How Progesterone & Estrogen Influence Neurotransmitters — And Why Hormones Can Impact Mental Health

Written by Dr. Chelsea Smithback, ND

Most women intuitively notice that mood, stress tolerance, and emotional sensitivity fluctuate across the menstrual cycle. But the deeper reason goes beyond “PMS” — it lies in how estrogen and progesterone directly interact with the brain’s neurotransmitters. These hormones aren’t just reproductive messengers; they are neuroactive steroids that affect mood, cognition, sleep, pain perception, and emotional regulation.

When hormones rise or fall too quickly — or when they’re chronically imbalanced, as in PMS, PMDD, perimenopause, or PCOS — mental health symptoms can follow.

Here’s how it works.

Estrogen: The Mood-Enhancing, Brain-Stimulating Hormone

Estrogen has a powerful effect on the central nervous system. It modulates several key neurotransmitters involved in mood stability and cognitive function.

1. Estrogen increases serotonin

• Boosts serotonin synthesis
  
  

• Upregulates serotonin receptors
  
  

• Slows serotonin breakdown
  
  

• Explains why low estrogen states (early follicular phase, postpartum, perimenopause) are associated with mood dips, irritability, and increased sensitivity to stress
  
  

2. Estrogen enhances dopamine activity

• Supports motivation, reward, focus, and energy
  
  

• Too little dopamine → apathy, low motivation
  
  

• Too much → anxiety or overstimulation
  This is why some women feel more energized and mentally sharp around ovulation — peak estrogen.
  
  

3. Estrogen supports GABA modulation

While progesterone is more strongly tied to GABA, estrogen still helps regulate the balance between calmness and alertness.

Low estrogen = less serotonin + less dopamine = more irritability, low mood, and brain fog.

Progesterone: The Calming, Stabilizing Neurosteroid

Progesterone and its metabolite, allopregnanolone, have profound effects on the brain — similar to natural anti-anxiety agents.

1. Progesterone strongly enhances GABA

• GABA is the brain’s main calming, anti-anxiety neurotransmitter
  
  

• Progesterone → allopregnanolone → increases GABA receptor sensitivity
  
  

• Leads to improved sleep quality, relaxation, and decreased reactivity
  
  

2. When progesterone drops suddenly, mood symptoms rise

This is why symptoms occur:

• In the late luteal phase (PMS, PMDD)
  
  

• Postpartum, when progesterone plummets
  
  

• In perimenopause, when progesterone becomes erratic and often low
  
  

Low or unstable progesterone is associated with:

• anxiety
  
  

• heightened stress response
  
  

• insomnia
  
  

• irritability
  
  

• feeling “on edge”
  
  

3. Progesterone also influences serotonin and dopamine indirectly

By calming the central nervous system, it helps stabilize how the brain responds to these neurotransmitters.

When Hormones Become Imbalanced: The Mental Health Ripple Effect

Hormonal shifts are normal, but when estrogen or progesterone are too low, too high, or fluctuate too rapidly, common symptoms can appear:

• Anxiety or panic
  
  

• Depression or low mood
  
  

• Irritability and emotional sensitivity
  
  

• Insomnia or restless sleep
  
  

• Brain fog or decreased concentration
  
  

• Low motivation or apathy
  
  

• Feeling “not like yourself”
  
  

This is particularly common in:

• PMS/PMDD
  
  

• Perimenopause
  
  

• Postpartum period
  
  

• PCOS (where anovulation = chronically low progesterone)
  
  

• Hypothyroidism (which alters estrogen/progesterone metabolism)
  
  

Because hormones and neurotransmitters are so interconnected, psychological symptoms can be the first sign of hormonal imbalance.

Why This Matters for Women’s Health

Many women are told their mood symptoms are “just anxiety” or “just stress,” but hormonal physiology plays a major role. Addressing hormone balance — not just neurotransmitters — often leads to profound improvement in mental health and quality of life.

Supporting healthy estrogen and progesterone levels may include:

• targeted nutrition and micronutrient support
  
  

• addressing insulin resistance
  
  

• improving ovulation
  
  

• supporting adrenal health
  
  

• bioidentical hormone therapy (when appropriate)
  
  

• lifestyle strategies that stabilize HPA-axis function
  
  

Mood symptoms are not just psychological — they can be biochemical.

The Bottom Line

Estrogen and progesterone are deeply intertwined with serotonin, dopamine, and GABA. When these hormones are in balance, women often feel grounded, resilient, focused, and emotionally stable. When they are dysregulated, mental health symptoms can surface quickly. Understanding this connection is the first step toward real, root-cause-focused care.