Early Lyme Disease Looks Different in Women Than in Men, Johns Hopkins Finds

Lyme disease is the most commonly reported vector-borne illness in the United States, with approximately 476,000 cases diagnosed annually according to CDC estimates. The disease is caused by the bacterium Borrelia burgdorferi, transmitted primarily through the bite of infected black-legged ticks. Most cases of early Lyme disease present with a characteristic expanding rash -- erythema migrans -- often accompanied by fever, fatigue, and musculoskeletal symptoms.

What clinical guides have treated as a relatively uniform early presentation may be more variable than previously recognized. A study from Johns Hopkins Medicine, analyzing a cohort of patients with confirmed early Lyme disease, found that sex and menopausal status significantly influenced how the disease presented at first clinical encounter.

What the Study Found

Researchers analyzed clinical data from Johns Hopkins patients with confirmed early Lyme disease, comparing symptom profiles by sex and, among women, by menopausal status. The analysis found statistically significant differences in how the disease presented across these groups.

Women in the study were more likely than men to report certain systemic symptoms including fatigue and mood changes. Men showed higher rates of specific musculoskeletal manifestations. Post-menopausal women showed a symptom profile distinct from pre-menopausal women, with some measures falling between the female and male patterns and others showing their own distinct distribution.

The erythema migrans rash -- the hallmark sign used for clinical diagnosis -- did not differ significantly in prevalence across groups, but the accompanying constellation of symptoms did. This matters clinically because physicians use the totality of the clinical picture to decide how urgently to treat, how extensively to work up a patient, and how to counsel patients about expected recovery.

Why Sex Differences Might Exist

The immune system responds differently to infection in males and females -- a well-documented finding extending across many infectious diseases. Estrogen tends to promote more vigorous antibody responses and certain inflammatory pathways; testosterone has immunosuppressive effects at physiological concentrations. These differences influence not just susceptibility to infection but the severity and character of the immune response once infection occurs.

In Lyme disease, the symptoms of early infection are substantially driven by the immune response itself, not by direct tissue damage from the bacterium. Fever, fatigue, and malaise reflect cytokine release and systemic inflammation -- processes whose composition and intensity differ between men and women, particularly when estrogen levels differ substantially.

The observation that post-menopausal women showed a distinct presentation supports a role for hormonal factors rather than simply chromosomal sex. If the difference were driven purely by genetic or anatomical sex differences, pre- and post-menopausal women would be expected to present more similarly to each other than either does to men.

Limitations

The study is observational and based on a single institution's clinical records. Johns Hopkins is a tertiary referral center, which means its patient population may differ from the broader population of people with early Lyme disease in ways that could affect generalizability. Patients at a referral center may have more complex or atypical presentations, more comorbidities, or more severe illness than those treated in primary care settings.

The sample size, while not reported precisely in available descriptions, is likely modest relative to what would be needed to characterize subtle differences in symptom frequencies with high statistical power. The observed differences should be treated as hypotheses to be confirmed in larger, more representative cohorts rather than as established clinical facts. Hormonal replacement therapy status in post-menopausal women, which would influence the magnitude of hormonal differences, is not specified in available descriptions of the study.

Clinical Implications

Diagnostic delay in Lyme disease carries real costs. Early disease is highly treatable with standard antibiotics. Disease that goes undiagnosed for weeks to months can progress to involve the heart, nervous system, and joints, producing manifestations that are more difficult to treat and may result in persistent symptoms. A clinician who is aware that a post-menopausal woman may present with a different symptom constellation than a man with the same infection is better positioned to recognize atypical presentations and avoid diagnostic delay.

The research also points to a broader gap: many infectious diseases have been studied primarily in male subjects or in mixed cohorts analyzed without stratification by sex or hormonal status. Findings that depend on this kind of stratification will be missed if the analysis is not designed to look for them.