Decreased fertility in male rats administered the 5 alpha-reductase inhibitor, finasteride, is due to deficits in copulatory plug formation.
Oral administration of 80 mg/kg/day of finasteride, a potent specific inhibitor of 5 alpha-reductase, to sexually mature male Sprague-Dawley rats for 24 to 38 weeks caused an approximate 30% to 40% decrease in fertility. There were no effects on mating indices or implants per pregnant female. From the mating trials, a selected group of treated males with poor reproductive performance was compared to a selected group of control males with good reproductive performance. Observed matings showed no qualitative effects on mating behavior or ejaculation. However, finasteride-treated males did not form or formed small and improperly positioned copulatory plugs, which are required in rats to transport sperm into the uterus. Intrauterine insemination of epididymal sperm from males that were nonfertile by natural mating resulted in similar numbers of embryos and unfertilized oocytes recovered from controls and finasteride-treated males, confirming that there was no effect of finasteride on the ability of sperm to fertilize. Decreased fertility of finasteride-treated males was due to failure to form copulatory plugs and is related to decreased weight of seminal vesicles and prostate, an expected pharmacologic effect. Testes weight was unaffected. Decreased fertility in male rats after finasteride administration is considered a species specific effect. The mechanism of the decrease in rats is not likely to be relevant to species that do not form copulatory plugs.
Cukierski
M A
MA
Department of Safety Assessment, Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania 19486.
Sina
J L
JL
Prahalada
S
S
Wise
L D
LD
Antonello
J M
JM
MacDonald
J S
JS
Robertson
R T
RT
D058891:5-alpha Reductase Inhibitors; D000736:Androstenes / Q000494:pharmacology*; D000818:Animals; D001378:Azasteroids / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D003307:Copulation / Q000502:physiology*; D003864:Depression, Chemical; D004622:Embryo, Mammalian / Q000187:drug effects; D004822:Epididymis / Q000166:cytology; D004971:Estrus / Q000187:drug effects; D005260:Female; D005298:Fertility / Q000187:drug effects*; D005306:Fertilization / Q000187:drug effects; D018120:Finasteride; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012098:Reproduction / Q000187:drug effects; D012661:Semen / Q000187:drug effects*; D012726:Sexual Behavior, Animal / Q000187:drug effects; D013076:Sperm Count / Q000187:drug effects
D058891:5-alpha Reductase Inhibitors; D000736:Androstenes; D001378:Azasteroids; D018120:Finasteride