Clinical Indicators for Perimenopausal Hormone Replacement Therapy: An Evidence-Based Narrative Review

Clinical guidance for perimenopausal hormone replacement therapy (HRT) varies across regions, creating uncertainty when clinicians need to balance safety with testing burden and cost. We conducted an evidence-based narrative review to summarize the clinical value of key indicators used in perimenopausal HRT decision-making. To gather relevant evidence, we searched PubMed, Web of Science, and Scopus for studies published from January 2014 to December 2025 using keywords related to perimenopause, HRT, biomarkers, clinical decision-making, and risk stratification. We focused on indicators from hormonal, skeletal, and cardiometabolic domains, as well as selected imaging and symptom measures. Traditional hormones such as follicle-stimulating hormone (FSH) and estradiol are useful for staging, but single measurements are limited by cyclic fluctuations. For bone health, combining bone mineral density with bone turnover markers (e.g., β-CTX and PINP) may improve the assessment of fracture risk and treatment response. For cardiometabolic safety, lipid profiles and inflammatory markers (e.g., C-reactive protein) support risk evaluation. Based on the literature, we propose a tiered evaluation framework: utilizing standard, widely available tests for routine assessment, while reserving advanced biomarkers for high-risk or unclear cases. This approach aims to support practical clinical assessment without replacing individualized clinical judgment, offering a highly cost-effective strategy tailored for resource-limited settings.