Neurosteroids and premenstrual dysphoric disorder

Area of Science:

• Neuroscience
• Psychiatry
• Endocrinology

Background:

• Premenstrual dysphoric disorder (PMDD) affects at least 3% of women, characterized by mood symptoms like depression, irritability, and anxiety.
• The condition is closely linked to the luteal phase of the menstrual cycle, with neurosteroids, particularly allopregnanolone, implicated in its pathophysiology.

Purpose of the Study:

• To review current research on the role of positive allosteric modulators (PAMs) and other neuroactive steroids in the development of PMDD.
• To explore the link between neurosteroid fluctuations and PMDD symptomatology.

Main Methods:

• A literature search was conducted using PubMed with terms related to Premenstrual Syndrome, neurosteroids, allopregnanolone, GABA, and estradiol.
• Relevant animal research and additional publications known to the authors were also included.

Main Results:

• Allopregnanolone and other GABA_A receptor PAMs can cause sedation at high doses and anxiety/irritability at lower doses in sensitive individuals.
• Studies show differences in brain function and GABA_A receptor composition in women with PMDD compared to controls, linked to allopregnanolone levels.
• Fluctuating neuroactive steroid levels appear to exacerbate PMDD symptoms; ovulation suppression is effective but requires hormone add-back to manage side effects.

Conclusions:

• Currently, no definitive effective treatment for PMDD exists.
• Allopregnanolone is identified as a key factor provoking PMDD symptoms in susceptible individuals.
• Future research should investigate interventions targeting neurosteroid effects or GABA_A receptor plasticity.