Effects of Metformin and Theory-Based Education in Women With Polycystic Ovary Syndrome

This study is a prospective, three-arm, parallel-group randomized controlled trial conducted among women diagnosed with polycystic ovary syndrome (PCOS). The study was conducted from August 2025 to February 2026 in obstetrics and gynecology clinics affiliated with the Ministry of Health, Jordan. The intervention and follow-up period lasted six months.

A total of 900 eligible participants were initially randomized in a 1:1:1 ratio to one of three study groups: a matching placebo group, a metformin group, and a combined metformin plus theory-based behavioral educational intervention group. All participants received routine clinical care for PCOS.

Participants assigned to the matching placebo group received routine clinical care together with matching placebo tablets identical to the metformin tablets in appearance, size, and form. Participants in the metformin group received routine clinical care together with metformin at a total daily dose of 1500 mg, administered as 500 mg three times daily, for six months. Participants in the combined intervention group received the same metformin regimen together with a structured theory-based behavioral educational program.

The behavioral educational intervention was grounded in Bandura's Self-Efficacy Theory and incorporated educational and lifestyle domains relevant to PCOS self-management. The program consisted of five structured sessions of approximately 60 minutes each. The sessions addressed understanding PCOS and self-management; healthy dietary practices; physical activity, sedentary behavior, and weight and waist management; metformin adherence, metabolic health, and symptom monitoring; and sleep, stress management, problem solving, and maintenance of behavioral changes. Individualized education, practical examples, achievable goals, self-monitoring, reinforcement, and follow-up contacts were incorporated to support behavioral change.

Clinical and laboratory assessments were performed at baseline and at six months. The primary objective was to compare changes from baseline to six months among the three study groups in anthropometric parameters, metabolic parameters, vitamin B12, iron-status biomarkers, erythropoietin, and hematological indices. Metabolic assessments included measures of glucose regulation and insulin resistance and lipid parameters. Iron-status assessments included serum iron, total iron-binding capacity, transferrin saturation, and ferritin. Hematological assessments included hemoglobin, hematocrit, red blood cell count, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, red cell distribution width, white blood cell count, differential leukocyte counts, and platelet count.

A secondary objective was to evaluate changes in PCOS-related knowledge and lifestyle practices among participants receiving the combined metformin and theory-based behavioral educational intervention. Knowledge domains included the definition of PCOS, causes and risk factors, signs and symptoms, complications, and treatment and management. Lifestyle domains included dietary practices, physical activity, leisure activities, and sleep.

The study was designed to provide a controlled comparison of routine care with matching placebo, metformin therapy, and metformin combined with structured behavioral education. Participants receiving the educational intervention could not be blinded to the educational component because they were aware of their participation in the program. Standardized procedures were used for clinical assessment, laboratory measurements, data collection, and statistical analysis.

Inclusion criteria

• Women aged 18-40 years.
• Specialist-confirmed diagnosis of polycystic ovary syndrome (PCOS).
• Ability and willingness to participate in the six-month study follow-up.
• Ability to comply with the study procedures and assessments.

Exclusion criteria

• Chronic hemolytic anemia.
• Chronic kidney disease.
• Hepatic disorders.
• Other endocrine, metabolic, or cardiovascular conditions that could affect glucose metabolism, vitamin B12 status, iron status, erythropoietin levels, or hematological parameters.
• Previous use of insulin-sensitizing medications other than the study metformin.
• Current or recent hormonal therapy that could affect the study outcomes.
• Current use of iron or vitamin B12 supplements.
• Use of medications that could substantially affect glucose metabolism, vitamin B12 status, iron status, erythropoietin levels, or hematological parameters.
• Any condition that could interfere with adherence to the intervention or completion of the six-month follow-up.