The Effects of OCP and Metformin on Clinical, Hormonal, Metabolic and Ultrasonographic Characteristics in PCOS
|ClinicalTrials.gov Identifier: NCT02866786|
Recruitment Status : Completed
First Posted : August 15, 2016
Last Update Posted : April 20, 2018
|Condition or disease||Intervention/treatment||Phase|
|Polycystic Ovary Syndrome||Drug: Metformin Drug: ethinyl estradiol and cyproterone acetate||Phase 4|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||101 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Single (Outcomes Assessor)|
|Official Title:||The Effects of Treatment With Oral Contraceptive Pill Containing Ethinyl Estradiol-Cyproterone Acetate and Metformin on Clinical, Hormonal, Metabolic and Ultrasonographic Characteristics in Polycystic Ovarian Syndrome|
|Actual Study Start Date :||August 15, 2016|
|Actual Primary Completion Date :||April 20, 2017|
|Actual Study Completion Date :||August 1, 2017|
Active Comparator: OCP only arm
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.
Drug: ethinyl estradiol and cyproterone acetate
Oral Contraceptive Pill
Active Comparator: Metformin arm
Metformin 500mg bid in morning and evening after meals to be taken for 6 months.
- Improvement in menstrual cycle pattern [ Time Frame: 6 months ]All the participants will be asked to maintain a menstrual calendar and fill a questionnaire before and at the end of study. The questionnaire will include menstrual cycle dates, duration and amount from which improvement of menstrual pattern will be assessed.
- Change in Abdominal Fat as measured by Waist Circumference in centimeter [ Time Frame: 6 months ]
- Change in weight as measured in kg [ Time Frame: 6 months ]
- Improvement in hirsutism measured by Modified Ferriman and Gallwey scores [ Time Frame: 6 months ]
- Improvement in glucose tolerance (measured by of fasting plasma glucose and 2-hour post prandial plasma glucose) [ Time Frame: 6 months ]
- Change in waist-to-hip ratio [ Time Frame: 6 months ]
- Change in Body mass index (kg/m2) [ Time Frame: 6 months ]
- Lipid profile (Cholesterol, LDL, HDL and Triglyceride) improvement [ Time Frame: 6 months ]The serum levels of Cholesterol, LDL, HDL and Triglyceride were measured in mg/dl before and after of treatment in both groups.
- Change in blood level of luteinizing hormone [LH] (mIU/ml) [ Time Frame: 6 months ]
- Change in blood level of follicle stimulating hormone [FSH] (mIU/ml) [ Time Frame: 6 months ]
- Change in blood level of Testosterone (nmol/L) [ Time Frame: 6 months ]
- Change in blood level of Sex hormone binding globulin (SHBG) (ng/ml) [ Time Frame: 6 months ]
- Change in Free androgen Index (FAI) [ Time Frame: 6 months ]Free Androgen Index or FAI is a ratio used to determine abnormal androgen status. The ratio is the total testosterone level divided by the sex hormone binding globulin (SHBG) level, and then multiplying by 100.
- Change in Dehydroepiandrosterone sulfate (DHEAS) level (microgram/dl) [ Time Frame: 6 months ]
- Changes in fasting serum insulin levels (mIU/L) [ Time Frame: 6 months ]
- Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) [ Time Frame: 6 months ]Homeostatic model assessment (HOMA) is a method for assessing β-cell function and insulin resistance (IR) from basal (fasting) glucose and insulin concentrations. HOMA-IR = (Glucose x Insulin) / 405; Glucose is expressed in mg/dl and Insulin is expressed in mIU/L
- Ovarian Stromal artery Pulsatility index [ Time Frame: 6 months ]
- Ovarian Stromal artery Resistivity index [ Time Frame: 6 months ]
- Chang in ovarian Follicle number by Ultrasonography (USG) [ Time Frame: 6 months ]Largest cross-sectional plane of the ovary will be evaluated for follicle number
- Change in ovarian Follicle diameter (in mm) by USG [ Time Frame: 6 months ]Largest cross-sectional plane of the ovary will be evaluated for follicle diameter
- Change in Ovarian volume (in cc) by USG [ Time Frame: 6 months ]Ovarian volume, estimated according to the formula 1/2 (A x B x C), where A is the longitudinal diameter, B the anteroposterior diameter, and C the transverse diameter of the ovary
- Change in Endometrial thickness (in mm) [ Time Frame: 6 months ]
- Change in ovarian stromal/total area ratio (S/A) [ Time Frame: 6 months ]Ovarian area, evaluated by outlining with the caliper the external limits of the ovary in the maximum plane section. Ovarian stromal area, evaluated by outlining with the caliper the peripheral profile of the stroma, identified by a central area slightly hyperechoic with respect to the other ovarian area.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02866786
|Department of Obstetrics & Gynecology|
|Cuttack, Odisha, India, 753007|
|Principal Investigator:||Mahija Sahu, MD||S.C.B. Medical College and Hospital|
|Principal Investigator:||Priyadarshini Tripathy, MD||S.C.B. Medical College and Hospital|