Which enzyme primarily converts testosterone to dihydrotestosterone (DHT) in benign prostatic hyperplasia: aromatase or 5‑alpha‑reductase?

5-Alpha-Reductase is the Enzyme Responsible for Converting Testosterone to DHT in Benign Prostatic Hyperplasia

5-alpha-reductase (5-AR) is the enzyme that converts testosterone to dihydrotestosterone (DHT), the primary androgen driving prostatic growth in benign prostatic hyperplasia. 1

Enzymatic Mechanism

• 5-alpha-reductase catalyzes the reduction of testosterone into DHT, which has a higher affinity for the androgen receptor and is the more potent androgenic steroid hormone responsible for prostate development, growth, and hyperplasia. 1

• The testosterone/DHT-androgen receptor complex transports to the nucleus of prostate cells, initiating DNA transcription and translation that leads to prostatic cellular proliferation. 1

• DHT is primarily responsible for prostate development and the pathogenesis of BPH, not testosterone itself. 2

Two Isoenzyme Forms

• 5-alpha-reductase exists as two distinct isoenzymes: type 1 and type 2, both of which are expressed in prostatic tissue. 1, 3

• Type 2 isoenzyme is expressed predominantly in the prostate and is the primary target of finasteride, while type 1 is expressed more in liver and skin. 2, 4

• Immunohistochemical studies show type 1 isoenzyme is expressed predominantly in epithelial cells, whereas type 2 is expressed in both stromal and epithelial cells of the prostate. 3

• Real-time RT-PCR demonstrates that type 1 isoenzyme mRNA copy numbers are significantly higher than type 2 in BPH tissue, suggesting both isoenzymes play significant roles in maintaining prostate enlargement. 3

Clinical Relevance to BPH Treatment

• 5-alpha-reductase inhibitors (5-ARIs) such as finasteride and dutasteride are effective treatments for BPH because they block the conversion of testosterone to DHT, reducing prostatic size by 20-30% through induction of apoptosis and ductal atrophy. 1, 2

• Finasteride inhibits only the type 2 isoenzyme, while dutasteride inhibits both type 1 and type 2 isoenzymes, achieving more complete DHT suppression. 1, 5

• 5-ARIs are appropriate treatments only for patients with demonstrable prostatic enlargement (prostate volume >30cc or PSA >1.5 ng/mL), as they are ineffective in men without enlarged prostates. 1, 6

Why Aromatase is Not the Answer

• Aromatase converts testosterone to estradiol (an estrogen), not to DHT, and therefore plays no role in the androgenic stimulation of prostatic growth in BPH. 7

• The question specifically asks about the conversion to DHT, which is exclusively mediated by 5-alpha-reductase, not aromatase.