Why Men Suffer More Skin Infections, How Testosterone Helps Bacteria Talk and Turn Rogue
Doctors have known for a while that men experience more skin infections than women. From common boils and cellulitis to more serious staphylococcal abscesses, the clinical evidence has long pointed to a significant sex-based disparity. But the reasons have remained elusive. Behavioural explanations—men are less hygienic, more likely to engage in activities that cause minor skin trauma, or less likely to seek early treatment—have been proposed. Physiological explanations—differences in skin thickness, sebum production, or immune responses—have also been suggested. Yet the exact mechanism has been unclear.
Now, a groundbreaking study from scientists at UT Southwestern Medical Center in Texas, published in the prestigious journal Nature Microbiology, has unravelled the mystery. The answer lies not in behaviour or basic physiology alone, but in the very hormones that define male sex: androgens, including testosterone. The researchers have discovered that these male sex hormones help bacteria communicate and cause skin infections by activating a bacterial signalling system called quorum sensing.
This finding is not merely an academic curiosity. It has profound implications for how we treat bacterial infections, combat the growing threat of antibiotic resistance, and even manage chronic inflammatory skin diseases like psoriasis and eczema. This article examines the study’s methodology, its key findings, the potential for a paradigm shift in infection treatment, and what it means for the future of dermatology and microbiology.
Part I: The Long-Observed Disparity – Men and Skin Infections
The observation that men suffer more skin infections than women is not new. Epidemiological studies across multiple countries and healthcare systems have consistently shown higher rates of staphylococcal skin infections, cellulitis, and abscesses in males across all age groups, from infancy to old age. In hospital settings, male patients are overrepresented in dermatology wards for infectious conditions. In general practice, male patients receive more prescriptions for topical and oral antibiotics for skin infections.
But correlation is not causation. For years, the medical community has speculated. One prominent theory was behavioural: men are less likely to wash their hands, more likely to share razors or towels, and more likely to sustain minor cuts and abrasions through physical work or sports. Another theory pointed to physiological differences: male skin is thicker, produces more sebum (oil), and has a different pH, creating a more hospitable environment for certain bacteria. A third theory focused on the immune system: oestrogen, the female sex hormone, is known to enhance certain immune responses, potentially giving women an edge in fighting off infections.
None of these theories, however, provided a complete or mechanistically satisfying explanation. The UT Southwestern study has now filled that gap by showing that the bacteria themselves—specifically Staphylococcus aureus, the leading cause of skin infections worldwide—are directly responding to the presence of testosterone.
Part II: The Skin as a Hormone Factory – A Surprising Discovery
To understand the study, one must first appreciate a surprising fact about the skin. Sex hormones are generally thought to be produced by the gonads: the testes in males and the ovaries in females. However, Tania Harris-Tryon, Associate Professor of Dermatology and Immunology at UT Southwestern, and her team had previously shown, using an advanced technique called liquid chromatography tandem mass spectrometry, that the skin also generates and secretes extremely small concentrations of these hormones.
The skin, it turns out, is a hormonally responsive organ. Its sebaceous glands—the tiny oil-producing glands attached to hair follicles—are not just passive targets of hormones circulating in the blood. They can actively produce hormones themselves. This means that testosterone is readily available to microbes living on the skin’s surface, right where they need it, without having to wait for it to diffuse from the bloodstream.
“We continue to be fascinated by how the skin makes sex hormones and how this changes in skin diseases,” Dr. Harris-Tryon said. This local production of hormones creates a unique microenvironment on the skin’s surface, one that bacteria like S. aureus have evolved to exploit.
Part III: Quorum Sensing – How Bacteria Talk and Coordinate Attacks
Bacteria are not solitary creatures. They communicate with each other using a sophisticated chemical language called quorum sensing. Here is how it works: bacteria release small chemical signals into their environment. As the bacterial population grows, the concentration of these signals rises. When the concentration reaches a critical threshold—a “quorum”—the bacteria collectively switch on specific genes. In the case of pathogenic bacteria like S. aureus, those genes include the machinery for producing toxins, forming biofilms, and invading host tissue.
