Progesterone implants extend the capacity for 4-day estrous cycles in aging C57BL/6J mice and protect against acyclicity induced by estradiol

The onset of age-related acyclicity in rodents can be accelerated or attenuated by chronic treatment with estradiol (E2) or progesterone (P4), respectively. Because of the physiological effects of exogenous E2 and P4 on age-like reproductive changes, we sought to demonstrate if P4 could antagonize the acceleration of acyclicity by E2 in C57BL/6J mice. Mice were treated for 6 or 12 wk with P4 and/or orally administered E2. Twelve but not six weeks of E2 caused permanent acyclicity, whereas P4-treated mice had more 4-day cycles than did controls in both studies. The combination of E2 and P4 also caused a striking increase in 4-day cycles after treatment even greater than that from the P4 treatment alone. Thus, P4 transiently increases cycle regularity with a greater incidence of 4-day cycles and antagonizes the premature onset of acyclicity caused by chronic E2 treatment.