Women with pre-menstrual dysphoric disorder (PMDD) who received hormonal suppression with leuprolide experienced an elimination of their mood symptoms, and after the “add-back” of hormones, those symptoms returned, according to a report that appears in AJP. Women without PMDD did not experience mood symptoms under either condition.
The study, a replication of an earlier study using a much larger sample size, “confirmed that the concept of a differential sensitivity to ovarian steroids is a key component of the pathophysiology of PMDD,” wrote lead author Shau-Ming Wei, Ph.D., of the National Institutes of Mental Health, and colleagues.
Over 12 weeks, 41 women with PMDD and 76 healthy participants completed daily self-ratings for seven core PMDD symptoms—anxiety, sadness, irritability, mood swings, bloating, food cravings, and breast pain—while undergoing ovarian suppression with the gonadotropin-releasing hormone agonist leuprolide.
After this period, 34 women with PMDD who responded to leuprolide and significantly reduced their mood symptoms (along with all comparison women) proceeded to add back estradiol and progesterone over 12 additional weeks. Each hormone was administered for five weeks with a two-week break in between—and in a random order for each woman.
PMDD symptoms during the last eight weeks of leuprolide suppression were compared with symptoms during the first four weeks of estradiol add-back and the first four weeks of progesterone add-back.
Of the 34 PMDD responders, 13 (38%) had symptom recurrence for at least one of the four mood symptoms during both estradiol add-back and progesterone add-back. An additional seven women (21%) had symptom recurrence only during progesterone add-back, and four (12%) had symptom recurrence only during estradiol add-back. In contrast, bloating and food cravings remained elevated regardless of hormone condition, while breast pain was reported as slightly more severe during estradiol addback.
Women in the healthy comparison group had low mood symptoms overall and did not report differences in their symptoms during estradiol add-back or progesterone add-back compared with leuprolide alone.
“The findings of this study provide important directions for understanding the underlying pathophysiology of PMDD as well as directions toward the development of novel therapeutics,” the researchers concluded.
(Image: Getty Images/iStock/Doucefleur)