In other words, bacteria do not begin an infection immediately upon landing on the skin. Instead, they wait, multiply, and activate their disease-causing machinery only once the population is dense enough to have a fighting chance against the host’s immune system. This is a clever evolutionary strategy: why reveal your presence and trigger an immune response when you are too few to win?
The UT Southwestern researchers made a critical connection. They noticed that S. aureus seemed to respond not only to its own quorum sensing signals but also to the host’s hormones. Bioinformatics analysis revealed that the bacteria have molecular sensors that can detect and respond to androgens like testosterone. This led to a hypothesis: perhaps testosterone from the skin was hijacking the bacteria’s quorum sensing system, tricking them into thinking they had reached a quorum earlier than they actually had, and thus triggering an infection prematurely.
Part IV: The Experiments – Proving the Link
To test this hypothesis, the researchers designed a series of elegant experiments using mouse models.
First, they engineered mice that were unable to produce testosterone in their skin. These animals, when exposed to S. aureus, had markedly less severe infections and less skin barrier damage compared to normal mice. The absence of local testosterone made the mice more resistant to infection.
Next, they took the opposite approach. They applied testosterone to hormone-deficient female mice. These female mice, which would normally be more resistant to skin infections, became more vulnerable. The infection became more severe, mimicking the pattern seen in males.
To confirm that the effect was specific to androgens, the researchers also tested female sex hormones—oestradiol and progesterone. These had no effect on the bacteria’s quorum sensing. The bacteria did not respond to them. The effect was uniquely and specifically driven by male hormones.
Finally, the researchers looked at what was happening at the molecular level. They found that testosterone was activating a specific component of the S. aureus quorum sensing system, essentially turning up the volume on the bacteria’s communication network. The bacteria, sensing a falsely high level of chemical signals, switched on their virulence genes even when their population was still relatively small. This led to earlier, more aggressive infections.
Part V: The Host-Bacteria Conversation – A Two-Way Street
Clinician-scientist Ferric C. Fang of the University of Washington School of Medicine, commenting on the study, noted: “The bacteria not only talk to each other, but the host also talks to the bacteria. This may help to explain why men are more susceptible to staphylococcal skin infections than women.”
This is a profound shift in perspective. We tend to think of infections as a one-way assault: bacteria attack, and the host defends. But the reality is a continuous, two-way conversation. The host produces hormones, and bacteria have evolved to listen in on that conversation. When the host’s hormonal profile changes—as it does with sex, age, or disease—the bacteria change their behaviour accordingly.
This may also explain why certain skin conditions flare up at specific times of life. Adolescent boys, with their surge in testosterone, become more prone to acne—which is driven in part by S. aureus and other bacteria. Elderly men, with declining but still present testosterone, continue to have higher rates of skin infections than elderly women. The bacterial conversation never stops.
Part VI: Beyond Antibiotics – A Paradigm Shift in Treatment
The most exciting implication of this research is not just explaining a long-standing mystery but opening a completely new avenue for treating infections. The current approach to bacterial infections is predominantly antibiotic-based: we try to kill the bacteria. But antibiotics have major drawbacks. They kill beneficial bacteria along with harmful ones, disrupting the body’s microbiome. They create selective pressure for antibiotic-resistant strains. And they are becoming less effective as resistance spreads.
The UT Southwestern researchers asked a different question: what if, instead of killing the bacteria, we simply calmed them down?
Maria Sindhura John, the study’s first author and a postdoctoral researcher at UT Southwestern, offered a powerful analogy: “I imagine if someone is angry—you don’t remove or kill the person. Rather, you calm them down so they behave normally again. We are doing something similar with bacteria.”
