The effect of 5α reductase 2 deficiency on human fertility

Males homozygous for 5a-reductase deficiency are born with ambiguous external genitalia from reduced conversion of T to dihydrotestosterone.We discuss this syndrome and its impact on human fertility.

Hey-Joo Kang, M.D., Julianne Imperato-McGinley, M.D., Yuan-Shan Zhu, M.B., Ph.D., Zev Rosenwaks, M.D.

Volume 101, Issue 2, Pages 310-316, February 2014


A most interesting and intriguing male disorder of sexual differentiation is due to 5α-reductase-2 isoenzyme deficiency. These male infants are born with ambiguous external genitalia due to a deficiency in their ability to catalyze the conversion of T to dihydrotestosterone. Dihydrotestosterone is a potent androgen responsible for differentiation of the urogenital sinus and genital tubercle into the external genitalia, urethra, and prostate. Affected males are born with a clitoral-like phallus, bifid scrotum, hypospadias, blind shallow vaginal pouch from incomplete closure of the urogenital sinus, and a rudimentary prostate. At puberty, the surge in mainly T production prompts virilization, causing most boys to choose gender reassignment to male. Fertility is a challenge for affected men for several reasons. Uncorrected cryptorchidism is associated with low sperm production, and there is evidence of defective transformation of spermatogonia into spermatocytes. The underdeveloped prostate and consequent low semen volumes affect sperm transport. In addition, semen may not liquefy due to a lack of prostate-specific antigen. In the present review, we discuss the 5α-reductase-2 deficiency syndrome and its impact on human fertility.

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