Comparison of a gonadotropin releasing-hormone antagonist plus testosterone (T) versus T alone as potential male contraceptive regimens
Date
1993-08Author
Rivier, Jean E.
Christensen, Richard B.
Bremner, William J.
Bagatell, Carrie J.
Matsumoto, Alvin M.
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Show full item recordAbstract
Efforts to develop a hormonal contraceptive regimen for men have focused
on administration of testosterone (T), alone or together with other
agents. Previous regimens have successfully induced azoospermia in only
50-70% of subjects, however. GnRH antagonists, alone or in combination
with T, have been shown to induce azoospermia in a very high percentage of
nonhuman primates. We tested the hypothesis that the addition of a GnRH
antagonist to a high-dose T regimen would lead to a higher percentage of
men developing azoospermia than would T alone. We administered the GnRH
antagonist, Nal-Glu (100 micrograms/kg.day sc), plus T enanthate, 200 mg
im weekly or placebo sc injections daily plus T enanthate, 200 mg im
weekly, to separate groups of healthy men for 16-20 weeks. Seven of 10 men
who received Nal-Glu plus T and 6 of 9 men who received T alone became
azoospermic; gonadotropin levels were suppressed and T levels were
increased similarly in both groups. There was a trend toward higher
pretreatment gonadotropin levels and lower sperm counts in men who became
azoospermic. Weight gain, development of acne, and increases in hematocrit
and hemoglobin were similar in the two groups. In the majority of the men,
sperm counts returned to the baseline levels within 4-5 months after
treatment ended. We conclude that with the dosages of Nal-Glu and T we
used in this study, the addition of GnRH antagonist to a high-dose T
regimen does not increase the ability of T to suppress spermatogenesis in
healthy men. Use of a higher dose of Nal-Glu, a lower dose of T, delaying
the start of T replacement until several weeks after Nal-Glu injections
are initiated, or prolonged hormonal administration might lead to a
combination regimen that will suppress spermatogenesis more fully than
does T alone.