I'm on TRT But Still Exhausted
You're on testosterone. That's probably all they gave you.
Maybe they check your levels every few months. Maybe they tell you you're "in range." Maybe they shrug when you say you're still tired.
Here's what they don't tell you:
"In range" is not the same as optimized. Most XXY men on TRT are under-dosed, poorly monitored, or on protocols designed for acquired hypogonadism – not lifelong chromosomal difference. Getting TRT truly optimized can take years of self-advocacy, manual testing, and guesswork. The system doesn't help you get there.
And even if you do optimize it – TRT alone often isn't enough. Testosterone addresses one system. XXY affects several.
You're not imagining the fatigue. And it's not just you.
Two Problems, Not One
If you're on TRT and still exhausted, there are two possibilities:
- Your TRT itself isn't optimized – dosing, frequency, delivery method, estradiol management, free T vs total T. This is its own rabbit hole, and most endocrinologists don't go deep enough.
- TRT is as good as it's going to get, but other systems are dysregulated – metabolism, thyroid, vitamin D, sleep, inflammation, mental health. These don't respond to testosterone.
Usually it's both.
This page focuses on the second problem – what else to investigate when TRT alone isn't resolving fatigue.
(For the first problem – TRT optimization itself – see Is Your TRT Actually Optimized? Coming Soon)
Why TRT Alone Doesn't Fix It
When testosterone replacement doesn't resolve fatigue, the cause is usually in one of these domains:
Metabolic Dysfunction
XXY men have 4.4x higher rates of metabolic syndrome – insulin resistance, abnormal lipids, elevated inflammation. This persists even on TRT.
The research is explicit: testosterone does not normalize body composition in XXY men. Treated and untreated men show the same body composition patterns.
If your metabolism is dysregulated, you'll be tired regardless of testosterone status.
Signs: Carrying weight around the middle, energy crashes after meals, brain fog, elevated fasting glucose or HbA1c.
→ Understand metabolic health in XXY (Coming Soon)
Vitamin D Deficiency
Vitamin D deficiency is common in XXY and often overlooked. It causes fatigue independent of testosterone.
Research shows vitamin D predicts bone density in XXY better than testosterone levels – suggesting it plays a larger role than typically assumed.
Most standard care doesn't test it. Or tests it once and doesn't follow up.
Signs: Fatigue, muscle weakness, bone pain, low mood, frequent illness.
→ Understand bone health and vitamin D (Coming Soon)
Thyroid Dysfunction
XXY men have 2.7x higher risk of hypothyroidism. An underactive thyroid causes fatigue that looks identical to low testosterone – and won't respond to TRT.
If your thyroid hasn't been checked, or was checked once years ago, it's worth re-testing.
Signs: Fatigue, weight gain, cold intolerance, dry skin, constipation, slow thinking.
→ Understand autoimmune risks (Coming Soon)
Sleep Disorders
Sleep apnea is more common in XXY and often undiagnosed. TRT can actually worsen sleep apnea in some cases.
If you snore, wake unrefreshed despite adequate hours, or have been told you stop breathing at night, this needs evaluation.
Signs: Loud snoring, gasping at night, morning headaches, unrefreshing sleep, daytime sleepiness regardless of hours slept.
→ Discuss sleep study referral with your GP
Mental Health
Here's what the research shows that no one tells you:
Testosterone does not improve anxiety or depression in XXY men.
A Danish study specifically tested this. TRT had no effect on anxiety or depression scores. The mediating factor was neuroticism and executive function deficits – psychological patterns, not hormone levels.
If your fatigue has a depression component – low motivation, anhedonia, heaviness – testosterone optimization won't address it. Psychological support will.
Signs: Fatigue concentrated in motivation rather than physical energy, loss of interest, emotional flatness, persistent low mood despite "good" hormone levels.
→ Understand mental health in XXY (Coming Soon)
Inflammation
Elevated inflammatory markers (hsCRP) are common in XXY and associated with fatigue, cardiovascular risk, and metabolic dysfunction.
Standard care doesn't routinely test this. It should.
Signs: Generalized fatigue, joint aches, frequent minor illness, slow recovery.
What Your Doctor Probably Checked
- Testosterone levels (total T, maybe)
What Your Doctor Probably Didn't Check
- Free testosterone, estradiol, SHBG (the full hormone picture)
- HbA1c and fasting insulin
- 25-OH Vitamin D
- TSH and thyroid antibodies
- hsCRP
- Sleep study referral
- Mental health screening beyond "how are you feeling?"
The gap between these two lists is where your fatigue might be hiding.
What To Do
Step 1: Expand the Investigation
Request the tests that weren't done. We've prepared scripts you can take to your doctor:
→ Full test request list with GP scripts
Step 2: Consider the Full Picture
Fatigue in XXY is usually multifactorial. It's rarely one thing. The investigation often looks like:
- Assess TRT protocol itself – is it actually optimized, or just "in range"?
- Rule out thyroid
- Check vitamin D, optimize if low
- Assess metabolic markers (insulin resistance, inflammation)
- Evaluate sleep
- Screen mental health properly
- Only then conclude "it's managed"
If your care stopped at "testosterone is fine," it stopped too early.
The Core Message
TRT is necessary. It addresses real deficiency.
TRT is not sufficient. It doesn't fix metabolism, doesn't restore vitamin D, doesn't treat thyroid, doesn't resolve sleep apnea, doesn't improve depression.
And TRT "in range" is not the same as TRT optimized. Most XXY men never get there because the system doesn't help them get there.
If you're on testosterone and still feel wrong, the answer isn't "try harder" or "it's in your head."
The answer is: keep looking. At the TRT itself. At everything else.
The research shows where to look. This page points you there.