Figure 1. Recurrence of sadness in women with premenstrual syndrome during estradiol or progesterone add-back in the context of GnRH agonist-induced ovarian suppression. Ten women with premenstrual syndrome and 15 control women had minimal mood symptoms while receiving leuprolide acetate (a GnRH agonist). In contrast, the women with premenstrual syndrome but not the controls had a significant increase in sadness during the administration of either estradiol or progesterone. Values are the means (SE) of the seven daily scores on the sadness scale of the Daily Rating Form for each of the 8 weeks preceding hormone replacement (leuprolide alone) and during the 4 weeks of estradiol (plus leuprolide) and progesterone (plus leuprolide) replacement. A score of 1 indicates that the symptom was not present, and a score of 6 indicates that it was present in the extreme. P=0.003 for interaction of treatment condition, diagnostic group, and week. From ref 36: Schmidt PJ, Nieman LK, Danaceau MA, Adams LF, Rubinow DR. Differential behavioral effects of gonadal steroids in women with and in those without premenstrual syndrome N Engl J Med. 338(4):209-216. Copyright © 1998, Massachusetts Medical Society. Reprinted with permission.