What Causes DHT (Dihydrotestosterone)?
DHT is produced by the enzymatic conversion of testosterone through the action of 5α-reductase enzymes, which exist as two isoenzymes (Type 1 and Type 2) that catalyze this irreversible reduction in various tissues throughout the body. 1
Enzymatic Conversion Process
The formation of DHT occurs through a specific biochemical pathway:
- 5α-reductase enzyme converts testosterone to DHT through an irreversible reduction reaction 1, 2
- Type 2 5α-reductase is the predominant isoenzyme in genital tissues, including the prostate, liver, and skin 1, 2
- Type 1 5α-reductase is present in most body tissues where 5α-reductase is expressed and is the dominant form in sebaceous glands 3
- DHT has a higher affinity for the androgen receptor than testosterone, making it the more potent androgenic steroid hormone 1
Tissue Distribution and Function
DHT production varies by anatomical location:
- In the prostate gland, Type 2 5α-reductase is responsible for approximately 85-90% of DHT production 4, 3
- In the liver and skin, both isoenzyme types contribute to DHT synthesis 2
- DHT forms a complex with the androgen receptor that is transported to the cell nucleus, where it initiates DNA transcription and translation 1
Clinical Relevance
Understanding DHT production is essential for several conditions:
- DHT is required for normal prostate development but can contribute to pathologic prostate growth in adults, including benign prostatic hyperplasia 1, 5
- Physiological DHT levels remain relatively constant in the prostate despite declining plasma testosterone levels with aging 4, 3
- DHT cannot be aromatized to estrogen, distinguishing it from testosterone in metabolic pathways 6
Pharmacologic Inhibition
The enzymatic pathway can be therapeutically targeted:
- Finasteride selectively inhibits Type 2 5α-reductase, reducing serum DHT by approximately 70% and prostatic DHT by 85-90% 1, 4, 3
- Dutasteride inhibits both Type 1 and Type 2 isoenzymes, achieving greater DHT suppression of approximately 94-98% 1, 7
- 5α-reductase inhibitors form stable enzyme complexes with extremely slow turnover (half-life ~30 days) 2
Important Caveats
When considering DHT physiology:
- The enzyme 5α-reductase has no affinity for the androgen receptor itself—only its product DHT binds to androgen receptors 2
- Testosterone levels typically increase by 10-20% when DHT production is inhibited, but remain within the physiologic range 2
- Individuals with genetic Type 2 5α-reductase deficiency have decreased DHT levels throughout life, small prostates, and do not develop BPH 2