ESTROGEN REPLACEMENT IN OVARIECTOMIZED RATS RESULTS IN PHYSIOLOGICALLY SIGNIFICANT LEVELS OF CIRCULATING PROGESTERONE, AND COADMINISTRATIONOF PROGESTERONE MARKEDLY REDUCES THE CIRCULATING ESTROGEN

Estrogen or progesterone replacement in ovariectomized rats is an ofte n-used experimental system for determination of the specific effects o f these hormones. In this study, two different delivery systems and tw o different dosage levels of estrogen, progesterone or a combination o f 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). A lso, co-administration of progesterone (23.7 +/- 2.0 ng/mL) with estro gen 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 withou t progesterone). Thus, contrary to expectations, estrogen replacement therapy is not specific to estrogen and some of the antagonistic effec ts of progesterone are the result of a decrease in circulating estroge n, and not a specific effect on a target tissue. Whereas the mechanism of these effects has not been determined, obvious artifactitious phen omena have been excluded as being their cause. These results could hav e a major impact on the interpretation of past and future experiments of this kind.