Safe and Effective Method for Chronic 17β-Estradiol Administration to Mice

Supraphysiological 17β-estradiol treatment administered via subcutaneous pellets is commonly used in mice. However, despite its efficacy in eliciting a uterotrophic response, we demonstrate that this regimen also was associated with urine retention, hydronephrosis, and ultimately premature death. To determine a safer yet still effective method to chronically treat mice with 17 β-estradiol, we initiated a placebo-controlled study to treat ovariectomized C57BL/6J mice for 6 weeks with various doses of 17 β-estradiol administered either in their drinking water (0.3 to 1000 nM) or via pellets (0.72 mg or 1.7 mg). Uterine weights demonstrated a dose-dependent effect of 17β-estradiol administered either orally or via pellets; however, the pellet treatments resulted in urine retention. Treatment with either 200 or 1000 nM 17β-estradiol in the drinking water yielded physiological and supraphysiological uterotrophic responses, respectively, without urine retention, providing safe, effective, and economical ways to treat mice chronically with 17β-estradiol.