Background Hormones play a pivotal role in women’s health. Estrogen, for example, not only regulates reproduction but also protects against several chronic conditions, such as heart disease and osteoporosis. As women age, the transition to menopause—a period characterized by a significant drop in estrogen levels—triggers physiological changes that can affect their overall health and quality of life. These changes extend beyond typical menopausal symptoms like hot flashes and vaginal dryness, potentially leading to increased cardiovascular risk, cognitive decline, and bone density loss.

Hypercholesterolemia is a critical risk factor for atherosclerotic cardiovascular disease and is associated with significant comorbidities, particularly in postmenopausal women. Understanding the sex-specific differences in the progression and impact of hypercholesterolemia is essential for improving patient outcomes.

Objective This study explores the implications of hormonal transition, particularly menopause, on women’s health and highlights the potential of real-world data (RWD) to address these gaps. By integrating sex and gender considerations into clinical decision-making. To achieve so, sex-based differences in the prevalence, progression, and comorbidity patterns of hypercholesterolemia are analyzed at region-wide level, using real-world data (RWD) from the Andalusian Population Health Database (BPS).

Methods A retrospective cohort of 557,034 patients diagnosed with hypercholesterolemia between 2016 and 2022 was analyzed. Patients were stratified by sex and age groups (<50 and ≥50 years). A comparative analysis was performed to assess differences in the prevalence of hypercholesterolemia and associated comorbidities.

Results Women were diagnosed later than men, with an average age of 59.1 years compared to 56.0 years for men. Postmenopausal women exhibited a sharp rise in hypercholesterolemia prevalence, surpassing men in older age groups. Women also displayed higher rates of comorbidities, including osteoporosis, anxiety disorders, and hypertension, particularly during the menopausal transition. The analysis revealed a significant influence of estrogen decline on lipid profiles and comorbidities risk in women. Conversely, men had higher hypercholesterolemia prevalence in younger age groups, likely due to lifestyle and genetic factors.

Conclusions This study demonstrates that menopause is a critical period influencing the progression of hypercholesterolemia and associated comorbidities in women. These findings underscore the importance of sex-specific approaches in the prevention and management of hypercholesterolemia. The use of RWD allowed for a comprehensive evaluation of sex and age disparities, providing actionable insights for clinical practice.

The authors have declared no competing interest.

The infrastructure where this work has been carried out has been funded by the Consejeria de Salud y Consumo, Junta de Andalucia (IE19_259 FPS).

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The Andalusian Biomedical Research Ethics Coordinating Committee approved the study entitled: "Retrospective observational study to determine the characteristics and treatment patterns in patients with atherosclerotic cardiovascular disease and familial hypercholesterolemia in Andalusia. " (March 28, 2023, Minutes 03/23) and waived informed consent for the secondary use of clinical data for research purposes.

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