Longitudinal clinical course in patients with 5α-reductase type 2 deficiency treated with testosterone and dihydrotestosterone during infancy and puberty

5 alpha-reductase type 2 (5 alpha RD2) deficiency is a 46,XY disorder of sex development caused by impaired conversion of testosterone (T) to dihydrotestosterone (DHT). Penile enlargement therapy is important for male patients with 46,XY 5 alpha RD2 deficiency who have undermasculinized external genitalia, such as severe micropenis. High-dose T and percutaneous DHT replacement are reportedly efficacious for penile enlargement in patients with this disorder. We presented herein the longitudinal course of four patients with 46,XY 5 alpha RD2 deficiency who received T and DHT. T replacement therapy during infancy increased the stretched penile length (SPL) in three of the patients but was ineffective in one patient. DHT was administered to the three patients after T replacement therapy and further increased the SPL. During and after puberty, two patients asked for and received T replacement therapy, which contributed to increasing their SPL. A semen test in one patient with T replacement therapy at age 27 years revealed cryptozoospermia despite normal testicular volume. The clinical course of our patients during infancy indicated that DHT therapy may be preferrable to T replacement therapy for penile enlargement in patients with 5 alpha RD2 deficiency. During and after puberty, T replacement therapy promoted penile enlargement possibly because of increased conversion of T to DHT via increased 5 alpha-reductase type 1 activity even in patients in whom it was ineffective during infancy. In conclusion, DHT is effective for penile enlargement during infancy in patients with 5 alpha RD2 deficiency while T replacement therapy is a viable option during puberty.

Automated summary

5 alpha-reductase type 2 (5 alpha RD2) deficiency is a disorder of sex development in which the conversion of testosterone to dihydrotestosterone is impaired. Penile enlargement therapy using high-dose testosterone and percutaneous dihydrotestosterone replacement is effective in patients with this disorder. However, the effectiveness of testosterone replacement therapy varies during infancy and puberty. Dihydrotestosterone therapy may be preferable to testosterone replacement therapy for penile enlargement during infancy, while testosterone replacement therapy can be an option during puberty.