In the 20 yr since it was established that impairment of dihydrotestosterone 
formation is the cause of a rare form of human intersex, a wealth of information 
has accumulated about the genetics, endocrinology, and variable phenotypic 
manifestations, culminating in the cloning of cDNAs encoding two 5 
alpha-reductase genes and documentation that mutations in the steroid 5 
alpha-reductase 2 gene are the cause of 5 alpha-reductase deficiency. Perplexing 
and difficult problems remain unresolved, e.g. whether the variability in 
manifestations is due to variable expressions of steroid 5 alpha-reductase 1 or 
to effects of testosterone itself. It is also imperative to establish whether 
defects in steroid 5 alpha-reductase 2, perhaps in the heterozygous state, are 
responsible for a portion of cases of sporadic hypospadias, to determine whether 
5 alpha-reductase plays a role in progesterone action in women, and to elucidate 
the relation between androgen action and gender role behavior.