Testosterone has a complex relationship with the immune system. It doesn’t simply “boost” or “weaken” immunity. Instead, it acts as an immune modulator, dialing down certain inflammatory responses while potentially supporting other aspects of immune defense. This dual role helps explain why men are less prone to autoimmune diseases than women but often fare worse during acute infections.
How Testosterone Affects Immune Cells
Immune cells throughout the body carry androgen receptors, which means they can detect and respond to testosterone directly. This includes cells from both branches of the immune system: innate immune cells like macrophages (the body’s first responders to infection) and adaptive immune cells like T-cells and B-cells (which mount targeted, long-term defenses).
When testosterone binds to these receptors, it reduces the production of key inflammatory signaling molecules. Specifically, testosterone lowers output of TNF and interferon-gamma from macrophages, two proteins that drive inflammation. Importantly, it does this without suppressing IL-10, an anti-inflammatory molecule. The net effect is a shift away from excessive inflammation. This effect appears to be independent of genetic sex, meaning it works the same way in both male and female cells.
Testosterone replacement therapy in men with low levels shows similar patterns. Supplementation has been linked to reduced production of IL-6 and TNF-alpha, two inflammatory markers commonly elevated in chronic disease. In practical terms, testosterone keeps the immune system from overreacting, which is protective in some situations and a liability in others.
Protection Against Autoimmune Disease
The most clear-cut benefit of testosterone for immune health is its role in preventing autoimmune conditions. Women develop autoimmune diseases like lupus, rheumatoid arthritis, and multiple sclerosis at dramatically higher rates than men, and testosterone is a major reason why.
Testosterone appears to promote B-cell tolerance, which means it helps the immune system avoid mistakenly attacking the body’s own tissues. In animal studies, removing testosterone production led to higher levels of antibodies directed against the body’s own proteins, specifically citrullinated proteins that are central to rheumatoid arthritis. These effects worked through both innate and adaptive immune pathways. When testosterone was absent, macrophages became more reactive to bacterial signals, and the adaptive immune system produced more self-targeting antibodies.
Clinical observations in transgender individuals reinforce this picture. Transgender men receiving testosterone have experienced improvement in subacute cutaneous lupus, while transgender women receiving estrogen (and suppressing testosterone) have developed lupus and lupus-related kidney disease. These cases suggest the protection isn’t just about having male chromosomes; it’s specifically about circulating testosterone levels.
The Tradeoff During Infections
The same anti-inflammatory properties that protect against autoimmunity can become a disadvantage during serious infections, when a strong inflammatory response is exactly what you need. This tradeoff became visible during COVID-19, where men consistently experienced worse outcomes than women.
However, the relationship between testosterone and infection severity is more nuanced than “testosterone weakens your defenses.” A study of hospitalized male COVID-19 patients found that those with the most severe illness actually had the lowest testosterone levels. Patients who avoided the ICU saw their testosterone gradually recover as the disease progressed, while ICU patients’ testosterone remained suppressed. By the second week of illness, testosterone level was the single best predictor of disease severity, outperforming standard markers like C-reactive protein, lymphocyte count, and IL-6. A level below 3.26 nmol/L predicted severe disease with 97% specificity.
This suggests that while testosterone’s immune-dampening effects may contribute to initial vulnerability, maintaining adequate testosterone levels during illness is associated with better outcomes. Severe infection itself crashes testosterone levels, which may then remove its anti-inflammatory benefits and allow a runaway inflammatory cascade.
Testosterone and Vaccine Response
One area where testosterone appears to directly support immune function is vaccine response. A study of healthcare workers who received COVID-19 vaccines found a significant positive association between testosterone levels and antibody production in men. Men with higher testosterone generated stronger antibody responses to the spike protein. Interestingly, estrogen and progesterone levels did not show the same linear relationship with antibody levels in either sex.
This finding challenges the older assumption that testosterone uniformly suppresses adaptive immunity. It’s possible that while testosterone restrains inflammatory responses, it supports the more targeted process of generating antibodies after vaccination.
Wound Healing: A Clear Downside
Not all of testosterone’s immune effects are beneficial. Testosterone consistently slows wound healing. In preclinical studies using both mouse and pig models, testosterone exposure increased wound size by roughly 25% compared to controls. The hormone disrupted the balance between two essential healing processes: it ramped up the formation of new blood vessels and granulation tissue (the raw, rebuilding tissue) while suppressing re-epithelialization, which is the skin closing back over the wound.
Blocking the androgen receptor reversed these effects, confirming testosterone was directly responsible. This may partly explain why older women, who have very low testosterone, often heal skin wounds faster than older men.
The Aging Feedback Loop
Testosterone levels decline naturally with age, and this decline feeds into a cycle that progressively weakens immune regulation. As men age, the Leydig cells responsible for producing testosterone lose mitochondrial function and produce less hormone. At the same time, immune cells in the testes shift from anti-inflammatory to pro-inflammatory states, secreting IL-6 and TNF-alpha, which further impair testosterone production.
This creates a self-reinforcing loop: less testosterone leads to more inflammation, which damages testosterone-producing cells, which leads to even less testosterone. The consequence extends beyond the testes. Falling testosterone reduces the activity of regulatory T-cells throughout the body, the immune cells responsible for preventing the immune system from attacking healthy tissue. This “immune-metabolic axis” helps explain why aging men experience both rising systemic inflammation and increasing vulnerability to autoimmune-like conditions.
What This Means in Practice
Testosterone is neither a pure immune booster nor a pure immune suppressant. Its primary immune role is as a brake on inflammation. That brake protects against autoimmune disease and prevents the kind of immune overreaction that damages organs during severe infections. But it also slows wound healing and may reduce the initial inflammatory response needed to contain pathogens early in an infection.
For men with clinically low testosterone, supplementation has been shown to reduce inflammatory markers and may help restore healthier immune regulation. For men with normal levels, the immune system is already benefiting from testosterone’s modulatory effects. The strongest evidence points to maintaining adequate testosterone, rather than maximizing it, as the most relevant goal for immune health.