SEX Hormones:

the relationship with ADHD & Dopamine

TESTOSTERONE

1. Cholesterol (Steroid Precursor – Master Molecule of Hormone Synthesis)

🔹 Function:
✅ Essential building block for all steroid hormones, including testosterone, estrogen, progesterone, cortisol, and aldosterone.
✅ Provides structural integrity to cell membranes, ensuring proper function.
✅ Precursor to vitamin D and bile acids, which are vital for digestion and metabolism.
✅ Synthesized in the liver and transported in the blood via lipoproteins (LDL & HDL).
✅ Converted into Pregnenolone via the enzyme CYP11A1 (P450scc) in mitochondria.
✅ Important in brain function: Helps form myelin sheaths, supporting neuronal transmission.

2. Pregnenolone (Neurosteroid & Hormone Precursor)

🔹 Function:
✅ First steroid hormone derived from cholesterol; acts as the precursor for all other steroid hormones.
✅ Synthesized in the adrenal glands, brain, liver, and gonads.
✅ Converts into Progesterone, Cortisol, Aldosterone, Testosterone, and Estrogen depending on enzymatic pathways.
✅ Functions as a neurosteroid, enhancing memory, cognition, and neuroplasticity.
✅ Modulates GABA, NMDA, and dopamine receptors, influencing anxiety, motivation, and ADHD symptoms.
✅ Plays a role in stress adaptation, brain repair, and mood regulation.

3. Progesterone (Female Reproductive & Neuroprotective Hormone)

🔹 Function:
✅ Supports the menstrual cycle, pregnancy, and fetal development.
✅ Precursor for testosterone, cortisol, and aldosterone.
✅ Calms the nervous system by modulating GABA receptors, reducing anxiety and stress.
✅ Enhances brain repair and protects neurons from oxidative stress.
✅ Plays a role in immune regulation and anti-inflammatory processes.

4. Testosterone (Androgen – Male Sex Hormone)

🔹 Function:
✅ Primary male sex hormone, responsible for muscle growth, libido, and sperm production.
✅ Influences dopamine release and ADHD symptoms.
✅ Increases motivation, aggression, and competitive behavior.
✅ Can be converted into DHT (Dihydrotestosterone) via 5α-reductase or Estrogen via Aromatase (CYP19A1).
✅ Supports bone density, red blood cell production, and cardiovascular health.

5. Dihydrotestosterone (DHT – Potent Androgen)

🔹 Function:
✅ More potent form of testosterone, critical for male sexual development.
✅ Responsible for body hair growth, deepening of voice, and prostate function.
✅ Plays a role in dopamine receptor desensitisation, potentially affecting ADHD symptoms.
✅ May contribute to male-pattern baldness and prostate enlargement.

6. Estrogen (Estradiol, Estrone, Estriol – Female Sex Hormones)

🔹 Function:
✅ Regulates female reproductive health, menstrual cycles, and pregnancy.
✅ Enhances dopamine function and receptor sensitivity, influencing cognition and ADHD.
✅ Supports bone health, mood stability, and brain function.
✅ Protects against neurodegeneration and cardiovascular disease.
✅ Can be produced from testosterone via the Aromatase enzyme.

7. Cortisol (Stress Hormone)

🔹 Function:
✅ Regulates stress response, metabolism, and immune function.
✅ Increases blood sugar to provide energy during stress.
✅ Chronic high levels reduce dopamine function, exacerbating ADHD symptoms.
✅ Helps control inflammation and immune responses.
✅ Involved in the fight-or-flight response, can cause anxiety & cognitive issues if chronically elevated.

8. Aldosterone (Mineralocorticoid – Blood Pressure Regulator)

🔹 Function:
✅ Regulates blood pressure and sodium-water balance in the kidneys.
✅ Maintains fluid levels and electrolyte balance.
✅ Works alongside cortisol in adrenal function.

9. Dopamine (Neurotransmitter – Motivation & Reward System)

🔹 Function:
✅ Critical for motivation, attention, and executive function.
✅ Low dopamine levels are strongly linked to ADHD symptoms.
✅ Involved in reward processing, learning, and impulse control.
✅ Modulated by testosterone, estrogen, and cortisol.
✅ Plays a key role in risk-taking, addiction, and emotional regulation.

10. Dopamine Receptors (D1, D2 Receptors – Brain Communication Sites)

🔹 Function:
✅ Mediate dopamine’s effects on motivation, focus, and impulse control.
✅ ADHD symptoms arise from impaired dopamine receptor signaling.
✅ D1 receptors are involved in goal-directed behavior and working memory.
✅ D2 receptors regulate habit formation, addiction, and emotional stability.
✅ Testosterone may desensitise dopamine receptors, contributing to ADHD symptoms in males.

11. Metabolized Hormones (Liver Breakdown – Deactivation & Excretion)

🔹 Function:
✅ Phase I (Hydroxylation – CYP450 Enzymes): Modifies hormones to prepare them for elimination.
✅ Phase II (Glucuronidation/Sulfation – UGT/SULT Enzymes): Adds sugar/sulfate = hormones water-soluble.
✅ Ensures hormonal balance by removing excess testosterone, estrogen, and cortisol.
✅ Excreted via urine and bile through the kidneys and liver.

How These Hormones Link to ADHD:

🔥 Testosterone & DHT → Increases dopamine but desensitises receptors, potentially worsening ADHD in males.
🔥 Estrogen → Enhances dopamine function, improving focus and impulse control, helping ADHD in females.
🔥 Cortisol (Stress Hormone) → Chronic stress reduces dopamine, worsening ADHD symptoms.
🔥 Dopamine Dysfunction → Low dopamine + impaired receptor signaling = Core issue in ADHD.