The Effects of OCP and Metformin on Clinical, Hormonal, Metabolic and Ultrasonographic Characteristics in PCOS

S.C.B. Medical College and Hospital

Status and phase: Completed; Phase 4

Conditions: Polycystic Ovary Syndrome

Treatments: Drug: Metformin; Drug: ethinyl estradiol and cyproterone acetate

Study type: Interventional

Funder types: Other

Identifiers

NCT02866786

OG/2016/13

Details and patient eligibility

About

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorder in women of reproductive age and is a leading cause of infertility due to anovulation. Oral contraceptive pills (OCPs) are considered as first line medical therapy to regularize menses in woman with PCOS. However they may worsen the metabolic profile of patients by elevating insulin resistance which is already deranged in PCOS. As there is higher prevalence of insulin resistance in Indian women with PCOS, insulin sensitisers like metformin may be more beneficial. Hence this study is undertaken to compare the combined effect of metformin and OCPs on the clinical, hormonal, metabolic and ovarian ultrasonographic characteristics in patients with PCOS and to evaluate whether this combination of drugs is more advantageous than OCPs or metformin alone in improving the clinical and metabolic profile.

Full description

We aim to enroll about 120 patients fulfilling the Rotterdam diagnostic criteria for PCOS in our study. Patients will have a baseline clinical examination (Body weight, Body mass index, Waist circumference, Hirsutism score), hormonal profile (FSH, LH, fasting Insulin/glucose ratio, DHEAS, testosterone levels), metabolic profile (fasting and 2 hour post prandial plasma glucose, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides level), ultrasound examination (ovarian volume and subcapsular follicle count, stromal echogenicity) and doppler blood flow study (ovarian stromal velocity, Pulsatility index, Resistivity index, Systolic/Diastolic ratio and stromal vascularization index).

Patients will be then randomized using a computer generated randomization program into two groups according to BMI (<25 and >25). The randomization will be stratified in order to achieve a homogenous distribution of PCOS patients in both arms of the study with respect to age and body mass index. Each group will be further subdivided into three treatment arms. 1st treatment arm will receive OCP containing 35 microgram ethinyl estradiol and 2 mg cyproterone acetate cyclically (21 days regimen) daily; 2nd treatment arm will receive OCP containing 35 microgram ethinyl estradiol and 2 mg cyproterone acetate cyclically (21 days regimen) while the 3rd treatment arm will receive OCP plus metformin 500 mg twice daily for a period of six months. Each patient will be asked to keep a diary of her menstrual periods over the study period. The patients will be followed up at 3 and 6 months of treatment to evaluate the changes in the above mentioned parameters. Analysis of the data will be done through descriptive and perceptive statistical methods by using Statistical Package for the Social Sciences (SPSS) software.

Enrollment: 101 patients

Sex: Female

Ages: 18 to 35 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Patients will be included into study who fulfill the Rotterdam diagnostic criteria (2003) for PCOS.

Exclusion criteria

• Current or previous use of oral contraceptives, glucocorticoids, antiandrogens, ovulation induction agents, antidiabetic and anti-obesity drugs or other hormonal drugs.
• Medical or surgical treatment of PCOS during the previous 3 months
• Presence of other endocrinopathies; except treated hypothyroidism on stable replacement doses of thyroid hormone
• Pregnancy, breastfeeding or desire for pregnancy during study interval (6 months)
• Inability to understand the proposal of the study precluding effective informed consent

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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101 participants in 2 patient groups

OCP only arm

Active Comparator group

Description:

OCP containing 35 microgram ethinyl estradiol and 2 milligram cyproterone acetate to taken from the first day of the menstruation, oral administration of one pill daily for 21 days consecutively, then discontinue using the pill for seven days, and on the eighth day, restart taking the pill. OCP to be taken for 6 months.

Treatment:

Drug: ethinyl estradiol and cyproterone acetate

Metformin arm

Active Comparator group

Description:

Metformin 500mg bid in morning and evening after meals to be taken for 6 months.

Treatment:

Drug: Metformin