Metformin and Oral Contraceptives in PCOS

Study Overview
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Brief Summary
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Background: PCOS is a common condition with a prevalence of 5-8 % in premenopausal women. More than 50% of PCOS patients are insulin resistant and have a diabetes risk 5-8 times higher than age- and weight-matched controls. Studies using insulin sensitizers in PCOS found increased insulin sensitivity and decreased insulin levels to be followed by decreased androgen levels and improved ovulatory function. No studies however, evaluated the long term effects of insulin sensitizing treatment. Oral contraceptives normalize menstrual cycles and suppress androgen levels in PCOS, however no long-term studies evaluated the effects of combined treatment with metformin and oral contraceptives in PCOS. Design: Randomized open study in 3*30 PCOS patients. Patients are randomised to 24 months of treatment with 1: metformin, 2: metformin and oral contraceptives or 3: oral contraceptives. Primary outcome measures: fasting insulin, AUC insulin. Secundary endpoints: BMI, WHR, LH, FSH, total and free-testosterone, c-peptid, urinary cortisol, AUC for insulin, glucose and c-peptid during OGTT. Inclusioncriteria: Irregular menses or anovulaty cycles High free testosterone > 0,035 nmol/l or hirsutism PCO in vaginal US Criteria 1 and 2 OR 2 and 3. Design:

Detailed Description
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90 patients are included and randomized to 12 months of treatment with metformin (1000+1000 mg/d) or OCP (150 mg desogestrel 30 microgram ethinylestradiol) or combined treatment (metformin+OCP). Patients attend a biochemical and physical examination at study inclusion and at 12 months. Patients attend for registration of side effects and compliance after 6 months of study duration. Safety tests are performed at all three visits and include weight, blood pressure, HbA1c, liver enzymes, electrolytes, and white blood cell count. Pregnancy tests are performed by the participants each month. Patients are given general advice on lifestyle intervention. Patients are excluded if they initiated medical treatment with possible hormonal and metabolic effects during the intervention period. Lifestyle intervention is allowed. Laser treatment is offered to patients with moderate or severe facial hirsutism and patients are allowed to shave/wax. The patients accept not applying cosmetic treatment 3-4 days before attending for evaluation at the clinic.

Official Title
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Metformin and Oral Contraceptives in PCOS

Conditions
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Polycystic Ovary Syndrome

Intervention / Treatment
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* Drug: Metformin
* Drug: Desorelle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Irregular menses or anovulaty cycles High free testosterone > 0.035 nmol/l or hirsutism PCO in vaginal US Criteria 1 and 2 OR 2 and 3 Exclusion Criteria: Age > 18 years Postmenopausal Diagnosis diabetes mellitus Use of medicine known to affect hormones measured in the project Pregnancy or planned pregnancy during study period Non-Caucasian Previous tromboembolic disease Heavy smoker > 35 years and BMI > 35 kg/m2

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>metformin | Drug: Metformin<br>* 500 mg 2 tablets 2 times a day<br>|
| Active Comparator: 2<br>desorelle | Drug: Desorelle<br>* 1 tablet/day in 21 days<br>|
| Active Comparator: 3<br>desorelle + metformin | Drug: Metformin<br>* 500 mg 2 tablets 2 times a day<br>Drug: Desorelle<br>* 1 tablet/day in 21 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in fasting insulin and area under the curve for insulin (2 hours) |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in BMD, BMI, WHR, LH, FSH, total and free testosterone, fasting blood glucose, fasting C-peptide, urine-cortisol secretion, body composition, number of hypoglycaemic cases, AUC for insulin, glucose and C-peptide during OGTT (2 and 5 ho |  | 12 months | 
| Changes in cortisol metabolism |  | 12 months | 
| Changes in the prevalence of reactive hypoglycemia and areal under the curve for glucose (5 hours) |  | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Polycystic ovary syndrome