Effects of pre- and post-pubertal dihydrotestosterone treatment on penile length in 5α-reductase type 2 deficiency.

Steroid 5 alpha-reductase type 2 deficiency (5 alpha RD2) is a congenital disorder of sex development caused by impairment of conversion from testosterone (T) to 5 alpha-dihydrotestosterone (DHT). DHT deficiency leads to various degrees of undervirilized external genitalia including micropenis, primarily correlated with mutations of the SRD5A2 gene that encodes 5 alpha-reductase type 2. Four Japanese boys with isolated micropenis were diagnosed as 5 alpha RD2 by elevated ratios of serum T/DHT, and decreased ratios of urinary 5 alpha/5 beta-reduced steroid metabolites. Genetic analyses for SRD5A2 identified that the four patients shared a hypomorphic mutation 12.227Q that has a residual activity related to the mild-form of 5 alpha RD2. For prepubertal micropenis, DHT was transdennally applied to the four patients at the ages of 4-11 year, increasing a median of stretched penile lengths (SPLs) from 2.6 cm (-2.5 SD) to 4.4 cm (-0.2 SD). Nevertheless. the post-pubertal penile growth was apparently retarded, despite normal levels of T secreted from well-developed testes. The second course of DHT treatment underwent at ages of 12-18 year, but unable to normalize SPLs at a range of 6.0 to 7.0 cm to 2.4 SD). The prostate volumes of two patients were variable at 8.1 and 21 cm(3), and a sperm cell count of one patient was normal as young adult. DHT treatment contributes to development of the penis and prostate, which are favorable for the potential fertility of 5 alpha RD2 adults. Meanwhile, the retarded penile growth and a risk of prostate overgrowth may complicate the post-pubertal management with DHT for 5 alpha RD2 males.