Skip to main content
OpenTrials
Completed

NCT Number: NCT07793838

Metformin Effects on Metabolic, Vitamin B12, Iron, Erythropoietin, and Hematological Parameters in Women With PCOS

This double-blind, placebo-controlled, parallel-group randomized controlled trial evaluated changes in metabolic, vitamin B12, iron-status, erythropoietic, and hematological parameters among women with polycystic ovary syndrome (PCOS) receiving metformin therapy.

Women aged 18-40 years with a diagnosis of PCOS confirmed by a specialist in Obstetrics and Gynecology were randomly assigned in a 1:1 ratio to either a metformin intervention group or a matching placebo group. Participants in the metformin group received a total daily dose of 1500 mg metformin, administered in three divided doses with meals, while participants in the control group received a matching placebo. Both groups continued to receive routine clinical care.

Clinical and laboratory assessments were performed at baseline, 3 months, and 6 months. The study evaluated metabolic measures, including fasting blood glucose, serum insulin, HOMA-IR, total cholesterol, triglycerides, LDL-C, HDL-C, and body mass index. Iron-status measures included serum iron, total iron-binding capacity, ferritin, and transferrin saturation. Serum vitamin B12 and erythropoietin were also assessed, together with hematological parameters including hemoglobin, hematocrit, red blood cell indices, white blood cell counts and differential counts, and platelet count.

The study enrolled 400 participants, with 200 participants initially allocated to each treatment group. After loss to follow-up, 300 participants completed the required assessments and were included in the final longitudinal analysis, with 150 participants in each group.

The study was designed to characterize longitudinal changes in metabolic, nutritional, iron-related, erythropoietic, and hematological parameters during six months of metformin therapy in women with PCOS.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Polycystic Ovary Syndrome (PCOS) Women Adnexal Diseases Cysts Endocrine System Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genital Diseases Genital Diseases, Female Glucose Metabolism Disorders Gonadal Disorders Hyperinsulinism Insulin Resistance Metabolic Diseases Neoplasms Nutritional and Metabolic Diseases Ovarian Cysts Ovarian Diseases Polycystic Ovary Syndrome Urogenital Diseases

Age range

18 year–40 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 4

Primary location

obstetrics and gynecology clinics affiliated with the Ministry of Health in Jordan،

Amman, 009627, Jordan

About this study

Polycystic ovary syndrome (PCOS) is a common and heterogeneous endocrine and metabolic disorder characterized by reproductive, endocrine, and metabolic abnormalities. Insulin resistance, hyperinsulinemia, dyslipidemia, excess weight, and disturbances in reproductive function are important components of the PCOS phenotype. Metformin is an insulin-sensitizing medication widely used to address metabolic abnormalities associated with PCOS.

This double-blind, placebo-controlled, parallel-group randomized controlled trial was designed to evaluate longitudinal changes in metabolic, vitamin B12, iron-status, erythropoietic, and hematological parameters among women with PCOS during six months of metformin therapy. The study also examined selected associations among demographic, clinical, reproductive, familial, metabolic, vitamin B12, iron-status, erythropoietic, and hematological characteristics.

Women aged 18-40 years with PCOS confirmed by a specialist in Obstetrics and Gynecology were eligible for participation. Participants were excluded if they had chronic hemolytic anemia, chronic kidney disease, endocrine disorders other than PCOS, hepatic disorders, metabolic disorders, cardiovascular disease, or other concurrent medical conditions that could influence glucose metabolism, iron status, vitamin B12, erythropoietin, or hematological parameters. Women who had received insulin-sensitizing agents, iron supplementation, hormonal therapy, vitamin B12 supplementation, or other medications known to substantially affect the study outcomes during the predefined period before enrollment were also excluded.

Following baseline assessment, eligible participants were randomly allocated in a 1:1 ratio using a computer-generated random allocation sequence to either the metformin intervention group or the matching placebo group. Participants in the intervention group received metformin at a total daily dose of 1500 mg, administered in three divided doses with meals. Participants in the control group received a corresponding matching placebo according to the same administration schedule. Both groups continued to receive routine clinical care.

The double-blind design was maintained throughout the study. Participants were blinded to treatment allocation, and investigators involved in participant assessment and outcome evaluation were also blinded to treatment assignment. Matching preparations were used to minimize the possibility of identifying treatment allocation based on appearance.

