Polycystic Ovary Syndrome (PCOS) Women
Conditions
Keywords
Metformin, PCOS, heory-Based Behavioral Education, Lifestyle Education, Vitamin B12, Iron Status, Erythropoietin, Metabolic Outcomes, Hematological Parameters
Brief summary
Polycystic ovary syndrome (PCOS) is a common condition associated with metabolic abnormalities, including insulin resistance, impaired glucose regulation, and abnormal lipid levels. Metformin is commonly used to improve metabolic outcomes in women with PCOS, while lifestyle modification and behavioral education are important components of PCOS management. This study evaluates whether metformin, alone or combined with a theory-based behavioral educational program, is associated with changes in metabolic, vitamin B12, iron-status, erythropoietin, and hematological parameters compared with matching placebo. This is a prospective, three-arm, parallel-group randomized controlled trial conducted among women aged 18-40 years with specialist-confirmed PCOS in Ministry of Health obstetrics and gynecology clinics in Jordan. A total of 900 participants were initially randomized in a 1:1:1 ratio to receive matching placebo, metformin, or metformin combined with a theory-based behavioral educational program. The metformin groups received 1500 mg/day, administered as 500 mg three times daily, for six months. The combined intervention group additionally received five structured educational sessions addressing PCOS self-management, healthy dietary practices, physical activity, weight and waist management, metformin adherence, sleep, stress management, problem solving, and maintenance of healthy behaviors. Clinical and laboratory outcomes were assessed at baseline and after six months. The primary outcomes include changes in anthropometric, metabolic, vitamin B12, iron-status, erythropoietic, and hematological parameters. Changes in PCOS-related knowledge and lifestyle practices were also evaluated among participants receiving the combined intervention.
Detailed description
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.
Interventions
DRUGMetFORMIN
Metformin was administered at a total daily dose of 1500 mg, given as 500 mg three times daily, for six months.
DRUGMatching Placebo
Matching placebo tablets identical to the metformin tablets in appearance, size, and form were administered for six months.
BEHAVIORALTheory-Based Behavioral Educational Program
A structured behavioral educational program grounded in Bandura's Self-Efficacy Theory was provided to participants in the combined intervention group. The program consisted of five structured sessions addressing PCOS self-management, healthy dietary practices, physical activity and sedentary behavior, weight and waist management, metformin adherence, metabolic health, sleep, stress management, problem solving, and maintenance of behavioral changes.
Sponsors
Jerash Private University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
The educational intervention could not be masked because participants were aware of their participation in the behavioral educational program. The pharmacological groups received either metformin or matching placebo tablets. Standardized procedures were used for clinical assessment, laboratory measurements, data collection, and statistical analysis.
Intervention model description
Participants were randomly allocated in a 1:1:1 ratio to three parallel groups: matching placebo, metformin, or metformin combined with a theory-based behavioral educational program. All groups received routine clinical care and were followed for six months.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
1. Women aged 18-40 years. 2. Specialist-confirmed diagnosis of polycystic ovary syndrome (PCOS). 3. Ability and willingness to participate in the six-month study follow-up. 4. Ability to comply with the study procedures and assessments.
