Emerging Insights into Sex-Based Differences in Early Lyme Disease Presentation: A Johns Hopkins Medicine Study
A groundbreaking investigation by Johns Hopkins Medicine researchers has unveiled notable sex-based differences in the clinical presentation of early Lyme disease, revealing a complex interplay of biological factors influencing symptomatology, laboratory diagnostics, and physical findings. This seminal study, recently published in the peer-reviewed journal Clinical and Experimental Medicine, sheds critical light on how males and females experience Lyme disease distinctly, with significant implications for diagnosis, treatment, and understanding disease pathophysiology.
Lyme disease, a multisystemic bacterial infection caused by Borrelia burgdorferi, is transmitted via the bite of infected black-legged ticks and affects nearly half a million individuals annually in the United States alone, per Centers for Disease Control and Prevention (CDC) estimates. Characteristically, early infection manifests with erythema migrans, a hallmark red, circular skin lesion, accompanied by a constellation of systemic symptoms. However, this Johns Hopkins cohort study involving 243 adults (125 males and 118 females), spanning ages 20 to 84, demonstrates that clinical expression and laboratory markers of Lyme disease are not monolithic but instead differ significantly between sexes.
One of the pivotal findings of the research is the higher likelihood of males to test positive for Lyme disease via laboratory assays at the time of diagnosis. Furthermore, males exhibited more pronounced and severe disease indicators, including additional laboratory abnormalities, compared to females. Surprisingly, the duration of illness prior to diagnosis was equivalent across sexes, suggesting that these disparities are not attributable to differences in healthcare-seeking behavior or temporal disease progression but may be intrinsically linked to biological sex determinants.
Symptomatology analysis further revealed distinct sex-specific patterns. Females reported greater incidence of symptoms such as heart palpitations, vomiting, and photophobia (light sensitivity) relative to their male counterparts. Specifically, heart palpitations were reported by nearly 12% of females compared to 4% of males; vomiting, while uncommon overall, was disproportionately higher in females (7.6% vs. under 1%), and heightened light sensitivity affected 17% of women versus 8.8% of men. Conversely, sleep disturbances were noted more frequently among males, with 40% experiencing this symptom as opposed to 24.6% of females. These findings underscore a sexually dimorphic clinical spectrum in early Lyme disease that has been hitherto underappreciated.
The study’s lead investigator, Dr. John Aucott, director of the Johns Hopkins Lyme Disease Clinical Research Center, observes that the male clinical profile resembled that of postmenopausal females more than premenopausal ones, hinting at a potential influence of sex hormones and menopausal status on disease expression. It raises the compelling hypothesis that estrogen and other hormonal mediators may modulate immune responses, symptom presentation, and even the pathogen-host interaction during Lyme disease.
Biological underpinnings driving these differences may reside in variations in innate and adaptive immune responses modulated by sex chromosomes and hormonal milieus. For instance, estrogen is known to influence cytokine production, immune cell activation, and inflammatory pathways, which could alter the clinical manifestations and serological test sensitivity in females. Conversely, testosterone and other androgens may prime different immune dynamics in males, leading to the observed spectrum of laboratory abnormalities and symptom intensities.
The study’s robust methodology included a comprehensive assessment of symptom reports, standardized physical examinations, and extensive laboratory testing before and after antibiotic treatment. This multidimensional approach permitted differentiation of sex-specific clinical features while controlling for confounding variables such as illness duration and age. The age range encompassing young to elderly adults allowed examination of menopausal effects, further enriching the dataset’s relevance.
Given the complexity of Lyme disease diagnostics, which often rely on indirect serological markers and clinical judgment, tailoring diagnostic and therapeutic approaches based on sex differences could enhance early detection and improve patient outcomes. The implications are far-reaching: recognizing that males and females may present different signs and symptoms could lead to sex-specific clinical algorithms, optimizing accuracy and reducing misdiagnosis or delayed diagnosis risks.
Moreover, the study calls for an expanded research focus to elucidate the molecular and hormonal mechanisms that underpin these observed sex-based distinctions. Future investigations analyzing hormone levels, genetic regulators, and immune system parameters hold promise for unraveling the biological basis of Lyme disease sex differences. This could pave the way for personalized medicine strategies that integrate sex and hormonal status into Lyme disease management.
Funding from the Steven & Alexandra Cohen Foundation, Global Lyme Alliance, and Bay Area Lyme Foundation supported this pivotal research, reflecting the growing commitment to addressing Lyme disease as a major public health challenge. The multidisciplinary team, including co-authors Alison W. Rebman and Ting Yang, brings a wealth of expertise to this field, advancing our understanding of sex-specific disease facets.
In summary, this Johns Hopkins Medicine study represents a significant advance in Lyme disease research by demonstrating that sex and menopausal status profoundly influence symptom presentation, physical findings, and laboratory results in early infection. This insight highlights the necessity of integrating sex as a biological variable in clinical research and practice, ultimately informing more nuanced and effective approaches to Lyme disease diagnosis and treatment worldwide.
Subject of Research:
Sex differences in early Lyme disease clinical presentation and laboratory findings
Article Title:
Sex-Based Differences in Clinical and Laboratory Presentation of Early Lyme Disease: Findings from a Johns Hopkins Medicine Cohort
News Publication Date:
February 7, 2026
Web References:
https://link.springer.com/epdf/10.1007/s10238-026-02063-0
https://www.hopkinsmedicine.org/health/conditions-and-diseases/lyme-disease
References:
Rebman AW, Yang T, Aucott JA, et al. Sex-based variations in early Lyme disease presentation: Clinical and laboratory studies. Clinical and Experimental Medicine. 2026.
Image Credits:
Not provided in the original release.
Keywords:
Infectious diseases, Lyme disease, Sex differences, Immunology, Tick-borne infections, Clinical research, Biomarkers, Hormonal influence, Early diagnosis, Epidemiology, Johns Hopkins Medicine