Clinical, anthropometric, biochemical, iron-status, vitamin B12, erythropoietic, and hematological assessments were performed at three predefined time points: baseline, 3 months, and 6 months. Metabolic assessments included body mass index, fasting blood glucose, serum insulin, HOMA-IR, total cholesterol, triglycerides, LDL-C, and HDL-C. Iron-status assessments included serum iron, total iron-binding capacity, ferritin, and transferrin saturation. Serum vitamin B12 and erythropoietin were also assessed. 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, lymphocytes, neutrophils, eosinophils, basophils, monocytes, and platelet count.

The study was conducted in obstetrics and gynecology clinics affiliated with the Ministry of Health in Jordan. The study period extended from August 2025 to February 2026. A total of 400 women were initially enrolled and randomly allocated, with 200 participants assigned to each treatment group. During the six-month follow-up period, 100 participants did not complete the required assessments, leaving 300 participants in the final longitudinal analysis, comprising 150 participants in the metformin group and 150 participants in the matching placebo group.

No additional structured educational, behavioral, lifestyle, or self-management intervention was introduced as part of the study protocol. Participants continued to receive routine clinical care. Lifestyle behaviors, including physical activity, dietary intake, and adherence to lifestyle recommendations, were not systematically quantified using validated assessment instruments.

Longitudinal changes across baseline, 3 months, and 6 months were evaluated using repeated-measures analysis of variance. Associations between selected continuous variables were examined using Pearson's correlation coefficient when appropriate, while Spearman's rank-order correlation coefficient was used for ordinal variables or variables that did not meet the assumptions required for Pearson correlation. Correlation analyses were considered exploratory and hypothesis-generating because multiple associations were examined.

The study received ethical approval from the Ethical Board of the Jordanian Ministry of Health, Amman, Jordan (Approval No. 99923), and the Institutional Review Board of Al-Ahliyya Amman University (Approval No. 2026-2025/30/1). Written informed consent was obtained from all participants before enrollment. The study was conducted in accordance with the ethical principles of the Declaration of Helsinki.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Women aged 18-40 years.
  • Diagnosis of polycystic ovary syndrome (PCOS) confirmed by a specialist in Obstetrics and Gynecology.
  • Eligible participants who met the study requirements and provided written informed consent.

Exclusion criteria

  • Chronic hemolytic anemia.
  • Chronic kidney disease.
  • Endocrine disorders other than PCOS.
  • Hepatic disorders.
  • Metabolic disorders.
  • Cardiovascular disease.
  • Other concurrent medical conditions that could influence glucose metabolism, iron status, vitamin B12, erythropoietin, or hematological parameters.
  • Previous use of insulin-sensitizing agents, iron supplementation, hormonal therapy, vitamin B12 supplementation, or other medications known to substantially affect glucose metabolism, iron metabolism, erythropoietin levels, or hematological parameters during the predefined period before enrollment.

Treatment and study plan

metformin

Drug

Metformin was administered at a total daily dose of 1500 mg in three divided doses with meals for six months.

Matching Placebo

Drug

A matching placebo was administered according to the same schedule as the metformin intervention for six months.

Primary outcomes

  1. Longitudinal change in serum iron

    Time frame: Baseline, 3 months, and 6 months

    Change in serum iron from baseline through 3 months and 6 months during the study intervention.

  2. Longitudinal change in total iron-binding capacity

    Time frame: Baseline, 3 months, and 6 months

    Change in total iron-binding capacity (TIBC) from baseline through 3 months and 6 months during the study intervention.

  3. Longitudinal change in serum ferritin

    Time frame: Baseline, 3 months, and 6 months

    Change in serum ferritin from baseline through 3 months and 6 months during the study intervention.

  4. Longitudinal change in transferrin saturation

    Time frame: Baseline, 3 months, and 6 months

    Change in transferrin saturation (TSAT) from baseline through 3 months and 6 months during the study intervention.

  5. Longitudinal change in serum vitamin B12

    Time frame: Baseline, 3 months, and 6 months.

    Change in serum vitamin B12 level from baseline through 3 months and 6 months during the study intervention.

  6. Longitudinal change in erythropoietin

    Time frame: Baseline, 3 months, and 6 months.

    Change in serum erythropoietin (EPO) level from baseline through 3 months and 6 months during the study intervention.

  7. Longitudinal change in hemoglobin

    Time frame: Baseline, 3 months, and 6 months.

    Change in hemoglobin (Hb) from baseline through 3 months and 6 months during the study intervention.

  8. Longitudinal change in hematocrit

    Time frame: Baseline, 3 months, and 6 months.