Exclusion criteria
1. Chronic hemolytic anemia. 2. Chronic kidney disease. 3. Hepatic disorders. 4. Other endocrine, metabolic, or cardiovascular conditions that could affect glucose metabolism, vitamin B12 status, iron status, erythropoietin levels, or hematological parameters. 5. Previous use of insulin-sensitizing medications other than the study metformin. 6. Current or recent hormonal therapy that could affect the study outcomes. 7. Current use of iron or vitamin B12 supplements. 8. Use of medications that could substantially affect glucose metabolism, vitamin B12 status, iron status, erythropoietin levels, or hematological parameters. 9. Any condition that could interfere with adherence to the intervention or completion of the six-month follow-up.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Body Mass Index (BMI) From Baseline to 6 Months | Baseline to 6 months | Change in body mass index (BMI) from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups. |
| Change in Serum Insulin From Baseline to 6 Months | Baseline to 6 months | Change in serum insulin from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups. |
| Change in HOMA-IR From Baseline to 6 Months | Baseline to 6 months | Change in homeostasis model assessment of insulin resistance (HOMA-IR) from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups. |
| Change in Total Cholesterol (TC) From Baseline to 6 Months | Baseline to 6 months | Change in total cholesterol (TC) from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups. |
| Change in Triglycerides (TG) From Baseline to 6 Months | Baseline to 6 months | Change in triglycerides (TG) from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups. |
| Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to 6 Months | Baseline to 6 months | Change in low-density lipoprotein cholesterol (LDL-C) from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups. |
| Change in High-Density Lipoprotein Cholesterol (HDL-C) From Baseline to 6 Months | Baseline to 6 months | Change in high-density lipoprotein cholesterol (HDL-C) from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups. |
| Change in Serum Vitamin B12 From Baseline to 6 Months | Baseline to 6 months | Change in serum vitamin B12 concentration from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups. |
| Change in Serum Iron From Baseline to 6 Months | Baseline to 6 months | Change in serum iron concentration from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups. |
| Change in Serum Ferritin From Baseline to 6 Months | Baseline to 6 months | Change in serum ferritin concentration from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups. |
| Change in Total Iron-Binding Capacity (TIBC) From Baseline to 6 Months | Baseline to 6 months | Change in total iron-binding capacity (TIBC) from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups. |
| Change in Transferrin Saturation (TSAT) From Baseline to 6 Months | Baseline to 6 months | Change in transferrin saturation (TSAT) from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups. |
| Change in Serum Erythropoietin (EPO) From Baseline to 6 Months | Baseline to 6 months | Change in serum erythropoietin (EPO) concentration from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups. |
| Change in Hemoglobin (Hb) From Baseline to 6 Months | Baseline to 6 months | Change in hemoglobin (Hb) concentration from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups. |
| Change in Hematocrit (Hct) From Baseline to 6 Months | Baseline to 6 months | Change in hematocrit (Hct) from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups. |
| Change in Mean Corpuscular Volume (MCV) From Baseline to 6 Months | Baseline to 6 months | Change in mean corpuscular volume (MCV) from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups. |
| Change in Mean Corpuscular Hemoglobin (MCH) From Baseline to 6 Months | Baseline to 6 months | Change in mean corpuscular hemoglobin (MCH) from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups. |
| Change in Mean Corpuscular Hemoglobin Concentration (MCHC) From Baseline to 6 Months | Baseline to 6 months | Change in mean corpuscular hemoglobin concentration (MCHC) from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups. |
| Change in Red Cell Distribution Width (RDW) From Baseline to 6 Months | Baseline to 6 months | Change in red cell distribution width (RDW) from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups. |
| Change in White Blood Cell (WBC) Count From Baseline to 6 Months | Baseline to 6 months | Change in neutrophil count from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups. |
| Change in Lymphocyte Count From Baseline to 6 Months | Baseline to 6 months | Change in lymphocyte count from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups. |
| Change in Eosinophil Count From Baseline to 6 Months | Baseline to 6 months | Change in eosinophil count from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups. |
| Change in Basophil Count From Baseline to 6 Months | Baseline to 6 months | Change in basophil count from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups. |
| Change in Platelet Count From Baseline to 6 Months | Baseline to 6 months | Change in platelet count from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in PCOS-Related Knowledge and Lifestyle Practices From Baseline to 6 Months | Baseline to 6 months | Change from baseline to 6 months in PCOS-related knowledge and lifestyle-practice scores among participants receiving metformin combined with the theory-based behavioral educational program. The assessment included PCOS-related knowledge and lifestyle domains covering food habits, physical activity, leisure time, and sleep pattern. |
Countries
Jordan
Outcome results
None listed