E3 PreliminaryPreliminaryPEM not requiredMechanisticPeer-reviewedReviewed
Females have stronger neurogenic response than males after non-specific nasal challenge in patients with seasonal allergic rhinitis.
Tomljenovic, Dejan, Baudoin, Tomislav, Megla, Zeljka Bukovec et al. · Medical hypotheses · 2018 · DOI
Quick Summary
This study looked at how men and women with seasonal allergies respond differently to nasal irritants. Researchers found that women had stronger burning sensations and higher levels of a nerve-signaling chemical called substance P compared to men when exposed to salt water or allergen challenges. This suggests that women's bodies may process nasal irritation through a different biological pathway involving both immune cells and nerve signals.
Why It Matters
ME/CFS shares several features with the conditions discussed in this study—including female predominance, neurogenic inflammation, and abnormal mast cell activation. Understanding gender-specific differences in neurogenic inflammatory pathways and substance P regulation may help explain why ME/CFS predominantly affects women and could inform development of gender-tailored therapeutic approaches targeting nerve-immune interactions.
Observed Findings
- Female allergic subjects had higher baseline substance P concentrations than males before challenges.
- Female patients showed a highly significant difference in substance P between post-allergen and post-hypertonic saline responses (p=0.001), whereas males did not (p=0.14).
- Female patients reported significantly stronger burning sensation after hypertonic saline challenge compared to males.
- Substance P elevation was greater in females after non-specific (salt water) nasal challenge.
- The pattern suggests gender-related differences in the interaction between inflammatory cells and neurogenic response pathways.
Inferred Conclusions
- Female and male patients with allergic rhinitis have different interactions between mast cell activation and neurogenic inflammation, particularly regarding substance P release.
- Estrogen and sex hormones may regulate mast cell-nerve signaling interactions differently in females, amplifying neurogenic inflammatory responses.
- Gender-related differences in neurogenic inflammation regulation may affect symptom profiles and disease endotyping in respiratory and related disorders beyond allergic rhinitis, including asthma, chronic rhinosinusitis, and irritant-induced cough.
- This gender difference may reflect a broader principle of sex-hormone-mediated modulation of neuroinflammatory pathways that could apply to other conditions with female predominance.
What This Study Does Not Prove
This study does not establish causation between estrogen and the observed neurogenic differences; it is a mechanistic hypothesis study in a specific respiratory condition (allergic rhinitis) that may not directly translate to ME/CFS. The findings are correlational and the study does not directly test ME/CFS patients, so applicability to ME/CFS pathophysiology remains speculative. Small sample sizes and lack of detailed demographic/hormonal data limit generalizability.
Tags
Symptom:PainSensory Sensitivity
Biomarker:Cytokines
Method Flag:Small SampleExploratory OnlySex-Stratified
Metadata
- DOI
- 10.1016/j.mehy.2018.04.021
- PMID
- 29857893
- Review status
- Editor reviewed
- Evidence level
- Early hypothesis, preprint, editorial, or weak support
- Last updated
- 12 April 2026
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
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