Estradiol enhances sociosexual behavior and can have proliferative effects in ovariectomized rats

Although estradiol (E(2)) may have some beneficial effects as a treatment for menopause symptoms, E(2) also has trophic effects that can increase vulnerability to some cancers, such as breast cancer. In the present study, a model to investigate the concomitant behavioral and proliferative effects of E(2) was developed. First, the effects of different duration of chronic E(2) exposure (2 vs 6 months), or no such exposure, on proliferation (tumor incidence and weight, uterine weight) in adult, ovariectomized (OVX) rats was determined. Second, the effects of different dosages of E(2) (0.03 or 0.09 mg/kg) compared to vehicle only on sexual behavior, and measures of proliferation of adult OVX rats treated with a chemical carcinogen (DMBA; 1.25, 12.50, or 25.00 mg), or inert vehicle, were investigated. Vehicle or E(2) was administered subcutaneously (SC) to OVX rats once per week for 14 weeks. Six months of continuous E(2) exposure increased tumor incidence, tumor weight, and uterine weight, compared to 2 months of E(2) or no E(2) exposure. Rats administered DMBA had increased incidence, number, and size of tumors compared to vehicle treatment, and this effect appeared to be augmented by E(2). Compared to vehicle, E(2) increased lordosis and uterine weight. Thus, E(2) may have the unfavorable effect of increasing proliferation when administered in chronic situations. Studies investigating the action of E(2) for these effects are ongoing.