5 alpha-reductase deficiency in patients with micropenis

The enzyme 5 alpha-reductase (5 alpha R), by virtue of its peripheral 5 alpha-reduction of testosterone (T) to dihydrotestosterone (DHT), is believed to play a major role in the differentiation and the subsequent growth of the penis. However, recent studies have reported 5 alpha R deficiency (5 alpha RD) in patients with isolated micropenis and hypothesized that 5 alpha RD is not invariably associated with genital ambiguity. In Egypt, 5 alpha RD has been reported frequently among intersex patients. The aim of this study was to assess the role of 5 alpha RD in the development of micropenis among Egyptian patients with abnormal sexual development. The study included 29 patients who were categorized into three groups (isolated micropenis, 9 patients; microphallus with genital ambiguity, 11 patients; genital ambiguity with normal-sized phallus, 9 patients). Activity of 5 alpha R was assessed by estimating T/DHT ratios in the basal state in pubertal subjects and following human chorionic gonadotropin (HCG) stimulation test in prepubertals. The results showed that the incidence of 5 alpha RD was much higher in cases of ambiguous genitalia with micropenis (5 families out of 10, 50%) than in those with isolated microphallus (1/9, 11.1%) or those with ambiguous genitalia and normal-sized phallus (1/8, 12.5%). In conclusion, the study showed that isolated micropenis is a heterogeneous disorder and that 5 alpha RD, despite its relative prevalence in Egypt, has a minimal role in the aetiology. On the other hand, 5 alpha RD seems to correlate with penile length in intersex cases.