Medroxyprogesterone acetate decreases the sexual activity of male cynomolgus monkeys (Macaca fascicularis): an action on the brain?

Medroxyprogesterone acetate (MPA), a synthetic progestin with androgen-depleting activity, is used to treat the deviant behavior of male sex offenders. In male cynomolgus monkeys, MPA reduces plasma testosterone (T) levels and sexual behavior, but the behavioral effects are clearly different from those of surgical castration. Because MPA is selectively taken up in unchanged form by the nuclei of neurons in the hypothalamus and preoptic area of male cynomolgus monkeys, and because it interferes with the uptake of T throughout the brain and pituitary gland, we have proposed that the behavioral effects of MPA may be mediated by brain mechanisms regulating sexual motivation that are relatively independent of circulating T levels. To test this hypothesis, eight castrated male cynomolgus monkeys bearing Silastic T implants SC were each observed during 60 min behavior tests with an ovariectomized, estrogen-treated female throughout three 4-week periods separated by 4-week periods without testing. After the first 4 weeks of testing, males received weekly IM injections of 40 mg MPA (six males) or vehicle (two males); the dose of MPA being equivalent on a body weight basis to those used clinically. Although plasma T was maintained in the upper range for intact males throughout the study, MPA treatment resulted in significantly decreased ejaculations and mounting attempts by weeks 5-6. These results demonstrated that the inhibitory effects of MPA on male behavior were independent of the reduction of plasma T levels, which points to a direct action on brain mechanisms controlling male sexual behavior.