The Effect of GLP-1 Agonists Versus OCs on Reproductive Disorders and Cardiovascular Risks in Overweight PCOS

Study Overview
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Brief Summary
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Polycystic ovary syndrome (PCOS) is a health problem that affects one in 10 women of childbearing age, which is usually characterized by hormonal imbalance and metabolism problems such as hyperandrogenism and obesity. Diane 35 pills are classified as oral contraceptives, which effectively reduces circulating androgens and are treatment for hyperandrogenism caused androgenic skin symptoms and irregular menstrual cycles. GLP-1 Receptor Agonist(e.g. exenatide, liraglutide) have the effects of lowering blood sugar and weight control by inhibiting of gastric emptying and reducing food intake. This study aims to evaluate the effect of metformin-GLP-1 Receptor agonist combination versus metformin-Diane-35 combination treatment on lipid metabolism and cardiovascular risks in overweight polycystic ovarian syndrome (PCOS) patients.

Detailed Description
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Groups: Experimental treatment: Metformin-GLP-1 Receptor Agonist Therapy. Regular treatment: Metformin-Oral Contraceptive(OC) Therapy. Time Point: Initial treatment; Post-treatment (4w); Post-treatment (8w); Post-treatment (12w); Assess reproductive functions and cardiovascular risk factors.

Official Title
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Randomized Clinical Trial to Evaluate The Effect of Metformin-GLP-1 Receptor Agonist Versus Oral Contraceptive (OC) Therapy on Reproductive Disorders and Cardiovascular Risks in Overweight Polycystic Ovarian Syndrome (PCOS) Patients

Conditions
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Polycystic Ovary Syndrome (PCOS), Overweight, Obesity

Intervention / Treatment
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* Drug: Metformin-GLP-1 Receptor Agonist
* Drug: Metformin-Oral Contraceptive(OC)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of PCOS according to the Rotterdam criteria based on the presence of two of three criteria: oligomenorrhoea, clinical or biochemical hyperandrogenism and polycystic ovaries on ultrasound after exclusion of other endocrine causes of hyperandrogenism. Participants had no concurrent illness and were not on any prescription or over-the-counter medication that was likely to affect insulin sensitivity or lipids for the preceding 12 weeks. Participants were advised not to change physical activity or dietary habits during the study period. All subjects were overweight/obese [body mass index (BMI) >=24 kg/m2 or waistline>=85cm ]. All subjects had normal thyroid-stimulating hormone and prolactin levels. Exclusion Criteria: smoking, alcohol use, or having taken medication within 2 months of the study that is known to affect reproductive or metabolic functions. age below 18 yr or over 50 yr. postmenopausal. uncontrolled hypertension (blood pressure >=160/100 mm Hg). preexisting OPs or GLP-1 agonists supplementation alcohol intake greater than 20 g/d, or pregnancy. signs of liver or renal failure or active liver disease (ALT > 2.5× the upper limit of normal values). PLT<60*10^9/L,Hb<100g/L, smoking, alcohol use. The patient that cannot complete the intervention or have other conditions that is not appropriate to enter the group, such as patients who are taking glucocorticoid steroids or malignant tumor treatment, etc.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metformin-GLP-1 Receptor Agonist<br>Metformin-GLP-1 Receptor Agonist Therapy: metformin 0.5 g/time by mouth, 3 times per day, with 5 ug exenatide subcutaneous injection twice per day, for 4 weeks, then change to 10ug exenatide subcutaneous injection twice per day for 8 weeks; or metformin 0.5 g/time by mouth, 3 times per day, with 0.6mg liraglutide subcutaneous injection once per day, for 1 weeks, then change to 1.2-1.8 mg liraglutide subcutaneous injection according to patient's blood glucose condition, twice per day for 8 weeks. | Drug: Metformin-GLP-1 Receptor Agonist<br>* metformin oral with exenatide/liraglutide subcutaneous injection.<br>* Other names: Metformin-exenatide/liraglutide Therapy;|
| Active Comparator: Metformin-Oral Contraceptive(OC)<br>Metformin-Oral Contraceptive(OC) Therapy: metformin 0.5 g/ time by mouth, 3 times per day, with Diane 35(OC) 1 piece per day by mouth, for 12 weeks. | Drug: Metformin-Oral Contraceptive(OC)<br>* metformin with Diane 35 oral intake.<br>* Other names: Metformin, Diane 35;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of Reproductive Functions | Concentration of LH was measured in mIU/ml. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Basic Vital Signs | Weight and height will be combined to report BMI in kg/m^2. | 12 weeks | 
| Assessment of Liver Function | Alanine transaminase was measured in IU/L. | 12 weeks | 
| Assessment of Blood Pressure | Systolic blood pressure was measured in mmHg. | 12 weeks | 
| Assessment of Reproductive Function | Changes in testosterone levels were measured | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Polycystic Ovary Syndrome (PCOS), Overweight, Obesity, GLP-1 Agonist, Oral contraceptives (OCs), Metformin, Reproductive Disorders, Cardiovascular risk factor, Lipid Metabolism