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Premenstrual Syndrome and Progesterone Suppositories-Reply

Ellen Freeman, PhD; Karl Rickels, MD; Steven J. Sondheimer, MD; Marcia Polansky, ScD
JAMA. 1991;265(1):26. doi:10.1001/jama.1991.03460010026012.
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In Reply.—  Dr Mackenzie and Ms Holton, regrettably, have not provided placebo-controlled data to support their statements about progesterone dosage. Our progesterone dose was equal to or higher than that in other controlled studies. We found that symptoms decreased for both progesterone and placebo when the number of suppositories was increased. We therefore would predict that higher dosages may lead to more significant findings in favor of placebo, the opposite of Mackenzie and Holton's prediction.Higher progesterone doses do not seem to be warranted on the basis of our placebo-controlled studies of plasma progesterone levels. To determine whether progesterone was absorbed, we measured plasma progesterone levels before and after administration of 400-mg suppositories. Our published results1 showed that the serum progesterone levels achieved were consistent with those described in other reports.2-4 Furthermore, there was a highly significant negative correlation between the duration of treatment and the increase in


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