Your Brain on Thyroid

Happy Monday!

I love the fact that hormone replacement therapy is starting to go mainstream.

But for every 100 men and women beginning their HRT/TRT journey, about 80-90% are unaware of how crucial their thyroid hormones are.

Most people think of the thyroid as a metabolic gland, but it’s also profoundly tied to mood, clarity, cognition, and mental health.

When your thyroid isn’t firing properly, you can look physically “okay” and yet still feel emotionally off.

HRT/TRT can help, but unfortunately, many patients on HRT never get their thyroid system optimized.

They may be prescribed estrogen, testosterone, peptides, and so on, but their thyroid quietly remains under-supported.

This results in a half-functioning brain, a subpar mood, and reduced cognitive function.

When we look at studies, hypothyroidism (both overt and subclinical) is repeatedly correlated with higher rates of depression, anxiety, cognitive slowing, and “brain fog.”

If your thyroid health isn’t addressed, no amount of hormone tweaks elsewhere may restore mental vitality.

Today, we’ll look at how important the thyroid is for mood and brain health.

Why Thyroid Hormones Matter

Your brain needs fuel, signalling, and regulation, and thyroid hormones (T4 and especially T3) play a central role in all three.

T4 is the “pro-hormone,” while T3 is the active hormone that gets into brain cells.

If conversion is sub-optimal, brain tissue may be “starved” of T3 even when blood tests appear “normal.”

T3 influences neurotransmitters (like serotonin and dopamine), supports synaptic connections, and stabilizes neural networks involved in attention, memory, mood regulation, and mental speed.

Research shows that hypothyroid brains often show reduced metabolism and slower processing, which correlates with cognitive issues and low mood.

If the thyroid signal to the brain is weak, expect mood dips, foggy thinking, slower recall, and even depressive symptoms.

When thyroid health is optimized, you can expect clearer thinking, faster recall, and improved mood stability.

Optimized Thyroid & Longevity

Here’s where it gets really interesting.

A big new observational study found that patients with hypothyroidism who were treated only with T4 (levothyroxine), even when their labs looked “normal”, still had significantly higher risks of dementia and mortality over 20 years.

This suggests that hitting the lab targets may not be enough if your brain’s not getting the T3 it needs.

Another randomized crossover trial of 70 patients comparing DTE to T4 monotherapy found that while on group-level mood/cognitive tests were similar, 48.6% of participants preferred the DTE phase, reporting better subjective well-being and losing modest weight. 

Optimized thyroid treatment (especially with T3-inclusive therapies) is protecting brain health in the long term.

Starting with DTE

DTE (natural desiccated thyroid extract) often outperforms standard approaches for mood and cognition in the right individual.

DTE supplies T4 and T3 in a ratio closer to that of a healthy human thyroid, rather than T4-only treatments, which require the body to convert T4 to T3.

DTE essentially “jumps in” with a portion of pre-formed T3, which can translate into a faster uptick in mental clarity, improved mood, better cognitive speed, and more energy.

The 2013 RCT (Hoang et al.) showed that those who preferred DTE experienced greater subjective well-being and modest weight loss, despite similar lab outcomes. 

If you still feel inferior while on T4 monotherapy (brain fog, mood issues, “just okay” energy), switching to DTE is a logical next step.

What to Watch & How to Apply It

Here’s what I would do to get a pulse on your thyroid health.

1. Check your thyroid panel: TSH, free T4, free T3, plus optional reverse T3 and thyroid-antibodies (TPO, TG) if mood/cognition is an issue.

2. If you’re on T4 monotherapy and still have mood/cognitive complaints (despite “normal labs”), consider a trial of DTE under physician supervision.

3. Track symptoms: Use validated tools (BDI for mood, GHQ-12 for general health, cognitive checklists) and subjective reports (brain fog, clarity, motivation).

4. Monitor labs every 6-12 weeks after a dose change. Watch for signs of “too much” (palpitations, insomnia, anxiety) and adjust.

5. Prioritize brain health long-term: The data suggest that optimized thyroid treatment may reduce dementia and mortality risks in the long run.

6. Work with a practitioner who understands thyroid nuance (conversion issues, T3-need individuals) and supports your brain/mood/cognition goals.

Final Thoughts

The thyroid is one of our most underrated levers for inner clarity and mental well-being.

When thyroid health is optimized, the brain lights up with better focus, clearer thinking, more energy, and an elevated mood.

In contrast, when thyroid health is “adequately treated” in lab terms but not optimized in functional terms, you may settle for “just okay” instead of exceptional.

Take your thyroid as seriously as you do your testosterone levels.

Optimizing thyroid function is excellent for metabolism and fat loss, but the implications for brain health and mood are equally important!

Best,

Hunter Williams

P.S. I have zero affiliation with this company, but I know many people who have had success getting their desiccated thyroid from this online pharmacy called TelyRx.

Further Reading

• Hoang TD, Olsen CH, Mai VQ, Clyde PW, Shakir MK. “Desiccated Thyroid Extract Compared with Levothyroxine in the Treatment of Hypothyroidism: A Randomized, Double-Blind, Crossover Study.” J Clin Endocrinol Metab. 2013;98(5):1982-1990. PubMed link

• “Comparative effectiveness of Levothyroxine, Desiccated Thyroid Extract, and Levothyroxine + Liothyronine in Hypothyroidism: A Subset of Hypothyroid Patients Responds to Combination Therapy Containing T3.” J Clin Endocrinol Metab. 2021;106(11):e4400-e4413. PMC article link

• UTMB News. “UTMB Study Suggests Combination Thyroid Therapy May Reduce Dementia and Mortality Risk in Hypothyroidism.” June 23 2025. UTMB News link

• Alšauskė SV. “The Association of Thyroid Disease With Risk of Dementia and Cognitive Impairment.” Medicina (Kaunas). 2024;60(12):1917. MDPI link