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

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ClinicalTrials.gov Identifier: NCT02866786
Recruitment Status : Completed
First Posted : August 15, 2016
Last Update Posted : April 20, 2018
Sponsor:
Information provided by (Responsible Party):
S.C.B. Medical College and Hospital

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.

Condition or disease Intervention/treatment Phase
Polycystic Ovary Syndrome Drug: Metformin Drug: ethinyl estradiol and cyproterone acetate Phase 4

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 101 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
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


Arm Intervention/treatment
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.
Drug: Metformin



Primary Outcome Measures :
  1. 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.

  2. Change in Abdominal Fat as measured by Waist Circumference in centimeter [ Time Frame: 6 months ]
  3. Change in weight as measured in kg [ Time Frame: 6 months ]
  4. Improvement in hirsutism measured by Modified Ferriman and Gallwey scores [ Time Frame: 6 months ]
  5. Improvement in glucose tolerance (measured by of fasting plasma glucose and 2-hour post prandial plasma glucose) [ Time Frame: 6 months ]
  6. Change in waist-to-hip ratio [ Time Frame: 6 months ]
  7. Change in Body mass index (kg/m2) [ Time Frame: 6 months ]

Secondary Outcome Measures :
  1. 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.

  2. Change in blood level of luteinizing hormone [LH] (mIU/ml) [ Time Frame: 6 months ]
  3. Change in blood level of follicle stimulating hormone [FSH] (mIU/ml) [ Time Frame: 6 months ]
  4. Change in blood level of Testosterone (nmol/L) [ Time Frame: 6 months ]
  5. Change in blood level of Sex hormone binding globulin (SHBG) (ng/ml) [ Time Frame: 6 months ]
  6. 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.

  7. Change in Dehydroepiandrosterone sulfate (DHEAS) level (microgram/dl) [ Time Frame: 6 months ]
  8. Changes in fasting serum insulin levels (mIU/L) [ Time Frame: 6 months ]
  9. 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

  10. Ovarian Stromal artery Pulsatility index [ Time Frame: 6 months ]
  11. Ovarian Stromal artery Resistivity index [ Time Frame: 6 months ]
  12. 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

  13. 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

  14. 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

  15. Change in Endometrial thickness (in mm) [ Time Frame: 6 months ]
  16. 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.



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Ages Eligible for Study:   18 Years to 35 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02866786


Locations
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India
Department of Obstetrics & Gynecology
Cuttack, Odisha, India, 753007
Sponsors and Collaborators
S.C.B. Medical College and Hospital
Investigators
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Principal Investigator: Mahija Sahu, MD S.C.B. Medical College and Hospital
Principal Investigator: Priyadarshini Tripathy, MD S.C.B. Medical College and Hospital

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Responsible Party: S.C.B. Medical College and Hospital
ClinicalTrials.gov Identifier: NCT02866786     History of Changes
Other Study ID Numbers: OG/2016/13
First Posted: August 15, 2016    Key Record Dates
Last Update Posted: April 20, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

Additional relevant MeSH terms:
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Syndrome
Polycystic Ovary Syndrome
Disease
Pathologic Processes
Ovarian Cysts
Cysts
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Gonadal Disorders
Endocrine System Diseases
Metformin
Estradiol
Polyestradiol phosphate
Ethinyl Estradiol
Estradiol 3-benzoate
Estradiol 17 beta-cypionate
Cyproterone Acetate
Contraceptives, Oral
Contraceptives, Oral, Combined
Cyproterone
Hypoglycemic Agents
Physiological Effects of Drugs
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Contraceptive Agents
Reproductive Control Agents
Contraceptive Agents, Female