Human Reproduction, Vol 12, 1409-1415, Copyright © 1997 by Oxford University Press
GM Butterstein, DR Mann, K Gould and VD Castracane
In castrated male rats, a single s.c. injection of danazol has been shown
to result in an inordinately prolonged inhibition of serum luteinizing
hormone (LH) and follicle stimulating hormone (FSH) concentrations. In the
present study, we have examined whether the same and similar routes of
administration suppresses ovarian function in normally cycling 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 duration of the dioestrous
interval until the next oestrous smear was followed daily and cycle lengths
were compared with vehicle-treated groups. Six normally cycling cynomolgus
monkeys were followed by daily observation and blood sampling at 2-3 day
intervals. After one normal cycle, danazol (200 mg/kg) was administered as
a single s.c. injection. Monkeys were followed until the next menses and
one cycle thereafter and blood 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 the dioestrous interval to 31.3 days (P <0.001)
and a similar prolongation was observed with this high dose when
administered i.m. (27.7 days; P <0.001). In normally cycling monkeys,
the menstrual cycle length was 30.2 days, but following a single danazol
administration, the mean duration 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 hiatus, a subsequent menstrual cycle was normal in length and
endocrine pattern. A single s.c. administration of danazol resulted in a
prolonged suppression of ovarian cyclicity in both normally cycling rats
and cynomolgus monkeys.
ARTICLES
Prolonged inhibition of normal ovarian cycles in the rat and cynomolgus monkeys following a single s.c. injection of danazol
Department of Biology, Union College, Schenectady, New York, USA.
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