Allopregnanolone concentration and mood—a bimodal association in postmenopausal women treated with oral progesterone

Abstract

Allopregnanolone effects on mood in postmenopausal women are unclear thus far. Allopregnanolone is a neuroactive steroid with contradictory effects. Anaesthetic, sedative, and anxiolytic as well as aggressive and anxiogenic properties have been reported. The aim of this study is to compare severity of negative mood between women receiving different serum allopregnanolone concentrations during progesterone treatment. A randomized, placebo-controlled, double-blind, crossover study of postmenopausal women (n=43) treated with 2 mg estradiol daily during four treatment cycles. Oral micronized progesterone at 30, 60, and 200 mg/day, and placebo were added sequentially to each cycle. Participants kept daily symptom ratings using a validated rating scale. Blood samples for progesterone and allopregnanolone analyses were collected during each treatment cycle. During progesterone treatment, women had significantly higher negative mood scores when allopregnanolone serum concentration was in the range of 1.5–2 nmol/l compared to lower and higher concentrations. In addition, women displayed a significant increase in negative mood during the progesterone treatment period, compared to the estradiol-only period when 30 mg progesterone daily was used. On the other hand, treatment with higher doses of progesterone had no influence on negative mood. Mood effects during progesterone treatment seem to be related to allopregnanolone concentration, and a bimodal association between allopregnanolone and adverse mood is evident.