Clinical trial NCT02866786: The Effects of OCP and Metformin on Clinical, Hormonal, Metabolic and Ultrasonographic Characteristics in PCOS
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Polycystic Ovary Syndrome
Lead sponsor: S.C.B. Medical College and Hospital
Sponsor class: OTHER
First posted: 2016-08-15
Enrollment: 101
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Improvement in menstrual cycle pattern
timeFrame: 6 months
measure: Change in Abdominal Fat as measured by Waist Circumference in centimeter
timeFrame: 6 months
measure: Change in weight as measured in kg
timeFrame: 6 months
measure: Improvement in hirsutism measured by Modified Ferriman and Gallwey scores
timeFrame: 6 months
measure: Improvement in glucose tolerance (measured by of fasting plasma glucose and 2-hour post prandial plasma glucose)
timeFrame: 6 months
measure: Change in waist-to-hip ratio
timeFrame: 6 months
measure: Change in Body mass index (kg/m2)
timeFrame: 6 months
Secondary outcomes:
measure: Lipid profile (Cholesterol, LDL, HDL and Triglyceride) improvement
timeFrame: 6 months
measure: Change in blood level of luteinizing hormone [LH] (mIU/ml)
timeFrame: 6 months
measure: Change in blood level of follicle stimulating hormone [FSH] (mIU/ml)
timeFrame: 6 months
measure: Change in blood level of Testosterone (nmol/L)
timeFrame: 6 months
measure: Change in blood level of Sex hormone binding globulin (SHBG) (ng/ml)
timeFrame: 6 months
measure: Change in Free androgen Index (FAI)
timeFrame: 6 months
measure: Change in Dehydroepiandrosterone sulfate (DHEAS) level (microgram/dl)
timeFrame: 6 months
measure: Changes in fasting serum insulin levels (mIU/L)
timeFrame: 6 months
measure: Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)
timeFrame: 6 months
measure: Ovarian Stromal artery Pulsatility index
timeFrame: 6 months
measure: Ovarian Stromal artery Resistivity index
timeFrame: 6 months
measure: Chang in ovarian Follicle number by Ultrasonography (USG)
timeFrame: 6 months
measure: Change in ovarian Follicle diameter (in mm) by USG
timeFrame: 6 months
measure: Change in Ovarian volume (in cc) by USG
timeFrame: 6 months
measure: Change in Endometrial thickness (in mm)
timeFrame: 6 months
measure: Change in ovarian stromal/total area ratio (S/A)
timeFrame: 6 months
Other outcomes:
Locations:
city: Cuttack
country: India
facility: Department of Obstetrics & Gynecology
state: Odisha
Study officials:
affiliation: S.C.B. Medical College and Hospital
name: Mahija Sahu, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: S.C.B. Medical College and Hospital
name: Priyadarshini Tripathy, MD
role: PRINCIPAL_INVESTIGATOR
References: