% **High-Yield:** 5-AR inhibitors reduce prostate volume by ~25% over 6–12 months and improve LUTS in men with enlarged prostates. They are particularly effective in men with PSA >1.5 ng/mL and prostate volume >30 mL. **Mnemonic:** **FAST** = **F**inasteride and dutasteride block **A**ndrogen conversion via **S**teroid **T**ransformation (5-AR inhibitors). ### Drug Comparison: 5-AR Inhibitors | Drug | Type Selectivity | Onset | PSA Reduction | Prostate Shrinkage | |------|------------------|-------|---------------|-------------------| | Finasteride | Type 2 selective | 6–12 months | 50% | 20–25% | | Dutasteride | Type 1 + 2 inhibitor | 3–6 months | 50% | 25–30% | **Clinical Pearl:** 5-AR inhibitors reduce PSA by ~50%, which must be accounted for when screening for prostate cancer in treated patients (double the measured PSA for comparison to untreated baseline).