Optimizing Metformin Use in Polycystic Ovary Syndrome

NCT ID: NCT07120815

Last Updated: 2025-08-13

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 184 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-09-01
• Study Completion Date: 2028-12-31

Brief Summary

The goal of this clinical trial is to learn if a metformin dose of 1500 mg or 2250 mg per day is better to treat polycystic ovary syndrome (PCOS) in adults. It will also learn about the adverse effects of metformin. The trial aims to evaluate which metformin dose is better for:

1. improving biochemical and clinical outcomes

2. gastrointestinal side-effects

3. mental health and quality of life

Participants will:

• Be randomized to take metformin at a dose of either 1500mg or 2250mg every day for 6 months
• Visit the clinic three times during the trial for checkups and tests
• Answer questionnaires on menstrual cyclicity, mental health, quality of life and side-effects

Detailed Description

INTRODUCTION Polycystic ovary syndrome (PCOS) remains a key public health burden as it is one of the most common endocrine and metabolic disorders affecting up to 13% of women globally. The Rotterdam diagnostic criteria were updated and internationally endorsed in the 2023 International PCOS guideline and include a) ovulatory and menstrual dysfunction, b) biochemical and/or clinical hyperandrogenism and c) polycystic ovary morphology (PCOM) at ultra-sound. For a diagnosis in adults two of three criteria are required, with PCOM remaining nonspecific for PCOS in adolescents.

Women with PCOS present with diverse features; metabolic (weight gain, obesity, insulin resistance and diabetes) reproductive (infertility and pregnancy complications), endocrine (hyperandrogenism, hirsutism and acne) and psychosocial (depression, anxiety and poor quality of life).

While lifestyle management is strongly recommended for weight management, for those with higher body mass index (BMI), sustainable efficacy for weight loss can be limited and additional pharmacological treatment may be needed. The 2023 Updated International PCOS Guideline recommends that metformin, in addition to lifestyle, should be considered in adults with PCOS and BMI ≥ 25 kg/m2 for prevention of weight gain and management of weight and metabolic disorders. Metformin may be considered in adults with BMI < 25 kg/m2 and adolescents with PCOS, acknowledging more limited evidence.

The aim of this randomized controlled trial (RCT) is to evaluate whether a metformin dose of 1500 mg is inferior compared to a dose of 2250 mg per day for females 18-37 years of age with PCOS in:

1. improving biochemical and clinical outcomes

2. gastrointestinal side-effects

3. mental health and quality of life

MATERIALS AND METHODS A double-blind, randomized controlled trial, including adults (age 18-37 years) with PCOS and a BMI ≥ 25 kg/m2 will be carried out. The randomization will be computer-generated and performed by the hospital pharmacy with 1:1 allocation in random blocks. Power analysis has indicated that a total number of 184 females (92 in each group) will be needed to reveal a 4 kg weight reduction (equals 5% weight reduction for a person weighting 80 kg) with an 80% power. We estimated a 15% drop-out in our power analysis.

Potential participants for the study will be recruited from females referred to the Reproductive Medicine Unit at Helsinki University Hospital and by advertising via the patient organization for those with PCOS (Korento). The internationally indorsed Rotterdam criteria will be used to diagnose women with PCOS. Pregnant women, women breastfeeding, women with untreated thyroid disease, hyperprolactinemia, other conditions with hyperandrogenism or use of hormonal contraceptive during the last three months will be excluded.

Women willing to participate in the study will be randomized to metformin 1500mg or 2250 mg per day for a 6-month period. Blood samples (on hyperandrogenism and metabolism), clinical examination (anthropometry and hirsutism) and a questionnaire (menstrual cyclicity, mental health, quality of life, side-effects) will be performed before starting the metformin medication, as well as at 3 and 6 months after onset of medication. Polycystic ovary morphology will be evaluated by measuring anti-mullerian hormone levels (AMH) and by vaginal ultrasound.

Conditions

Polycystic Ovary Syndrome (PCOS)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Women 18-37 years old with a BMI ≥ 25 kg/m2, metformin 2250mg per day

metformin tablets 2250 mg per day

Group Type: ACTIVE_COMPARATOR

Metformin 2250 mg daily

Intervention Type: DRUG

Metformin 750mg, 3 times daily

Women 18-37 years old with a BMI ≥ 25 kg/m2, metformin 1500mg per day

metformin tablets 1500 mg per day

Group Type: EXPERIMENTAL

Metformin 1500 mg daily

Intervention Type: DRUG

metformin 500mg tablets, 3 times per day

Interventions

Metformin 1500 mg daily

metformin 500mg tablets, 3 times per day

Intervention Type: DRUG

Metformin 2250 mg daily

Metformin 750mg, 3 times daily

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Diagnosed PCOS (According to the International evidence-based Guideline for PCOS 2023)
• Age: 18-37 years
• BMI: ≥ 25 and <40 kg/m2
• Signed informed consent and willingness to comply with the trial procedures
• Sufficient skills in the Finnish or Swedish language

Exclusion Criteria

• Not meeting the criteria according to the International evidence-based Guideline for PCOS 2023)
• Use of hormonal contraceptive during the last 3 months
• Pregnancy
• Breastfeeding
• Untreated diabetes
• Hypothyroidism
• Hyperprolactinemia
• Use of medications for diabetes,
• Use of medications for high cholesterol
• Use of medications for obesity
• Use of medications for cortisone (per oral)
• Hypersensitivity to metformin
• Acute metabolic acidosis
• Renal impairment
• Hepatic insufficiency
• Heart- or respiratory failure
• Serious mental illness
• Alcoholism
• Investigator site staff directly involved in the conduct of the study and their family members

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 37 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Valtion tutkimusraha (funding)

UNKNOWN

Sponsor Role: collaborator

Sakari Alhopuro foundation (funding)

UNKNOWN

Sponsor Role: collaborator

The Medical Society of Finland (funding)

UNKNOWN

Sponsor Role: collaborator

Helsinki University Central Hospital

OTHER

Sponsor Role: lead

Responsible Party

Johanna Melin

MD, PhD, specialist in obstetrics & gynecology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Johanna M Melin, MD

Role: PRINCIPAL_INVESTIGATOR

The Reproductive Medicine Unit, Helsinki University Hospital

Locations

The Reproductive Medicine Unit, Helsinki University Hospital

Helsinki, , Finland

Countries

Finland

Central Contacts

Johanna M Melin, MD

Role: CONTACT

johanna.melin@hus.fi

+358505382526

Facility Contacts

Johanna M Melin, MD

Role: primary

johanna.melin@hus.fi

+358505382526

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2023-509259-15-01

Identifier Type: CTIS

Identifier Source: secondary_id

HUS8428/TYH2024323

Identifier Type: -

Identifier Source: org_study_id