Dihydrotestosterone: a rationale for its use as a non-aromatizable androgen replacement therapeutic agent

Testosterone therapy is commonly used to treat male hypogonadism, androgen deficiency of severe illness, androgen deficiency of ageing and microphallus in infancy. The effects of testosterone are mediated directly as testosterone or after conversion to either dihydrotestosterone (DHT) or oestradiol. DHT is a potent androgen and cannot be aromatized to oestrogens, therefore acting as a pure androgen. DHT has been proposed as an androgen replacement therapy, with possible advantages over testosterone in certain circumstances in the ageing population as well as in patients with gynaecomastia and microphallus. A potential advantage of DHT over testosterone as an androgen replacement therapy is the reported and seemingly paradoxically muted effects of DHT on prostate growth. The decreased effect of DHT compared with testosterone on the prostate gland of humans may be due to the decrease in intraprostatic oestradiol levels. The potential beneficial effect of less prostate growth after DHT requires substantiation and, if true, must be balanced against any negative effects that might occur on bone, lipids and sexuality when a pure androgen replaces treatment with an aromatizable androgen.