scale. Testosterone enantate injections produced azoospermia in only 65% of males in
a pivotal multicentre study. Danazol (5.59), a gonadotropin inhibitor in females, is also
only partially active in males, even if it is taken together with long-acting testosterone
derivatives. Cyproterone acetate, the potent antiandrogen, likewise failed to yield reli-
able contraception. To date, no complete spermatozoan elimination has been achieved
with male contraceptive agents, although arguably a total absence of sperm is probably
not necessary for sterility.
Gossypol (5.60), a phenolic compound isolated from cottonseed oil, has direct anti-
spermatogenic activity. Gossypol does not affect endocrine function but seems to act on
the spermatid phase of spermatogenesis. In some studies it is 99% effective in reducing
sperm counts. It has been most extensively studied in China. Unfortunately, it has con-
siderable and only partly reversible side effects. The most noteworthy of these is the
production of transient paralysis. Due to its toxicity, gossypol will never succeed as a
drug molecule. Nevertheless, it may be an important “lead compound” around which to
design improved agents. Gossypol does have interesting structural chemistry, existing
as two different optical isomers. Despite the fact that the (+) and (−) enantiomers have
HORMONES AND THEIR RECEPTORS 331