Impact of Sex and Gender on Lung Health and Disease

Introduction to Sex and Gender Differences in Lung Function

The relationship between sex, gender, and lung health is a critically important area of research that has profound implications for understanding lung function and disease. Traditionally, lung function assessments and disease diagnoses have been based on male physiology, often overlooking the significant differences that exist between sexes and the impact of gender. Biological sex refers to the physical and physiological differences between males and females, while gender encompasses the roles, behaviors, and expectations that society associates with being male or female. Understanding these distinctions is essential for developing effective prevention and treatment strategies for respiratory diseases. Recent studies have shown that sex and gender differences can influence lung development, function, and susceptibility to various pulmonary diseases, including chronic obstructive pulmonary disease (COPD), asthma, and lung cancer (Tondo et al., 2024).

Key Factors Influencing Lung Development Across the Lifespan

Lung development is a complex process that begins as early as the embryonic stage and continues through childhood into adulthood. Factors influencing this development include genetic, hormonal, and environmental influences which differ significantly between males and females. For instance, hormonal differences are prominent during puberty, where males generally experience greater lung growth, resulting in larger lung volumes compared to females. This disparity can lead to differences in respiratory function, with males typically exhibiting higher forced vital capacity (FVC) and forced expiratory volume (FEV1) than females by adulthood (Tondo et al., 2024).

Hormonal influences extend beyond puberty. Estrogen and testosterone play crucial roles in lung development and function throughout life. Studies suggest that estrogen may promote lung maturation and improve respiratory function, while testosterone can influence airway reactivity and vulnerability to respiratory diseases (Zubieta-Calleja, 2024). These hormonal influences are compounded by environmental exposures such as air pollution and smoking, which can also affect lung development and disease risk in a sex-specific manner (Tondo et al., 2024).

Table 1: Differences in Lung Function by Sex

Clinical Implications of Preserved Ratio Impaired Spirometry

Preserved Ratio Impaired Spirometry (PRISm) is a condition characterized by a preserved FEV1/FVC ratio but with reduced FEV1, indicating early lung dysfunction that does not meet the criteria for COPD. This condition is increasingly recognized as a precursor to chronic obstructive pulmonary disease (COPD) and is often associated with higher body mass index (BMI), female sex, and smoking history (Jin et al., 2025).

The clinical significance of PRISm lies in its association with various comorbidities, including metabolic disorders and cardiovascular diseases. Recent studies have demonstrated that individuals with PRISm are at increased risk for cardiovascular events, highlighting the need for careful monitoring and management (Jin et al., 2025). Additionally, imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) are essential for evaluating lung structure and function in patients with PRISm, providing insights into disease progression and treatment efficacy (Jin et al., 2025).

Role of MicroRNAs in Endometriosis and Fertility Issues

Endometriosis (EM) is a prevalent condition among women of reproductive age characterized by the presence of endometrial-like tissue outside the uterus. This condition can lead to severe pain and infertility, affecting approximately 25-50% of women with infertility issues (Decreased expression of miR-200a and miR-223-3p in endometriosis during the secretory phase of menstrual cycle: Insights from a case-control study on molecular biomarkers and disease-related infertility).

Recent research has identified microRNAs (miRNAs) as crucial regulators in endometrial receptivity and implantation processes. In women with endometriosis, the expression of specific miRNAs, such as miR-200a and miR-223-3p, has been found to be significantly lower, which may contribute to the infertility associated with the condition (Decreased expression of miR-200a and miR-223-3p in endometriosis during the secretory phase of menstrual cycle: Insights from a case-control study on molecular biomarkers and disease-related infertility). Understanding the role of these miRNAs could pave the way for novel diagnostic and therapeutic strategies aimed at improving fertility outcomes in affected women.

Table 2: MicroRNA Expression in Endometriosis

Advances in Imaging Techniques for Lung Disease Assessment

Recent advancements in imaging technologies, particularly in computed tomography (CT) and magnetic resonance imaging (MRI), have significantly enhanced the ability to assess lung diseases. CT scans provide detailed views of lung structure, allowing for the quantification of lung volumes, density, and vascular parameters, which are essential for diagnosing conditions like PRISm (Jin et al., 2025). Furthermore, MRI technology has emerged as a powerful tool for evaluating ventilation and pulmonary blood flow, offering insights that traditional spirometry cannot provide (Jin et al., 2025).

Artificial intelligence (AI) is also being integrated into imaging techniques, facilitating the identification of subtle changes in lung structures and function. AI algorithms can analyze large datasets, improving the accuracy of diagnoses and prognostic assessments for patients with chronic lung diseases (Jin et al., 2025). As research continues, the role of AI in lung imaging is expected to expand, providing more personalized approaches to patient care.

Future Perspectives on Personalized Respiratory Medicine

The future of respiratory medicine lies in the development of personalized approaches that consider the unique physiological characteristics of individuals based on their sex and gender. By understanding the differences in lung function and disease susceptibility, healthcare providers can tailor prevention and treatment strategies to better meet the needs of their patients.

Emerging research on biomarkers, such as miRNAs, and advancements in imaging techniques will play a pivotal role in this personalized approach. Furthermore, the integration of AI in analyzing lung function data will enhance the ability to predict disease progression and treatment responses. Ultimately, the goal is to create a healthcare system that recognizes and addresses the diverse needs of all individuals, thereby improving health outcomes for everyone.

FAQ

What are the main differences in lung function between males and females? Males typically have higher forced vital capacity (FVC) and forced expiratory volume (FEV1) compared to females due to differences in lung size and growth patterns influenced by sex hormones.

How does preserved ratio impaired spirometry (PRISm) relate to COPD? PRISm is considered a precursor to chronic obstructive pulmonary disease (COPD) characterized by a preserved FEV1/FVC ratio despite reduced FEV1, indicating early lung dysfunction.

What role do microRNAs play in endometriosis? MicroRNAs, such as miR-200a and miR-223-3p, are involved in regulating endometrial receptivity and implantation processes. Their reduced expression in women with endometriosis may contribute to infertility.

How are imaging techniques advancing lung disease assessment? Advances in CT and MRI have enhanced the assessment of lung diseases by providing detailed structural and functional evaluations. The integration of AI further improves diagnostic accuracy and personalized treatment strategies.

Why is it important to consider sex and gender in respiratory medicine? Understanding sex and gender differences in lung health is essential for developing effective prevention and treatment strategies tailored to individuals’ unique physiological characteristics.

References

1. Zubieta-Calleja, G. (2024). Decreased expression of miR-200a and miR-223-3p in endometriosis during the secretory phase of menstrual cycle: Insights from a case-control study on molecular biomarkers and disease-related infertility. doi:10.18502/ijrm.v22i12.18066

2. Tondo, P., Meschi, C., Mantero, M., Scioscia, G., Siciliano, M., Bradicich, M., & Stella, G. M. (2024). Sex and gender differences during the lung lifespan: unveiling a pivotal impact. doi:10.1183/16000617.0121-2024

3. Jin, Q., Zhang, Z., Zhou, T., Zhou, X., Jiang, X., Xia, Y., Guan, Y., & Fan, L. (2025). Preserved ratio impaired spirometry: clinical, imaging and artificial intelligence perspective. doi:10.21037/jtd-24-1582

4. Schafer, K. A., Atzpodien, E., Bach, U., Bartoe, J., Booler, H., Brassard, J., … & Teixeira, L. (2024). International Harmonization of Nomenclature and Diagnostic Criteria (INHAND): Nonproliferative and Proliferative Lesions of Nonrodent Ocular Tissues. doi:10.1177/01926233241283708