    Change in hematocrit (Hct) from baseline through 3 months and 6 months during the study intervention.

  9. Longitudinal change in red blood cell count

    Time frame: Baseline, 3 months, and 6 months.

    Change in red blood cell (RBC) count from baseline through 3 months and 6 months during the study intervention.

  10. Longitudinal change in mean corpuscular volume

    Time frame: Baseline, 3 months, and 6 months.

    Change in mean corpuscular volume (MCV) from baseline through 3 months and 6 months during the study intervention.

  11. Longitudinal change in mean corpuscular hemoglobin

    Time frame: Baseline, 3 months, and 6 months.

    Change in mean corpuscular hemoglobin (MCH) from baseline through 3 months and 6 months during the study intervention.

  12. Longitudinal change in mean corpuscular hemoglobin concentration

    Time frame: Baseline, 3 months, and 6 months.

    Change in mean corpuscular hemoglobin concentration (MCHC) from baseline through 3 months and 6 months during the study intervention.

  13. Longitudinal change in red cell distribution width

    Time frame: Baseline, 3 months, and 6 months.

    Change in red cell distribution width (RDW-CV) from baseline through 3 months and 6 months during the study intervention.

  14. Longitudinal change in white blood cell count

    Time frame: Baseline, 3 months, and 6 months.

    Change in white blood cell (WBC) count from baseline through 3 months and 6 months during the study intervention.

  15. Longitudinal change in lymphocyte count

    Time frame: Baseline, 3 months, and 6 months.

    Change in lymphocyte count from baseline through 3 months and 6 months during the study intervention.

  16. Longitudinal change in neutrophil count

    Time frame: Baseline, 3 months, and 6 months.

    Change in neutrophil count from baseline through 3 months and 6 months during the study intervention.

  17. Longitudinal change in eosinophil count

    Time frame: Baseline, 3 months, and 6 months.

    Change in eosinophil count from baseline through 3 months and 6 months during the study intervention.

  18. Longitudinal change in basophil count

    Time frame: Baseline, 3 months, and 6 months.

    Change in basophil count from baseline through 3 months and 6 months during the study intervention.

  19. Longitudinal change in monocyte count

    Time frame: Baseline, 3 months, and 6 months.

    Change in monocyte count from baseline through 3 months and 6 months during the study intervention.

  20. Longitudinal change in platelet count

    Time frame: Baseline, 3 months, and 6 months.

    Change in platelet (PLT) count from baseline through 3 months and 6 months during the study intervention.

  21. Longitudinal change in HOMA-IR

    Time frame: Baseline, 3 months, and 6 months

    Change in homeostasis model assessment of insulin resistance (HOMA-IR) from baseline through 3 months and 6 months during the study intervention.

  22. Longitudinal change in fasting blood glucose

    Time frame: Baseline, 3 months, and 6 months

    Change in fasting blood glucose (FBG) from baseline through 3 months and 6 months during the study intervention.

  23. Longitudinal change in total cholesterol

    Time frame: Baseline, 3 months, and 6 months

    Change in total cholesterol (TC) from baseline through 3 months and 6 months during the study intervention.

  24. Longitudinal change in triglycerides

    Time frame: Baseline, 3 months, and 6 months

    Change in triglycerides (TG) from baseline through 3 months and 6 months during the study intervention.

  25. Longitudinal change in low-density lipoprotein cholesterol

    Time frame: Baseline, 3 months, and 6 months.

    Change in low-density lipoprotein cholesterol (LDL-C) from baseline through 3 months and 6 months during the study intervention.

  26. Longitudinal change in high-density lipoprotein cholesterol

    Time frame: Baseline, 3 months, and 6 months.

    Change in high-density lipoprotein cholesterol (HDL-C) from baseline through 3 months and 6 months during the study intervention.

  27. Longitudinal change in body mass index

    Time frame: Baseline, 3 months, and 6 months.

    Change in body mass index (BMI) from baseline through 3 months and 6 months during the study intervention.

Sponsors and collaborators

Lead sponsor

Jerash Private University

Other

Registry information

Official study title

The Effects of Metformin Therapy on Changes in Metabolic, Vitamin B12, Iron Status, Erythropoietin, and Hematological Parameters Among Women With Polycystic Ovary Syndrome: A Double-Blind Randomized Controlled Trial

Acronym: MET-PCOS

Important dates

Study start
2025
Primary completion
2026
Study completion
2026
First posted
Aug 31, 2026
Registry last updated
Aug 31, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.