Hormonal changes can add to, and even cause, depression by affecting brain chemistry, neurotransmitter function, and overall emotional regulation.

Here’s how different hormones influence mood and mental health:

1. Cortisol (stress hormone)

• • Chronic stress leads to elevated cortisol levels, which can disrupt brain function, particularly in areas like the hippocampus (linked to memory and mood regulation).
  • High cortisol concentrations are associated with an increased risk of depression and anxiety.

2. Estrogen and progesterone (sex hormones)

• • Fluctuations in estrogen and progesterone could affect serotonin and dopamine levels, which are critical for mood regulation.
  • This is why many women experience premenstrual dysphoric disorder (PMDD), postpartum depression, and perimenopausal mood swings.

3. Thyroid hormones

• • Hypothyroidism (low thyroid hormone levels) can lead to symptoms of depression, fatigue, and brain fog.
  • Hyperthyroidism (high thyroid hormone levels) can cause anxiety and mood instability.

4. Testosterone

• • Low testosterone levels in men (and sometimes in women) are linked to low mood, fatigue, and loss of motivation.
  • This is why age-related testosterone decline can contribute to depression in some individuals.

5. Insulin and blood sugar fluctuations

• • Insulin resistance and blood sugar imbalances can influence mood swings, fatigue, and depressive symptoms, often seen in conditions like PCOS and diabetes.

6. Melatonin (sleep hormone)

• • Disruptions in melatonin production often cause disturbances to our circadian rhythm, which can lead to sleep disorders and depression.

7. Oxytocin (bonding hormone)

• • Low oxytocin levels can reduce our sense of social connection and loneliness.

8. Growth hormone deficiency

• • The growth hormone (GH) secreted by the pituitary gland plays a role in brain function.
  • Low GH levels are often seen in aging or pituitary disorders and are associated with fatigue, social withdrawal, and depressive symptoms.

9. Leptin and ghrelin (hunger hormones)

• • Leptin (satiety hormone) and ghrelin (hunger hormone) regulate appetite but also impact mood.
  • Leptin resistance (common in obesity) is linked to depressive symptoms.
  • Ghrelin has antidepressant-like effects, which means that disruptions in these hormones can worsen mood.

10. Prolactin (lactation and reproductive hormone)

• • Elevated prolactin levels (hyperprolactinemia) frequently cause fatigue, low libido, and depression, often seen in pituitary tumors or medication side effects.

11. Inflammatory cytokines and hormone interaction

• • Hormonal shifts (like estrogen decline) can trigger chronic inflammation.
  • Inflammatory markers like IL-6 and TNF-alpha interfere with neurotransmitter balance.

12. Vasopressin (water balance and mood regulation)

• • Low vasopressin levels (often linked to diabetes insipidus or chronic stress) can cause apathy, fatigue, and depressive symptoms.

13. Dopamine and reward system disruption

• • Certain hormonal changes (like low testosterone, high cortisol, or insulin resistance) can dull dopamine signaling, reducing motivation and pleasure.
  • This is why conditions like PCOS, metabolic syndrome, and chronic stress often lead to mood disorders.

14. Gut hormones and microbiome

• • Hormones like GLP-1 and peptide YY (PYY) regulate metabolism but also influence brain function.
  • Gut dysbiosis (imbalance in gut bacteria) can add to depression by affecting serotonin production.

15. Adrenal fatigue and HPA axis dysfunction

• • Chronic stress can lead to low energy, burnout, and depressive symptoms by deregulating the hypothalamic-pituitary-adrenal (HPA) axis.

16. Menopause and andropause

• • Beyond estrogen/testosterone shifts, menopause and andropause involve multiple hormonal cascades, impacting brain function, sleep, and emotional stability.

17. Serotonin disruption due to estrogen and progesterone

• • Estrogen helps increase serotonin production and receptor sensitivity, which is why low estrogen levels (menopause, postpartum, PMS) can add to mental disorders.
  • Progesterone is calming in moderate amounts but can sometimes excessively stimulate GABA receptors, leading to fatigue, sluggishness, and low motivation.

18. Altered endocannabinoid system function

• • Hormones like cortisol, estrogen, and oxytocin play a role in mood, stress resilience, and motivation by regulating the endocannabinoid system.
  • Hormonal imbalances can lower our happiness by disrupting anandamide (a “bliss” molecule) levels.

19. Histamine sensitivity and estrogen link

• • Estrogen increases histamine levels, and some people experience mood swings or anxiety due to histamine sensitivity.
  • High histamine can cause brain inflammation, leading to irritability and depressive symptoms.

20. Changes in mitochondrial energy production

• • Hormones like thyroid, cortisol, and insulin are critical for energy production in brain cells since they regulate mitochondrial function.
  • The brain can’t produce enough energy when these hormones are imbalanced, leading to mental fatigue, brain fog, and depression.

21. Deregulated testosterone in women (not just men!)

• • Low testosterone in women can cause low mood, exhaustion, and loss of motivation. That’s especially true after menopause.
  • PCOS (Polycystic Ovary Syndrome) can cause extra testosterone, which may lead to irritability, anxiety, and depression in some instances.

22. Seasonal hormonal shifts and vitamin D deficiency

• • Sunlight affects melatonin, serotonin, and vitamin D. These are all hormone-like substances that affect mood.
  • Seasonal Affective Disorder (SAD) is partially due to reduced vitamin D and serotonin levels in winter months.

23. Estrogen’s role in gut barrier integrity

• • Estrogen helps maintain a healthy gut lining, which is important because gut bacteria produce neurotransmitters like serotonin.
  • Low estrogen levels (like in menopause) can increase intestinal permeability (“leaky gut”), creating inflammation and mental illnesses.

24. Insulin and dopamine sensitivity

• • Chronic insulin resistance (often due to poor diet, stress, or PCOS) reduces dopamine receptor sensitivity.
  • This can lead to a blunted reward system and depression, since dopamine is key for motivation and pleasure.

25. Adrenaline (epinephrine) burnout

• • Chronic stress can cause adrenaline dysregulation, leading to periods of hyperactivity followed by crashes, mimicking bipolar-like mood swings.
  • Low adrenaline levels can cause extreme fatigue and depression if the adrenal glands become depleted.

Final thoughts

Hormonal imbalances don’t necessarily cause depression on their own, but they can substantially influence mood as well through neurotransmitter imbalances, inflammation, gut health, mitochondrial function, and the stress response. That’s because hormonal alterations impact nearly every system in the body.

It’s worth getting a comprehensive hormonal panel (testing cortisol, sex hormones, thyroid, insulin, etc.) and discussing options with a doctor if you suspect a hormonal imbalance is affecting your mental (or physical) health for the worse.