PMDD Hormones & Brain Chemistry
- Amy Simpson
- Jul 22
- 4 min read
While conventional frameworks often dismiss the role of hormones in PMDD, this blog takes a different lens and explores the complex interplay between hormonal shifts, neurotransmitter sensitivity, and inflammation to help understand why PMDD is so severe and why standard treatments often fall short.
Each month, many women experience intense mood, cognitive, and physical symptoms that far exceed typical PMS. For 3-9% of people who menstruate, this is Premenstrual Dysphoric Disorder (PMDD) a serious, cyclical condition that severely disrupts daily life. For some people it can last for half of the menstrual cycle.
Despite its impact, PMDD was not recognised in the DSM-5 until 2013 and only added to the ICD-11 in 2019. Though classified as a genitourinary disorder, its hallmark symptoms like mood swings, anxiety, rage, and dysphoria align closely with depressive disorders.
PMDD is likely under reported and under diagnosed or misdiagnosed with conditions like generalised anxiety disorder or bipolar disorder. Misdiagnosis may be particularly common for those with undiagnosed ADHD, where comorbidity is increasingly recognised. My last blog explored the medical model for treating PMDD compared with naturopathic care, head there if you need strategies to support yourself right now.
This blog covers:
Understanding Key Neurotransmitters in PMDD
Several neurotransmitters are central to understanding PMDD:
GABA: Our main calming chemical in the brain. It helps regulate mood and promote a sense of calm. In PMDD, the GABA may respond differently to changes in progesterone, which can lead to symptoms like anxiety, irritability, and low mood.
Dopamine: Involved in reward processing, motivation, and executive function. Dysregulation of dopamine pathways may contribute to dysphoria, reduced motivation, and cognitive dysfunction commonly reported in PMDD.
Serotonin: Critical for mood, sleep, appetite, and emotional regulation. Luteal phase reductions in serotonin function, potentially due to hormonal withdrawal or nutrient depletion (e.g., oestrogen, tryptophan), are strongly implicated in the emergence of PMDD symptoms.
Understanding Key Hormones in PMDD
The surges and drop-offs of our key hormones may play a greater role in PMDD than once thought. Rather than absolute levels, it appears that the brain's sensitivity to fluctuations, particularly rapid changes across the cycle is what drives symptoms in susceptible individuals.
Oestrogen: Oestrogen affects mood by influencing serotonin, dopamine, and other key neurotransmitters. In PMDD, the premenstrual drop in oestrogen may trigger mood instability, low motivation, and irritability.
Progesterone: Progesterone rises after ovulation and is metabolised into another molecule called allopregnanolone ('ALLO' for short). ALLO interacts with GABA receptors in the brain. In PMDD, it’s not progesterone itself, but perhaps the sensitivity to its rise and sharp fall of ALLO that may contribute to anxiety, tension, and mood swings.
Prolactin: Often overlooked, prolactin can rise in response to stress and fluctuating hormone levels. Elevated prolactin may disrupt the balance of dopamine and contribute to fatigue, breast tenderness, and low mood in the luteal phase.
Deep Dive 👇
Want to know more? If you're interested in learning more, here is a summary of emerging theories about PMDD that explore the interaction between hormones and neurotransmitters.
Oestrogen + Serotonin
Oestrogen Withdrawal and Serotonin Dysregulation: One hypothesis of PMDD attributes premenstrual mood symptoms to the decline in oestrogen levels that occurs during the late luteal phase. This reduction may lead to dysregulation of the serotonin system, particularly transport and availability.
Oestrogen is known to influence serotonin synthesis, receptor expression, and transporter function.
Clinical efficacy of selective serotonin reuptake inhibitors (SSRI medication like Sertraline or Fluoxetine) in alleviating symptoms of PMS and PMDD for some people may support this theory of serotonin’s role in the pathophysiology of PMDD.
Additional evidence highlights the exacerbation of symptoms following depletion of tryptophan, the amino acid precursor to serotonin, which may further compromise serotonergic tone during the luteal phase.
Progesterone + GABA
A second prominent theory implicates progesterone and its neuroactive metabolite, allopregnanolone (ALLO), in impacting GABA signalling.
Individuals with PMDD may exhibit increased sensitivity to the cyclical rise and fall of ALLO during the luteal phase.
The rapid withdrawal of ALLO is hypothesised to induce a paradoxical (opposite of normal) impact on anxiety or dysphoria which manifests as mood instability, anxiety, and rage.
Notably, SSRIs may also exert part of their clinical benefit in PMDD through modulation of ALLO levels, in addition to their serotonin effects.
Systemic + Brain Inflammation
New research suggests that inflammation, especially in the brain, may play a role in PMDD.
People with PMDD often show higher levels of inflammation in the body, and those levels tend to rise when symptoms are most severe.
Inflammatory chemicals called cytokines can interfere with how brain chemicals (neurotransmitters) are made, released, and received. This can affect mood, memory, and focus.
Inflammation may also disrupt communication between the brain and the reproductive system, leading to further imbalances in hormones and emotional regulation.
If you suspect you’re living with PMDD, ADHD, or struggling with challenging moods and anxiety, I'd love to support you to find steadiness and happiness in your cycle:
Amy is a degree-qualified naturopath dedicated to helping busy, tired clients regain their energy and vitality.
She combines evidence-based naturopathic medicine, nutrition, and lifestyle interventions to empower clients on their journey to optimal health. Whether it’s reclaiming energy, balancing hormones, resolving digestive issues, or enhancing overall well-being and longevity, her personalised approach focuses on identifying and addressing the root cause of health concerns. With a Bachelor of Health Science, ongoing studies in a Master of Advanced Practice, and full membership in the Naturopaths and Herbalists Association of Australia, Amy offers a unique blend of traditional wisdom and science to support individuals and families at every stage of life.
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