The Complete Guide to PMDD: Hormones, the HPA Axis & the Nervous System

Amy Sergeant
6 days ago
6 min read

Premenstrual Dysphoric Disorder (PMDD) is more than just a hormone problem. It is a complex systems-level interaction between reproductive hormones, brain chemistry, and the stress-response network that affects your mood, energy, and sense of safety.

This guide breaks down each hormone and system involved so you can understand exactly what happens in the body and why your symptoms feel so intense.

1. Estrogen

Estrogen is one of the most influential hormones in PMDD because it directly affects serotonin and dopamine, both are vital neurotransmitters in how the brain regulates mood and emotions. When estrogen drops in the late luteal phase, serotonin signalling becomes less efficient, which can trigger low mood, weepiness, anxiety, and fatigue. Many women with PMDD are highly sensitive to normal estrogen fluctuations, not because estrogen is “too low” or “too high,” but because the brain reacts more intensely to the shift. This hormone sensitivity, is one of the core combinates of PMDD.

2. Progesterone

Progesterone is often misunderstood. The issue in PMDD is rarely the amount of progesterone, but how the brain responds to its metabolites, especially allopregnanolone (ALLO). ALLO normally calms the nervous system by activating GABA receptors, but in PMDD the brain becomes paradoxically irritated by the production of ALLO. So Instead of relaxation, ALLO can then trigger anxiety, dysphoria, irritability, and a sense of overwhelm. This is why symptoms peak when progesterone is highest, because ALLO is highest.

3. Allopregnanolone (ALLO)

Allopregnanolone is the neurosteroid responsible for calming the mind, supporting sleep, and reducing stress reactivity. In PMDD, the brain’s GABA receptors do not respond normally to ALLO, creating an internal misfiring, the brain expects to feel more relaxed but feels agitation instead. This is one of the most biologically validating explanations for PMDD. It is also why symptoms can feel like there is a switch that flips before the period because ALLO sensitivity changes dramatically during the luteal phase.

4. Serotonin

Serotonin regulation is central to PMDD, which is why SSRIs can be helpful, however, meditation does not work for everyone. Estrogen boosts serotonin, however progesterone and ALLO alter how serotonin receptors function. During the luteal phase, serotonin signalling becomes less stable, creating vulnerability to mood swings, intrusive thoughts, emotional flooding, and intense sadness. Women with PMDD are not serotonin-deficient all month, only during the luteal phase, when hormone shifts alter receptor sensitivity.

5. Dopamine

Dopamine is responsible for motivation, pleasure, focus, and emotional reward. During the second half of the cycle, dopamine becomes more fragile due to fluctuating estrogen. This can trigger classic PMDD symptoms such as reduced motivation, an inability to feel pleasure, rejection sensitivity, emotional numbness, or sudden moments of intense cravings. Stress also lowers dopamine, which adds on another layer if the HPA axis is dysregulated.

6. Norepinephrine

Norepinephrine is the brain’s alertness and survival hormone. When the HPA axis is strained, norepinephrine spikes more easily, making the luteal phase more overstimulating, activating the fight-or-flight, and creating a plethora of symptoms including irritability, anxiety, poor sleep, startle response, and difficulty calming down. PMDD makes the nervous system act like it’s under threat, even when nothing is happening externally.

7. Cortisol (HPA Axis Hormone)

Cortisol connects directly to PMDD because the HPA axis becomes more reactive during the luteal phase. For women with PMDD, cortisol spikes faster, stays elevated longer, and takes longer to come down and come back to a base line of regulation. This can cause fatigue, inflammation, emotional dysregulation, and a constant sense of being overwhelmed. Chronic stress, trauma history, sleep disruption, or nicotine/sugar use amplifies this effect.

8. CRH & ACTH (Stress-Signal Hormones)

CRH (corticotropin-releasing hormone) and ACTH (adrenocorticotropic hormone) are the messaging hormones of the stress response. When hormonal fluctuations interact with a sensitive HPA axis, these signals become exaggerated. Even small stressors can feel catastrophic. This is why PMDD can produce symptoms so intense they feel unlike your “normal self” the messaging system is literally firing differently during this phase.

9. GABA

GABA is the brain’s main calming neurotransmitter. Progesterone’s metabolite ALLO normally binds to GABA receptors to induce relaxation. In PMDD, the GABA system becomes unstable, instead of calming to the brain it becomes irritable, overstimulated, or panicked. This is why meditation is harder, sleep is lighter, and the nervous system feels “raw” in the luteal phase.

10. Glutamate

Glutamate is the brain’s excitatory, active neurotransmitter. In PMDD, glutamate can become dominant when GABA is low or unstable. This creates the classic PMDD storm of: racing thoughts, sensory sensitivity, emotional intensity, and difficulty grounding. When ALLO misfires, glutamate becomes too loud and overwhelming.

