How Hormones Affect Mental Health

Your labs look “normal.” You’re eating well, moving your body, maybe even meditating. Yet you still feel stressed, irritable, or flat. You might struggle with focus, motivation, or mood swings that seem to come out of nowhere. If this resonates, you’re far from alone.

Challenges with mood and cognitive function are among the fastest-rising health concerns worldwide. But too often, the conversation is reduced to neurotransmitters alone—serotonin, dopamine, GABA—without considering the deeper regulators that orchestrate how those very brain chemicals function: your hormones.

Hormones are chemical messengers that bridge the brain and body. They shape how you respond to stress, how well you sleep, how stable your energy is, your motivation, focus, and of course, reproductive and physical characteristics too. When they drift out of balance, whether subtly or profoundly, emotional well-being often suffers too.

The New Paradigm

The old story of mental health focused almost exclusively on neurotransmitters. But modern research paints a richer picture: the endocrine system, stress response, metabolism, and immune health are deeply intertwined with mood and cognition.

For example, chronic stress and HPA axis dysfunction blunt your ability to adapt, leaving you wired, tired, or both.

● Low DHEA, often suppressed by high cortisol, reduces resilience, neuroprotection, and anabolic repair.

● Sex hormone imbalances, such as low testosterone or fluctuating estrogen, directly affect motivation, emotional regulation, and brain plasticity.

● Thyroid dysfunction slows metabolism and cognitive processing, while insulin resistance destabilizes energy and can contribute to low mood or heightened stress sensitivity.

Just as fatigue isn’t simply “not enough sleep,” mental health isn’t just “too little serotonin.” It’s the cumulative story of how your internal systems are or aren’t working in balance.

Let’s Look at the Numbers

● Up to 30% of individuals with major depression show measurable disturbances in cortisol regulation (Stetler & Miller, 2011).

● Low testosterone is linked with higher rates of depression in both men and women, particularly in midlife and aging (Zarrouf et al., 2009).

● Perimenopausal estrogen fluctuations can nearly double the likelihood of mood challenges (Soares, 2014).

● Chronic stress leads to cortisol-DHEA imbalance, a hallmark of burnout and emotional vulnerability (Izawa et al., 2013).

● Flattened cortisol rhythms are strongly associated with poor sleep, fogginess, and difficulty regulating emotions (Kudielka et al., 2012).

● Around 30% of people with hypothyroidism experience low mood, while feelings of stress, anxiety, and unease are common in hyperthyroidism (Hage & Azar, 2012).

Hormonal Pathways That Shape the Mind

HPA Axis Dysfunction: Cortisol & DHEA

The hypothalamic-pituitary-adrenal (HPA) axis is the body’s stress command center. Cortisol, its primary output, helps us rise to challenges. But chronic activation flattens cortisol rhythms, leading to fatigue, sleep disruptions, and stress sensitivity.

DHEA acts as cortisol’s counterbalance. It’s an anabolic, neuroprotective hormone that supports resilience, memory, and mood stability. When DHEA is low, the brain loses an important buffer against stress, often manifesting as burnout, brain fog, or low mood.

Beyond mood, the HPA axis also connects directly to inflammation and immunity. Elevated or dysregulated cortisol alters cytokine signaling—often suppressing immunity short term, but in chronic stress, paradoxically driving low-grade inflammation (Irwin & Cole, 2011). This inflammatory signaling feeds back into the brain, influencing mood regulation and stress sensitivity (Miller & Raison, 2016). This field is sometimes referred to as neuroendocrinoimmunology and has important implications for mental health and general wellbeing.

Neuro-Endocrine System: The Inseparable Influence of Hormones on Neurotransmitters and Vice Versa

● Estrogen modulates serotonin and dopamine systems, supports synaptic growth, and stabilizes mood. It enhances serotonin synthesis and receptor activity and fluctuations can trigger stress, irritability, or low mood (Borrow & Cameron, 2014).

● Progesterone metabolites act on GABA-A receptors, producing calming effects (Schiller et al., 2014).

● Testosterone fuels motivation, drive, and reward sensitivity. It supports dopamine release in reward pathways (Aubele & Kritzer, 2011). Low levels are linked to apathy, irritability, and low mood, while restoration can improve emotional balance and cognitive performance. .

● Cortisol interacts with glutamate, often heightening excitotoxicity under stress (Popoli et al., 2012).

● Mood swings often mirror blood sugar swings. Insulin resistance increases inflammation, destabilizes energy supply to the brain, and can exacerbate feelings of low mood or stress sensitivity. For example, insulin influences dopamine signaling and brain energy balance (Kleinridders et al., 2015).

● Thyroid hormones regulate metabolism in every cell, including neurons. Low thyroid function slows neurotransmitter turnover, blunts cognition, and contributes to low mood and brain fog. For example, thyroid hormones regulate norepinephrine and serotonin turnover, shaping energy and mood (Bauer et al., 2002).

Together, this shows hormones aren’t just background players solely influencing sexual characteristics and libido. They intricately shape the neurotransmitter landscape itself.

What You Can Do at Home Today

● Anchor your circadian rhythm: Morning sunlight, consistent bedtimes, and limiting blue light at night stabilize cortisol and melatonin.

● Balance blood sugar: Pair protein and fat with every meal; reduce refined carbs and sugar spikes.

