Dihydrotestosterone (DHT) (Endocrine Sciences)

The Dihydrotestosterone (DHT) (Endocrine Sciences) test assists in the differential diagnosis of disorders of sexual differentiation/development. It helps identify 5α-reductase deficiency when DHT is inappropriately low relative to testosterone and for interpretation of the testosterone:DHT ratio. The assay contributes to evaluation of benign prostatic hyperplasia, androgenetic alopecia in males and females, primary and secondary hypogonadism in men, age-related androgen deficiency presenting with low libido and erectile dysfunction, androgen insensitivity (Morris) syndrome, and hyperandrogenism in women, including hyperandrogenic dermopathy. DHT testing is also used to monitor the effectiveness of 5α-reductase inhibitor therapy in benign prostatic hyperplasia or androgenetic alopecia.

Dihydrotestosterone (DHT) is produced from testosterone by 5α-reductase. In men, circulating DHT reflects both testicular secretion and, to a greater extent, peripheral conversion of testosterone; in women, adrenal production predominates with a smaller ovarian contribution, often via androstenedione. Although present at lower circulating concentrations than testosterone, DHT binds the androgen receptor with higher affinity and mediates stronger androgenic effects. Target tissues include hair follicles, the external genitalia, and skeletal muscle. Within the prostate, DHT drives cellular proliferation more robustly than testosterone. Excess DHT, including elevations occurring during exogenous testosterone therapy, contributes to prostate enlargement, and DHT concentrations vary in parallel with prostate size during treatment with 5α-reductase inhibitors. Reduced DHT arising from diminished testosterone synthesis or impaired 5α-reductase activity results in undervirilization in boys, with sparse facial, pubic, and axillary hair, micropenis, small testes, external genital anomalies, and reduced muscle mass; with aging, it is associated with erectile dysfunction and decreased libido. Conversely, DHT excess suppresses scalp hair growth and causes alopecia in both sexes; in women, hyperandrogenic dermopathy may occur with menstrual disturbance and infertility. Two genes encode 5α-reductase isoenzymes: SRD5A1 on chromosome 5 and SRD5A2 on chromosome 2. Pathogenic SRD5A2 variants cause a 46,XY disorder of sex development—pseudovaginal perineoscrotal hypospadias—due to impaired DHT-dependent masculinization of the external genitalia.