Effects of tioconazole on parturition and serum levels of 17 beta-oestradiol, progesterone, LH and PRL in the rat.

Tioconazole, an imidazole antifungal agent, was administered orally at 100 mg/kg/day to pregnant rats according to two regimens; in one, treatment started on day 15 post-insemination (p.i.) and in the other it started on day 18 p.i. The first regimen caused a delay in onset of parturition and a prolongation of labour. Serum progesterone was decreased from days 17 to 21 p.i., 17 beta-oestradiol decreased on day 21 p.i., LH increased on day 17 p.i., and the normal surge of prolactin on day 21 p.i. abolished. The parturition disorders disappeared when 17 beta-oestradiol (0.125 microgram/animal/day s.c.) was given with tioconazole from day 15 p.i. In the second regimen, tioconazole treatment advanced by about 24 hours the onset of parturition and the normal fall in serum progesterone and the surge in prolactin. Serum 17 beta-oestradiol was unaffected, but LH was raised on days 19 and 20 p.i. In animals receiving progesterone (2.5 mg/animal/day, s.c.) and tioconazole from day 18 p.i. parturition was no longer advanced. In conclusion, the parturition disorders observed in rats during tioconazole treatment are associated with a modification of progesterone and 17 beta-oestradiol serum levels. These findings have questionable relevance for the human situation as the roles of these steroid hormones in parturition in women are different from those in rats.