Neuroactive steroid hormone trajectories across the menstrual cycle in premenstrual dysphoric disorder (PMDD): the PHASE study.

It is presently not known whether endogenous neuroactive steroid hormone trajectories across the menstrual cycle are distinguishable in women with premenstrual dysphoric disorder (PMDD). To improve the rigor in this area of research, we implemented a validated study methodology, involving blood sample collection at 8 key menstrual cycle timepoints, following which the study data is realigned so that all women are compared at the same biological window (i.e., menstrual cycle subphase). Using liquid chromatography-mass spectrometry (LC-MS), we analyzed serum levels of nine steroid hormones previously implicated in the etiology of PMDD, including allopregnanolone. Other than progesterone (p ≤ 0.001), none of the steroid hormones displayed significant changes across menstrual cycle subphases when comparing participants with PMDD to the healthy controls. A thorough investigation of the progesterone trajectory showed that its left shift in the luteal phase (e.g., earlier rise in progesterone) exposes women with PMDD to a higher periovulatory progesterone and a more acute withdrawal in the late luteal subphase. Results of the present study indicate that the largely overlooked brief periovulatory subphase should be thoroughly examined in PMDD and agree with prior conclusions that rapid progesterone withdrawal associates with the development of negative affect.