Effects of the opioid analgesic oxymorphone hydrochloride on reproductive function in male and female rats.
BACKGROUND
Endogenous opioids seem to regulate hypothalamic gonadotropin release in both males and females, as evidenced by the effects of opioid agonists and antagonists on LHRH release and reproductive hormone levels. The effects of long-term oral administration of opioid analgesics on reproductive function have not been well characterized.


METHODS
The reproductive effects of oxymorphone, a potent opioid agonist, were investigated in male and female Crl:CD(SD) IGS BR rats at oral doses of 0, 5, 10, and 25 mg/kg/day (25 animals/sex/group). Males were treated for approximately 9 weeks (mated after 4 weeks of dosing). Females were treated for 14 days before mating, and through Gestation Day (GD) 7. Estrous cycling was evaluated during the premating period. On GD15, pregnancy status and the numbers of corpora lutea, implantation sites, live and dead embryos were determined. Epididymal and testicular sperm counts and epididymal sperm motility and morphology were evaluated in males.


RESULTS
Two males given 25 mg/kg/day died. Behavioral changes and deficits in body weight gain occurred at all doses. There were no effects of oxymorphone on reproductive function or sperm parameters in males. The estrous cycle was prolonged in females given 25 mg/kg/day (mean of 5.3 vs. 4.3 days in controls). A small, but consistent decrease in the numbers of corpora lutea (with associated decreases in implantation sites and embryos) occurred in females given > or =10 mg/kg/day. There were no effects on mating or fertility in females.


CONCLUSIONS
Oxymorphone seems to partially inhibit ovulation in female rats, with no significant effects on male reproductive outcome.
Shuey
Dana L
DL
Endo Pharmaceuticals, Chadds Ford, Pennsylvania, USA. shuey.dana@endo.com
Stump
Donald G
DG
Carliss
Richard D
RD
Gerson
Ronald J
RJ
D000284:Administration, Oral; D000701:Analgesics, Opioid / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005298:Fertility / Q000187:drug effects; D008297:Male; D018811:Maternal Exposure; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D010060:Ovulation / Q000187:drug effects; D010111:Oxymorphone / Q000633:toxicity*; D018812:Paternal Exposure; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects*
D000701:Analgesics, Opioid; D010111:Oxymorphone