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SO286

Allopregnanolone and symptom improvement following selective progesterone receptor modulation in premenstrual dysphoric disorder

ALLOPREGNANOLONE AND SYMPTOM IMPROVEMENT IN PREMENSTRUAL DYSPHORIC DISORDER FOLLOWING SELECTIVE PROGESTERONE RECEPTOR MODULATION

A selective progesterone receptor modulator markedly reduced luteal-phase allopregnanolone levels, but symptom improvement was not associated with the magnitude of the change.

The aim of the study was to examine the effect of selective progesterone receptor modulator (SPRM) treatment on serum allopregnanolone (ALLO) levels and to assess whether changes in allopregnanolone were associated with improvements in mood symptoms. The sample comprised 38 participants from a randomized controlled trial (RCT) conducted in women diagnosed with premenstrual dysphoric disorder (PMDD) according to DSM criteria; participants received an SPRM (ulipristal acetate, n=20) or placebo (n=18) for three menstrual cycles. Blood samples were collected during the late luteal phase before treatment and at the end of the third treatment cycle. Serum ALLO was measured using ultra-performance supercritical fluid chromatography–tandem mass spectrometry, PMDD symptoms were assessed using the Daily Record of Severity of Problems (DRSP), and ALLO levels were compared using a general linear model. Allopregnanolone levels decreased from baseline to the end of treatment in both the treatment and placebo groups, with a significant time-by-treatment interaction indicating a greater reduction in the SPRM group than in the placebo group (F(1, 36)=9.74; p=0.004; partial eta squared=0.21). Changes in allopregnanolone were not associated with post-treatment PMDD symptom severity (p=0.28). The authors conclude that selective progesterone receptor modulation markedly reduces luteal-phase allopregnanolone levels and that symptom improvement appears to be related to hormonal stabilization rather than the magnitude of the change, noting that this supports the hypothesis of altered neurosteroid sensitivity in PMDD.

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