S. aureus is usually a normal resident of human skin. It lives on most of us without causing harm. It becomes harmful only when its environment changes—when it receives the wrong signals, when the immune system is compromised, or when it reaches a critical density. The researchers wanted to suppress its virulence and maintain a harmless state, rather than eradicating it entirely. “This way, we reduce antibiotic resistance and maintain skin balance,” Dr. Sindhura John said.
Part VII: The Mirror-Image Molecule – ent-Testosterone
In a remarkable twist, the researchers identified a mirror-image form of testosterone, which they called ent-testosterone (ent-T) . In chemistry, molecules can exist in left-handed and right-handed forms that are mirror images of each other, like a pair of gloves. The natural testosterone produced by the human body is one form. The mirror-image form, ent-T, does not occur naturally but can be synthesised in the laboratory.
When the researchers tested ent-T, they found something astonishing. While natural testosterone activated quorum sensing and made infections worse, ent-T blocked the bacterial communication pathway. It acted as an antagonist, jamming the chemical signals. In laboratory experiments, ent-T reduced toxicity to human skin cells, red blood cells, and neutrophils (a type of immune cell). The bacteria were still present, but they were no longer acting like pathogens.
Computational modelling revealed how ent-T interacted with the bacterial quorum sensing receptors, showing a precise molecular fit that blocked the natural signal. “This was an unexpected but exciting discovery,” Dr. Sindhura John said.
This is the essence of a new therapeutic strategy: find molecules that selectively disrupt the harmful behaviour of bacteria without killing them. This approach, sometimes called anti-virulence therapy, has been a dream of microbiologists for decades. The UT Southwestern study has brought that dream significantly closer to reality.
Part VIII: Implications for Chronic Inflammatory Diseases
The study’s findings extend beyond acute skin infections. S. aureus is the leading cause of skin infections worldwide, but it is also implicated in chronic inflammatory diseases. The bacteria’s ability to colonise the skin and establish a complex relationship with the immune system could lead to the development or exacerbation of conditions such as psoriasis, eczema (atopic dermatitis), and rheumatoid arthritis.
In these diseases, the immune system is in a state of chronic, low-grade activation. S. aureus toxins and other bacterial products can act as triggers or amplifiers of that inflammation. By calming the bacteria down—by reducing their production of virulence factors—ent-T or similar molecules might not only prevent acute infections but also reduce the severity of chronic inflammatory flares.
The researchers are now planning to test these findings in human skin models. If successful, they will move to early-phase clinical trials to assess safety and efficacy. They are also keen to understand how these mechanisms operate within the complexity of the human microbiome—the vast community of bacteria, fungi, and viruses that lives on and in every human body.
Part IX: A Paradigm Shift in Treating Infections
Simon J. Foster, the West Riding Chair in Microbiology at the University of Sheffield, who was not involved in the study, commented: “The interaction between humans and bacteria is complex and poorly understood. This study provides an interesting new angle, with the potential to exploit the need to develop ways to combat important human infections.”
That “new angle” is nothing less than a potential paradigm shift. For a century, the dominant paradigm in treating bacterial infections has been: find the bacteria, and kill them. Antibiotics have saved hundreds of millions of lives. But we are now facing an antibiotic resistance crisis. The World Health Organization has declared antimicrobial resistance one of the top ten global public health threats. New classes of antibiotics are urgently needed, but the pipeline is dry.
Anti-virulence therapy offers an alternative. Instead of killing bacteria, we disarm them. We take away their weapons—the toxins, the adhesion factors, the biofilm machinery—but leave them alive. This imposes much less selective pressure for resistance because the bacteria are not fighting for their lives. They can still multiply, but they cannot cause disease. The immune system, which has evolved over millions of years to clear bacteria, can then do its job more easily.
“If successful, this approach could represent a paradigm shift in how we treat infections—moving away from broadly killing bacteria toward more precise modulation of their behaviour,” Dr. Sindhura John said.