● Train stress resilience: Meditation, breathwork, and resistance training lower cortisol and support DHEA production.

● Support hormone balance: Adequate sleep, healthy fats, resistance training, and minimizing alcohol all support testosterone and estrogen regulation.

● Minimize exposure to hormone disruptors: Avoid xenoestrogens like BPA (found in some plastics), phthalates (in plastics, cosmetics, and personal care products), parabens, and other endocrine-disrupting chemicals that can interfere with hormone signaling.

● Nutrient basics: Ensure sufficient zinc, magnesium, vitamin D, B vitamins, omega-3s, and cholesterol in moderation—critical cofactors for hormone and neurotransmitter synthesis.

How We Can Help

If your mood, focus, or energy feel out of sync and basic self-care isn’t cutting it, it may be time to explore your hormonal landscape more deeply.

At Seed to Fruit, we use functional assessments to uncover hidden imbalances, including:

● Salivary or dried urine cortisol/DHEA testing → reveals stress adaptation and resilience.

● Sex hormone panels → measure testosterone, estrogen, progesterone balance.

● Thyroid testing → looks beyond TSH to free T3, T4, and antibodies.

● Metabolic & blood sugar markers → insulin sensitivity, glucose control.

● Lifestyle mapping → identifying daily patterns that reinforce or disrupt hormone balance.

This data allows us to personalize protocols that restore balance, improve resilience, and enhance mental well-being. By addressing hormones as part of an integrated system, we can create lasting stability and the strength to support mental, emotional, and physical balance, holistically.

References

● Aubele, T., & Kritzer, M. F. (2011). Androgen influence on prefrontal dopamine systems in adult male rats: Behavioral and neurochemical consequences. Psychoneuroendocrinology, 36(10), 1452–1462. https://doi.org/10.1016/j.psyneuen.2011.03.010

● Bauer, M., Heinz, A., Whybrow, P. C. (2002). Thyroid hormones, serotonin and mood: Of synergy and significance in the adult brain. Molecular Psychiatry, 7(2), 140–156. https://doi.org/10.1038/sj.mp.4000963

● Borrow, A. P., & Cameron, N. M. (2014). Estrogenic mediation of serotonergic and neurotrophic systems: Implications for depression and anxiety. Frontiers in Neuroendocrinology, 35(4), 477–491. https://doi.org/10.1016/j.yfrne.2014.03.007

● Hage, M. P., & Azar, S. T. (2012). The link between thyroid function and depression. Journal of Thyroid Research, 2012, 590648. https://doi.org/10.1155/2012/590648

● Irwin, M. R., & Cole, S. W. (2011). Reciprocal regulation of the neural and innate immune systems. Nature Reviews Immunology, 11(9), 625–632. https://doi.org/10.1038/nri3042

● Izawa, S., Miki, K., Tsuchiya, M., et al. (2013). Cortisol and DHEA reactivity to psychosocial stress in workers: The moderating role of stress-related factors. Frontiers in Endocrinology, 4, 116. https://doi.org/10.3389/fendo.2013.00116

● Kleinridders, A., Cai, W., Cappellucci, L., Ghazarian, A., Collins, W. R., Vienberg, S. G., & Pothos, E. N. (2015). Insulin resistance in brain alters dopamine turnover and causes behavioral disorders. Proceedings of the National Academy of Sciences, 112(11), 3463–3468. https://doi.org/10.1073/pnas.1500877112

● Kudielka, B. M., Bellingrath, S., & Hellhammer, D. H. (2012). Cortisol in burnout and vital exhaustion: An overview. Giornale Italiano di Medicina del Lavoro ed Ergonomia, 34(3 Suppl), 44–52. PMID: 23033673

● Miller, A. H., & Raison, C. L. (2016). The role of inflammation in depression: From evolutionary imperative to modern treatment target. Nature Reviews Immunology, 16(1), 22–34. https://doi.org/10.1038/nri.2015.5

● Popoli, M., Yan, Z., McEwen, B. S., & Sanacora, G. (2012). The stressed synapse: The impact of stress and glucocorticoids on glutamate transmission. Nature Reviews Neuroscience, 13(1), 22–37. https://doi.org/10.1038/nrn3138

● Schiller, C. E., Schmidt, P. J., Rubinow, D. R. (2014). Allopregnanolone as a mediator of affective switching in reproductive mood disorders. Psychopharmacology, 231(17), 3557–3567. https://doi.org/10.1007/s00213-014-3599-x

● Soares, C. N. (2014). Depression and menopause: Current knowledge and clinical recommendations for a critical window. Psychiatric Clinics of North America, 37(4), 629–640. https://doi.org/10.1016/j.psc.2014.08.004

● Stetler, C., & Miller, G. E. (2011). Depression and hypothalamic–pituitary–adrenal activation: A quantitative summary of four decades of research. Psychosomatic Medicine, 73(2), 114–126. https://doi.org/10.1097/PSY.0b013e31820ad12b

● Zarrouf, F. A., Artz, S., Griffith, J., Sirbu, C., & Kommor, M. (2009). Testosterone and depression: Systematic review and meta-analysis. Journal of Psychiatric Practice, 15(4), 289–305. https://doi.org/10.1097/01.pra.0000358315.88931.fc