What is Dihydrotestosterone (DHT)?
Dihydrotestosterone (DHT) is the most potent naturally occurring androgen in the human body, formed when the enzyme 5α-reductase converts testosterone into DHT. 1, 2
Biochemical Properties and Formation
DHT is produced through the peripheral conversion of testosterone by 5α-reductase enzymes, which exist in two isoenzyme forms (types 1 and 2). 1 DHT has a significantly higher affinity for the androgen receptor compared to testosterone, making it the more potent androgenic steroid hormone. 1
- Type 2 5α-reductase (inhibited by finasteride) reduces serum DHT by approximately 70% when blocked 1
- Type 1 and 2 5α-reductase (both inhibited by dutasteride) reduces serum DHT by approximately 95% when blocked 1
- In prostate tissue specifically, DHT reduction is approximately 80% with finasteride and 94% with dutasteride, since type 2 is far more common than type 1 in the prostate 1
DHT functions primarily as a paracrine hormone, meaning it is formed and acts locally in target tissues rather than circulating systemically. 3 Blood DHT levels are not reliable indicators of total body DHT formation, as DHT is produced and metabolized predominantly within target tissues. 3
Physiological Roles
DHT is responsible for the normal growth and development of male sex organs and maintenance of secondary sex characteristics. 2 These effects include:
- Growth and maturation of the prostate, seminal vesicles, penis, and scrotum 2
- Development of male hair distribution (facial, pubic, chest, and axillary hair) 2
- Laryngeal enlargement and vocal chord thickening 2
- Alterations in body musculature and fat distribution 2
DHT and testosterone are both necessary for normal development of secondary sex characteristics, with DHT providing an amplification mechanism for testosterone action. 4
Clinical Significance
In Benign Prostatic Hyperplasia (BPH)
DHT plays a central obligatory role in the development and progression of benign prostatic hyperplasia. 1, 4 The T/DHT-androgen receptor complex within prostate cell nuclei initiates transcription and translation, leading to normal development, growth, and hyperplasia of the prostate. 1 BPH develops due to an imbalance between cellular growth and apoptosis (cell death) favoring growth, causing increased cellular mass. 1
In Androgen Measurement
DHT measurement has limited clinical utility in most conditions. 5 The specific clinical indications for measuring serum DHT are:
- Investigation of 5α-reductase deficiency in infants with ambiguous genitalia and palpable gonads 5
- Men with delayed puberty and/or undescended testes 5
- Confirmation of active testicular tissue presence 5
In women with polycystic ovary syndrome (PCOS), DHT is one of several androgens that can be measured, though testosterone remains the primary diagnostic marker. 1
Sex Differences in DHT Metabolism
Women have a significantly higher circulating DHT-to-testosterone ratio (1:4) compared to men (1:13). 6 This paradoxical finding occurs despite men having higher expression of 5α-reductase type 2 in reproductive tissues. 7 Recent evidence suggests that gut microbiota 5α-reductase activity contributes substantially to the elevated DHT/testosterone ratio in females. 7
Metabolism and Excretion
DHT is a major active metabolite of testosterone, along with estradiol. 2 Approximately 90% of testosterone given intramuscularly is excreted in urine as glucuronic and sulfuric acid conjugates of testosterone and its metabolites, with about 6% excreted in feces. 2 3α-androstanediol glucuronide (3α-diol G) is a major metabolite of DHT and serves as the best available marker of DHT formation in target tissues such as skin. 3