11. Melatonin

Melatonin is indirectly affected in PMDD through estrogen, cortisol, and nervous system arousal. Poor sleep quality in the luteal phase can cause restlessness, night waking, early morning anxiety and often comes from altered melatonin regulation. Sleep deprivation then worsens irritability, low mood, cravings, and stress sensitivity creating a vicious cycle.

12. Thyroid Hormones (T3, T4, TSH)

The thyroid interacts closely with the HPA axis. Stress hormones suppress thyroid function, and women with PMDD often experience temporary “functional hypothyroid” symptoms during the luteal phase such as heavy fatigue, cold sensitivity, slow digestion, constipation, and brain fog. This is not always thyroid disease, it is often stress + hormone sensitivity.

13. Insulin & Blood Sugar Hormones

Blood sugar levels can become more unstable in the luteal phase because progesterone increases insulin resistance. When combined with stress and emotional dysregulation, this can cause cravings, shakiness, emotional eating, mood dips, irritability, and fatigue. Many PMDD symptoms worsen when blood sugar levels are unstable.

The Role of the HPA Axis in PMDD

The HPA axis (hypothalamic–pituitary–adrenal) is the stress-response system that controls cortisol, emotional regulation, energy levels, and resilience. In PMDD, hormonal fluctuations collide with a stress system that is more reactive or more easily overwhelmed. This interaction can creates emotional intensity, dysphoria, and the feeling that you are not yourself.

When the HPA axis is dysregulated, the luteal phase becomes a time of increased inflammation, lowered stress tolerance, increased sleep disturbance, stronger emotional reactions, and sharper hormonal sensitivity. This is why PMDD feels like both a hormonal and a nervous system disorder because it genuinely is both.

The Nervous System + Hormones + HPA Axis = The PMDD Experience

PMDD symptoms arise from three systems interacting:

Reproductive Hormones
Neurotransmitters (serotonin, GABA, dopamine)
The Stress System (HPA axis + cortisol)

This triad explains why the symptoms are so real, so intense, and often so misunderstood. It's not weakness. It's a neurobiological sensitivity that requires holistic support, nutritional, emotional, nervous-system oriented, and lifestyle-based.

Supporting your stress system is one of the most powerful ways to ease PMDD, PMS, and PME symptoms. When the HPA axis finds balance again, emotional resilience returns. Your mood steadies, your energy evens out, and your body feels safer inside.

At The Feminine Rhythm, we believe knowledge creates power, and power creates freedom. We support women in understanding their bodies, their patterns, and their emotional responses so they can live with greater clarity, ease, and sovereignty.

If you’re ready to begin that journey:

Peer Connections

We run a biweekly Support Group where we share experiences, reduce isolation and help normalise what can otherwise feel overwhelming or confusing.

PMDD 1–1 Healing

1–1 Coaching structured, individual guidance that helps you build routines and rituals that work with your cycle rather than against it.

HPA Axis and Nervous System Regulation

Somatic Course Empowering and educating you with both theory and practical tools to retrain your stress system, regulate your stress responses, and build resilience across every phase of your cycle.

Here are key scientific references to support the information in your PMDD guide:

Hantsoo, L., & Epperson, C. N. (2023). Neurobiological mechanisms of PMDD: hormone sensitivity and brain function. Frontiers in Global Women's Health.https://www.frontiersin.org/articles/10.3389/fgwh.2025.1595083/full
Schiller, C. E., et al. (2014). Neurosteroid regulation of GABA-A receptors and affective switching in PMDD. Frontiers in Neuroscience.https://www.frontiersin.org/articles/10.3389/fnins.2014.00344/full
Yonkers, K. A., et al. (2008). Epidemiology and treatment of premenstrual disorders. Journal of Clinical Psychiatry.https://pubmed.ncbi.nlm.nih.gov/18771543/
National Center for Biotechnology Information (NCBI) Bookshelf (2023). Premenstrual Dysphoric Disorder.https://www.ncbi.nlm.nih.gov/books/NBK532307/
Cheng, Y., et al. (2025). HPA axis dysregulation in PMDD: interaction of stress and hormonal sensitivity. Frontiers in Endocrinology.https://www.frontiersin.org/articles/10.3389/fendo.2025.1561848/full
Ayhan, Y., et al. (2021). The role of neurotransmitters in PMDD. Journal of Medicine and Biochemistry.https://journalmeddbu.com/full-text/250
Rapkin, A. J., & Lewis, E. I. (2013). Treatment of Premenstrual Dysphoric Disorder. Women’s Health.https://www.liebertpub.com/doi/10.1089/jwh.2013.4418