Relationship Between Metformin Treatment, Anemia, and Erythropoietin Levels in Women With Polycystic Ovary Syndrome in Jordan

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders affecting women of reproductive age and is frequently associated with insulin resistance, dyslipidemia, obesity, and an increased risk of metabolic complications. Although metformin is widely prescribed to improve insulin sensitivity in women with PCOS, its effects on iron metabolism, erythropoietin concentrations, and hematological parameters remain incompletely understood.

This prospective longitudinal interventional study was conducted among adult women with PCOS attending obstetrics and gynecology clinics of the Jordanian Ministry of Health. Eligible participants received routine metformin therapy (500 mg twice daily) for six months as part of standard clinical practice. No additional behavioral, lifestyle, dietary, or educational interventions were provided as part of the study protocol.

Clinical and laboratory assessments were performed at baseline, after three months, and after six months of treatment. Outcome measures included body mass index (BMI), fasting blood glucose (FBG), fasting serum insulin, homeostatic model assessment of insulin resistance (HOMA-IR), lipid profile (total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol), serum ferritin, serum iron, erythropoietin (EPO), hemoglobin concentration, complete blood count, and red blood cell indices.

The primary objective was to determine the effects of routine metformin therapy on insulin resistance, iron metabolism, erythropoietin concentrations, and hematological parameters in women with PCOS. Secondary objectives included evaluating changes in lipid profile and investigating the associations among metabolic, iron-related, and hematological biomarkers during the six-month follow-up period.

The findings of this study are expected to improve understanding of the metabolic and hematological effects of routine metformin therapy in women with PCOS and to clarify the relationship between insulin resistance, iron homeostasis, erythropoietin, and metabolic outcomes in this population.

Inclusion criteria

• Women aged 18-45 years.
• Diagnosis of polycystic ovary syndrome (PCOS) according to the Rotterdam diagnostic criteria.
• Eligible for routine metformin therapy as determined by the treating gynecologist.
• Willing and able to provide written informed consent.
• Willing to attend scheduled follow-up visits and complete all study assessments over the six-month study period.

Exclusion criteria

• Pregnancy or breastfeeding.
• Diagnosis of type 1 diabetes mellitus or established type 2 diabetes requiring insulin therapy.
• History of chronic kidney disease, chronic liver disease, hematological disorders, malignancy, or other severe systemic diseases.
• Current use of medications known to affect glucose metabolism, iron metabolism, erythropoietin levels, or hematological parameters within the previous three months, other than routine metformin prescribed as part of the study.
• Known hypersensitivity or contraindication to metformin. Inability or unwillingness to complete the scheduled follow-up assessments.
• Participation in another interventional clinical trial during the study period.