PROLONGED INHIBITION OF NORMAL OVARIAN CYCLES IN THE RAT AND CYNOMOLGUS MONKEYS FOLLOWING A SINGLE SC INJECTION OF DANAZOL

In castrated male rats, a single s.c. injection of danazol has been sh own to result in an inordinately prolonged inhibition of serum luteini zing hormone (LH) and follicle stimulating hormone (FSH) concentration s, In the present study, we have examined whether the same and similar routes of administration suppresses ovarian function in normally cycl ing rats and cynomolgus monkeys, Normally cycling female rats received danazol as a single administration either orally, i.m. or s.c. and a separate group also received danazol in silastic capsules, The duratio n of the dioestrous interval until the next oestrous smear was followe d daily and cycle lengths were compared with vehicle-treated groups, S ix normally cycling cynomolgus monkeys were followed by daily observat ion and blood sampling at 2-3 day intervals, After one normal cycle, d anazol (200 mg/kg) was administered as a single s.c. injection, Monkey s were followed until the next menses and one cycle thereafter and blo od samples were assayed for oestradiol, progesterone and bioactive LH. Oestrous cycle length in vehicle-treated control rats was 4.7 days, A single administration of danazol s.c. at the higher dose prolonged th e dioestrous interval to 31.3 days (P <0.001) and a similar prolongati on was observed with this high dose when administered i.m. (27.7 days; P <0.001). In normally cycling monkeys, the menstrual cycle length wa s 30.2 days, but following a single danazol administration, the mean d uration to the next menses was prolonged to 117.5 days (P <0.001). In five out of six monkeys, there was a decrease in LH and an absence of normal oestradiol and progesterone patterns, After this prolonged hiat us, a subsequent menstrual cycle was normal in length and endocrine pa ttern, A single s.c. administration of danazol resulted in a prolonged suppression of ovarian cyclicity in both normally cycling rats and cy nomolgus monkeys.