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

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Abstract

Rationale

Allopregnanolone effects on mood in postmenopausal women are unclear thus far.

Objectives

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.

Materials and methods

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.

Results

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.

Conclusions

Mood effects during progesterone treatment seem to be related to allopregnanolone concentration, and a bimodal association between allopregnanolone and adverse mood is evident.

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Acknowledgements

This work was supported by the Swedish Medical Research Council (Proj. 4X-11198), Umeå sjukvård, spjutspetsanslag, Visare Norr Norra Regionen and by a grant from the EU Regional Funds, Objective 1. Agneta Andersson is acknowledged for skillful technical assistance, Margatetha Jänes and Ingrid Otterbring for skillful technical assistance.

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Authors and Affiliations

  1. Umeå Neurosteroid Research Center, Department of Clinical Science, Obstetrics and Gynecology, Norrlands University Hospital, SE-901 85, Umeå, Sweden

    Lotta Andréen, Marie Bixo, Sigrid Nyberg & Torbjörn Bäckström

  2. Department of Women’s and Children’s Health, University Hospital, Uppsala, Sweden

    Inger Sundström-Poromaa

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  1. Lotta Andréen
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  2. Inger Sundström-Poromaa
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  3. Marie Bixo
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  5. Torbjörn Bäckström
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Correspondence to Torbjörn Bäckström.

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Andréen, L., Sundström-Poromaa, I., Bixo, M. et al. Allopregnanolone concentration and mood—a bimodal association in postmenopausal women treated with oral progesterone. Psychopharmacology 187, 209–221 (2006). https://doi.org/10.1007/s00213-006-0417-0

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  • DOI: https://doi.org/10.1007/s00213-006-0417-0

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