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Medroxyprogesterone acetate, aggression, and sexual behavior in male cynomolgus monkeys (Macaca fascicularis)
D Zumpe1, R W Bonsall, M H Kutner
1Department of Psychiatry, Emory University School of Medicine, Atlanta, Georgia 30306.
Abstract:
Medroxyprogesterone acetate (MPA) is used clinically to treat male sex offenders, but there are conflicting reports about its effects on aggression. To investigate these matters in a nonhuman primate, four intact male cynomolgus monkeys were studied in a testing paradigm that involved the presence of a caged, aggression-arousing stimulus male either immediately before or during a pair-test with an ovariectomized, untreated female partner. After two 4-week periods of pretreatment baseline, males received weekly injections of 40 mg MPA either alone (two 4-week treatment periods) or in combination with testosterone replacement with sc implants (one period) and additional daily injections of 2 mg testosterone propionate (two periods). MPA was then withdrawn while testosterone replacement continued (three periods). The testing paradigm was effective in maintaining aggression, especially male-male aggression, for many months. Male-male aggression increased with MPA treatment, and increased further with testosterone replacement, whereas male-female aggression tended to change in the opposite direction. As in earlier studies, MPA decreased both plasma testosterone and male sexual activity, but restoring plasma testosterone levels in treated males failed to restore their sexual activity. MPA therefore has behavioral effects that are not mediated primarily by its suppression of circulating androgens.
Insights
Medroxyprogesterone acetate (MPA) increases male-male aggression in cynomolgus monkeys, even when testosterone is replaced. MPA
Area of Science:
- Primate behavior
- Endocrinology
- Neuroscience
Background:
- Medroxyprogesterone acetate (MPA) is used to treat sex offenders, but its effects on aggression are debated.
- Nonhuman primates offer a model to study hormonal influences on aggression.
Purpose of the Study:
- To investigate the effects of MPA on aggression in male cynomolgus monkeys.
- To determine if MPA's behavioral effects are mediated by testosterone suppression.
Main Methods:
- Four male cynomolgus monkeys were tested in aggression paradigms with stimulus males and female partners.
- Males received MPA injections, with and without testosterone replacement therapy.
- Aggression and sexual activity were monitored, along with plasma testosterone levels.
Main Results:
- MPA treatment increased male-male aggression, with further increases during testosterone replacement.
- Male-female aggression showed an inverse trend compared to male-male aggression.
- MPA decreased testosterone and sexual activity; restoring testosterone did not restore sexual activity.
Conclusions:
- MPA has significant effects on aggression that are not solely due to testosterone suppression.
- MPA may exert direct behavioral effects independent of androgen levels.
- Findings suggest complex neurobiological mechanisms underlying MPA's action on aggression.