Editors' ChoiceBehavioral Disorders

Stable hormones for stable moods

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Science Translational Medicine  24 May 2017:
Vol. 9, Issue 391, eaan4293
DOI: 10.1126/scitranslmed.aan4293


The rise in ovarian hormones triggers premenstrual dysphoric disorder symptoms in women.

Premenstrual dysphoric disorder (PMDD) is defined as an increase in emotional symptoms and cognitive dysfunction during the luteal phase of the menstrual cycle and affects millions of women worldwide. The involvement of ovarian hormones, estradiol and progesterone, in the etiology of PMDD is highlighted by the fact that ovariectomy and pharmacological ovarian suppression can eliminate symptoms of PMDD, and a re-exposure to the two ovarian hormones can re-evoke PMDD. Absolute concentrations of estradiol and progesterone are not different between women with and without PMDD; therefore, Schmidt and colleagues leveraged a within-subjects study design to determine whether the onset of PMDD symptoms is triggered by the rise in ovarian hormone concentrations over the course of the menstrual cycle or by stable concentrations of ovarian hormones above a critical threshold permissive for PMDD symptom development.

Investigators studied 20 women who met criteria for PMDD, had regular menstrual cycles, and reported PMDD symptoms in the luteal phase of their cycle for 3 months before hormonal manipulation. All women underwent pharmacological suppression of ovarian function to decrease endogenous estradiol and progesterone concentrations. The 10 women who were compliant with research protocols and whose PMDD symptoms remitted with ovarian suppression continued to receive gonadal suppression along with placebo treatment for 1 month, and then exogenous estradiol and progesterone replacement for 3 months. Assessment of symptoms throughout these hormonal manipulations showed that PMDD symptoms were increased during the first month of hormone replacement compared with the last month of ovarian suppression, the one-month placebo period, and the second and third months of estradiol and progesterone replacement. Based on these data, the authors concluded that the increase in estradiol and progesterone, and not stable concentrations of these ovarian hormones, is critical for the induction of behavioral and cognitive symptoms in women with PMDD. Although the results of this study suggest a new therapeutic target (increased ovarian hormones in the follicular phase) for alleviating the burden of PMDD, the generalizability of the results is somewhat limited by the fact that only 70% of the study sample responded to ovarian suppression. This lack of an effect in all women with PMDD suggests that other factors may contribute to PMDD and that PMDD may have different etiologies and may benefit from different treatments. Further studies are necessary to replicate these findings and to assess the effectiveness of inhibiting the increase in ovarian hormones before ovulation for the treatment of PMDD, especially because such interventions would not be compatible with fertility.

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