Källén Bengt
Tornblad Institute, University of Lund, Lund, Sweden.
Basic Clin Pharmacol Toxicol. 2004 Jan;94(1):51-4. doi: 10.1111/j.1742-7843.2004.pto_940109.x.
The use of valproic acid during human pregnancy increases the risk of hypospadias in the offspring. Rats exposed in utero to valproic acid did not develop hypospadias and even had a slightly increased anogenital distance in males 3-4 days after birth. A classical antiandrogenic drug, flutamide, caused hypospadias as well as a reduction of the anogenital distance in males. At the age of 3 months, rats exposed in utero with either valproic acid or flutamide showed a reduced testicular weight and hypoplasia of tubules, which seemed not to be related to the antiandrogenic activity of flutamide as it did not correlate with the presence of hypospadias. The mechanism through which valproic acid causes hypospadias in man and affects testicular development in rat is unknown. Hypospadias caused by valproic acid in man is apparently not due to anti-androgenic properties of the drug.
人类孕期使用丙戊酸会增加后代患尿道下裂的风险。子宫内暴露于丙戊酸的大鼠并未出现尿道下裂，甚至在出生后3 - 4天雄性大鼠的肛殖距略有增加。一种经典的抗雄激素药物氟他胺，会导致雄性大鼠出现尿道下裂以及肛殖距减小。在3个月大时，子宫内暴露于丙戊酸或氟他胺的大鼠睾丸重量减轻，曲细精管发育不全，这似乎与氟他胺的抗雄激素活性无关，因为它与尿道下裂的存在并无关联。丙戊酸导致人类尿道下裂以及影响大鼠睾丸发育的机制尚不清楚。丙戊酸在人类中引起的尿道下裂显然并非由于该药物的抗雄激素特性。
