Metformin and Oral Contraceptives in PCOS
Metformin and Oral Contraceptives in PCOS
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:

 1. Irregular menses or anovulaty cycles

 2. High free testosterone > 0,035 nmol/l or hirsutism

 3. PCO in vaginal US Criteria 1 and 2 OR 2 and 3.

 Design:
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.
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