Contraceptive Properties of the Anti-androgen Cyproterone Acetate

Abstract

REVERSIBLE sterility has been demonstrated using a variety of chemical compounds¹. The most popular and effective chemicals used as contraceptives in human populations have been the anti-ovulatory hormones and the spermacidal vaginal foams and jellies used by women^1,2. During the last two decades the possibility of a chemical contraceptive for males has received increasing attention¹. The inhibition of either spermatogenesis or sperm motility has been the apparent mechanism of action for most of the compounds reportedly tried in laboratory animals^1,3. The bulk of these compounds are, however, alkylating agents which effectively block spermatogenic meiosis and/or mitosis by an apparently non-specific interference with DNA replication¹. Thus they have not been used in studies with humans due to their inherent carcinogenic and mutagenic potential¹. Another group of compounds the contraceptive potentials of which have hitherto received only academic interest¹ are the anti-androgens. To be a practical contraceptive agent an anti-androgen, or any other compound, should not reduce libido or sex drive, nor should it interfere with the external sexual organs, nor should it produce irreversible effects. The synthetic steroidal anti-androgen cyproterone acetate (6-chloro-17-hydroxy-lα,2α-methyl-enepregna-4,6-diene-3,20-dione acetate) (CA) appears to possess these characteristics. CA does not inhibit the normal display of sexual behaviour, nor does it alter the histological characteristics of the glans penis^4,5. In an apparently competitive manner^6,7, however, CA is capable of blocking many of the stimulatory effects of both endogenous and exogenous androgens including the maintenance of weight and normal histology of the seminal vesicles and the ventral prostate^5,6. Furthermore, in hypophysectomized male rats CA can prevent the completion of spermatogenesis, otherwise maintained by exogenous androgen therapy⁸. These findings, which indicate that CA can have a strong inhibitory action on some of the internal accessory sex organs, and an apparent lack of effect on the penis and on sexual behaviour, led us to conjecture that this anti-androgen might serve as an effective contraceptive agent when administered to intact male rats.