Background: Respiratory tract infections (RTIs) are a major public health concern. Global studies published in Lancet Infect. Dis. highlight the persistent morbidity and mortality from RTIs, with upper- and lower-RTIs collectively accounting for more than 100 million disability-adjusted-life-years per year.

During menopause, hormonal changes alongside other factors increase the risk for illnesses, such as RTIs, COPD, cardiovascular disease, and diabetes. However, it remains unknown how hormone-replacement therapy during menopause might impact the frequency or severity of RTIs. While hormone replacement therapy (HRT) is often prescribed for menopausal symptom relief, its potential impact on RTI risk and severity has not been examined.

Objective: This observational cohort study aims to compare and predict the risk of RTI among postmenopausal women, with a particular focus on the influence of HRT. The principal aim is to compare the rates and severity of respiratory tract infections in postmenopausal women taking or not taking HRT. The secondary aims are to characterize risk factors for RTI in postmenopausal women and identify signals in wearable data that predict the onset of an RTI before symptoms become apparent.

Methods: 400 women aged 40-60 will be studied, stratified into two groups: postmenopausal women taking HRT, and postmenopausal women not taking HRT. Participants will each be followed for six months, with RTI episodes recorded through self-reporting and confirmed by laboratory tests. Wearable devices will continuously monitor physiological parameters (e.g., heart rate, sleep patterns), and questionnaires will assess lifestyle factors, medical history, and environmental exposure. Statistical modeling and machine learning approaches will be used to analyze infection predictors and develop a model that predicts the risk of onset of an RTI.

Impact: Half of the world's population inevitably undergoes menopause, and this important life transition has wide-ranging impacts on women's health and quality of life for decades. Studies show that women spend more of their lives in poor health than men, with far-reaching impacts on a woman's participation in society, career performance, and ability to care for other family members. A better understanding of risk factors for respiratory infections in menopausal women and whether hormone-replacement therapy influences RTIs will contribute much-needed knowledge to enable better health management strategies for women. Furthermore, an "early-warning" system based on wearable signals will provide a valuable tool for quick intervention and to reduce the spread of infectious illnesses. Such an "early-warning" system will subsequently be tested for applicability across a broader representation of society as a preventive health measure and tool for pandemic preparedness.

Conclusion: Findings will enhance understanding of RTI risk and management in menopausal women and contribute to the development of personalized prevention strategies. Future applications include a wearable-based medical device for real-time RTI risk assessment, potentially reducing antibiotic overuse and improving healthcare efficiency. By enabling early detection and risk stratification, this study paves the way for a proactive and personalized approach to respiratory health in postmenopausal women, ultimately shifting the focus to prevention.

Inclusion Criteria:

• Biological sex: female
• Age: 40-60 years
• Self-determined decision to participate, confirmed by signing the informed consent form (ICF)
• Fluent in German
• Agreement to wear a smartwatch (Garmin Vivosmart 5) for most of the time over six months
• Ownership of a smartphone compatible with the Fitrockr application
• Confirmed post-menopausal status: Spontaneous amenorrhea for ≥12 consecutive months without other causes OR ≥6 months of spontaneous amenorrhea with biochemical confirmation (FSH > 40 IU/L OR FSH > 30 IU/L for women aged ≥50 using hormonal contraception) OR bilateral oophorectomy ≥6 weeks before enrollment

Exclusion Criteria:

• Inability to provide informed consent
• Known allergic reaction to polycarbonate (smartwatch wristband material)
• Asthma not well-controlled (ACT score <20 despite medication)
• Use of injectable asthma drugs with broad immunomodulatory activity
• Coronary artery disease
• Diagnosis of diabetes mellitus
• Cancer diagnosis
• Diagnosis of chronic kidney disease
• Confirmed diagnosis of familial hypercholesterolemia (genetic)
• Sleep apnea managed with bi-level positive airway pressure (PAP)
• Chronic rhinosinusitis
• Severe (stage 3 or 4) chronic obstructive pulmonary disease (COPD) or interstitial lung disease with hospitalization within the prior 12 months for respiratory symptoms
• Any other condition/treatment deemed incompatible with the study objectives by the PI or delegated co-investigators
• Current employment in the Section of Gynecological Endocrinology and Reproductive Medicine (Inselspital Bern) or any other relation to the principal investigator
• Concurrent participation in a clinical interventional study
• Technical inability to pair the participant's smartphone with the smartwatch
• Inability to comply with study procedures (e.g., due to language, psychiatric illness, or inability to attend study site)

This study targets post-menopausal women aged 40-60 years, recruited from the University Hospital (Inselspital Bern), affiliated clinics, and the general public in Switzerland. Participants will be assigned to two observational cohorts based on their use of hormone replacement therapy (HRT vs. no HRT).