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CLINICAL EXPERIENCE WITH A NEW LONG-ACTING INJECTION OF TESTOSTERONE
UNDECANOATE
Saad, F.
Schering AG, Male Health Care, D-13342 Berlin, Germany
For more than 50 years, testosterone has been available for the effective
treatment of male hypogonadism. However, until recently,
almost all preparations were rather inconvenient.
In the 1990s, the first transdermal administration
forms came to the market. In 2000, patches were followed
by the first testosterone gel which immediately became
the most successful product in the U.S. Interestingly,
the majority of patients worldwide is still treated
with testosterone injections. This may partly be due
to affordability and partly to physicians' and patients'
preference. Therefore, a new injectable formulation
of testosterone undecanoate was investigated starting
in the second half of the 1990s. The clinical development
programme followed the classical pattern starting
with a single-dose kinetics study. The results indicated
that testosterone levels would be maintained within
the physiological range for approximately 6 weeks.
However, the second study, a multiple-dose kinetics
trial, revealed that repeated injections in 6-week
intervals led to an accumulation of testosterone levels.
The study was further extended and injection intervals
stepwise prolonged until they reached 12 weeks. Meanwhile,
some patients who were included in this trial initially
and still are under observation are approaching 7
years of treatment with the new testosterone undecanoate
injection. In a direct comparison trial between testosterone
enanthate (TE) and testosterone undecanoate, both
kinetics and efficacy parameters were assessed. It
was shown convincingly that testosterone undecanoate
administered every 9 weeks was equally effective as
testosterone enanthate given every 3 weeks. After
30 weeks, all patients were switched to testosterone
undecanoate and intervals extended to 12 weeks. Those
patients who were switched from TE stated that local
tolerance and pain at the injection site were equal
between both preparations although TE had a smaller
injection volume (1 mL vs. 4 mL). It has been reported
by the investigators that a few patients do very well
on 14-week intervals. It is well understood in endocrinology
that depot preparations must be adjusted individually.
With the experience from all clinical trials, the
recommended treatment regimen is to start with one
interval of 6 weeks to quickly achieve a steady state
and then continue with 12-week intervals.
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