Testosterone and Your Immune System: Why Men Get Sicker

Every household knows the joke. He has a cold, and the house grinds to a halt.

The joke survives because the underlying observation is real. Men do worse with respiratory infections than women, across almost every pathogen studied, and the difference is large enough to show up in mortality statistics rather than only in domestic complaints.

Testosterone is usually blamed. That explanation is partly right, considerably more complicated than it appears, and in one important respect probably backwards.

The sex difference is real

Start with what is not in dispute.

Women mount stronger immune responses to infection and to vaccination than men. They also have more frequent adverse reactions to vaccines, which is the same mechanism seen from the other side. And they account for the large majority of autoimmune disease, which is what an immune system tuned towards vigour looks like when it turns inward.

Men, correspondingly, tend to have more severe infections and worse outcomes.

These differences appear after puberty and largely disappear after reproductive age, which is what points at hormones rather than only at chromosomes.

The classic explanation

In 1992, two biologists proposed the immunocompetence handicap hypothesis. Testosterone, they argued, suppresses immune function, so only genuinely healthy males can afford to produce a lot of it. Antlers, plumage and muscle became honest signals precisely because they cost something.

It is an elegant idea, and it has shaped how testosterone and immunity are discussed for three decades.

The strongest human evidence came in 2014. Researchers analysing responses to influenza vaccination found that men with the highest testosterone, together with an associated gene signature, produced the lowest antibody responses. The genes involved related to lipid metabolism, which suggested a mechanism rather than only an association.

Where it stops being simple

Three findings complicate that picture, and honest coverage includes them.

The animal evidence is weaker than assumed. A meta-analysis pooling studies across species found the link between elevated testosterone and immunosuppression was not statistically significant once multiple studies on the same species were accounted for. It found no effect on direct measures such as white cell counts or antibody production.

One human study found the opposite. Researchers examining ninety-seven healthy men measured free testosterone, total testosterone, DHT and DHEA against multiple measures of innate and adaptive immunity. Free testosterone was positively correlated with the strength of the influenza vaccination response. Total testosterone showed no effect at all.

Their interpretation is worth quoting in spirit: in a well-fed population, men with higher free testosterone could afford to invest more in immunity. The handicap only bites when resources are scarce.

The newest work shows modulation rather than suppression. A 2024 study followed twenty-three trans men through testosterone therapy with detailed immune analysis, and found testosterone shifting the balance between type-I interferon and tumour necrosis factor signalling. Not switching immunity off. Retuning which arm dominates.

That is a meaningfully different claim, and it fits the clinical picture better than blanket suppression.

The finding that reverses the story

Now the part that matters most, because it inverts what most men assume.

During COVID-19, researchers examined hormone levels in hospitalised men. The men who did worst did not have high testosterone. They had low testosterone.

Lower testosterone and a higher oestradiol-to-testosterone ratio during admission were associated with higher inflammatory cytokine concentrations, greater disease severity, more ventilator use, more intensive care admission and higher mortality. The association held after adjusting for age, BMI, other conditions, smoking and race.

Two explanations, and both are probably true.

Acute illness suppresses testosterone. Severe infection shuts down non-essential systems, and reproduction is non-essential when you are fighting for air. So low testosterone may be a consequence rather than a cause.

Testosterone restrains inflammation. The damage in severe respiratory infection often comes from the immune response rather than the pathogen. A dampening influence on that response is protective, not harmful.

Which reframes the whole question. The immunosuppressive property that looks like a handicap against infection may be an advantage against the overreaction that kills people.

Studies of reconstructed 1918 influenza in animals show death driven by uncontrolled cytokine release, and suppressing that response reduced mortality. Same logic, different century.

What this actually means for you

Five practical points, and none of them is what the supplement adverts suggest.

High testosterone does not make you fragile. The evidence for suppressed immunity is weaker than the popular version, and one good human study found the reverse.

