Triphasic oral contraceptive treatment alters the behavior and neurobiology of female cynomolgus monkeys.

Oral contraceptives (OCs) are the most widely prescribed and effective of the reversible contraceptive methods. In addition to inhibiting ovulation, OCs alter central nervous system function in women; however, methodological problems have prevented clear human studies. Thus, in this experiment we investigated the effects of OC treatment on behavior, hypothalamic- pituitary-adrenal axis function and the central nervous system in 75 adult female cynomolgus monkeys (Macaca fascicularis) housed in social groups of four to five monkeys per pen. Monkey social groups were randomly divided into either a control or an OC treatment group which was administered a clinically prescribed OC (Triphasil(R), levonorgestrel and ethinyl estradiol tablets) for 2 years. OC treatment increased the frequency of contact aggression received, time spent in locomotion, and sitting close to another animal, and decreased time spent fearfully scanning. OC treatment decreased heart rate, increased activity levels, and increased baseline cortisol concentrations and the cortisol response to adrenocorticotropin compared to control animals. OC treatment decreased the prolactin response to fenfluramine suggesting decreased serotonergic activity. These results suggest that this triphasic OC disrupts social behavior, hypothalamic-pituitary-adrenal axis regulation and the underlying central nervous system function.