Comparison of Two Methods of Estradiol Replacement: their Physiological and Behavioral Outcomes

Fluctuating sex steroids during the estrous or menstrual cycle of mammalian females make it difficult to determine their role on behaviors and physiology. To avoid this, many investigators ovariectomize their animals and administer progesterone, estradiol or a combination of both. Several different strategies are used to administer estradiol, which confounds interpretation of results. This study compared two methods of estradiol replacement implants: Silastic tubes filled with crystalline estradiol benzoate (E2) and commercially available estradiol benzoate pellets. Implants were placed subcutaneously in adult ovariectomized (OVX) rats and blood samples obtained weekly. Control OVX rats received empty Silastic tubes or placebo pellets. Our data shows that E2 plasma levels from rats with Silastic implants peaked after one week and decreased slowly thereafter. In contrast, plasma E2 from commercial pellets peaked after two weeks, increasing and decreasing over time. To validate hormone release, body weight was monitored. All E2 treated animals maintained a similar body weight over the four weeks period whereas an increase in body weight over time was observed in the OVX group that received empty implants, confirming E2 release and supporting the role of E2 in the regulation of body weight. Furthermore, the effects of E2 on basal locomotor activity were assessed using animal activity cages. Results showed no difference between E2 and control group in several locomotor activities. These results indicate that Silastic implants achieve more stable plasma estradiol levels than pellets and thus are a better alternative for studies of estradiol on brain function and behavior.