Metformin and Oral Contraceptives in PCOS

Odense University Hospital

Status and phase: Completed; Phase 4

Conditions: Polycystic Ovary Syndrome

Treatments: Drug: Metformin; Drug: Desorelle

Study type: Interventional

Funder types: Other

Identifiers

NCT00451568

027

Details and patient eligibility

About

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:

Full description

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.

Enrollment: 90 patients

Sex: Female

Ages: 18 to 40 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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90 participants in 3 patient groups

1

Active Comparator group

Description:

metformin

Treatment:

Drug: Metformin

2

Active Comparator group

Description:

desorelle

Treatment:

Drug: Desorelle

3

Active Comparator group

Description:

desorelle + metformin

Treatment:

Drug: Desorelle

Drug: Metformin