Dihydrotestosterone (DHT)

5-alpha reductase (5αR) catalyses the irreversible reduction of testosterone to DHT. Two isoforms are clinically significant: type 1 predominates in skin and liver; type 2 is the primary isoform in the prostate, seminal vesicles, and hair follicles. Approximately 5-10% of daily testosterone production is converted to DHT in peripheral tissues.

DHT cannot be aromatised to oestrogen. It circulates largely bound to SHBG (approximately 70%) and albumin. Its metabolic clearance rate is lower than testosterone, contributing to its potency. DHT levels do not uniformly track testosterone; factors such as 5αR activity, genetics, and tissue-specific enzyme expression modulate the testosterone-to-DHT conversion ratio.

Finasteride and dutasteride are pharmaceutical 5αR inhibitors that reduce circulating DHT by 60-90%. They are approved for BPH and androgenetic alopecia and have also been studied in prostate cancer risk reduction.

During foetal development, DHT derived from fetal testicular testosterone (and adrenal precursors via an alternative 'backdoor' pathway) is required for virilisation of the external genitalia. Genetic 5αR2 deficiency presents as undervirilisation at birth with spontaneous virilisation at puberty — demonstrating the developmental primacy of DHT.

In adult males, DHT maintains prostate growth, scrotal development, and sebaceous gland activity. It is also the primary androgen signal driving terminal hair follicle miniaturisation in genetically susceptible individuals — the molecular basis of androgenetic alopecia.

Central nervous system: DHT acts locally in the brain and appears to have distinct neurological effects from testosterone, including influence on mood and dominance behaviours, though this remains an active area of research.

Serum DHT in adult men typically ranges from 1.03 to 2.92 nmol/L (300-850 pg/mL). Values are highly dependent on the assay methodology — mass spectrometry-based assays are preferred over immunoassays due to cross-reactivity artefacts.

DHT is not routinely measured in standard men's health panels. Clinical measurement is most relevant in cases of suspected 5αR deficiency, assessment of androgen-mediated hair loss, evaluation of BPH severity, or monitoring response to 5αR inhibitor therapy.

Elevated DHT may be observed in men with high testosterone or high peripheral 5αR activity, polycystic ovary syndrome (PCOS) in women, or adrenal androgen excess.

Benign prostatic hyperplasia (BPH): DHT is the principal androgen driving prostate enlargement. 5αR inhibitors (finasteride, dutasteride) reduce prostate volume by 20-30% and are first-line medical therapy for BPH.

Androgenetic alopecia: DHT miniaturises susceptible follicles in a genetically determined pattern. Finasteride (1 mg/day) reduces scalp DHT by approximately 60% and slows hair loss in the majority of men, with partial regrowth in many.

Post-finasteride syndrome: a subset of men report persistent sexual, neurological, and psychological symptoms after stopping 5αR inhibitors, though the mechanistic basis remains contested and under investigation.

Prostate cancer: early prostate cancer cells are typically androgen-dependent and DHT-sensitive; androgen deprivation therapy targets this axis. The role of DHT reduction in prostate cancer prevention (via 5αR inhibitors) has been studied but clinical guidelines vary.

DHT exists at the end of the androgen activation cascade: cholesterol → pregnenolone → DHEA → androstenedione → testosterone → DHT. Its plasma concentrations are approximately 10-fold lower than testosterone but its androgen receptor binding affinity and slower dissociation rate produce disproportionate biological impact in DHT-sensitive tissues.

Unlike testosterone, DHT does not convert to oestradiol and therefore cannot exert oestrogenic effects. This makes the testosterone:DHT ratio a potentially useful clinical parameter when evaluating androgenic versus oestrogenic hormonal balance, particularly in men undergoing testosterone replacement therapy.