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Estradiol/progesterone changes may trigger premenstrual dysphoric disorder onset

Onset of premenstrual dysphoric disorder symptoms was associated with estradiol/progesterone levels changing from low to high, according to recent findings.

“Premenstrual dysphoric disorder (PMDD) symptoms are eliminated by ovarian suppression and stimulated by administration of ovarian steroids, yet they appear with ovarian steroid levels indistinguishable from those in women without PMDD. Thus, symptoms could be precipitated either by an acute change in ovarian steroid levels or by stable levels above a critical threshold playing a permissive role in expression of an underlying infradian affective ‘pacemaker,’” Peter J. Schmidt, MD, of the NIMH’s Behavioral Endocrinology Branch, and colleagues wrote.

To assess what condition triggers PMDD symptoms, researchers evaluated 22 women with PMDD, aged 30 to 50 years. Twelve participants who experienced symptom remission after 2 to 3 months of GnRH agonist-induced ovarian suppression via leuprolide received 1 month of single-blind placebo and then 3 months of continuous combination estradiol/progesterone.

Self- and observer-reported scores on the Rating for Premenstrual Tension were significantly higher, indicating more symptoms, during the first month of combination estradiol/progesterone, compared with the last month of leuprolide alone, the placebo month, and the second and third months of estradiol/progesterone.

Symptom severity did not significantly differ between the last month of leuprolide alone, placebo month, or second and third months of estradiol/progesterone.

Rating for Premenstrual Tension scores did not significantly differ between the second and third months of estradiol/progesterone.

“Although the mechanisms underlying the mood-destabilizing effects of ovarian steroids in PMDD remain to be better characterized, as does the source of susceptibility to this trigger, our findings provide a new target for interventions. Specifically, therapeutic efforts to inhibit the change in steroid levels proximate to ovulation, similar to those reported by Martinez et al, merit further study,” the researchers concluded. – by Amanda Oldt

Disclosure: Schmidt reports no relevant financial disclosures. Please see the study for a full list of relevant financial disclosures.