High Dose Androgen Therapy

We describe the clinical and biochemical features of six men with male pseudohermaphroditism due to androgen resistance. Each of the subjects had male-gender behavior but incomplete virilization. The underlying defects in androgen metabolism were defined by studies of the 5a-reductase enzyme and the androgen receptor in fibroblasts cultured from biopsies of genital skin. Four of the six have 5a-reductase deficiency, and two have defects of the androgen receptor (the Reifenstein syndrome). The responses of these men to androgen treatment were assessed by monitoring nitrogen balance, plasma luteinizing hormone (LH) values, and clinical parameters of virilization including penile growth, potency and ejaculatory volume, muscle bulk, and growth of body and facial hair. In all of the subjects with 5a-reductase deficiency and one man with the Reifenstein syndrome significant response occurred, as evidenced by nitrogen retention, lowered plasma LH levels, and improved virilization, with doses of parenteral testosterone esters that raised plasma testosterone levels above the normal male range and brought plasma dihydrotestosterone levels into the normal male range. The subject who did not respond with clinical virilization nevertheless showed nitrogen retention in response to acute testosterone Dr. Price was a Medical Research Council Training Fellow. Receivedfor publication 19 April 1984 and in revisedform 26 June 1984. administration. This patient had a profound deficiency of the androgen receptor, whereas the man with a receptor defect who did respond clinically to therapy had normal amounts of a qualitatively abnormal receptor. We conclude that high dose androgen therapy may be of benefit in improving virilization, self-image, and sexual performance in subjects with 5a-reductase deficiency who have male-gender behavior and in some subjects with defects of the androgen receptor.