Hormones play an important role in the development and progression of depression since these chemical messengers significantly impact mood and behavior.

Here’s how hormones can influence depression:

1. Cortisol (stress hormone)

• • Cortisol is produced by the adrenal glands in response to stress.
    Chronic stress can lead to elevated cortisol levels, which have been linked to depression in some research.
    High cortisol levels can cause changes in brain structure and function, particularly affecting areas like the hippocampus (important for memory) and prefrontal cortex (involved in decision-making and emotional regulation)​.
  • Studies have found that people with depression often have hyperactive HPA (hypothalamic-pituitary-adrenal) axis function, resulting in persistently high cortisol levels, which can worsen depressive symptoms by contributing to anxiety, insomnia, and reduced neurogenesis (the growth of new neurons)​.

2. Serotonin and norepinephrine

• • Serotonin is a neurotransmitter that plays a key role in regulating mood, sleep, and appetite.
    Having too little serotonin is strongly associated with depression, which is why many antidepressants (like SSRIs) aim to increase serotonin availability in the brain​.
  • Norepinephrine, another neurotransmitter and hormone, is involved in the body’s fight-or-flight response.
    Imbalances can lead to symptoms like a lack of energy and a reduced ability to experience pleasure, which are common features of depression​.

3. Estrogen and progesterone
   

• • Estrogen has a neuroprotective effect and helps modulate the production of serotonin.
    Fluctuations in estrogen levels, such as during pregnancy, postpartum, and menopause, can increase the risk of developing depression. This is why some women experience postpartum depression or premenstrual dysphoric disorder (PMDD)​.
    
  • Progesterone has calming effects but can also contribute to mood swings and irritability when levels drop suddenly, such as before menstruation.
    Disruption in the balance between estrogen and progesterone is thought to be a factor in hormonal depression​.

4. Thyroid hormones

• • Thyroid dysfunction, especially hypothyroidism (low thyroid hormone levels), is often linked with depression.
    Low levels of thyroid hormones can lead to symptoms like fatigue, low energy, and mood disturbances. Treating thyroid imbalances can help alleviate depressive symptoms in some cases​.

5. Testosterone

• • While testosterone is typically associated with men, it also affects women.
    Being deficient in testosterone can lead to decreased motivation, fatigue, and depression in both sexes.
    Studies show that testosterone supplementation in men with low levels can improve mood and reduce depressive symptoms​.

6. Oxytocin (love hormone)
   
   

• • Oxytocin is involved in social bonding, trust, and emotional regulation.
    Insufficient oxytocin has been linked to social withdrawal, anxiety, and depression.
    Trauma and stress can reduce oxytocin levels and impact the ability to form healthy emotional connections, potentially leading to mood disorders.​

7. Dysregulation of the HPA axis (hypothalamic-pituitary-adrenal axis)

• • The HPA axis regulates the body’s response to stress through the production of cortisol.
    Chronic activation of this system due to prolonged stress or trauma can lead to an imbalance in cortisol levels.
  • Interestingly, both elevated and suppressed cortisol levels have been observed in people with depression. This dysregulation is associated with symptoms like fatigue, poor concentration, and disrupted sleep​.

8. Role of inflammatory hormones (cytokines)

• • There is growing evidence that links inflammation to depression.
    The body can release inflammatory cytokines like interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) when experiencing chronic tension.
    Elevated levels of these cytokines can affect brain function and lead to neuroinflammation, possibly leading to depressive symptoms​.
  • Individuals with major depressive disorder frequently show higher levels of inflammatory markers, which can influence neurotransmitter systems like serotonin, reducing mood stability​

9. Ghrelin and leptin (appetite-regulating hormones)

• • Hormones like ghrelin (hunger hormone) and leptin (satiety hormone) not only regulate appetite but also influence temperament.
    Ghrelin has been found to have antidepressant-like effects, possibly because it activates the brain’s reward centers.
    Low levels of ghrelin may be linked to sensations such as low motivation and anhedonia (lack of pleasure)​.
  • Conversely, leptin, which regulates body fat and satiety, has been shown to have mood-regulating properties.
    Depleted leptin levels have been associated with depression in cases involving eating disorders​.

10. Insulin and blood sugar regulation
    
    

• • Insulin is the hormone responsible for regulating blood sugar levels, but it can also impact mood.
    Insulin resistance is linked to an increased risk of depression and is typically seen in metabolic disorders like diabetes.
    Poor blood sugar control can lead to mood swings, fatigue, and cognitive difficulties.​
  • Additionally, there is evidence suggesting that diabetes-related hormonal imbalances might affect the brain’s neurotransmitter levels​.

11. Melatonin (sleep and circadian rhythms)

• • Melatonin is the hormone that regulates the sleep cycle, but also plays a significant role in mood regulation.
    Disrupted melatonin levels regularly happen due to poor sleep hygiene or circadian rhythm disturbances (like shift work or jet lag) and can trigger or worsen depression.
  • People with depression, specifically those with seasonal affective disorder (SAD), often have irregular melatonin production.
    Restoring normal melatonin levels through light therapy or supplements can improve mood and alleviate a negative mental state.

12. DHEA (dehydroepiandrosterone)

• • DHEA is a hormone produced by the adrenal glands and is involved in the production of other hormones, such as estrogen and testosterone.
    Being deficient in DHEA has been linked to depression in older adults​.
  • Some studies suggest that DHEA supplementation may have mood-enhancing effects and help reduce symptoms of depression in people with low baseline levels of this hormone​.

Conclusion

Hormonal imbalances can directly and indirectly influence the development of depression and other mood disorders by affecting mood regulation, stress response, and brain function.

Understanding these hormonal connections is critical for developing more targeted treatments, such as hormone therapy or medications that address specific neurotransmitter imbalances.