Sex steroid induced negative mood may be explained by the paradoxical effect mediated by GABAA modulators

Conclusion: Progesterone and progestagens induce negative mood, most probably via their GABAA receptor active metabolites. In postmenopausal women treated with progesterone and animals treated with allopregnanolone, there is a bimodal association between serum allopregnanolone concentration and adverse mood, resembling an inverted U-shaped curve. In humans, the maximal effective concentration of allopregnanolone for producing negative mood is within the range of physiological luteal phase serum concentrations.