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Women with premenstrual dysphoric disorder have altered sensitivity to allopregnanolone over the menstrual cycle compared to controls—a pilot study

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Abstract

Rationale

In premenstrual dysphoric disorder (PMDD), a condition that afflicts 3–8 % of women in fertile ages, the cyclic recurrence of debilitating mood symptoms is restricted to the luteal phase of the menstrual cycle. The progesterone metabolite allopregnanolone is produced by the corpus luteum, and circulating levels are reflected in the brain. Allopregnanolone is a modulator of the GABAA receptor, enhancing the effect of γ-aminobutyric acid (GABA). Previous studies have demonstrated different sensitivity to other GABAA receptor agonists, i.e., benzodiazepines, alcohol, and pregnanolone, in PMDD patients compared to controls.

Objectives

This study aimed to investigate the sensitivity to intravenous allopregnanolone over the menstrual cycle in PMDD patients.

Methods

Allopregnanolone, 0.05 mg/kg, was administered intravenously once in the mid-follicular and once in the luteal phase of the menstrual cycle to 10 PMDD patients and 10 control subjects. The saccadic eye velocity (SEV) was recorded by electrooculography as a measurement of functional GABAA receptor activity, at baseline and repeatedly after the injection. A mixed model was used to analyze data.

Results

There was a highly significant group × phase interaction in the SEV response to allopregnanolone (F(1,327.489) = 12.747, p < 0.001). In the PMDD group, the SEV response was decreased in the follicular phase compared to the luteal phase (F(1,168) = 7.776, p = 0.006), whereas in the control group, the difference was opposite during the menstrual cycle (F(1,158.45) = 5.70, p = 0.018).

Conclusions

The effect of exogenous allopregnanolone is associated with menstrual cycle phase in PMDD patients and in controls. The results suggest an altered sensitivity to allopregnanolone in PMDD patients.

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Acknowledgments

This study was supported by grants from the Swedish Research Council, medicine proj. 4X-11198, Västerbottens läns landsting centrala ALF and Spjutspets and Umeå University foundations. The authors are thankful to Elisabeth Zingmark för excellent laboratory work.

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Authors and Affiliations

  1. Department of Clinical Science, Umeå University, 901 85, Umeå, Sweden

    Erika Timby, Torbjörn Bäckström, Sigrid Nyberg, Anna-Carin N. Wihlbäck & Marie Bixo

  2. Department of Public Health and Clinical Medicine, Umeå University, 901 85, Umeå, Sweden

    Hans Stenlund

  3. Department of Clinical Science, Obstetrics and Gynecology, Umeå University, 901 85, Umeå, Sweden

    Marie Bixo

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  1. Erika Timby
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  2. Torbjörn Bäckström
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Correspondence to Marie Bixo.

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Torbjörn Bäckström has shares in Umecrine AB. None of the other authors declare any conflicts of interest.

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Timby, E., Bäckström, T., Nyberg, S. et al. Women with premenstrual dysphoric disorder have altered sensitivity to allopregnanolone over the menstrual cycle compared to controls—a pilot study. Psychopharmacology 233, 2109–2117 (2016). https://doi.org/10.1007/s00213-016-4258-1

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