Biochemical, Metabolic, Cardiovascular, and Histopathological Predictors of Anemia Severity and Treatment Response in Women with Heavy Menstrual Bleeding: A Prospective Cohort Study

Abstract

Background: Heavy menstrual bleeding (HMB) is a major cause of iron-deficiency anemia in reproductive-aged women, but anemia severity and treatment response may also be influenced by metabolic, inflammatory, cardiovascular, and endometrial factors.

Methods: This prospective cohort study included 130 women with HMB and anemia recruited from the Department of Biochemistry, Gujranwala Medical College, Gujranwala, and Lahore General Hospital, Lahore, Pakistan, from January 2025 to January 2026. Hematological indices, ferritin, transferrin saturation, C-reactive protein (CRP), metabolic parameters, HOMA-IR, cardiovascular measurements, menstrual blood loss, and clinically indicated endometrial histopathology were assessed. Participants were reassessed after 12 weeks. Treatment response was defined as hemoglobin improvement ≥2.0 g/dL or achievement of hemoglobin ≥12.0 g/dL.

Results: Mild, moderate, and severe anemia occurred in 25.4%, 55.4%, and 19.2% of participants, respectively. Greater anemia severity was independently associated with higher PBAC score, lower ferritin, CRP >5 mg/L, HOMA-IR ≥2.5, and increased resting heart rate. At 12 weeks, 92 women (70.8%) achieved hematological response. Ferritin <10 ng/mL, elevated CRP, insulin resistance, persistent PBAC ≥150, and endometrial hyperplasia predicted non-response. The combined model showed strong discrimination for severe anemia (AUC 0.90) and good discrimination for treatment non-response (AUC 0.84).

Conclusion: HMB-associated anemia is influenced by interconnected hematological, metabolic, inflammatory, cardiovascular, and endometrial factors. Multidomain assessment may improve early risk stratification and treatment planning.