Depression and Possible Hormonal link

Understanding the Connections and Treatment Options


Depression can be affected by hormonal imbalances, which often go unrecognized in traditional psychiatric evaluations. Both males and females may experience mood changes due to disrupted levels of sex hormones, thyroid hormones, adrenal hormones, and neurosteroids.



 Hormones That Affect Mood

In Females:

  • Estrogen: Supports serotonin and dopamine; low levels can cause irritability, anxiety, and low mood
  • Progesterone: Calming via GABA receptor effects; low levels may worsen anxiety, insomnia
  • Thyroid hormones (T3/T4): Low thyroid function often mimics depression
  • Cortisol: Chronic stress leads to HPA axis dysfunction and depressive symptoms


In Males:

  • Testosterone: Low levels are linked to apathy, fatigue, and low libido
  • DHEA: Low levels may reduce resilience, energy, and mood
  • Thyroid and cortisol: As with females, can contribute to fatigue and depression



Hormone Testing to Consider

  • Total and Free Testosterone (especially in men)
  • Estradiol, Progesterone
  • DHEA-S
  • Thyroid panel: TSH, Free T3, Free T4, TPO antibodies
  • Morning and evening cortisol
  • Vitamin D, B12, folate, magnesium



  When Standard Antidepressants Aren’t Working

Evaluate for hormonal causes if:

  • Antidepressants partially help or stop working
  • Worsening mood with hormonal shifts (e.g., menstrual cycle, menopause, andropause)
  • No response despite multiple medication trials


Psych Meds That May Worsen Hormonal Depression:

  • SSRIs: May lower testosterone and cause emotional blunting
  • Antipsychotics: Can raise prolactin and lower sex hormones
  • Benzodiazepines: Sedating, may worsen fatigue or motivation



 

 Natural & Hormonal Treatment Options


Females:

  • Bioidentical progesterone
  • Estradiol transdermal patch, cream or pill (if peri or menopausal)
  • Thyroid optimization (especially if Free T3 is low)
  • Adaptogens for adrenal support (ashwagandha, rhodiola)
  • Supplements: Magnesium Vitamin D, B-complex, omega-3s
  • Testosterone therapy if indicated



Males:

  • Testosterone therapy if indicated
  • DHEA (monitor for estrogen conversion)
  • Thyroid and adrenal support
  • Progesterone at night for GABA support (off-label)
  • Supplements: Zinc, Vitamin D, magnesium, B6, omega-3s



  Additional Treatments to Consider

  • Low Dose Naltrexone (LDN): Immunomodulatory, mood-stabilizing effects
  • Pregnenolone: Neurosteroid for mood, sleep, cognition
  • SAMe or methylated B vitamins: For methylation support (especially if MTHFR mutation present)
  • Ketamine therapy or TMS: For refractory cases



   Diet and Lifestyle

  • Anti-inflammatory diet (high in omega-3s, leafy greens, low sugar)
  • Regular exercise (especially resistance training and walking)
  • Sunlight and circadian rhythm support
  • Therapy: CBT, EMDR, somatic therapy



  Hormonal imbalance can underlie or worsen depression, especially when symptoms are resistant to standard psychiatric medications. A personalized, hormone-informed approach may provide lasting relief. Testing, supplementation, and in some cases bioidentical hormone therapy should be considered in both men and women with persistent depressive symptoms.


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