---
title: How do hormone changes affect brain chemistry in PMDD? | Niyora
description: This review article proposes that PMDD occurs when the hormone allopregnanolone drops during the luteal phase, reducing sensitivity of brain receptors that no
url: https://niyora.com/research/papers/role-of-allopregnanolone-mediated-aminobutyric-acid-a-receptor-sensitivity-in-2023/
---

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- How do hormone changes affect brain chemistry in PMDD?

Survey study, 2023

# How do hormone changes affect brain chemistry in PMDD?

This review article proposes that PMDD occurs when the hormone allopregnanolone drops during the luteal phase, reducing sensitivity of brain receptors that normally calm activity. Targeting these receptors could be a strategy for treating PMDD.

 Early or limited evidence

Review article; not a study of people; based on animal experiments and clinical observations

## What they did

Literature review synthesizing animal studies and clinical observations on the hormone allopregnanolone, brain GABA-A receptors, and PMDD. Authors described how hormone changes affect brain cell activity and proposed mechanisms for PMDD.

## What they found

A rapid decrease in allopregnanolone reduces the sensitivity of GABA-A receptors, which reduces the calming effect on brain cells and increases their excitability, producing PMDD-like symptoms. The authors propose that drugs targeting GABA-A receptors may alleviate PMDD.

## What it means for you

This explains one proposed biological mechanism for how hormone fluctuations cause PMDD symptoms. The theory is based on animal experiments and some clinical observations but has not been fully tested in women with PMDD. It's speculative about whether new drugs based on this mechanism would work.

allopregnanolone

hormone proposed as key to PMDD

GABA-A

brain receptor implicated in the mechanism

luteal phase

when hormone drops and symptoms occur

## About the study

Original title Role of allopregnanolone-mediated γ-aminobutyric acid A receptor sensitivity in the pathogenesis of premenstrual dysphoric disorder: Toward precise targets for translational medicine and drug development Authors Gao Q, Sun W, Wang YR et al. Journal Frontiers in psychiatry Year 2023 Study design Survey study What was tested Proposed therapeutic targeting of GABA-A receptors (not tested in this review) Open access Yes Read the paper [doi.org/10.3389/fpsyt.2023.1140796](https://doi.org/10.3389/fpsyt.2023.1140796) Original abstract

Premenstrual dysphoric disorder (PMDD) can be conceptualized as a disorder of suboptimal sensitivity to neuroactive steroid hormones. Its core symptoms (emotional instability, irritability, depression, and anxiety) are related to the increase of stress sensitivity due to the fluctuation of hormone level in luteal phase of the menstrual cycle. In this review, we describe the emotional regulatory effect of allopregnanolone (ALLO), and summarize the relationship between ALLO and γ-aminobutyric acid A (GABA A ) receptor subunits based on rodent experiments and clinical observations. A rapid decrease in ALLO reduces the sensitivity of GABA A receptor, and reduces the chloride influx, hindered the inhibitory effect of GABAergic neurons on pyramidal neurons, and then increased the excitability of pyramidal neurons, resulting in PMDD-like behavior. Finally, we discuss in depth the treatment of PMDD with targeted GABA A receptors, hoping to find a precise target for drug development and subsequent clinical application. In conclusion, PMDD pathophysiology is rooted in GABA A receptor sensitivity changes caused by rapid changes in ALLO levels. Targeting GABA A receptors may alleviate the occurrence of PMDD.

Reproduced under CC-BY.

## Topics

[Premenstrual syndrome (PMS)](https://niyora.com/research/topics/condition-pms/)[Premenstrual dysphoric disorder (PMDD)](https://niyora.com/research/topics/condition-pmdd/)[Menstrual cycle and mood](https://niyora.com/research/topics/condition-cycle-mood/)[Low mood and depression](https://niyora.com/research/topics/symptom-depression-mood/)[Neurosteroids (allopregnanolone)](https://niyora.com/research/topics/treatment-neurosteroids/)[Pregnancy and postpartum](https://niyora.com/research/topics/comorbidity-postpartum/)

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