Conclusion: From Mystery to Therapy
The observation that men suffer more skin infections than women has puzzled doctors for generations. Thanks to the meticulous work of the UT Southwestern team, we now know why. Testosterone, produced locally by the skin’s sebaceous glands, activates quorum sensing in Staphylococcus aureus, tricking the bacteria into switching on their virulence genes prematurely. This leads to more frequent and more severe infections in males.
But this discovery is not just an explanation. It is a roadmap. The identification of ent-testosterone—a mirror-image molecule that blocks the bacterial communication pathway—opens the door to a completely new class of therapeutics. Instead of killing bacteria, we can calm them. Instead of fueling antibiotic resistance, we can sidestep it. Instead of disrupting the microbiome, we can preserve it.
The journey from the laboratory to the clinic is long. Human trials are still ahead. But for the first time, we have a clear, mechanistically grounded strategy to address a long-observed clinical disparity. And in doing so, we may also have found a new way to fight one of the most common and troublesome bacterial pathogens on the planet. The bacteria are talking. Now, finally, we are learning to listen—and to talk back.
5 Questions & Answers Based on the Article
Q1. What has been the long-standing clinical observation regarding skin infections in men versus women, and what explanations were previously proposed?
A1. Doctors have long observed that men experience more skin infections than women, including boils, cellulitis, and staphylococcal abscesses. Previously proposed explanations included behavioural factors (men being less hygienic, more prone to skin trauma, or less likely to seek early treatment) and physiological factors (differences in skin thickness, sebum production, pH, and immune responses, with oestrogen potentially enhancing immunity in women). However, none of these provided a complete or mechanistically satisfying explanation.
Q2. What is the key discovery made by the UT Southwestern researchers regarding testosterone and bacterial infection?
A2. The researchers discovered that testosterone and other androgens (male sex hormones) help bacteria communicate and cause skin infections by activating a bacterial signalling system called quorum sensing. When testosterone is present, it tricks Staphylococcus aureus bacteria into switching on their virulence (disease-causing) genes earlier than they normally would, leading to more severe infections. The researchers demonstrated this by showing that mice unable to produce testosterone in their skin had milder infections, while applying testosterone to female mice made their infections more severe.
Q3. What is quorum sensing, and how does testosterone interfere with it?
A3. Quorum sensing is a chemical communication system bacteria use to coordinate their behaviour. Bacteria release chemical signals into their environment; as the bacterial population grows, the concentration of these signals rises. When a critical threshold (a “quorum”) is reached, the bacteria collectively switch on specific genes—including those for toxins and invasion. The UT Southwestern study found that testosterone activates the same quorum sensing pathway, essentially tricking the bacteria into thinking they have reached a quorum when their population is still small. This causes them to launch an infection prematurely and more aggressively.
Q4. What is ent-testosterone (ent-T), and why is it significant for developing new treatments?
A4. Ent-testosterone (ent-T) is a mirror-image form of natural testosterone. While natural testosterone activates bacterial quorum sensing and worsens infections, ent-T does the opposite: it blocks the bacterial communication pathway, reducing toxicity to human skin cells, red blood cells, and immune cells. The bacteria remain present but are no longer harmful. This is significant because it offers a potential anti-virulence therapy—calming the bacteria rather than killing them—which could reduce antibiotic resistance, preserve the beneficial microbiome, and represent a paradigm shift in how infections are treated.
Q5. How does the study’s lead researcher, Dr. Maria Sindhura John, use the analogy of an angry person to explain the new treatment approach?
A5. Dr. Sindhura John uses the analogy: “I imagine if someone is angry—you don’t remove or kill the person. Rather, you calm them down so they behave normally again. We are doing something similar with bacteria.” This means that instead of using antibiotics to kill Staphylococcus aureus (which can drive resistance and disrupt the microbiome), the researchers want to suppress the bacteria’s virulence and maintain a harmless state. The bacteria remain on the skin (where they are normally present), but they stop producing toxins and causing disease. This approach is called anti-virulence therapy.
