Background: Menopause signifies the eternal termination of menstruation in women as a consequence of ovarian action loss, typically occurring around the age of 51 years. Cardiovascular disease is the leading cause of death among post-menopausal women, which may be due to lower levels of estrogen and lipid profile. The present study was undertaken to evaluate serum estrogen and lipid profile status to assess the risk of atherosclerosis in both pre-and post-menopausal women.Objectives: The objective of this study is to explore the relationship between estrogen and lipid levels of women in pre-and post-menopausal stages.Methodology: A comparative cross-sectional study was conducted at Railway General Hospital Rawalpindi. A total of 100 participants were included of which 50 were pre-menopausal and 50 were post-menopausal women. Laboratory examination and questionnaires from the study population were used for data collection. Through the enzymatic method, serum cholesterol, triglycerides, low-density lipoprotein, and high-density lipoprotein (HDL) were assessed. Serum very low-density lipoprotein (VLDL) levels were calculated via Friedwald's components VLDL=TG/5.0. An enzyme-linked immunosorbent assay kit was used for estrogen measurement. For statistical analysis, Student's t-test and the Pearson correlation test were used.Results: Women after menopause have significantly high serum cholesterol, low-density lipoproteins, VLDLs, and triglycerides while HDL-c levels were significantly low (P<0.001). Levels of estrogen were low in post-menopausal females (P<0.001) as compared to menstruating women. Estrogen with HDL concentrations showed a positive correlation with an r value of 0.08556 while LDL levels showed a negative correlation with a r value of -0.26219.Conclusion: This comparative study explores the relationship between estrogen and lipid levels in pre-and post-menopausal women. Low estrogen with changed lipid variables was observed. Decreased cardiovascular protective HDL-c marks that menopause is a phase that acts as an independent risk factor for atherosclerosis.