Abstract
Background: This study was designed to examine basal and stress-induced levels of
the neuroactive progesterone metabolite, allopregnanolone, in women with premenstrual
dysphoric disorder (PMDD) and healthy control subjects. Also, because evidence suggests
that allopregnanolone negatively modulates the hypothalamic–pituitary–adrenal axis,
plasma cortisol levels were examined. An additional goal was to investigate the relationship
between premenstrual symptom severity and luteal phase allopregnanolone levels.
Methods: Twenty-four women meeting prospective criteria for PMDD were compared with
12 controls during both the follicular and luteal phases of confirmed ovulatory cycles,
counterbalancing phase at first testing. Plasma allopregnanolone and cortisol were
sampled after an extended baseline period and again 17 min following the onset of
mental stress. Owing to low follicular phase allopregnanolone levels, only luteal
phase allopregnanolone and cortisol were analyzed.
Results: During the luteal phase, PMDD women had significantly greater allopregnanolone
levels, coupled with significantly lower cortisol levels, during both baseline and
mental stress. Moreover, significantly more controls (83%) showed the expected stress-induced
increases in allopregnanolone compared with PMDD women (42%). Premenstrual dysphoric
disorder women also exhibited a significantly greater allopregnanolone/progesterone
ratio than control subjects, suggesting alterations in the metabolic pathways involved
in the conversion of progesterone to allopregnanolone. Finally, PMDD women with greater
levels of premenstrual anxiety and irritability had significantly reduced allopregnanolone
levels in the luteal phase relative to less symptomatic PMDD women. No relationship
between symptom severity and allopregnanolone was observed in controls.
Conclusions: These results suggest dysregulation of allopregnanolone mechanisms in
PMDD and that continued investigations into a potential pathophysiologic role of allopregnanolone
in PMDD are warranted.
Keywords
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Article info
Publication history
Accepted:
August 11,
2000
Received in revised form:
June 12,
2000
Received in revised form:
August 7,
2000
Received:
December 23,
1999
Identification
Copyright
© 2001 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
