Wise L D, Minsker D H, Cukierski M A, Clark R L, Prahalada S, Antonello J M, MacDonald J S, Robertson R T
Merck Sharp & Dohme Research Laboratories, Department of Safety Assessment, West Point, Pennsylvania 19486.
Reprod Toxicol. 1991;5(4):337-46. doi: 10.1016/0890-6238(91)90092-t.
Finasteride, a 5 alpha-reductase inhibitor, was investigated for its effects on fertility in male rats as part of its preclinical safety assessment. Studies were initiated when the male Sprague-Dawley rats were either young (4 to 6 weeks old) or mature (15 weeks old). Treatment duration ranged from 6 to 32 weeks. Each male was cohabited with two untreated females at various periods during and after treatment. Litter parameters were evaluated on either day 14 or 20 of gestation. Males were necropsied at the end of treatment or 7 to 11 weeks following the end of treatment. The major findings of these studies were that 1) young rats given 20 to 80 mg/kg/day of finasteride first showed mild to moderate decreases in fertility after 12 weeks of treatment, whereas mature males (given only 80 mg/kg/day) did not show a similar decrease until 24 weeks of treatment, 2) fewer copulatory plugs and atrophy of prostates and seminal vesicles were associated with finasteride treatment, 3) the decreased fertility was only partial (ie, fertility index did not decrease below 48% of control in any study) and was not due to decreases in mating, 4) formation of copulatory plugs, organ weights, and fertility returned to normal levels after at least 6 weeks of drug withdrawal, and 5) the testes showed no histologic or weight changes that would explain the effect on fertility. These results show that the decreased fertility in male rats was associated with finasteride-induced inhibition of accessory gland secretions, an expected pharmacologic effect.
非那雄胺是一种5α-还原酶抑制剂，作为临床前安全性评估的一部分，对其在雄性大鼠中的生育影响进行了研究。当雄性斯普拉格-道利大鼠处于幼年（4至6周龄）或成年（15周龄）时开始研究。治疗持续时间为6至32周。在治疗期间及之后的不同时间段，每只雄性大鼠与两只未经治疗的雌性大鼠同居。在妊娠第14天或20天评估窝产参数。在治疗结束时或治疗结束后7至11周对雄性大鼠进行尸检。这些研究的主要发现是：1）给予20至80mg/kg/天非那雄胺的幼年大鼠在治疗12周后首先出现轻度至中度的生育力下降，而成年雄性大鼠（仅给予80mg/kg/天）直到治疗24周才出现类似下降；2）较少的交配栓以及前列腺和精囊萎缩与非那雄胺治疗有关；3）生育力下降只是部分性的（即，在任何研究中生育指数均未降至对照组的48%以下），且不是由于交配减少所致；4）至少停药6周后，交配栓的形成、器官重量和生育力恢复到正常水平；5）睾丸未显示出可解释对生育力影响的组织学或重量变化。这些结果表明，雄性大鼠生育力下降与非那雄胺诱导的附属腺分泌抑制有关，这是一种预期的药理作用。
