Estrogen replacement in ovariectomized rats results in physiologically significant levels of circulating progesterone, and co-administration of progesterone markedly reduces the circulating estrogen.

Estrogen and progesterone replacement in ovariectomized rats in an often-used experimental system for determination of the specific effects of these hormones. In this study, two different delivery systems and two different dosage levels of estrogen, progesterone or a combination of the two have been used. Estrogen and progesterone in the circulation have been measured in response to each treatment. It is reported that estrogen treatment (237.2 +/- 49.2 pg/mL) results in physiologically significant levels of circulating progesterone (11.1 +/- 1.3 ng/mL). Also, co-administration of progesterone (23.7 +/- 2.0 ng/mL) with estrogen decreases the level of estrogen over that seen with estrogen alone (96.7 +/- 19.2 pg/mL with progesterone vs 237.2 +/- 49.2 pg/mL without progesterone). Thus, contrary to expectations, estrogen replacement therapy is not specific to estrogen and some of the antagonistic effects of progesterone are the result of a decrease in circulating estrogen, and not a specific effect on a target tissue. Whereas the mechanism of these effects has not been determined, obvious artifactitous phenomena have been excluded as being their cause. These results could have a major impact on the interpretation of past and future experiments of this kind.