Hormone therapy effects on social behavior and activity levels of surgically postmenopausal cynomolgus monkeys

The purpose of the experiments reported here was to investigate central nervous system effects of commonly prescribed postmenopausal hormone therapies in a primate model, the cynomolgus monkey (Macaca fascicularis). The results of two experiments are reported. In the first, ovariectomized adult cynomolgus monkeys were treated for eight weeks each with oral micronized 17beta-estradiol (E2) (n=23), E2+medroxyprogesterone acetate (MPA) (n=23), E2+progesterone (P4) (n=23), and placebo (n=23) using a crossover design. In the second, ovariectomized adult cynomolgus monkeys were treated for eight weeks with oral micronized E2+oral micronized P4 (n=10), or E2+intravaginal micronized P4 delivered via a Silastic ring (n=8), or oral placebo and intravaginal placebo (n=5), using a parallel arm design. Behavior was recorded during weeks two through four. Cerebrospinal fluid (CSF) and blood were sampled, and 24h heart rate recorded by telemetry during weeks five through seven. Monoaminergic metabolites were assayed in CSF, and cortisol was assayed in serum. There were no significant effects of treatment on CSF monoaminergic metabolites or heart rate. E2+MPA increased cortisol concentrations. While there were some differences in effects between experiments, both progestogens and both routes of administration increased time spent resting, particularly resting in body contact, resulting in increased passive affiliative interaction. Thus, synthetic progestogens appear to be as sedating as progesterone, and the ring delivery system does not appear to protect the central nervous system from effects of progestogens. Further research is needed to explore social context as an important feature of behavioral response to steroid hormone regimens and to verify and extend knowledge of systemic effects of vaginal ring-delivered progestogens.