Haemochromatosis: The Iron Overload That Lowers Testosterone

He was 47, tired in a way sleep did not touch, and his knuckles ached. The second and third fingers on both hands, worst in the mornings.

His GP tested for rheumatoid arthritis. Negative. Someone suggested his testosterone, which came back at 8.1 nmol/L, and he was referred to a private clinic that offered him gel.

Nobody checked his ferritin.

Haemochromatosis is the most common inherited condition in people of northern European descent, and it is one of the few causes of low testosterone that damages several organs while it goes unrecognised.

What it is

Your body has no mechanism for excreting excess iron. It regulates how much it absorbs, and that is the only control it has.

In hereditary haemochromatosis, usually caused by two copies of a variant in the HFE gene, that control fails. You absorb several times more iron than you need, year after year, and it accumulates in organs.

Roughly one in 200 to 300 people of northern European ancestry carry two copies. In Ireland it is closer to one in 80. That makes it more common than most conditions doctors think of first.

Not everyone with the genes develops iron overload, which is part of why it is missed. But those who do, accumulate iron for decades before symptoms appear.

Why testosterone falls

Iron deposits in specific places: the liver, the pancreas, the heart, the joints, the skin, and the pituitary gland.

That last one is the mechanism here. Iron damages the pituitary cells producing LH and FSH, so the signal telling your testes to make testosterone weakens.

The resulting pattern is low testosterone with low or inappropriately normal LH and FSH: secondary hypogonadism, the same pattern seen with prolactinomas and opioid use.

Iron also deposits directly in the testes, adding a second mechanism on top.

Hypogonadism is among the most common endocrine complications of haemochromatosis, and in some men it is the first thing noticed. What causes low testosterone covers the wider list of things that produce this pattern.

The symptom that should prompt the test

Iron overload produces a collection of vague complaints, which is exactly why it goes unrecognised for years. Fatigue, joint pain, low libido, abdominal discomfort.

But one symptom is unusually specific, and it is worth knowing.

Pain in the second and third knuckles, the joints at the base of your index and middle fingers, is characteristic of haemochromatosis. Patients sometimes describe it as the handshake sign, because gripping hurts.

It is not universal, and it is not diagnostic on its own. But joint pain in that specific distribution, in a man with fatigue and low testosterone, should prompt an iron panel rather than another opinion on his hormones.

Other features worth noting: skin bronzing or greying, often mistaken for a tan that never fades; new diabetes, from iron in the pancreas, which is where the old name bronze diabetes came from; abnormal liver enzymes; and, later, heart rhythm problems or heart failure.

The test nobody orders

Diagnosis is straightforward and cheap, which makes the delay harder to justify.

Transferrin saturation is the more useful of the two. Above 45 per cent warrants investigation, and it rises before ferritin does.

Ferritin reflects stored iron. Above 300 ng/mL in men is raised, though ferritin also rises with inflammation, alcohol and fatty liver, so it is less specific.

Both should be requested together. Transferrin saturation without ferritin, or ferritin without saturation, each miss cases.

If both are raised, HFE genetic testing confirms it. If genetics are negative but iron is clearly high, other causes need excluding.

A reasonable request: "Could I have ferritin and transferrin saturation checked? I have fatigue, joint pain and low testosterone."

Note the direction here. Everywhere else on this site, ferritin comes up as something to check for deficiency. This is the opposite problem, and the same test finds it. How to read your blood test results covers what the numbers mean at both ends.

Why this matters more than most causes

Because untreated haemochromatosis damages organs permanently, and because treatment is simple.

Iron accumulation causes liver fibrosis and eventually cirrhosis, with a substantially increased risk of liver cancer. It causes diabetes. It causes cardiomyopathy. And it causes the hypogonadism that brought the man to the clinic in the first place.

Every one of those is preventable if iron is removed before the damage is done.

Which is why a man prescribed testosterone without an iron panel may be having his symptom treated while the process causing it continues.

The treatment

Venesection. You give blood, regularly, until iron stores normalise.

Initially that might be weekly or fortnightly, sometimes for months, until ferritin falls to target. After that, maintenance is typically a few times a year.

It is inexpensive, uses no drugs, and it works. Men diagnosed and treated before organ damage occurs have a normal life expectancy.

Two things about testosterone specifically.

If the pituitary has been damaged, testosterone may not recover fully even after iron is cleared, and replacement is then appropriate. But it is worth removing the iron first and reassessing, rather than assuming.

And if you have already started TRT, that does not preclude any of this. Get the iron panel anyway. The two are not alternatives.

Family matters here

This is inherited, which means a diagnosis has implications beyond you.

Siblings of someone with two HFE copies have a one in four chance of the same genotype. Children are at risk depending on the other parent.

Screening relatives is standard practice and picks up people decades before symptoms, which is precisely when treatment is most valuable.

If a relative has been diagnosed, that is reason enough to have your own iron studies regardless of symptoms.

The honest summary

Most men with low testosterone do not have haemochromatosis. It is not the first thing to think of.

But it is common enough that it should be excluded, cheap to test for, and damaging in a way that other causes are not. A man with low testosterone, fatigue and aching knuckles who has never had an iron panel has an unanswered question.

And unlike most of what appears on this site, this one has a clean ending. Remove the iron early enough and the outcome is normal.

Common questions

What is haemochromatosis?

An inherited condition, usually caused by two copies of an HFE gene variant, in which the body absorbs far more iron than it needs. Iron accumulates in the liver, pancreas, heart, joints and pituitary gland.

How common is it?

Around one in 200 to 300 people of northern European descent carry two copies, rising to about one in 80 in Ireland. Not everyone who carries them develops iron overload.

Why does it lower testosterone?

Iron damages the pituitary cells producing LH and FSH, weakening the signal to the testes. Iron also deposits in the testes directly. The result is low testosterone with low or normal LH and FSH.

What symptoms should prompt testing?

Fatigue and joint pain, particularly in the second and third knuckles, which is characteristic. Also skin bronzing, new diabetes, abnormal liver enzymes and low libido.

Which tests do I need?

Transferrin saturation and ferritin together. Saturation above 45 per cent or ferritin above 300 ng/mL in men warrants investigation, confirmed by HFE genetic testing.

How is it treated?

Venesection, meaning regular blood removal until iron normalises, then maintenance a few times a year. It is inexpensive and effective, and normal life expectancy follows treatment before organ damage.

Will my testosterone recover?

Sometimes. If the pituitary is damaged, it may not fully recover and replacement is appropriate. Removing the iron first and reassessing is the sensible order.

Should my family be tested?

Yes. Siblings have a one in four chance of the same genotype, and screening identifies people long before symptoms, which is when treatment matters most.

Sources: Kowdley KV et al., ACG clinical guideline: hereditary hemochromatosis, Am J Gastroenterol 2019;114(8):1202-18 · European Association for the Study of the Liver, EASL clinical practice guidelines on haemochromatosis, J Hepatol 2022;77(2):479-502 · McDermott JH, Walsh CH, Hypogonadism in hereditary hemochromatosis, J Clin Endocrinol Metab 2005;90(4):2451-5 · Educational only, not medical advice.

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