Polycystic ovary syndrome (PCOS) affects 10 to 15% of all women and is the most common female endocrine and metabolic disorder during the reproductive years. PCOS is characterized by anovulation, hyperandrogenism and metabolic dysfunction. Women with PCOS have a 3 to 7-fold increased risk of developing type 2 diabetes (T2D). MedDRA version: 18.1 Level: LLT Classification code 10012613 Term: Diabetes mellitus non-insulin-dependent System Organ Class: 100000004861 MedDRA version: 18.1 Level: LLT
Conditions
Interventions
Trade Name: Metformin
Product Name: Metformin
Pharmaceutical Form: Tablet
INN or Proposed INN: Metformin
CAS Number: 657-24-9
Current Sponsor code: PIAII
Other descriptive name: METFORMIN HYDROCHLORID
Sponsors
Karolinska Institutet
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria – women with PCOS 1. Age 18 to 40 years 2. BMI =25 to =40 (=23 to =37.5 Chinese) given that 95% of all women with PCOS with a BMI 25 are insulin resistant (27, 28). 3. PCOS diagnosis according to Rotterdam criteria 2003 with at least two of the following three symptoms (29): Clinical signs of hyperandrogenism (hirsutism or acne); oligo/amenorrhea; and/or polycystic ovaries (PCOS). Hirsutism is defined as a self-reported Ferriman-Gallwey (FG) score =8 (=5 Chinese) (30, 31). Acne is defined by a positive response to the question Do you have acne? Oligomenorrhea is defined as an intermenstrual interval >35 days and 25 to 4), evidence of PCO morphology on ultrasound. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 353 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Exclusion criteria for all women 1. Age >40 2. Exclusion of other endocrine disorders such as non-classic congenital adrenal hyperplasia (17-hydroxyprogesterone 160 / 100 mmHg 7. Pregnancy or breastfeeding the last 6 months 8. Acupuncture last 2 months 9. Daily smoking and alcoholic intake 10. Language barrier or disabled person with reduced ability to understand information.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary objective •To determine the clinical effectiveness of 4 months of 1) acupuncture + lifestyle management and 2) metformin + lifestyle management compared with 3) lifestyle management only for improvement of insulin sensitivity as measured by HOMA-IR, by the insulin response to glucose assessed by calculating the area under the curve (AUCinsulin) during the oral glucose tolerance test (OGTT), and by glucose regulation (assessed by analyzing Hba1c levels). ;Secondary Objective: Secondary objectives •To evaluate changes in secondary metabolic measures, including fasting insulin, c-peptide, glucose, and adipokines, calculation of HOMA-B (i.e. the Islet ß-cell function) and the c-peptide index, assessment of the adipokines and lipid profile, body size and proportions and body fat distribution. •To determine changes in gene expression and DNA methylation profiles related to insulin sensitivity in fat, muscle and endometrial tissue biopsies, and biomarkers in whole blood. •To evaluate endocrine measures including menstrual pattern and ovulation frequency, circulating hormones (sex steroids, AMH, gonadotropins), and excretion of metabolites of sex steroids in urine. •To determine changes in women’s health related quality of life (HRQL) and symptoms of anxiety and depression, and negative side-effects. •To evaluate the cost-effectiveness of the different treatments. ;Primary end point(s): Changes in insulin sensitivity as measured by HOMA-IR, by the insulin response to glucose assessed by calculating the area under the curve (AUCinsulin) during the oral glucose tolerance test (OGTT), and by glucose regulation (assessed by analyzing Hba1c levels).;Timepoint(s) of evaluation of this end point: 1.After 4 months of intervention | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Changes in secondary metabolic measures, including fasting insulin, c-peptide, glucose, and adipokines, calculation of HOMA-B (i.e. the Islet ß-cell function) and the c-peptide index, assessment of the adipokines and lipid profile, body size and proportions and body fat distribution. • Changes in gene expression and DNA methylation profiles related to insulin sensitivity in fat, muscle and endometrial tissue biopsies, and biomarkers in whole blood. • Changes in endocrine measures including menstrual pattern and ovulation frequency, circulating hormones (sex steroids, AMH, gonadotropins), and excretion of metabolites of sex steroids in urine. • Changes in women’s health related quality of life (HRQL) and symptoms of anxiety and depression, and negative side-effects and the cost-effectiveness of the different treatments. ;Timepoint(s) of evaluation of this end point: 1. After 4 months of intervention 2. Follow-up 4 months after last treatment. | — |
Countries
Sweden
Contacts
Public ContactElisabet Stener-Victorin
Karolinska Institutet
Outcome results
None listed