Low testosterone is not a reason to expect illness. The association with severe infection is real but the direction is unclear, and being ill lowers testosterone reliably.

Do not test your testosterone while you are ill. This is the genuinely useful takeaway. Acute infection suppresses it, so a reading taken during or shortly after illness will be low and will not represent your baseline. Wait until you have been well for several weeks. The blood test guide covers timing.

Nothing here tells you to take or avoid testosterone. No trial has tested whether treatment changes infection outcomes.

If you keep getting ill, look elsewhere first. Poor sleep, iron deficiency, uncontrolled blood sugar and chronic stress all impair immunity with far better evidence than hormones. Sleep apnoea and testosterone and testosterone and type 2 diabetes cover two of them.

Why men have less autoimmune disease

The same mechanism seen from the other direction.

Women account for roughly two thirds to four fifths of autoimmune disease, depending on the condition. An immune system tuned for vigour is better at clearing pathogens and more likely to mistake your own tissue for one.

Testosterone's restraining influence appears to be part of why men are relatively protected. It is the same property, with the sign reversed depending on what you are measuring.

That trade-off is the honest summary of this entire subject. There is no setting that is simply better.

The honest summary

Testosterone modulates immunity rather than suppressing it. The classic view, that high testosterone weakens men, comes from an elegant hypothesis and one strong vaccination study, and it does not survive contact with the wider evidence intact.

What is clearer: men mount weaker responses to infection and vaccination, testosterone is part of that, and the same restraint that reduces antibody production also limits the inflammatory overreaction that causes the worst outcomes.

The practical piece is smaller than the biology. Do not measure your testosterone while you are ill, and if you are ill more often than you should be, the answer is probably in your sleep, your iron or your blood sugar rather than your hormones.

Common questions

Does testosterone weaken the immune system?

It modulates it rather than simply suppressing it. Men with the highest testosterone produced the lowest antibody responses to influenza vaccination in one study, but another found free testosterone positively correlated with vaccine response, and pooled animal data did not show a significant effect.

Why do men get sicker than women?

Women mount stronger immune responses to both infection and vaccination. The difference appears after puberty and fades after reproductive age, which points at hormones alongside genetics.

Does low testosterone make infections worse?

Men hospitalised with COVID-19 who had lower testosterone had higher inflammatory markers, greater severity and higher mortality. But acute illness itself suppresses testosterone, so the direction of that relationship is unresolved.

Should I test my testosterone after being ill?

Not immediately. Acute infection suppresses testosterone, so a reading taken during or soon after illness will underestimate your baseline. Wait several weeks after full recovery.

Will TRT make me more prone to infection?

No trial has tested this, so there is no evidence-based answer. The theoretical concern comes from studies of natural variation, which are not the same thing as treatment.

Why do women get more autoimmune disease?

The same mechanism in reverse. A more vigorous immune system clears pathogens better and is more likely to attack your own tissue. Testosterone's restraining influence appears to be part of why men are relatively protected.

Sources: Furman D et al., Systems analysis of sex differences reveals an immunosuppressive role for testosterone in the response to influenza vaccination, Proc Natl Acad Sci USA 2014;111(2):869-74 · Nowak J et al., No evidence for the immunocompetence handicap hypothesis in male humans, Sci Rep 2018;8:7392 · Klein SL, Flanagan KL, Sex differences in immune responses, Nat Rev Immunol 2016;16(10):626-38 · Immune system adaptation during gender-affirming testosterone treatment, Nature 2024;633:155-64 · Dhindsa S et al., Association of circulating sex hormones with inflammation and disease severity in patients with COVID-19, JAMA Netw Open 2021;4(5):e2111398 · Educational only, not medical advice.

Keep reading: What causes low testosterone · Testosterone and type 2 diabetes · Sleep apnoea and testosterone · Blood test: what to check · Why testosterone is falling across generations · Free 2-minute testosterone test